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Adjusted incidence rate of cardiovascular (top) and allcause (bottom) mortality, by category of estimated glomerular filtration rate and albuminuria, Third National Health and Nutrition Examination Survey, 1988?2000. Models were adjusted to the incidence rates of a 60-year-old non-Hispanic White male.
Source publication
Decreased glomerular filtration rate (GFR) and albuminuria are used in combination to define chronic kidney disease, but their separate and combined effects on cardiovascular and all-cause mortality have not been studied in the general population. The linked mortality file of the Third National Health and Nutrition Examination Survey includes data...
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Citations
... Compared with levels for the general population, DKD confers a threefold higher risk of all-cause mortality and a 16-year loss in life expectancy. Reduced eGFR and albuminuria independently predict increased CV morbidity and mortality, and the presence of both exerts multiplicative effects on CV mortality risk (11,14,15). Recognition of the marked CV risk CKD portends is reflected in changes to clinical practice guidelines (8,16) that now include CKD among the highest-risk groups in screening and treatment recommendations (17). ...
Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding of the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD. Since its initial discovery, the blockade of the renin-angiotensin system has remained a cornerstone of DKD management, leaving a large component of residual risk to be dealt with. The advent of sodium–glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, to some extent, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has ushered in a resounding paradigm shift that supports a pillared approach in maximizing treatment to reduce outcomes. This pillared approach is like that derived from the approach to heart failure treatment. The approach mandates that all agents that have been shown in clinical trials to reduce cardiovascular outcomes and/or mortality to a greater extent than a single drug class alone should be used in combination. In this way, each drug class focuses on a specific aspect of the disease's pathophysiology. Thus, in heart failure, β-blockers, sacubitril/valsartan, a mineralocorticoid receptor antagonist, and a diuretic are used together. In this article, we review the evolution of the pillar concept of therapy as it applies to DKD and discuss how it should be used based on the outcome evidence. We also discuss the exciting possibility that GLP-1 RAs may be an additional pillar in the quest to further slow kidney disease progression in diabetes.
... 21 As many studies have shown, both decreased eGFR and increased albuminuria have been identified as independent risk factors for all-cause and CV-specific mortality in the general population. 22,23 Consideration of the interaction between eGFR and albuminuria status is important when considering the possibility of these variables as independent risk factors for major clinical outcomes in DKD patients. In this study, we found that the risk for all major clinical outcomes, including all-cause mortality and CV events, was highest in T2DM patients with albuminuric DKD with decreased eGFR compared to non-DKD patients. ...
Background
Diabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population.
Methods
A total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m2 were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m2) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR.
Results
Mean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m2). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02–2.33 and HR: 6.36, 95 % CI: 2.98–13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06–3.42 and HR: 6.70, 95 % CI: 2.70–16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74–6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06–2.75).
Conclusion
Thus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.
... These findings suggest that a lower eG-FRcystatin C/eGFRcreatinine ratio represents a new potential surrogate marker for arterial stiffness and sub-clinical atherosclero- The careful monitoring of cardiovascular risk is important in patients with T2DM. CKD is strongly associated with an increased risk for cardiovascular mortality, both among individuals with T2DM and in the general population [26][27][28][29][30]. Many studies have shown an increased cardiovascular risk beginning at stage 3 CKD, but some studies have reported the ASCVD risk to elevate in patients with milder renal impairment [10]. ...
... Our study demonstrated that the eGFRcystatin C/eGFRcreatinine ratio showed a good association with a high baPWV and an increased frequency of carotid artery plaque, especially in diabetic patients with preserved eGFR. In addition to albuminuria, a good predictor of cardiovascular risk in diabetic patients [28,32], these findings suggest that the eGFRcystatin C/eGFRcreatinine ratio can be used to determine the risk for adverse cardiovascular outcomes above and beyond what is possible using that eGFR alone in patients with diabetes, particularly those without CKD. ...
Background:
The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts.
Methods:
We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine.
Results:
A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD).
Conclusion:
We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.
... DKD is detected clinically by screening for persistent abnormal urine albumin excretion and decrease in the estimate of the glomerular filtration rate (eGFR) [16]. Decreased eGFR and increased albuminuria are the major causes of cardiovascular mortality [17][18][19]. The major cause of mortality among patients with DKD is the excess load on the cardiovascular system [20]. ...
... Inflammation and oxidative stress were possible reasons to account for the association [34]. Moreover, reduced eGFR levels were markers of renal function insufficiency, which could lead to decreased clearance of metabolic waste products in the body, causing accumulation of ASCVD serum markers in the body and a variety of metabolic abnormalities [38,39]. Finally, the interactions between the heart and kidneys were multiple and complex, with primary dysfunction in one of the heart and kidneys often leading to secondary impairment in the other, a phenomenon known as cardiorenal syndrome (CRS), and the reduced renal function itself might be a marker for the progression of cardiac insufficiency [40]. ...
Many studies suggest that cardiovascular-related mortality is higher in patients with end-stage renal disease, but few focus on the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with normal to slightly reduced kidney function. Our study aimed to explore the association between normal to slightly decreased estimated glomerular filtration rate (eGFR) and 10-year ASCVD risk levels among subjects with relative health conditions. A total of 12,986 subjects from the Chinese Physiological Constant and Health Condition survey were included. We used the Chronic Kidney Disease Epidemiology Collaboration equations to calculate eGFR and the 10-year ASCVD risk scores to assess the subjects’ risk of 10-year ASCVD. Ordinal logistic regression analysis was conducted to explore the association between ASCVD risk levels and eGFR, and adjust the possible confounding factors. Results indicated that the 10-year ASCVD risk scores gradually increased following the decrease in eGFR. Subjects who had smaller eGFR were more likely to have a greater risk of 10-year ASCVD. Additionally, the association between eGFR and 10-year ASCVD risk level changed with varying eGFR. The risk of one or more levels increasing in the 10-year ASCVD risk group was 5.20 times (Quartile 2 [Q2], 95%CI: 3.90, 6.94), 9.47 times (Q3, 95%CI: 7.15, 12.53) and 11.41 times (Q4, 95%CI: 8.61, 15.12) higher compared with Q1. We found that eGFR was significantly associated with 10-year ASCVD risk among Chinese subjects with normal to slightly reduced kidney function. Therefore, clinicians should strengthen the monitoring of cardiovascular risk in patients with renal impairment (even if renal function is only mildly reduced), assess the patients’ risk of ASCVD, and take early action in high-risk groups to reduce the risk of adverse atherosclerotic cardiovascular events.
... m 2 filtration at any level of albuminuria, detecting it contributes to optimize cardiovascular risk stratification. Patients with KF and albuminuria have 2.2 to 4 times higher risk of cardiovascular death and up to almost three times higher rates of all-cause mortality 22 . As previously described, this work has a low rate of albuminuria detection given that only 46.2% of the patients had this assessment performed. ...
... m 2 ) [13]. Less severe renal toxicity is also unfavorable since a decreased GFR is associated with increased risks of cardiovascular disease and all-cause mortality [28]. Current protocols do not offer guidance on long-term health issues in these survivors, but improved treatment will result in a larger group of patients that require monitoring of renal function and education concerning the risk and prevention of late treatment effects. ...
Objectives
To determine rates of vascular toxicity, acute kidney injury (AKI), chronic kidney disease (CKD) and survival in high-risk cervical cancer patients treated with platinum-based induction chemotherapy followed by thermoradiotherapy.
Methods
Between January 1999 and April 2017, patients with large primary tumors (>6cm) and/or para-aortic lymph node (LN) metastases >1 cm and/or para-iliac LN >2 cm were included. Patient and tumor characteristics, Common Toxicity Criteria v4.03 scores, laboratory tests and treatment data were retrieved from patient records. CT scans were reviewed for the presence of thrombo-embolic events (TEE). The study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, Rotterdam (MEC2017-133).
Results
The 105 included patients had a mean age of 47.9 years (range 22–79) and a median follow-up time of 43 months (IQR 14–72). Median tumor size was 6.0 cm (range 2.6–11.5), 30% had a clinical FIGO stage ≥ IIIB and 42% had enlarged para-aortic LN. Cisplatin-based therapy was started in 86 patients (82%), of whom 30 (35%) switched to carboplatin and 47% of patients completed six cycles of platinum-based chemotherapy. All patients received external beam radiotherapy as planned, 98 patients (93%) underwent brachytherapy as planned or received an external boost, and 95 patients (90%) completed all five planned hyperthermia treatments. During cisplatin chemotherapy, 34 patients experienced AKI (39%). At last follow-up, 35% of patients had chronic renal toxicity (GFR 59 − 15/min/1.73 m²). At presentation, a TEE was present in 10 (10%) and another 23 (22%) patients experienced a TEE (18% venous, 4% arterial) during chemotherapy. Five-year overall survival was 58% (95% CI 47.8–68.6 SE 0.053).
Conclusion
Achieving a five-year overall survival of 58%, platinum-based induction chemotherapy followed by thermoradiotherapy is an effective treatment for advanced-stage high-risk cervical cancer. However, treatment is accompanied by an unacceptably high prevalence of chemotherapy-associated TEE and acute kidney injury, as well as chronic kidney disease. Future studies should investigate the role of carboplatin in reducing toxicity and the effect of thromboprophylaxis in high-risk patients.
... Urine albumin-to-creatinine ratio, which is associated with vascular endothelial function and is a predictor of cardiovascular events [15][16][17], was not changed by treatment ( Table 2). ...
Background
Glucagon-like peptide-1 receptor (GLP1R) agonists decrease cardiovascular events in patients with type 2 diabetes, and cause weight loss regardless of diabetes status. The contribution of weight loss to the cardiovascular benefits of GLP1R agonists is unknown.
Methods
Obese pre-diabetic individuals were randomized to 14 weeks of the GLP1R agonist liraglutide, hypocaloric diet-mediated weight loss, or the dipeptidyl peptidase 4 inhibitor sitagliptin as an incretin-based drug comparator. Treatment with drug was double blind and placebo-controlled. Weight, metabolic and hemodynamic measures, endothelium-dependent vasodilation and fibrinolytic function were measured at baseline and after 2 and 14 weeks of treatment.
Results
Liraglutide and diet reduced weight, fasting blood glucose, and insulin resistance at 14 weeks, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilatory function as measured by flow-mediated dilation (FMD). Because baseline endothelial function was normal in the overall cohort, post-hoc subgroup analyses were conducted in participants stratified by FMD below or above the median for gender. All three treatments improved FMD at 2 weeks in individuals with baseline endothelial dysfunction and sitagliptin and diet also improved endothelium-dependent vasodilation at 14 weeks. Liraglutide and diet reduced plasminogen activator inhibitor-1 (PAI-1) at 14 weeks. GLP1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1 in the overall group. Exendin (9-39) attenuated the increase in FMD in the sitagliptin-treated group at two weeks.
Conclusions
Liraglutide and diet cause weight loss, improve insulin resistance and reduce PAI-1 at 14 weeks. The effect on PAI-1 is GLP1R-independent. In individuals with low baseline FMD, sitagliptin and diet improve FMD at two and 14 weeks, while liraglutide improves FMD at two weeks.
Clinical Trial Registration
NCT03101930 https://clinicaltrials.gov/ct2/show/NCT03101930
... Low eGFR levels have been reported to increase risk for HF 42 and mortality. [42][43][44][45] While the published literature reports an increased risk of stroke with decreasing levels of eGFR, 41,46 we did not find this in the current study. In patients with low index eGFR levels, especially 15 to 29 mL/min/1.73 ...
... With the exception of hospitalization for CeVD, patients with UACR 30 to 299 mg/g and ≥300 mg/g increased the risk for hospitalization for CVD (29.9% and 2.0 times) and HF (2.1 and 4.9 times), progression to ESKD (1.4 and 2.9 times) and all-cause mortality (1.6 and 2.4 times) compared to those without albuminuria. The relationships between elevated UACR levels or albuminuria with renal function, [47][48][49] CVD, 50-52 HF, 52 and mortality, 44,51,52 have been reported previously. However, 55% to 65% of the overall sample and patients with the pre-specified outcomes did not have any UACR values and >50% of the patients had no indication in the claims data that an UACR test was performed. ...
Introduction/Objective
Predictive risk models identifying patients at high risk for specific outcomes may provide valuable insights to providers and payers regarding points of intervention and modifiable factors. The goal of our study was to build predictive risk models to identify patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) at high risk for progression to end stage kidney disease (ESKD), mortality, and hospitalization for cardiovascular disease (CVD), cerebrovascular disease (CeVD), and heart failure (HF).
Methods
This was a retrospective observational cohort study utilizing administrative claims data in patients with CKD (stage 3-4) and T2D aged 65 to 89 years enrolled in a Medicare Advantage Drug Prescription plan offered by Humana Inc. between 1/1/2012 and 12/31/2017. Patients were enrolled ≥1 year pre-index and followed for outcomes, including hospitalization for CVD, CeVD and HF, ESKD, and mortality, 2 years post-index. Pre-index characteristics comprising demographic, comorbidities, laboratory values, and treatment (T2D and cardiovascular) were evaluated and included in the models. LASSO technique was used to identify predictors to be retained in the final models followed by logistic regression to generate parameter estimates and model performance statistics. Inverse probability censoring weighting was used to account for varying follow-up time.
Results
We identified 169 876 patients for inclusion. Declining estimated glomerular filtration rate (eGFR) increased the risk of hospitalization for CVD (38.6%-61.8%) and HF (2-3 times) for patients with eGFR 15 to 29 mL/min/1.73 m² compared to patients with eGFR 50 to 59 mL/min/1.73 m². Patients with urine albumin-to-creatinine ratio (UACR) ≥300 mg/g had greater chance for hospitalization for CVD (2.0 times) and HF (4.9 times), progression to ESKD (2.9 times) and all-cause mortality (2.4 times) than patients with UACR <30 mg/g. Elevated hemoglobin A1c (≥8%) increased the chances for hospitalization for CVD (21.3%), CeVD (45.4%), and death (20.6%). Among comorbidities, history of HF increased the risk for ESKD, mortality, and hospitalization for CVD, CeVD, and HF.
Conclusions
The predictive models developed in this study could potentially be used as decision support tools for physicians and payers, and the risk scores from these models can be applied to future outcomes studies focused on patients with T2D and CKD.
... In addition, in healthy people (UACR less than 30 mg/g), the urinary albumin to creatinine ratio as a risk indicator is controversial in predicting all-cause death in healthy people [20]. Their previous relationship and degree of association have not yet been specifically studied [2,17,21]. The few published studies on the urinary albumin to creatinine ratio and allcause mortality are aimed at smaller populations, relying on retrospectively collected data, or the population is a special population with underlying diseases such as diabetes and hypertension [6][7][8][9][22][23][24]. ...
Background
In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR< 30 mg/g), the clinical relevance of an increased urinary albumin excretion rate is still debated. We studied the relationship between UACR and all-cause mortality in community populations, and compared UACR groups within the normal range.
Methods
The participants were the inhabitants from the Wanshoulu community in Beijing, China. The average age is 71.48 years, and the proportion of women is 60.1%. A total of 2148 people completed random urine samples to determine the urinary albumin to creatinine ratio (UACR). The subjects were divided into three groups according to UACR: Group 1 (UACR< 10 mg/g), Group 2 (10 mg/g < UACR< 30 mg/g), Group 3 (UACR> 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality.
Results
At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality].
Conclusion
Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR< 30 mg/g), it occurs in people with high normal value (10 mg/g < UACR< 30 mg/g), the risk of all-cause death will also increase.
