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Synergistic association of uric acid and homocysteine with chronic kidney disease.
Source publication
Chronic kidney disease (CKD) is a major global public health issue. Both hyperhomocysteinemia (HHcy) and hyperuricemia are independent risk factors for CKD. In this study, we evaluated the association of HHcy and hyperuricemia with CKD in the middle-aged and elderly populations in Taiwan.
In this cross-sectional study, we collected the data of 5910...
Context in source publication
Context 1
... magnitude of increased ORs of CKD appeared to be more prominent in the normal UA group. Table 4 displays that both hyperuricemia (OR 2.9) and Q4 of Hcy (OR 8.1) were significant risk factors for CKD. Moreover, UA and Hcy had significant synergistic association (synergy index, 1.7, 95% confidence interval 1.1-2.5) ...Similar publications
Background
Metabolic syndrome (MetS), a clustering of traditional cardiovascular risk factors (CVRF), is currently one of the major global public health burdens. However, associations between MetS and non-traditional CVRF represented by uric acid (UA), homocysteine (HCY) and hypersensitive C-reactive protein (HsCRP) have not been well explored in t...
Citations
... Both UA and HCY contribute to oxidative stress and inflammation in endothelial cells and the extracellular matrix [42], leading to renal vascular sclerosis, reduced renal blood flow, increased renal vascular resistance, decreased eGFR, and overall deterioration of renal function [9,43,44]. A study among middle-aged and older individuals revealed a synergistic association between HUA and hyperhomocysteinemia with CKD, suggesting that the coexistence of these conditions may worsen CKD progression [45]. However, the effectiveness of treating hyperhomocysteinemia in delaying CKD progression and preventing complications remains debated. ...
Background
Hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia are all established risk factors for chronic kidney disease (CKD), and their interplay could exacerbate CKD progression. This study aims to evaluate the potential mediation effects of hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia on the association between hyperuricemia (HUA) and chronic kidney disease (CKD).
Methods
We collected electronic medical record data from 2055 participants who underwent physical examinations at the Affiliated Hospital of Qingdao University. The data were utilized to investigate the mediating effect of various factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), homocysteine (HCY), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose (Glu), and hemoglobin A1c (HbA1c) on the relationship between HUA and CKD.
Results
Upon adjusting for confounding variables, mediation analysis indicated that only HCY acted as a mediator in the HUA–CKD relationship (p value < 0.05), exhibiting a statistically significant mediation effect of 7.04%. However, after adjustment for multiple testing, none of these variables were statistically significant.
Conclusions
Considering the observed associations between hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and CKD, none of the factors of interest remained statistically significant after adjusting for multiple testing as potential mediators of hyperuricemia on CKD.
... It is well established that the main site of homocysteine (Hcy) metabolism is in the kidneys with serum Hcy levels in patients with CKD being higher than those in patients with normal renal function [3]. A prospective study showed patients in the highest tertile of plasma Hcy levels had an increased incidence of CKD compared with those in the lower tertile [4]. Previous studies also showed that elevated plasma Hcy levels are associated with decreased GFR in patients with renal impairment, with GFR gradually decreasing with elevated Hcy levels. ...
Background
Increasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies.
Methods
We searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population.
Results
People with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72–2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55–3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63–2.63).
Conclusions
People with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.
... Levels of SUA and Hcy rise in identical pathologies, and both variables display a positive direct relationship even in healthy adults [12][13][14][15][16][17]. A synergistic association of hyperuricemia and hyperhomocysteinemia (hyperHcy) with chronic kidney disease has been documented in middle-aged and elderly patients [18]; while combined hyperuricemia and hyperHcy additively increased the risk of manifestation of subclinical atrial fibrillation in patients with cardiac implantable electronic devices [19]. However, it is not fully clarified whether hyperuricemia and hyperHcy represent markers, or rather act as etiological agents in cardiovascular and other mentioned pathologies [20,21]. ...
Background:
Little research has been conducted into the effects of the combined manifestation of hyperuricemia and hyperhomocysteinemia on cardiometabolic risk factors and markers in young subjects.
Methods:
1298 males and 1402 females, 14-to-20-year-olds, were classified into four groups: 1/normouricemic/normohomocysteinemic, 2/normouricemic/hyperhormohomocysteinemic, 3/hyperuricemic/normohomocysteinemic, and 4/hyperuricemic/hyperhomocysteinemic. Anthropometric measures, blood pressure, plasma glucose, insulin, lipids, markers of renal function, C-reactive protein, asymmetric dimethylarginine, and blood counts were determined.
Results:
Hyperuricemic males (but not females) had higher odds for hyperhomocysteinemia than normouricemic ones (OR: 1.8; 95% CI: 1.4-2.3; p < 0.001). Homocysteine and uric acid levels correlated directly (males: r = 0.076, females: r = 0.120; p < 0.01, both). Two-factor analysis of variance did not reveal a significant impact of hyperhomocysteinemia on any of the investigated cardiometabolic variables in females; in males, hyperuricemia and hyperhomocysteinemia showed a synergic effect on asymmetric dimethylarginine levels. Among four groups, subjects concurrently manifesting hyperuricemia and hyperhomocysteinemia did not presented the highest continuous metabolic syndrome score-a proxy measure of cardiometabolic risk; neither the multivariate regression model indicated a concurrent significant effect of uric acid and homocysteine on continuous metabolic syndrome score in either sex.
Conclusion:
In young healthy subjects, hyperhomocysteinemia does not aggravate the negative health effects imposed by hyperuricemia.
Background
The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetic model for cerebral stroke. Although a recent study on a congenic SHRSP suggested that a nonsense mutation in stromal interaction molecule 1 ( Stim1 ) encoding a major component of store-operated Ca ²⁺ entry was a causal variant for stroke in SHRSP, this was not conclusive because the congenic region including Stim1 in that rat was too wide. On the other hand, we demonstrated that the Wistar–Kyoto (WKY)-derived congenic fragment adjacent to Stim1 exacerbated stroke susceptibility in a congenic SHRSP called SPwch1.71. In the present study, we directly examined the effects of the Stim1 genotype on stroke susceptibility using SHRSP in which wild-type Stim1 was knocked in (called Stim1 -KI SHRSP). The combined effects of Stim1 and the congenic fragment of SPwch1.71 were also investigated.
Methods
Stroke susceptibility was assessed by the stroke symptom-free and survival periods based on observations of behavioral symptoms and reductions in body weight.
Results
Stim1 -KI SHRSP was more resistant to, while SPwch1.71 was more susceptible to stroke than the original SHRSP. Introgression of the wild-type Stim1 of Stim1 -KI SHRSP into SPwch1.71 by the generation of F1 rats ameliorated stroke susceptibility in SPwch1.71. Gene expression, whole-genome sequencing, and biochemical analyses identified Art2b , Folr1 , and Pde2a as possible candidate genes accelerating stroke in SPwch1.71.
Conclusion
The substitution of SHRSP-type Stim1 to wild-type Stim1 ameliorated stroke susceptibility in both SHRSP and SPwch1.71, indicating that the nonsense mutation in Stim1 is causally related to stroke susceptibility in SHRSP.
Graphical Abstract, http://links.lww.com/HJH/C295
