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Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial
Abstract
The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency.
To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk.
Post hoc analysis.
The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers.
980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 micromol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 micromol/L (2.3 mg/dL) were excluded.
The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke.
Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference).
In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
... 166 RASi also reduced CV outcomes as compared to placebo in high-risk populations, particularly in subgroups with CKD, 166,167 independent of the presence or absence of high BP. 165,167,168 That said, there is limited evidence to use specific antihypertensive agents to treat high BP to target in CKD, and almost no evidence comparing antihypertensive combination therapies in CKD from outcome trials. Many people with CKD and BP of at least 20 mm Hg above the target will need combinations of several antihypertensive drugs. ...
... Balance of benefits and harms. The HOPE study, 163 167 It should be noted that approximately one-third of patients in the HOPE study had diabetes, and only half had high BP. In the overall HOPE study, the CV benefits of ramipril versus placebo were also present in those with moderately increased albuminuria (approximately 1900 cases/9360 patients). ...
... during a mean follow-up of 4.5 years. 167 In the overall HOPE study, 3577 patients had diabetes, and 2437 of them (roughly two-thirds) did not have albuminuria. 163 The PEACE substudy in those with CKD confirmed this notion. ...
... HF is a major global public health problem that affects more than 64 million people worldwide (29). Substantial data demonstrated that HF is more common in CKD patients compared to those without CKD (30)(31)(32)(33), and the prevalence *Abnormal distribution, using Wilcoxon paired signed rank test, a non-parametric 95%CI and an estimator for the pseudo-median of the difference of the location parameters is computed. The calculation of the p-value was based on the range of pseudo-median of the distribution of difference. ...
... increases with the renal function progression (31,33,34). In ESRD patients undergoing dialysis, the HF incidence increases to 12-36 times of the general population (31,34). ...
Aim
There are few data about the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). The present study was conducted to evaluate the association between sacubitril-valsartan treatment and peritoneal ultrafiltration (PUF) in PD patients.
Methods and Results
Forty-seven ESRD patients undergoing PD for at least 3 months without severe congestive heart failure (CHF) were included in this study. Sacubitril-valsartan (generally 100 mg b.i.d) was administered after consultation with the nephrologist. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) were required to be discontinued 36 h before prescribing sacubitril-valsartan. Other treatments and dialysis modality did not change. Baseline demographic and clinical parameters were collected before ARNI administration, and daily PUF, urine volume, total output, blood pressure (BP), and body weight were collected within 7 days before and after ARNI treatment. After treated with sacubitril-valsartan, 30 patients (63.8%) had a significant increase of PUF [up to 150.4 (110.7, 232.1) ml per day], while the remaining 17 (36.2%) had a slight decrease. The overall increase of PUF was 66.4 (21.4, 123.2) ml/24 h within the 7 days after sacubitril-valsartan administration, which was significantly higher than those before ( P = 0.004). Total output, BP, and body weight also significantly improved. No adverse drug reactions were observed.
Conclusions
Our study indicated that sacubitril-valsartan was associated with the increase of short-term PUF and total output in PD patients.
... Studi clinici, anche se limitati dal punto di vista del campione numerico, effettuati con fosinopril ne hanno dimostrato l'efficacia in tema di prevenzione primaria (6). ...
... Il trial HOPE, che ha escluso pazienti con valori di creatinina sierica >2.3 mg/dL, ha evidenziato il ruolo del ramipril nel ridurre l'endpoint composito per morte cardiovascolare, ictus e infarto del miocardio in una popolazione di pazienti affetti da arteriopatia periferica e CKD (6). ...
non disponibile (Cardionephrology)
... Препаратами первого ряда для лечения больных АГ и МС, а также с поражением почек являются блокаторы РАС [1,7,8]. Во многих крупномасштабных исследованиях продемонстрирована способность ИАПФ уменьшать выраженность протеинурии, в том числе приводить к исчезновению МАУ [43][44][45][46][47]. Cпособность ИАПФ уменьшать экскрецию белков с мочой была показана и в работе, прицельно изучавшей ассоциированную с ожирением нефропатию [43], позже она была подтверждена результатами других экспериментальных [44], а также клинических [45][46][47] исследований. ...
... Препаратами первого ряда для лечения больных АГ и МС, а также с поражением почек являются блокаторы РАС [1,7,8]. Во многих крупномасштабных исследованиях продемонстрирована способность ИАПФ уменьшать выраженность протеинурии, в том числе приводить к исчезновению МАУ [43][44][45][46][47]. Cпособность ИАПФ уменьшать экскрецию белков с мочой была показана и в работе, прицельно изучавшей ассоциированную с ожирением нефропатию [43], позже она была подтверждена результатами других экспериментальных [44], а также клинических [45][46][47] исследований. С учетом несомненного участия компонентов РАС, прежде всего АТ II, в становлении эндотелиальной дисфункции у больных с ожирением применение этих препаратов является одной из наиболее действенных стратегий лечения ассоциированной с ожирением нефропатии. ...
In the article shows the questions of prevalence, diagnosis and prognostic significance of renal damage in metabolic syndrome. Discusses the pathogenetic mechanisms of development and progression of chronic kidney disease in individuals with obesity. Approaches to selection of antihypertensive drugs, advantages and limitations of the major classes of antihypertensive drugs in the treatment of metabolic syndrome, arterial hypertension combined with renal disease.
... About 8 million adults are affected from chronic kidney disease in United States of at least stage 3 (glomerular filtration rate (GFR) of below 60 ml/min/1.73m 2 of body surface area) (13) is reported about the rates of death, cardiovascular disease. It was noticed that in the previous studies that elevation in the serum creatinine level from mild to moderate are the cause of increased rate of death (14)(15)(16) and also from the cardiovascular cause (17) but it also notify that chronic kidney disease itself increases the cardiovascular disease risk that has not been recognized (18,19). Inadequacy of health care resource programs about kidney replacement therapy is the huge distinction in the pervasiveness or popularity of ESRD amongst more and less developed countries. ...
Background: End Stage Renal Disease (ESRD) or Chronic kidney disease (CKD) is a group of diverse deformities that upshot the physiology and anatomy of the kidney. Kidney failure is the most severe outcome of the chronic kidney disease. Methodology: Comparative study. Sixty patients of End Stage Renal Disease (ESRD) and Fourty five age and gender matched clinically evidently fit persons were entitled for incorporation in the study. 5 ml blood sample were drawn and subjected to centrifuge at 4000-5000 rpm for 15 minutes for the separation of serum. Serum MDA, SOD, CAT, GSH, VIT A, VIT C, VIT E, Nitric oxide (NO), Neuraminidase, Electrolytes TNF-alpha and IL-2 were estimated. Results: Serum Sodium (Na +) level in the ESRD patients was elevated (179.53±3.26) as compared to control (147.26±4.26) and significant statistically (0.04<0.05). Serum Potassium level (K +) was also raised in the ESRD patients (16.12±5.26) as compared to control group (11.09±3.26) and also statistically substantial (0.03<0.05). Vitamin A level in ESRD patients was decreased (87.99±5.26) as compared to healthy subjects (102.25±14.26) and statistically substantial (0.002<0.05). MDA level shows elevated level in ESRD patients (8.06±1.5) as compared to control (1.25±0.65) and statistically significant (0.045<0.05). Conclusion: Present study showed that there is a correlation exist between Oxidative stress, Vitamins, Electrolytes, IL-2, TNF-alpha and CKD. These results indicate a perfect description related to circulating biomarkers and lipid peroxidation. Increased level of MDA as a biomarker of lipid peroxidation, increased IL-2 and TNF-alpha and Nitric oxide (NO) level is the cause for the progression of the disease.
... About 8 million adults are affected from chronic kidney disease in United States of at least stage 3 (glomerular filtration rate (GFR) of below 60 ml/min/1.73m 2 of body surface area) (13) is reported about the rates of death, cardiovascular disease. It was noticed that in the previous studies that elevation in the serum creatinine level from mild to moderate are the cause of increased rate of death (14)(15)(16) and also from the cardiovascular cause (17) but it also notify that chronic kidney disease itself increases the cardiovascular disease risk that has not been recognized (18,19). Inadequacy of health care resource programs about kidney replacement therapy is the huge distinction in the pervasiveness or popularity of ESRD amongst more and less developed countries. ...
Background: End Stage Renal Disease (ESRD) or Chronic kidney disease (CKD) is a group of diverse deformities that upshot the physiology and anatomy of the kidney. Kidney failure is the most severe outcome of the chronic kidney disease. Methodology: Comparative study. Sixty patients of End Stage Renal Disease (ESRD) and Fourty five age and gender matched clinically evidently fit persons were entitled for incorporation in the study. 5 ml blood sample were drawn and subjected to centrifuge at 4000-5000 rpm for 15 minutes for the separation of serum. Serum MDA, SOD, CAT, GSH, VIT A, VIT C, VIT E, Nitric oxide (NO), Neuraminidase, Electrolytes TNF-alpha and IL-2 were estimated. Results: Serum Sodium (Na +) level in the ESRD patients was elevated (179.53±3.26) as compared to control (147.26±4.26) and significant statistically (0.04<0.05). Serum Potassium level (K +) was also raised in the ESRD patients (16.12±5.26) as compared to control group (11.09±3.26) and also statistically substantial (0.03<0.05). Vitamin A level in ESRD patients was decreased (87.99±5.26) as compared to healthy subjects (102.25±14.26) and statistically substantial (0.002<0.05). MDA level shows elevated level in ESRD patients (8.06±1.5) as compared to control (1.25±0.65) and statistically significant (0.045<0.05). Conclusion: Present study showed that there is a correlation exist between Oxidative stress, Vitamins, Electrolytes, IL-2, TNF-alpha and CKD. These results indicate a perfect description related to circulating biomarkers and lipid peroxidation. Increased level of MDA as a biomarker of lipid peroxidation, increased IL-2 and TNF-alpha and Nitric oxide (NO) level is the cause for the progression of the disease.
... Considering microalbuminuria as risk factor for cardiovascular disease. A substudy of the heart outcomes prevention evaluation study found that microalbuminuria was strong predictor of cardiovascular disease (36). Level of hs-CRP was increased significantly in patients (4.91±0.177) ...
البيلة الألبومينية الزهيدة مرتبطة ارتباطًا وثيقًا بخطر الإصابة بأمراض القلب والأوعية الدموية ، وهي علامة خطر معترف بها على نطاق واسع وقوية ومستقلة لأمراض القلب والأوعية الدموية بين الأفراد المصابين بداء السكري. تمت هذه الدراسة في الفترة من تشرين الاول الى كانون الاول 2014 في المركز الوطني للسكري ، الجامعة المستنصرية ، بغداد ، العراق. مجموعة الدراسة ، تضم 50 مريضاً يعانون من داء السكري من النوع 2 وأمراض القلب والأوعية الدموية ، والمجموعة الثانية 30 مريضاً يعانون من داء السكري فقط كمجموعة تحكم ، وتراوحت أعمارهم بين (45-65) سنة. أظهرت النتائج زيادة في FBG و HbA1c و hs-CRP و LDL و TG و AIP و Urea و Creatinine و Microalbuminuria في المرضى مقارنة مع مجموعة التحكم عند (P <0.001). بينما كان تركيز HDL أقل معنويا في المرضى مقارنة مع مجموعة السيطرة عند (P <0.001). هناك علاقة إيجابية بين AIP و HbA1c و hs-CRP و TG و Urea و Creatinine و Microalbuminuria. لذلك أصبحت البيلة الألبومينية الزهيدة علامة تنبؤية لأمراض القلب والأوعية الدموية.
... However, when they observed the relationship between presence of albuminuria and renal insufficiency, 88.4% of patients with renal insufficiency showed albuminuria in those under 40 years of age, whereas only 43.6% of patients showed albuminuric renal insufficiency in those over 60-79 years of age 25 . In the Heart Outcomes and Prevention Evaluation (HOPE) study, two-thirds of elderly patients with renal insufficiency showed no signs of albuminuria 26 . The above studies suggest that proteinuria could reflect renal function impairment better in people under 40 years of age than in elder age. ...
Understanding the association between dipstick-detected proteinuria and oculomotor cranial nerve palsy (CNP) could have significant implications for understanding the mechanism of CNP development and for developing preventive strategies against CNP development in patients with proteinuria. This study aimed to determine the relationship between dipstick-determined proteinuria and ocular motor CNP using National Sample Cohort (NSC) database from Korea’s National Health Insurance Service (NHIS). A nationwide population-based cohort study was conducted using data from the NSC database of Korea’s NHIS. These data were collected from 2009 to 2018. A one-year time lag was established to prevent a situation in which the causal link was inverted. Participants aged 20 years or more who were diagnosed with proteinuria in 2009 were included. Individuals with specific pre-existing CNP, missing data, and those who were newly diagnosed with CNP or who died within one year of being tested were excluded. The study population was classified into six groups according to the degree of proteinuria (negative, trace, or between 1 + and 4 +) based on the urine dipstick test. A Cox proportional hazard regression analysis was performed to determine the linkage between the degree of proteinuria and ocular motor CNP. A total of 5,807 (0.14% of subjects) with ocular motor CNP were assigned to the ocular motor CNP group and 4,047,205 subjects were assigned to the control group. After full adjustment of comorbidities, hazard ratios (HRs) for 1 + , 2 + , 3 + and 4 + proteinuria groups were 1.449 (95% confidence interval [CI] 1.244–1.687), 2.081 (1.707–2.538), 1.96 (1.322–2.904), and 3.011 (1.507–6.014), respectively, for developing ocular motor CNP compared to the proteinuria-negative group. In subgroup analysis, the HR of patients with proteinuria for the development of ocular motor CNP was higher in the younger age group (less than 40 years) (P = 0.0242) and the group with DM (P = 0.04). Our population-based cohort study demonstrated a significant association between proteinuria and the incidence of CNP, suggesting that urine protein level could be a new clinical marker for predicting the development of CNP.
... About 8 million adults are affected from chronic kidney disease in United States of at least stage 3 (glomerular filtration rate (GFR) of below 60 ml/min/1.73m 2 of body surface area) (13) is reported about the rates of death, cardiovascular disease. It was noticed that in the previous studies that elevation in the serum creatinine level from mild to moderate are the cause of increased rate of death (14)(15)(16) and also from the cardiovascular cause (17) but it also notify that chronic kidney disease itself increases the cardiovascular disease risk that has not been recognized (18,19). Inadequacy of health care resource programs about kidney replacement therapy is the huge distinction in the pervasiveness or popularity of ESRD amongst more and less developed countries. ...
Background: End Stage Renal Disease (ESRD) or Chronic kidney disease (CKD) is a group of diverse deformities that upshot the physiology and anatomy of the kidney. Kidney failure is the most severe outcome of the chronic kidney disease. Methodology: Comparative study. Sixty patients of End Stage Renal Disease (ESRD) and Fourty five age and gender matched clinically evidently fit persons were entitled for incorporation in the study. 5 ml blood sample were drawn and subjected to centrifuge at 4000-5000 rpm for 15 minutes for the separation of serum. Serum MDA, SOD, CAT, GSH, VIT A, VIT C, VIT E, Nitric oxide (NO), Neuraminidase, Electrolytes TNF-alpha and IL-2 were estimated. Results: Serum Sodium (Na +) level in the ESRD patients was elevated (179.53±3.26) as compared to control (147.26±4.26) and significant statistically (0.04<0.05). Serum Potassium level (K +) was also raised in the ESRD patients (16.12±5.26) as compared to control group (11.09±3.26) and also statistically substantial (0.03<0.05). Vitamin A level in ESRD patients was decreased (87.99±5.26) as compared to healthy subjects (102.25±14.26) and statistically substantial (0.002<0.05). MDA level shows elevated level in ESRD patients (8.06±1.5) as compared to control (1.25±0.65) and statistically significant (0.045<0.05). Conclusion: Present study showed that there is a correlation exist between Oxidative stress, Vitamins, Electrolytes, IL-2, TNF-alpha and CKD. These results indicate a perfect description related to circulating biomarkers and lipid peroxidation. Increased level of MDA as a biomarker of lipid peroxidation, increased IL-2 and TNF-alpha and Nitric oxide (NO) level is the cause for the progression of the disease.
... In many studies, patients with rather than without mild renal insufficiency are considered to have poorer clinical baseline characteristics. Typically, these patients are older and more often have comorbid diabetes, hypertension and severe coronary risk factors [40][41][42][43]. ...
Objective: The severity and prognosis of coronary artery disease are closely associated with treatment strategy choice. To achieve timely, accurate, early selection of a suitable treatment plan and assess patients’ prognosis, we developed an effective predictive model for early identification of high-risk patients according to lesion severity.
Methods: Among the 510 patients with chest pain admitted to the Qinghai Red Cross Hospital between August 2018 and October 2019, 386 had coronary artery disease detected by coronary angiography. A total of 24 demographic characteristics and serum markers were analyzed in study participants. Least absolute shrinkage and selection operator regression was used to select variables, and multivariate logistic regression was used to build predictive models by using nominal plots. The discriminatory power of the models was evaluated with the area under the receiver operating characteristic curve (AUC). Predictive models were calibrated with calibration plots and the Hosmer–Lemeshow test. Their clinical validity was evaluated via decision curve analysis.
Results: Data were randomly divided (7:3) into training (358 cases) and test (152 cases) sets. The predictive model included sex, age, smoking status, heart rate, systolic blood pressure, diastolic blood pressure, albumin, urea nitrogen, creatinine, uric acid, total cholesterol, and high-density lipoprotein cholesterol as predictors. The AUCs for the training and test sets were 0.793 and 0.732, respectively. The predictive model showed a good fit, and decision curve analysis indicated the clinical validity of the predictive model.
Conclusions: We developed an effective risk predictive model with good clinical value for predicting multivessel disease. Smoking cessation, lowering creatinine, and increasing HDL cholesterol concentrations might decrease the risk of developing multivessel disease, thereby avoiding severe disease.
... The CVD benefits of RAAS blockade in CKD populations have yet to be firmly established and high-quality evidence in ESKD remains lacking [189][190][191][192]. Neither the Fosinopril in Dialysis (FOSIDIAL) nor the Olmesartan Clinical Trial in Okinawa Patients Under Okinawa Dialysis (OCTOPUS) studies demonstrated any CVD benefits with fosinopril or olmesartan in chronic HD patients respectively [193,194]. ...
Cardiovascular disease (CVD) accounts for more than 50% of deaths among patients with end-stage kidney disease (ESKD). Approximately 40–50% of ESKD patients have clinically significant coronary artery disease (CAD) due to atherosclerosis which accounts for a significant proportion of CVD risk. However, other CVD pathologies including myocardial fibrosis, vascular calcification and arterial stiffening play important contributory roles. The pathophysiology of CAD in ESKD is distinct from the general population. ESKD patients is typically have diffuse multi-vessel involvement with increased calcification that involves both intimal and medial layers of the arterial wall. There is a complex interplay between an increased burden of traditional Framingham risk factors and exposure to non-traditional risk factors including chronic inflammation and dialysis per se. Established treatments for CAD risk factors including cholesterol lowering with statin therapy have attenuated effects and ESKD patients also have worse outcomes after revascularisation. Recent trials such as the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) have established that direct modulation of inflammation improves CVD outcomes in the general population, which may prove to be a potential attractive therapeutic target in ESKD patients. Multiple retrospective observational studies comparing mortality outcomes between haemodialysis (HD) and peritoneal dialysis (PD) patients have been inconclusive. Randomised trials on this issue of clinical equipoise are clearly warranted but are unlikely to be feasible. Screening for stable CAD in asymptomatic ESKD patients remains a clinical dilemma which is unique to chronic dialysis patients being assessed for kidney transplantation. This has become particularly relevant in light of the recent ISCHEMIA-CKD trial which demonstrated no difference between optimal medical therapy and revascularisation upon CVD outcomes or mortality. The optimal strategy for screening is currently being investigated in the ongoing large international multi-centre CARSK trial. Here we discuss the pathophysiology, risk modification, treatment, screening and future directions of CAD in ESKD.
... Therefore, disrupting the classical RAAS pathway through inhibition of ACE or blocking of AT1R and promoting MASR are potential therapeutic targets to reduce muscle wasting. ACE inhibitors and ARB are the most commonly prescribed antihypertensive drugs in patients with CKD because of their effect on slowing the decline in kidney function, decreasing urine protein excretion, and adverse cardiovas- [164][165][166][167]. Along with renoprotective effects, these drugs are expected to inhibit muscle atrophy by blocking Ang II production. ...
Sarcopenia is a condition characterized by a loss of muscle mass and function. In chronic kidney disease (CKD), where a chronic catabolic state exists, sarcopenia commonly occurs through various mechanisms, resulting in muscle wasting and decreased muscle endurance. Sarcopenic patients with CKD have high morbidity and mortality rates. Indeed, the prevention and treatment of sarcopenia are mandatory. An imbalance between protein synthesis and degradation in muscle and increased oxidative stress and inflammation persist in CKD and induce muscle wasting. In addition, uremic toxins negatively affect muscle maintenance. A variety of potential therapeutic drugs targeting these muscle-wasting mechanisms in CKD have been investigated, but most of the trials focused on aged patients without CKD, and none of these drugs have been approved for the treatment of sarcopenia so far. Further studies on the molecular mechanisms of sarcopenia in CKD and targets for potential therapeutics are needed to improve the outcomes of sarcopenic patients with CKD.
... In clinical studies, elevated serum creatinine levels are generally considered as an adverse events or outcomes, often indicating renal impairment (2,3), meanwhile, studies have shown that impaired renal function is often accompanied by increased cardiovascular risk (4). Serum creatinine levels are not only a contributor to the development cardiovascular events, but also strongly associated with longitudinal risk for cardiovascular disease (CVD) and mortality (5,6). ...
Background:
Serum creatinine is associated with cardiovascular risk and cardiovascular events, however, the relationship between serum creatinine levels and cardiovascular risk is not well established in hypertensive population in Jiangsu Province. We aimed to evaluate the association of serum creatinine levels with traditional cardiovascular risk factors and 10-year cardiovascular risk in a Chinese hypertensive population.
Methods:
Participants were patients with hypertension registered and enrolled in health service centers in 5 counties or districts from January 2019 to May 2020 in Jiangsu Province of China followed strict inclusion and exclusion criteria, demographics as well as clinical indicators and disease history and lifestyle were collected. Participants were divided into four groups according to quartiles of serum creatinine levels, then the China-PAR model was used to calculate 10-year cardiovascular risk for each individual.
Results:
A total of 9978 participants were enrolled in this study, 4173(41.82%) were males. The blood pressure level and prevalence of dyslipidemia, elderly, current smokers and drinking as well as obesity were higher in the Q4 group than the Q1 group (all P < 0.05). Multivariable logistic regression showed that serum creatinine in the Q4 group compared with that in the Q1 group was positively associated with overweight and obesity (OR=1.432, 95% CI 1.237-1.658, P<0.001), while negatively associated with physical activity (OR=0.189, 95%CI 0.165-0.217, P<0.001), and so on. Multiple linear regression showed 10-year cardiovascular risk is positively associated with serum creatinine levels after adjusting for multiple risk factors (β=0.432, P< 0.001).
Conclusion:
Serum creatinine was associated with several traditional cardiovascular risk factors and the 10-year cardiovascular risk in hypertensive patients. Creatinine-reduction and kidney-sparing therapy are essential for patients with hypertension to optimize control of cardiovascular risk.
... Furthermore, previous studies have shown that renal impairment is an independent risk factor for CVD and total mortality (30,31). Moreover, decreased GFR has been found to be an independent risk factor in patients with diabetes and congestive heart failure for future CVD events and total mortality (32,33). In addition, percutaneous coronary interventions also have a less favorable outcome for patients with CKD (34). ...
Over the past decade, serum cystatin C (SCC) has been often suggested as a marker of kidney function. Strong evidence has shown that SCC may improve classification of the glomerular filtration rate (GFR) to identify chronic kidney disease in certain clinical populations. SCC equations based on the SCC reference standard are considered state–of–the–art to estimate kidney function and the latest chronic kidney disease guidelines included several suggestions and recommendations that relate to SCC. The results of several previous studies have also suggested that SCC may be more useful than just a marker of GFR, as it may also be useful as a clinical marker to provide complementary information to established risk determinants, especially for high–risk populations. Additionally, other studies have reported that SCC may be a useful prognostic indicator of cardiovascular disease.
... Consequently the prognosis of patients with CAD and MAU is worse when compared to patients without [9, 10]. Overall it has been shown that MAU seems to be more relevant than many established cardiovascular risk factors [11]. A recent multivariate analysis of the HOPE trial has shown that the probability of stroke, myocardial infarction and cardiovascular death was higher for patients with MAU as compared to those with PAD, diabetes or the impact of male gender.The analyses further support the notion that, for cardiovascular risk assessment, not only MAU but albumin excretion below the threshold (low grade albuminuria) is already reflected in a higher probability of cardiovascular disease (for a recent review see [12]). ...
... Conflicting evidence exists concerning whether mild to moderate kidney impairment was an independent risk factor for CV disease in the general population [9]. Several literature reports provided evidence of mild kidney impairment and the risk for subsequent CV events among patients having pre-existing vascular disease or high CV risk [10,11]. Evidence in Southeast Asian populations with high CV risk remains limited. ...
Background:
Decline of estimated glomerular filtration rate (eGFR) is associated with increased cardiovascular (CV) morbidity and mortality, but the predictive value of different eGFR on CV outcomes is limited in Southeast Asian populations.
Aims:
We aimed to stratify CV outcomes according to renal function among Thai patients with high atherosclerosis risk.
Methods:
We performed a secondary analysis in a 5-year national cohort entitled "CORE-Thailand study." Subjects were classified in 6 groups according to baseline kidney function: group I, eGFR ≥ 90; group II, eGFR 60-89; group IIIa, eGFR 45-59; group IIIb, eGFR 30-44; group IV, eGFR 15-29; group V, eGFR < 15 ml/min/1.73 m2 or receiving renal replacement therapy. The primary outcome was 4-point major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, CV mortality, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke.
Results:
A total of 6376 subjects (3467 men and 2909 women) were categorized in 6 groups. After adjusting covariates in the Cox proportional hazards model, compared to group I, subjects in groups II-V had a 1.65-fold, 2.17-fold, 2.67-fold, 4.24-fold, and 4.87-fold risk for 4-point MACE, respectively, with statistical significance at P < 0.05 in all groups. Kaplan-Meier analysis illustrated stepwise lower survivals from 4-point MACE following the groups with lower baseline eGFR (log-rank test with P < 0.001). All secondary outcomes showed similar trends as the primary outcome, except nonfatal stroke.
Conclusion:
Lower baseline kidney function was independently associated with increased risk of CV events and all-cause mortality in Thai populations at high CV risk.
... Furthermore, it is estimated that 30-40% of patients with diabetes develop diabetic kidney disease [82]. The progression of CKD increases the risk of CV death in patients with and without diabetes [89][90][91]. The ESC/EASD 2019 guidelines have identified CKD and microalbuminuria in diabetes as markers of high CV risk, with microalbuminuria also being a marker for the development of renal dysfunction [4]. ...
It is well known that diabetes is a prominent risk factor for cardiovascular (CV) events. The level of CV risk depends on the type and duration of diabetes, age and additional co-morbidities. Diabetes is an independent risk factor for atrial fibrillation (AF) and is frequently observed in patients with AF, which further increases their risk of stroke associated with this cardiac arrhythmia. Nearly one third of patients with diabetes globally have CV disease (CVD). Additionally, co-morbid AF and coronary artery disease are more frequently observed in patients with diabetes than the general population, further increasing the already high CV risk of these patients. To protect against thromboembolic events in patients with diabetes and AF or established CVD, guidelines recommend optimal CV risk factor control, including oral anticoagulation treatment. However, patients with diabetes exist in a prothrombotic and inflammatory state. Greater clinical benefit may therefore be seen with the use of stronger antithrombotic agents or innovative drug combinations in high-risk patients with diabetes, such as those who have concomitant AF or established CVD. In this review, we discuss CV risk management strategies in patients with diabetes and concomitant vascular disease, stroke prevention regimens in patients with diabetes and AF and how worsening renal function in these patients may complicate these approaches. Accumulating evidence from clinical trials and real-world evidence show a benefit to the administration of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with diabetes and AF.
... наличие достоверной взаимосвязи между пониженной СКф и ССз было зарегистрировано также другими многочисленными исследованиями, в которые были вовлечены больные как с высокими (аг, хроническая сердечная недостаточность, Сд, возраст выше 65 лет и т.д.), так и низкими факторами риска [41][42][43][44]. более того, K. matsushita и соавт. ...
In the recent years there is a tendency for progressive increase in the number of patients with chronic kidney failure (CKF) in the world and, importantly, that this growth does not tend to slow down in the future. Numerous studies have proven a clear relationship between the degree and duration of arterial hypertension (AH) and incidence of CKF. in this view during AH glomerular filtration rate (GFR) reflects early, intermediate and also late stages of kidney damage and in this case changes of GFR have diverse character. so, an increase of absolute values of GFR is typical for early stages of AH and a decrease of GFR is typical for the late stages of AH. in the same time during AH GFR can be presented as a predicting risk factor for other target organ damage and cardiovascular morbidity and mortality development as well. Thus the evaluation of GFR should be more widely introduced in the clinical practice with the purpose of revelation of other cardiovascular risk factors and associated pathological conditions, continuous monitoring and prevention of target organ damage.
... Similar findings come from another meta-analysis showing a 40% decrease in the risk of ESRD or the doubling of serum creatinine with ACEis compared to a placebo [48], and from a randomised trial enrolling non-diabetic patients with advanced CKD [49]. On the other hand, there is no clear evidence of any BP-lowering independent reno-or cardioprotective effects with ACEi treatment in patients with non-diabetic kidney disease and proteinuria lower than 500 mg/24 h [50][51][52]. Hence, ACEis are mainly beneficial in people with higher baseline levels of albuminuria or proteinuria, [53][54][55] a key point reflected in recent renal guidelines [11,21]. ...
Hypertension affects over a billion people worldwide and is the leading cause of cardiovascular disease and premature death worldwide, as well as one of the key determinants of chronic kidney disease worldwide. People with chronic kidney disease and hypertension are at very high risk of renal outcomes, including progression to end-stage renal disease, and, even more importantly, cardiovascular outcomes. Hence, blood pressure control is crucial in reducing the human and socio-economic burden of renal and cardiovascular outcomes in those patients. However, current guidelines from hypertension and renal societies have issued different and sometimes conflicting recommendations, which risk confusing clinicians and potentially contributing to a less effective prevention of renal and cardiovascular outcomes. In this review, we critically appraise existing evidence and key international guidelines, and we finally formulate our own opinion that clinicians should aim for a blood pressure target lower than 130/80 in all patients with chronic kidney disease and hypertension, unless they are frail or with multiple comorbidities. We also advocate for an even more ambitious systolic blood pressure target lower than 120 mmHg in younger patients with a lower burden of comorbidities, to minimise their risk of renal and cardiovascular events during their lifetime.
... It is coupled with several other complications including cardiovascular complications. For instance, studies suggests that patients having GFR from 15-59 ml/min are at 38% greater risk for the development of cardiovascular complications when compared with patients having GFR 90-150 ml/min [4,5]. CKD not only affect individuals quality of life but is global burden on health care system. ...
Chronic Kidney Disease (CKD) is considered as one of the most prevalent chronic inflammatory diseases with tremendous economic burden. Despite of being asymptomatic in premature stages, recent researches pursuit revealing its obscurity as early as possible to avoid renal progressive involvements. We aimed to assess the SCORED as a tool for identification and risk stratification of CKD.
... To the best of our knowledge, the MIC-K study is the first study to provide data on long-term clinical outcomes of Japanese patients with ACS who received acute care in cardiovascular centers and were later referred to general practitioners. The ma- [20][21][22][23][24][25][26][27][28][29][30][31][32][33] . Previous studies have demonstrated an association between renal dysfunction and adverse outcomes following MI [25][26][27][28][29][30] , PCI 31,32) , or CABG 33) . ...
... [15] Besides, CKD samples were marked by some deep-rooted risk factors of periodontitis such as diabetes and poor oral hygiene. [16,17] Moreover, CKD can affect oral structures such as oral mucosa, periodontium, tongue, and salivary glands, resulting in an adverse effect on the oral health status. [15] Moreover, evidence has shown that there are elevated serum levels of C reactive protein (CRP) and inflammatory cytokines such as different types of IL, which were observed in patients with long-term kidney disease and chronic periodontitis. ...
Aim: To systematically review the in vivo clinical studies available in the literature evaluating the effect of interleukin (IL) in patients with chronic kidney disease (CKD) and chronic periodontitis (CP). Materials and Methods: A search was initially performed using Scopus, PubMed, and Web of Science databases published from the year 2003 to 2020. Among the keywords used in the search were “periodontal diseases,” “interleukin,” “chronic kidney diseases,” and “inflammation.” After relevant articles were found, a critical assessment was made to select those that met the criteria for the systematic review. Among the inclusion criteria needed for the papers were randomized clinical trials, longitudinal clinical trials, clinical studies, no sample size limits, and only English language articles. Case reports, conference abstracts, and unpublished data were excluded for this study. Result: Based on the keywords, 16 of the relevant articles were listed and seven of them were selected for a systematic review. Conclusion: After reviewing the articles based on their results and conclusion, it can be concluded that serum IL level increased significantly in patients with CKD and CP and periodontal therapy can significantly reduce the level of serum IL. Moreover, the effect of modern periodontal therapy in CKD and CP is still unknown and inflammatory gene expression profile in patients with CKD will still need to be evaluated within different populations.
... It is estimated that 80% of chronic disease 13 deaths now occur in low-and middleincome countries . CKD is important among this group as, apart from its own morbidity, mortality and high risk for progression to end-stage renal disease (ESRD), it has also been found to be an 14,15 important independent risk factor for CVD . ...
Background: The present study was conduct in Motilal Nehru Medical College, Swaroop Rani Nehru Hospital Prayagraj, a tertiary care center and data was collected over a period from January 2019 to April 2020. All 78 patients of CKD attending OPD & IPD of General Medicine and Nephrology, diagnosed by suggestive symptoms and conrmed by physical examination and laboratory investigations were taken , Among the subjects, those having NAFLD were grouped as cases. Patients of Chronic Kidney disease not having NAFLD were grouped as controls. Aim & Objective: To study the prevalence of NAFLD in patients of CKD and establish the association between NAFLD and CKD by studying the effect of NAFLD on eGFR. Methodology: This was a 16 month case control study. Total 78 patients with age 18-65 years , Either sex with Chronic kidney disease diagnosed by USG, KFT, physical examination and having NAFLD Patients with known diagnosis of metabolic syndrome, diabetes and/or hypothyroidism. Those on hepatotoxic medication (amiodarone, barbiturates, glucocorticoids, etc.). The data so collected was entered into computer using Microsoft Excel 2013 software and was subjected to statistical analysis. Result : The ndings of present study thus reafrm the observations of previous studies that highlight a high prevalence of NAFLD in CKD patients and link it to the deranged metabolic factors. In present study we could not found a convincing evidence supporting a relationship between NAFLD and its severity with progression of CKD, probably owing to three major factors – rst, owing to Discussion 71 limitation of study population in only CKD stage 3 and secondly, owing to absence of retrospective data tracing the time of development of NAFLD in these patients and thirdly, inability to carry out long-time follow-up of patients. In present study, though minor changes in eGFR values in patients were seen, however, during the limited period of follow-up no shift from Stage 3 to other stages of CKD was observed. All the patients were regular in follow-up and had a good medical compliance and in general did not show a phenomenal deterioration in renal function within the short span of study. Keeping in view these limitations, further studies are recommended on a larger sample size with inclusion of patients from different stages of CKD spanning over a longer duration of follow-up to see whether NAFLD presence and its severity has a relationship with long-term progression of CKD. Conclusion: The present study showed that, CKD patients had a high prevalence of NAFLD. The ndings also show that FIB-4 scores are useful noninvasive methods for detection of NAFLD in CKD patients. The ndings showed a possible signicant association between NAFLD and lower eGFR rates. One of the limitations of the present study was presence of only Stage 3 CKD patients, owing to which the linear correlations between eGFR and NAFLD severity could not be assessed properly. Further studies on larger sample size with inclusion of patients with other CKD stages too are recommended.
... Echocardiographic indicators for diagnosing HFpEF included the average septal-lateral E/e' ratio, TR (tricuspid regurgitation peak velocity), and left atrial volume index (22). Substantial data have demonstrated CKD is an independent risk factor for cardiovascular (CV) events (23)(24)(25)(26). The overall rate of CV disease was higher in patients with CKD as compared to those without CKD, in particular, patients with ESKD have an increased incidence of CV death ∼10-20 times that of the general population. ...
Aims: The effect of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis.
Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II–IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50–100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5–21941.0) vs. 3034.0 (1493.2–6503.0), P = 0.002], and heart rate [80.0 (74.5–90.5) vs. 75.0 (70.3–87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3–12 months of follow-up. None of the patients showed adverse drug reactions.
Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.
... In the Hypertension Detection and Follow-up Program (HDFP) study, it showed that CKD patients' mortality rate due to cardiovascular disease was much higher than that due to Cr ≥ 1.7 mg/dl, of which 58% died of cardiovascular disease and only 19% died of kidney failure [31]. In the Heart Outcomes and Prevention Evaluation study (HOPE) experiment, it was found that that patients with mild chronic renal insufficiency [Cr in the range of 1.4 mg/dl to 2.3 mg/dl] have a significantly increased incidence of myocardial infarction [32]. After summarizing the most valuable studies, the American Heart Association (AHA) also believed that CKD is a risk factor for cardiogenic death [33]. ...
Objective:
The aim of this meta-analysis was to systematically evaluate the effectiveness and safety of the traditional Chinese medicine (TCM) formula Bushen Huoxue Decoction (BSHXD) in treating coronary heart disease (CHD).
Methods:
Randomized controlled trials (RCTS) of BSHXD in treating CHD were searched until March 2020, through six electronic databases: PubMed, Cochrane Library, CNKI, WanFang, SinoMed, and VIP. This study used the Cochrane Risk Test bias tool in the Cochrane Handbook to assess the quality of the methodology. Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied in the classification of evidence quality.
Results:
Ten RCTs involving 901 patients were finally included in this meta-analysis. It revealed that the effectiveness of BSHXD in treating CHD was significantly better than that of the conventional western medicine (CWM) treatment (P < 0.00001). The effective rate of BSHXD treatment group on ECG was also significantly higher than that of CWM group (P < 0.00001). The low-density lipoprotein cholesterol was decreased in the treatment groups compared with those in the control groups (P < 0.00001). There was also a reduction in frequency and duration of angina pectoris (P < 0.00001). There were no significant differences in TC level (P=0.08), TG level (P=0.86), and HDL level (P=0.76) between the treatment and control groups. Five studies had informed adverse events, including nausea and diarrhea.
Conclusion:
Our findings laid the foundation to the use of TCM Formula BSHXD in combination with conventional western medicine for treating CHD. However, due to the limitation of the quality of the included researches, in addition to potential reporting bias, the above conclusions still need verification by higher-quality and better-designed studies.
... Общепризнано, что при наличии хронической болезни почек особенно оправданна попытка применения ингибиторов ангиотензинпревращающего фермента (ИАПФ) и блокаторов рецепторов ангиотензина II, которые позволяют достичь как торможения прогрессирования почечной недостаточности, так и снижения риска основных сердечнососудистых осложнений и смерти [7]. Вместе с тем применение этих препаратов, особенно в полных дозах, нередко бывает ограничено ростом сывороточной концентрации креатинина и калия, связанной в том числе и с исходным наличием выраженного нефросклероза, своевременно не распознанным атеросклеротическим стенозом почечных артерий, длительным неконтролируемым приемом нестероидных противовоспалительных препаратов и ненаркотических анальгетиков. ...
The paper discusses the indications for use of loop diuretics to treat essential hypertension and the current limits in terms of their introduction into the practice of routine antihypertensive therapy. By using torasemide as an example, the author demonstrates prospects for using loop diuretics for the treatment of essential hypertension.
... Special Pathological Factors of Renal Insufficiency accelerated the deterioration of cardiovascular diseases, including calcium and phosphorus metabolic disorders that exacerbate vascular calcification, sympathetic nervous system long-term chronic activation and imbalance of vasoconstrictor factors of the system. 18 Chronic renal insufficiency appears to be an important predictor of adverse cardiovascular events in older patients with coronary heart disease. ...
Objective
To investigate the relationship between chronic kidney disease (CKD) and the severity and long-term prognosis of patients with coronary artery disease (CAD) after drug-eluting stent (DES) implantation.
Methods
There were 814 patients, who consecutively received a DES implantation, selected for this study. They were divided into two groups, according to whether or not they suffered CKD. There were 254 cases in the CKD group (31.2%), while there were 560 cases (68.8%) in the control group. The clinical characteristics, coronary artery lesions, and major adverse cardiac and cerebrovascular events (MACCE) of the two groups were compared, and the relationship between risk factors and MACCEs was analyzed by multivariate logistic regression.
Results
Compared with the control group, the CKD group had more severe coronary artery stenosis, expressed as the more diseased arteries (2.15 ± 0.82 vs 1.87 ± 0.83, p = 0.001), a high incidence of three diseased arteries (42.0% vs 28.3%, p = 0.001), and a higher Gensini score [37 (18.6, 66) vs 27.5 (12, 52.5), p = 0.009]. The one-year post-implant incidence of MACCE was higher in the CKD group compared with the control group (17.6% vs 9.9%, p = 0.006).
Conclusion
CKD appears to be an important predictor for the prognosis of CAD.
... Mild renal insuffiency has recently been defined as serum creatinine values above 1.5 mg/dl (132µ mol/L) in men and 1.4 mg/dl (123 µ mol/L) in women 59 . The renal damage is defined as an increment in serum creatinine above normal limits or a decrease in estimated creatinine clearance test [60][61][62] A simple explanation for renovascular hypertension is that decrease perfusion of renal tissue due to stenosis of a main or branch of renal artery activates the rennin-angiotensin system. Circulating angiotensin II elevates arterial pressure by directly causing vasoconstriction, and/or by stimulating the adrenergic nervous system. ...
BACKGROUND:
Hypertension is one of the leading causes to develop chronic kidney disease (CKD) and could be a risk factor for progression of chronic kidney disease to end stage renal disease (ESRD).Uncontrolled hypertension worsens CKD. Hypertension control may contribute to prevention of CKD in early stage and retards the progression of CKD stages to ESRD. Chronic kidney disease is a major public health problem. Improving outcome for people with chronic kidney disease requires a coordinated approach to prevention of adverse outcomes through defining the disease and its outcomes, estimating disease prevalence, identifying earlier stages of disease and antecedent risk factors, and detection and treatment for populations at increased risk for adverse outcomes.
OBJECTIVE
The aim of this study was to observe the prevalence of chronic kidney disease in newly diagnosed hypertensive patients visiting medical OPD and nephrology unit of TUTH from different area of Nepal. To see the correlation of metabolic changes with the stage of CKD, and correlation of stages of hypertension with stage of CKD.
METHODS:
Newly diagnosed hypertensive patients visiting medical OPD and nephrology unit of TUTH from different parts of Nepal were recruited for the study. Study was conducted from May 2008 to August 2009. Hypertension was defined as hypertension stage I (systolic 140 to 159 mm Hg or diastolic 90 to 99 mm Hg or both), and hypertension stage II (systolic ≥160 or diastolic ≥100 mm Hg or both). Blood pressure was measured using aneroid sphygmomanometer with an adequate cuff size. Chronic kidney disease is defined as per National kidney foundation guidelines. CKD is defined by the presence of kidney damage or kidney dysfunction or both. ACR is greater than 3.4 mg/mmol was taken as a marker for kidney damage. eGFR >60 mL/min/1.73 m2 with risk factor so, in this study hypertension is a risk factor was taken as a marker for kidney dysfunction. Then, different parameter related to kidney function was assessed and correlated to stage of disease.
RESULTS:
Among 106 newly diagnosed hypertensive patients, CKD was found in 51.9% and CKD was not found in 48.1% hypertensive patients. In 106 normal healthy controls i.e. with normal BP, CKD was found only in 23.6% and CKD was not found in 76.4%. This is statistically significant association between hypertension and CKD (p-Value <0.001). Difference in the mean value in eGFR and spot urine ACR (mg/mmol) between hypertensive and “normal blood pressure” control groups is significant (p-Value <0.001). Both systolic BP and diastolic BP negative significantly correlated with eGFR (p-Value < 0.001 and 0.024 respectively) and positive significantly correlated with ACR (p-Value 0.003 and 0.003 respectively). With the increase of age in hypertensive patients, there is decline in eGFR which is significantly associated (p-Value 0.011) and negative significantly correlated (p-Value < 0.001). Level of hemoglobin (p-Value 0.001), level of ACR (p-Value <0.001), level of total cholesterol (p-Value <0.001), level of LDL-cholesterol (p-Value 0.003) and level of TG (p-Value 0.019) are significantly associated with the stage of CKD.
DISCUSSION:
There is a strong association between hypertension and chronic kidney disease. Even in the earlier stage of CKD, there may be disturbed in synthetic function and homeostatic regulation of body which may start to govern the metabolic changes which is irrespective of clinical feature and diagnosis.
CONCLUSION:
Hypertension is the major risk factor to develop CKD. Assess of CKD can be done using eGFR as a marker for Kidney dysfunction and urine spot urine ACR as a marker for kidney damage. Metabolic changes should be assessed with stage of CKD.
Key words: Hypertension, Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) Albumin Cratinine Ratio (ACR), estimated GFR (eGFR)
... Although the diagnosis of renal impairment in clinical practice is based on the finding of a decrease in the glomerular filtration rate (GFR) and/or on the detection of elevated urinary excretion of albumin [3], we defined renal impairment as the estimated GFR (eGFR) ≤ 60 mL/min/1.73 m 2 , as in other studies, due to lack of urinary microalbumin concentration data during 2008-2010 and 2015-2017 [15,16]. ...
Background
The renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on individual differences in body fluid distribution and risk of chronic dehydration.
Methods
We conducted a cross-sectional analysis of the 2008–2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (< 20 mL/kg/day), low-moderate (20–29.9 mL/kg/day), high-moderate (30–49.9 mL/kg/day), and highest (≥ 50 mL/kg/day). We assessed the risk of renal impairment (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m ² ) according to water intake.
Results
In total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day.
Conclusions
High daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.
Background:
Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006.
Objectives:
We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease.
Search methods:
We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
Selection criteria:
We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease.
Data collection and analysis:
Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results:
One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I2 = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported.
Authors' conclusions:
ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.
Background:
Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012.
Objectives:
To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients.
Search methods:
We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
Selection criteria:
We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints.
Data collection and analysis:
Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results:
We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses.
Authors' conclusions:
We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.
Aim: The present study aims to assess the prevalence of risk factor of chronic kidney disease among diabetes mellitus and hypertensive client at karambakkam. Methods and Materials: A Non-experimental descriptive research design was used for the present study. A total 200 samples were collected using purposive sampling technique. The demographic of diabetes mellitus and level of knowledge of risk factor of chronic kidney diseases was assessed using structured questioner and, followed by that data was gathered and analyzed. Results: The results the study revealed that there is a significant association with the level of knowledge on risk factor of chronic kidney diseases among diabetes mellitus and hypertensive client at p<0.001. Conclusion: Thus, the present study concluded that majority of the clients with diabetes mellitus and hypertension had inadequate knowledge and it is recommended that they should be educated on the risk factors of CKD.
Almost a hundred years have passed since obstruction of the renal artery has been recognized to raise blood pressure. By now chronic renovascular disease (RVD) due to renal artery stenosis is recognized as a major source of renovascular hypertension and renal disease. In some patients, RVD unaccompanied by noteworthy renal dysfunction or blood pressure elevation may be incidentally identified during peripheral angiography. Nevertheless, in others, RVD might present as a progressive disease associated with diffuse atherosclerosis, leading to loss of renal function, renovascular hypertension, hemodynamic compromise, and a magnified risk for cardiovascular morbidity and mortality. Atherosclerotic RVD leads to renal atrophy, inflammation, and hypoxia but represents a potentially treatable cause of chronic renal failure because until severe fibrosis sets in the ischemic kidney, it retains a robust potential for vascular and tubular regeneration. This remarkable recovery capacity of the kidney begs for early diagnosis and treatment. However, accumulating evidence from both animal studies and randomized clinical trials has convincingly established the inadequate efficacy of renal artery revascularization to fully restore renal function or blood pressure control and has illuminated the potential of therapies targeted to the ischemic renal parenchyma to instigate renal regeneration. Some of the injurious mechanisms identified as potential therapeutic targets included oxidative stress, microvascular disease, inflammation, mitochondrial injury, and cellular senescence. This review recapitulates the intrinsic mechanisms that orchestrate renal damage and recovery in RVD and can be harnessed to introduce remedial opportunities.
Introduction
Acute myocardial infarction (AMI) remains a critical disease, characterized by a high fatality rate in several countries. In clinical practice, the incidence of AMI is increased in patients with chronic kidney disease (CKD). However, the early diagnosis of AMI in the above group of patients is still poor.
Methods
In the present study, a total of 829 patients with CKD, defined by an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m ² or 60–90 ml/min/1.73 m ² for patients with mildly reduced kidney function, who attended the Sichuan Provincial People's Hospital (SPPH) between January 2018 and November 2022 were enrolled. All patients underwent coronary angiography due to the presence of typical or atypical symptoms of AMI. Patients were divided into the following two groups: The training cohort, including 255 participants with AMI and 242 without AMI; and the testing cohort, including 165 and 167 subjects with and without AMI, respectively. Furthermore, a forward stepwise regression model and a multivariable logistic regression model, named SPPH-AMI-model, were constructed to select significant predictors and assist the diagnosis of AMI in patients with CKD, respectively.
Results
The following factors were evaluated in the model: Smoking status, high sensitivity cardiac troponin I, serum creatinine and uric acid levels, history of percutaneous coronary intervention and electrocardiogram. Additionally, the area under the curve (AUC) of the receiver operating characteristic curve were determined in the risk model in the training set [AUC, 0.78; 95% confidence interval (CI), 0.74–0.82] vs. the testing set (AUC, 0.74; 95% CI, 0.69–0.79) vs. the combined set (AUC, 0.76; 95% CI, 0.73–0.80). Finally, the sensitivity and specificity rates were 71.12 and 71.21%, respectively, the percentage of cases correctly classified was 71.14%, while positive and negative predictive values of 71.63 and 70.70%, respectively, were also recorded.
Discussion
The results of the current study suggested that the SPPH-AMI-model could be currently considered as the only risk scoring system for the early diagnosis of AMI in patients with CKD. This method could help clinicians and emergency physicians to quickly and accurately diagnose AMI in patients with CKD to promote the immediate and effective treatment of these patients.
Background:
Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of chronic kidney disease (CKD).
Methods:
We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two blood pressure lowering drugs, and a statin, with or without aspirin versus placebo or usual care. Here we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low estimated glomerular filtration rate (eGFR <60 ml/min/1.73m2; CKD-EPI formula) compared to a normal eGFR (≥60 ml/min/1.73m2). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization.
Results:
At baseline, mean level of eGFR was 76 ml/min/1.73m2 (17). 3,315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) of participants in the treatment group compared with 339 (5%) in control group (hazard ratio [HR], 0.68; 95% confidence interval [95%CI], 0.57-0.81; P<0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) of participants in the treatment group compared with 130 (8%) in control group (HR, 0.49; 95%CI, 0.36-0.66; P<0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies including aspirin compared to treatments without aspirin. Apart from dizziness, other side effects didn't differ between treatment and control groups regardless of the stage of their kidney function.
Conclusions:
A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR but relative and absolute risk reductions are larger in individuals with low eGFR.
Background:
Chronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. This is an update of a review that was last published in 2011.
Objectives:
To evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM).
Search methods:
We searched the Cochrane Kidney and Transplant Register of Studies up to 6 July 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and Embase, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
Selection criteria:
Randomised controlled trials (RCTs) reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have DM were selected for inclusion. Only studies of at least four weeks duration were selected. Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
Data collection and analysis:
Data extraction was carried out by two authors independently, using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. When more than one study reported similar outcomes, data were pooled using the random-effects model. Heterogeneity was analysed using a Chi² test and the I² test. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach MAIN RESULTS: Six studies randomising 9379 participants with CKD stages 1 to 3 (without DM) met our inclusion criteria. Participants were adults with hypertension; 79% were male from China, Europe, Japan, and the USA. Treatment periods ranged from 12 weeks to three years. Overall, studies were judged to be at unclear or high risk of bias across all domains, and the quality of the evidence was poor, with GRADE rated as low or very low certainty. In low certainty evidence, ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo may make little or no difference to death (any cause) (2 studies, 8873 participants): RR 2.00, 95% CI 0.26 to 15.37; I² = 76%), total cardiovascular events (2 studies, 8873 participants): RR 0.97, 95% CI 0.90 to 1.05; I² = 0%), cardiovascular-related death (2 studies, 8873 participants): RR 1.73, 95% CI 0.26 to 11.66; I² = 54%), stroke (2 studies, 8873 participants): RR 0.76, 95% CI 0.56 to 1.03; I² = 0%), myocardial infarction (2 studies, 8873 participants): RR 1.00, 95% CI 0.84 to 1.20; I² = 0%), and adverse events (2 studies, 8873 participants): RR 1.33, 95% CI 1.26 to 1.41; I² = 0%). It is uncertain whether ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo reduces congestive heart failure (1 study, 8290 participants): RR 0.75, 95% CI 0.59 to 0.95) or transient ischaemic attack (1 study, 583 participants): RR 0.94, 95% CI 0.06 to 15.01; I² = 0%) because the certainty of the evidence is very low. It is uncertain whether ARB (losartan 50 mg) compared to placebo (1 study, 226 participants) reduces: death (any-cause) (no events), adverse events (RR 19.34, 95% CI 1.14 to 328.30), eGFR rate of decline (MD 5.00 mL/min/1.73 m2, 95% CI 3.03 to 6.97), presence of proteinuria (MD -0.65 g/24 hours, 95% CI -0.78 to -0.52), systolic blood pressure (MD -0.80 mm Hg, 95% CI -3.89 to 2.29), or diastolic blood pressure (MD -1.10 mm Hg, 95% CI -3.29 to 1.09) because the certainty of the evidence is very low. It is uncertain whether ACEi (enalapril 20 mg, perindopril 2 mg or trandolapril 1 mg) compared to ARB (olmesartan 20 mg, losartan 25 mg or candesartan 4 mg) (1 study, 26 participants) reduces: proteinuria (MD -0.40, 95% CI -0.60 to -0.20), systolic blood pressure (MD -3.00 mm Hg, 95% CI -6.08 to 0.08) or diastolic blood pressure (MD -1.00 mm Hg, 95% CI -3.31 to 1.31) because the certainty of the evidence is very low.
Authors' conclusions:
There is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.
Background:
Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease.
Methods:
In the Medicare-linked OPTIMIZE-HF, 1582 patients with HFrEF (ejection fraction, ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 ml/min/1.73 m2). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 41 baseline characteristics (mean age, 78 years; 52% women; 10% African American; 73% receiving beta blockers). Hazard ratios (HR) and 95% CIs were estimated comparing 2-years outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs.
Results:
The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CIs) for all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85).
Conclusions:
The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.
Background and Objectives
The application of prognostic scoring systems to identify risk of death within 24 hours of CICU admission has significant consequences for clinical decision-making. Previous score of parameters collected after 24 hours was considered too late to predict mortality. As a result, we attempted to develop a CICU admission risk score to predict hospital mortality using indicators collected within 24 hours.
Methods
Data were obtained from SCIENCE registry from January 1, 2021 to December 21, 2021. Outcomes of 657 patients (mean age 58.91 ± 12.8 years) were recorded retrospectively. Demography, risk factors, comorbidities, vital signs, laboratory and echocardiography data at 24-hours of patient admitted to CICU were analysed by multivariate logistic regression to create two models of scoring system (probability and cut-off model) to predict in-hospital mortality of any cause.
Results
From a total of 657 patients, the hospital mortality was 15%. The significant predictors of mortality were male, acute heart failure, hemodynamic instability, pneumonia, baseline creatinine ≥ 1.5 mg/dl, TAPSE <17 mm, and the use of mechanical ventilator within first 24-hours of CICU admission. Based on Receiver Operating Characteristic (ROC) curve analysis a cut off of > 3 is considered to be a high risk of in-hospital mortality (sensitivity 75% and specificity 65%).
Conclusion
The initial 24-hour SCIENCE admission risk rating system can be used to predict in-hospital mortality in patients admitted to the CICU with a high degree of sensitivity and specificity
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3–5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73–17,276). The median follow-up was 38 months (range 24–58). The overall median of both primary and secondary outcomes was 0 (range 0–117 and range 0–55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1–117) and 7.5 (range: 1–55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1–117) and 22 (range 1–80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD.
Heart and kidney failure often co-exist and confer high morbidity and mortality. The complex bi-directional nature of heart and kidney dysfunction is referred to as cardiorenal syndrome, and can be induced by acute or chronic dysfunction of either organ or secondary to systemic diseases. The five clinical subtypes of cardiorenal syndrome are categorized by the perceived primary precipitant of organ injury but lack precision. Traditional biomarkers such as serum creatinine are also limited in their ability to provide an early and accurate diagnosis of cardiorenal syndrome. Novel biomarkers have the potential to assist in the diagnosis of cardiorenal syndrome and guide treatment by evaluating the relative roles of implicated pathophysiological pathways such as hemodynamic dysfunction, neurohormonal activation, endothelial dysfunction, inflammation and oxidative stress, and fibrosis. In this review, we assess the utility of biomarkers that correlate with kidney and cardiac (dys)function, inflammation/oxidative stress, fibrosis, and cell cycle arrest, as well as emerging novel biomarkers (thrombospondin-1/CD47, glycocalyx and interleukin-1β) that may provide prediction and prognostication of cardiorenal syndrome, and guide potential development of targeted therapeutics.
What is the issue?People with chronic kidney disease (CKD) have an increased risk of heart disease that can block the blood supply to the heart or brain causing a heart attack or stroke. Drugs that prevent blood clots from forming (antiplatelet agents) can prevent deaths caused by clots in arteries in the general adult population. However, there may be fewer benefits for people who have CKD, because blood clots in arteries is a less common cause of death or reason to be admitted to hospital compared with heart failure or sudden death in these people. People with CKD also have an increased tendency for bleeding due to changes in how the blood clots. Antiplatelet agents may therefore be more hazardous when CKD is present. What did we do? This updated review evaluated the benefits and harms of antiplatelet agents to prevent cardiovascular disease and death, and the impact on dialysis vascular access (fistula or graft) function in people who have CKD. We identified 90 studies comparing antiplatelet agents with placebo or no treatment and 29 studies directly comparing one antiplatelet agent with another. What did we find?Antiplatelet agents probably prevent heart attacks, but do not clearly reduce death or stroke. Treatment with these agents may increase the risk of major and minor bleeding. Clotting of dialysis access was prevented with antiplatelet agents. Conclusions
The benefits of antiplatelet agents for people with CKD is probably limited to the prevention of a heart attack. The treatment does not appear to prevent stroke or death and probably incurs excess serious bleeding that may require hospital admission or transfusion.
Objectives
Renin-angiotensin system inhibitors (RASi's) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials.
Design
CKD-REIN cohort study.
Setting and Participants
We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France.
Methods
The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age.
Results
Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28).
Conclusions and Implications
This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects.
Background:
Renin-angiotensin-aldosterone system inhibitors (RAASIs) are recommended for most patients with coronary artery disease (CAD). However, there is debate across guidelines as to which patients with CAD benefit the most from these agents. This study investigated the association between RAASIs and cardiovascular outcomes and acute kidney injury in a contemporary cohort of patients with CAD.
Methods:
Patients ≥65 years of age with CAD alive on April 1st, 2012 in Ontario, Canada were included. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction (MI), unstable angina, stroke or coronary revascularization) and acute kidney injury (AKI) hospitalizations at 4 years. Inverse probability of treatment-weighted Cox proportional hazards regression models were used to compare the rates of each outcome in patients treated with and without RAASIs (angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers).
Results:
There were 165,058 patients with CAD identified (mean age 75 years, 65.5% male, 64.7% prescribed RAASIs). After inverse-probability weighting, treatment with RAASIs was associated with a lower rate of MACE compared to treatment without RAASIs (17.6% vs. 18.2%, hazard ratio [HR]: 0.96, 95% CI: 0.89-0.96 respectively). However, treatment with RAASIs was associated with a higher rate of AKI compared to treatment without RAASIs (1.7% vs. 1.5%, HR: 1.14, 95% CI: 1.02-1.29, respectively). The reduction in MACE was greater in patients with prior MI (HR: 0.87, 95% CI: 0.82-0.92) compared to patients without prior MI (HR: 1.00, 95% CI: 0.97-1.04, interaction p<0.01). The increase in AKI was lower in patients with prior MI (HR: 0.82, 95% CI: 0.66-1.00) compared to patients without prior MI (HR: 1.37, 95% CI: 1.19-1.57, interaction p<0.01).
Conclusions:
This study supports the continued use of RAASIs in patients with CAD, although the benefit appears smaller in magnitude than observed in prior trials. High-risk patients, particularly those with prior MI, appear to benefit the most from RAASIs.
Purpose/Method: No studies have reported on prognostic markers in patients with chronic kidney disease (CKD) according to the severity of the disease. Therefore, in this multicenter, prospective trial performed as part of the Gunma CKD SPECT Multicenter Study, we recruited 311 patients with CKD (eGFR <60 min/mL/1.73 m²) including 50 patients on hemodialysis and followed them for 2 years. The study sample underwent stress 99mTc-tetrofosmin SPECT for suspected or possible ischemic heart disease. We evaluated the summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and cardiac function with electrocardiogram-gated SPECT. Then, we compared the differences in prognostic markers for major adverse cardiac, cerebrovascular, and renal events (MACCRE) between patients with mild CKD (30 min/mL/1.73 m² ≤ eGFR <60 min/mL/1.73 m²; n=184) and those with severe CKD (eGFR <30 min/mL/1.73 m²; n=97).
Results: Of 281 patients available for analysis, 91 experienced MACCRE. In a multivariate Cox proportional hazards analysis of factors related to MACCRE, in patients with mild CKD the significant prognostic markers were SDS (P=0.002) and end-systolic volume (ESV, P=0.034); and in the patients with severe CKD, they were eGFR (P=0.03) and diabetes-mellitus (DM, P=0.023).
Conclusions: Our findings indicate that SDS and ESV are significant prognostic markers for MACCRE in patients with mild CKD and eGFR and DM are significant prognostic markers in patients with severe CKD.
La maladie rénale chronique (MRC) touche 11% des adultes mais 30% des plus de 70 ans. La cohorte CKD REIN a inclus 3033 sujets atteints de MRC stades 3-4 en France (âge moyen 67 ans, 65% d’hommes) et a permis d’évaluer l’impact de l’âge sur la prise en charge des maladies cardiovasculaires (MCV) associées à la MRC et la néphroprotection. La prévalence totale des MCV était de 48%, avec des prévalences similaires pour les MCV athéromateuse et non-athéromateuse dans chaque groupe d’âge, excepté chez les ≥85 ans chez qui la MCV non-athéromateuse prédominait. Chez les patients <65 ans, 29% avaient au moins une MCV contre 75% des ≥85 ans. Un âge élevé était associé à une sous-utilisation des inhibiteurs du système rénine-angiotensine (iSRA) [odds ratio ajusté (ORa) (IC95%)=0,39 (0,16-0,89) pour les patients ≥85 ans, comparés aux <65 ans], des bétabloquants [ORa=0,31 (0,19-0,53) pour les patients [75-84] ans] et des hypolipémiants [p de tendance=0,01] dans la cardiopathie ischémique, mais pas des médicaments antithrombotiques recommandés dans plusieurs MCV. Enfin, l’utilisation des iSRA était associée à une diminution du risque combiné de décès et de MRC terminale [Hazard ratio (HR)=0,79 (0,64-0,98) avec score de propension, p d’interaction avec l’âge=0,56], mais pas au risque d’insuffisance rénale aigue et d’hyperkaliémie [HR=0,73 (0,51-1,06), p d’interaction=0,14]. En conclusion, cette thèse a mis en évidence le poids des MCV chez les sujets âgés atteints de MRC et le hiatus entre les recommandations et la pratique dans leur traitement chez ces patients. Elle apporte également des éléments en faveur de l’utilisation des iSRA chez les sujets âgés atteints de MRC.
Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed.
We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up.
Mean (+/-SD) plasma total homocysteine level decreased from 21.2+/-6.4 micromol/l at baseline to 14.2+/-4.6 at 3 months and remained at 12.8+/-3.7 micromol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268+/-129 to 399+/-234 micromol/l. Mean plasma folate concentration rose from 19+/-12 to 47+/-13 nmol/l and mean plasma vitamin B12 rose from 237+/-119 to 347+/-191 pmol/l from baseline to end of follow-up.
Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.
Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency.
Little is known about the prevalence of cardiovascular disease (CVD) and associated risk factors in individuals with mild renal insufficiency (RI). Furthermore, the long-term outcomes associated with mild RI in the community have not been described.
Serum creatinine (SCr) was measured in 6233 adult participants of the Framingham Heart Study (mean age 54 years, 54% women). Mild RI was defined as SCr 136 to 265 micromol/liter (1.5 to 3.0 mg/dl) in men and 120 to 265 micromol/liter (1.4 to 3.0 mg/dl) in women. The lower limits for mild RI were defined by the sex-specific 95th percentile SCr values in a healthy subgroup of our sample. The upper limit for mild RI was chosen to exclude those subjects with more advanced renal failure. Cox proportional hazards analyses were used to determine the relationship of baseline RI to CVD and all-cause mortality.
At baseline, 8.7% of men (N = 246) and 8.0% of women (N = 270) had mild RI. Nineteen percent of the subjects with mild RI had prevalent CVD. During 15 years of follow-up, there were 1000 CVD events and 1406 deaths. In women, mild RI was not associated with increased risk for CVD events [hazards ratio (HR) 1.04, 95% CI, 0.79 to 1.37] or all-cause mortality (HR 1.08, 95% CI, 0.87 to 1.34). In men, mild RI showed no significant associations with CVD events (HR 1.17, 95% CI, 0.88 to 1.57), but it was associated with all-cause mortality in age-adjusted (HR 1.42, 95% CI, 1.12 to 1.79) and multivariable adjusted (HR 1.31, 95% CI, 1.02 to 1.67) analyses.
Mild RI in the community is common and is associated with a high prevalence of CVD. The association of RI with risk for adverse outcomes is strongly related to coexisting CVD and CVD risk factors.
Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis.
We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor. These patients were randomly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor (ramipril) or matching placebo for a mean of 4.5 years (the results of the comparison of ramipril and placebo are reported in a companion article). The primary outcome was a composite of myocardial infarction, stroke, and death from cardiovascular causes. The secondary outcomes included unstable angina, congestive heart failure, revascularization or amputation, death from any cause, complications of diabetes, and cancer.
A total of 772 of the 4761 patients assigned to vitamin E (16.2 percent) and 739 of the 4780 assigned to placebo (15.5 percent) had a primary outcome event (relative risk, 1.05; 95 percent confidence interval, 0.95 to 1.16; P=0.33). There were no significant differences in the numbers of deaths from cardiovascular causes (342 of those assigned to vitamin E vs. 328 of those assigned to placebo; relative risk, 1.05; 95 percent confidence interval, 0.90 to 1.22), myocardial infarction (532 vs. 524; relative risk, 1.02; 95 percent confidence interval, 0.90 to 1.15), or stroke (209 vs. 180; relative risk, 1.17; 95 percent confidence interval, 0.95 to 1.42). There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause. There were no significant adverse effects of vitamin E.
In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.
Methods: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other pre- diction equations in the validation sample. Results: To simplify prediction of GFR, the equation in- cluded only demographic and serum variables. Indepen- dent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P , 0.001 for all factors). The multiple regression model explained 90.3% of the vari- ance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clear- ance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. Conclusion: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.
Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addition, healthy age-matched subjects. Insulin sensitivity and other variables of glucose metabolism were assessed using a frequent sampling intravenous glucose tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was assessed in renal patients using the inulin-clearance technique. Mean insulin sensitivity index (SI), that is, insulin sensitivity, was significantly lower (P < 0.001) in all patients combined than in matched healthy subjects (N = 16; 14 males, mean age 42 3 years; mean SI 8.6 0.8 min-1 U/ml). The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intact PTH (r = -0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82). Consequently, the mean SI was similar in renal patients with GFR within the normal range (N = 19; 17 males, mean age 41 2 years; mean GFR 119 5 ml/min/1.73 m2; mean SI 5.1 0.7 min-1 U/ml), in patients with mild to moderate renal failure (N = 16; 15 males, 46 3 years; 67 4 ml/min/1.73 m2; 5.1 0.7 min-1 U/ml) and in patients with advanced renal failure (N = 15; 13 males, 46 3 years; 25 2 ml/min/1.73 m2; 4.7 0.6 min-1 U/ml). Mean fasted plasma insulin concentration, the area under the curve for plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patients than in healthy subjects, reflecting hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration (r = -0.32, P < 0.009), AUC (r = -0.62, P < 0.0001) and TID (r = -0.34, P < 0.004) in patients were significantly correlated with insulin sensitivity (SI). The present data document that insulin resistance and concomitant hyperinsulinemia are present early in the course of renal disease, that is, even in patients with GFR within the normal range, irrespective of the type of renal disease. This observation may have potential implications with respect to the high cardiovascular morbidity and mortality in patients with renal disease.Keywords: ADPKD, insulin resistance, glucose metabolism, IgA glomerulonephritis, renal disease, uremia
The Hypertension Detection and Follow-up Program followed up 10,940 persons for 5 years in a community-based, randomized, controlled trial of treatment for hypertension. Participants were randomized to one of two treatment groups, stepped care and referred care. The primary end point of the study was all-cause mortality, with morbid events involving the heart, brain, and kidney as secondary end points. Loss of renal function, ascertained by a change in serum creatinine, was among these secondary events. Baseline serum creatinine concentration had a significant prognostic value for 8-year mortality. For persons with a serum creatinine concentration greater than or equal to 1.7 mg/dl, 8-year mortality was more than three times that of all other participants. The estimated 5-year incidence of substantial decline in renal function was 21.7/1,000 in the stepped-care group and 24.6/1,000 in the referred-care group. Among persons with a baseline serum creatinine level between 1.5 and 1.7 mg/dl, the 5-year incidence of decline was 113.3/1,000 (stepped care) and 226.6/1,000 (referred care) (p less than 0.01). The incidence of decline in renal function was greater in men, blacks, and older adults, as well as in those with higher entry diastolic blood pressure. Among persons with a baseline serum creatinine level greater than or equal to 1.7 mg/dl, serum creatinine concentration declined by 25% or more in 28.6% of stepped-care and 25.2% of referred-care participants. Although the incidence of clinically significant hypercreatininemia in a hypertensive population is low, an elevated serum creatinine concentration is a very potent independent risk factor for mortality. The slightly lower rate of development of hypercreatininemia and the higher rate of improvement in stepped-care compared with referred-care participants is consistent with the belief that aggressive treatment of hypertension may reduce renal damage and the associated increased risk of death.
To investigate the relationship between atherosclerotic vascular disease and age-associated changes in the normal human kidney, autopsy findings and renal histology from 57 individuals with mild systemic atherosclerosis (group I), were compared to 57 sex- and age-matched individuals with moderate-to-severe atherosclerosis (group II). Age, sex, body build, the presence or absence of hypertension, semiquantitative aorta and coronary-artery atherosclerosis scores, organ weights, and the percent of globally sclerotic glomeruli were determined in each. Glomerular area, arcuate/interlobular arteries, and percent interstitial fibrosis were measured using standard morphometric techniques. Group I individuals had a 8.3 +/- 7.0% incidence of sclerotic glomeruli, compared to 15.4 +/- 16.3% in group II (mean +/- SD, P less than 0.01). Relative intrarenal arterial wall area was increased in group II (60 +/- 12%) compared to group I (55 +/- 11%, P less than 0.05). The mean glomerular area of nonsclerotic glomeruli was greater in group II (23,700 +/- 6,000 sq mu) than in group I (19,600 +/- 3,700 sq mu, P less than 0.01), suggesting that there were compensatory increases in glomerular size in group II. Interstitial fibrosis was similar in both groups. The relative impact of age, sex, body build, hypertension, systemic atherosclerosis, intrarenal vascular disease and interstitial fibrosis on glomerulosclerosis and glomerular size was investigated using multiple linear regression. Both age and intrarenal vascular disease exhibited highly significant, independent associations with glomerulosclerosis. Glomerular area was positively correlated with heart weight and coronary artery atherosclerosis. In contrast, there was no independent correlation between glomerular area and glomerulosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.
In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.
At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.
Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.
In patients with diabetic nephropathy blood pressure increases progressively before the conventional threshold of normal blood pressure (140/90 mm Hg) is transgressed. In patients with glomerulonephritis, no information on this point is available. To clarify this issue we sequentially examined 20 untreated patients with biopsy-proven primary chronic glomerulonephritis (GN) who had casual blood pressure below 140/90 mm Hg and normal GFR by inulin clearance. Patients were compared with normotensive healthy controls who were matched for BMI, gender and age. We measured ambulatory 24-hour blood pressure (SpaceLab system), echocardiography (ASE criteria, Acuson 128 XP 10), CIn and CPAH, urinary Na excretion, PRA and insulin concentration. In patients with GN, the median 24 hour (P < 0.0005), daytime (P < 0.001) and nocturnal sleeping time (P < 0.0001) MAP values were significantly higher than in matched controls (daytime, mean 97 mm Hg, 85 to 106 GN vs. 89 controls range 82 to 102; nocturnal sleeping time, mean 80.3 mm Hg, 71 to 89.5 GN vs. 73 controls, range 63 to 84). Echocardiographic examination showed significantly greater posterior wall thickness (P < 0.01) and ventricular septal thickness (P < 0.003). In addition the early diastolic to late diastolic (E/A) ratio of mitral valve peak inflow velocity was significantly (P < 0.0008) lower in patients. The data point to left ventricular wall thickening accompanied by LV diastolic malfunction. The study documents elevated ambulatory blood pressure in patients with primary chronic glomerulonephritis despite normal body weight and normal GFR. This is associated with evidence of target organ damage in the heart. The findings suggest that in patients with glomerulonephritis blood pressure increases initially within the normotensive range. This observation in conjunction with evidence of early target organ changes provides an argument for early antihypertensive intervention, but controlled trials to test efficacy and safety of this proposal are necessary.
To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non-insulin-dependent diabetes mellitus (NIDDM) and to quantify the risk.
A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies.
A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias.
Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM.
Background:
The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study.
Methods:
97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat.
Findings:
During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy.
Interpretation:
In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.
Hypertension, left ventricular hypertrophy (LVH), hypercreatininemia, and microalbuminuria (MA) are independent risk factors for cardiovascular disease (CVD). Hypertension increases the risk of CVD by two- to three-fold and LVH (especially concentric) is a risk factor for coronary heart disease, heart failure, stroke, and peripheral arterial disease. In people with hypertension, a serum creatinine level of 1.7 mg/dL or more may be an even stronger CVD risk factor than diabetes, smoking, LVH, or systolic blood pressure. Similarly, MA is a strong and independent predictor of CVD morbidity and mortality in people with and without diabetes and/or hypertension. Impaired renal sodium handling and sodium retention are physiological hallmarks of the very early stages of heart failure. Heart failure is a physiologically delicate condition that can decompensate with excess dietary salt intake or over diuresis, or compensate with cautious therapy designed to block the sodium retention and simultaneously interrupt excessively activated neurohumoral mechanisms.
The problem of testing for a centre effect in multi-centre studies following a proportional hazards regression analysis is considered. Two approaches to the problem can be used. One fits a proportional hazards model with a fixed covariate included for each centre (except one). The need for a centre specific adjustment is evaluated using either a score, Wald or likelihood ratio test of the hypothesis that all the centre specific effects are equal to zero. An alternative approach is to introduce a random effect or frailty for each centre into the model. Recently, Commenges and Andersen have proposed a score test for this random effects model. By a Monte Carlo study we compare the performance of these two approaches when either the fixed or random effects model holds true. The study shows that for moderate samples the fixed effects tests have nominal levels much higher than specified, but the random effect test performs as expected under the null hypothesis. Under the alternative hypothesis the random effect test has good power to detect relatively small fixed or random centre effects. Also, if the centre effect is ignored the estimator of the main treatment effect may be quite biased and is inconsistent. The tests are illustrated on a retrospective multi-centre study of recovery from bone marrow transplantation.
The annual mortality from cardiovascular disease in dialysis patients is substantially higher than in the general population (Figure 1) (1). The 5-yr survival of men .64 yr old starting dialysis is worse than that of men with colon cancer and prostate cancer (2). The 5-yr survival of women .64 yr old starting dialysis is worse than that of women with breast cancer and colon cancer (2). About half the deaths in dialysis patients are attributed to cardiovascular disease (2). Hospitalizations of dialysis patients occur frequently and about one-third are the result of cardiovascular disease (2). Despite enormous morbid- ity and premature mortality resulting from cardiovascular dis- ease, it is only recently that the clinical epidemiology of cardiovascular disease in chronic renal failure has become a major focus of nephrology research. A task force convened by the National Kidney Foundation has considered whether strategies for prevention and treatment of cardiovascular disease in the general population are appli- cable in patients with chronic renal disease. Two target condi- tions (coronary artery disease and left ventricular hypertrophy) and four target populations (chronic renal insufficiency, hemo- dialysis, peritoneal dialysis, and renal transplantation) were considered. Detailed reports are available in a supplement of the American Journal of Kidney Diseases(3). The major focus was on traditional cardiac risk factors identified in the general population, including hyperlipidemia, hypertension, diabetes mellitus, tobacco use, menopause, and physical inactivity. In addition, a recent volume of Seminars in Dialysiswas devoted to consideration of potential uremia-related risk factors (4). These included risk factors altered by the uremic state, such as dyslipidemia, prothrombotic factors, hyperhomocysteinemia, and also risk factors characteristic of chronic uremia, such as hemodynamic overload, anemia, increased oxidant stress, hy- poalbuminemia, and divalent ion abnormalities (Table 1).
Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency [PMID: 0010594797] 5. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators
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Culleton BF, Larson MG, Wilson PW, Evans JC, Parfrey PS, Levy D.
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renal insufficiency. Kidney Int. 1999;56:2214-9. [PMID: 0010594797]
5. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation
Study Investigators. N Engl J Med. 2000;342:145-53. [PMID: 0010639539]
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Fliser D, Pacini G, Engelleiter R, Kautzky-Willer A, Prager R, Franek E, et
al. Insulin resistance and hyperinsulinemia are already present in patients with
incipient renal disease. Kidney Int. 1998;53:1343-7. [PMID: 0009573550]
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cardiovascular risk and of evolution of renal function in the HOT study [Abstract]. J Am Soc Nephrol. 2001;12:218-25.
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Stroke. 1997;28:557-63. [PMID: 0009056611]
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literature. Arch Intern Med. 1997;157:1413-8. [PMID: 0009224218]
Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators
- B F Culleton
- M G Larson
- P W Wilson
- J C Evans
- P S Parfrey
- D Levy
Culleton BF, Larson MG, Wilson PW, Evans JC, Parfrey PS, Levy D.
Cardiovascular disease and mortality in a community-based cohort with mild
renal insufficiency. Kidney Int. 1999;56:2214-9. [PMID: 0010594797]
5. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation
Study Investigators. N Engl J Med. 2000;342:145-53. [PMID: 0010639539]
Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators
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The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a
large, simple randomized trial of an angiotensin-converting enzyme inhibitor
(ramipril) and vitamin E in patients at high risk of cardiovascular events. The
HOPE study investigators. Can J Cardiol. 1996;12:127-37. [PMID: 0008605634]
Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure
- F Kronenberg
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- E Ritz
- R Junker
- P Konig
- G Kraatz
Kronenberg F, Kuen E, Ritz E, Junker R, Konig P, Kraatz G, et al. Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and
moderate renal failure. J Am Soc Nephrol. 2000;11:105-15. [PMID: 0010616846]
Serum creatinine as a predictor of cardiovascular risk and of evolution of renal function in the HOT study
- D Fliser
- G Pacini
- R Engelleiter
- A Kautzky-Willer
- R Prager
- E Franek
Fliser D, Pacini G, Engelleiter R, Kautzky-Willer A, Prager R, Franek E, et
al. Insulin resistance and hyperinsulinemia are already present in patients with
incipient renal disease. Kidney Int. 1998;53:1343-7. [PMID: 0009573550]
16. Ruilope LM, Zanchetti A, Hanson L. Serum creatinine as a predictor of
cardiovascular risk and of evolution of renal function in the HOT study [Abstract].
Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke
- S G Wannamethee
- A G Shaper
- I J Perry
Wannamethee SG, Shaper AG, Perry IJ. Serum creatinine concentration
and risk of cardiovascular disease: a possible marker for increased risk of stroke.
Stroke. 1997;28:557-63. [PMID: 0009056611]
Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group
- G Maschio
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Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, et al.
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