Serum amyloid A and risks of all-cause and cardiovascular mortality in chronic kidney disease: a systematic review and dose-response meta-analysis
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SUBMITTER: Li L
PROVIDER: S-EPMC10512819 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundConflicting results have been reported from studies evaluating serum uric acid (SUA) levels as an independent risk factor for cardiovascular mortality in patients with chronic kidney disease (CKD).MethodsWe systematically searched MEDLINE, Web of Science, and bibliographies of retrieved articles to identify studies reporting on the association between SUA levels and cardiovascular mortality in patients with CKD. Random-effects models were used to calculate the pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI).ResultsWe included 11 studies with an overall sample of 27,081 patients with CKD in this meta-analysis. By meta-analysis, restricted to 7 studies (n = 11,050), patients with the highest SUA were associated with an increased risk of cardiovascular mortality (HR 1.47, 95% CI 1.11-1.96) compared with patients with the lowest SUA. There was no indication of publication bias or significant heterogeneity (I2 = 40.4%; P = 0.109). Meta-analysis of 10 studies (n = 26,660) indicated that every 1 mg/dl increase in SUA levels increased a 12% risk in cardiovascular mortality (HR 1.12, 95% CI 1.02-1.24), with significant heterogeneity (I2 = 79.2%, P < 0.001).ConclusionsHigher SUA levels are associated with significantly increased risk of cardiovascular mortality in patients with CKD. More designed studies, especially randomized controlled trials, should be conducted to determine whether high SUA levels is a potentially modifiable risk factor for cardiovascular mortality in patients with CKD.
| S-EPMC6330757 | biostudies-literature
Project description:BackgroundCardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD.MethodsThe primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined.ResultsThe meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16.ConclusionsThese results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.
| S-EPMC8761349 | biostudies-literature
Project description:Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation.
| S-EPMC6054894 | biostudies-literature
Project description:Lycopene is one of the hydrocarbon carotenoids which is largely studied for its strong antioxidant and anti-inflammatory properties, as well as improvement of endothelial function and anti-arteriosclerosis effects. The use of lycopene has been shown to reduce mortality in the general population. However, few studies have examined the association between serum lycopene level and all-cause and cardiovascular mortality among participants with chronic kidney disease (CKD). This study included 7,683 adults with CKD from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and NHANES 2001-2006. Mortality status and cause of death were ascertained by linkage to National Death Index records through 31 December 2018. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all-cause and cardiovascular disease (CVD). During a median follow-up time of 309 months, there were 5,226 total deaths. The median (interquartile range) serum lycopene concentration was 20.0 (12.0, 32.0) μg/dl. After fully adjusted, restricted cubic spline analyses reported that higher serum lycopene concentrations were significantly associated with decreased risk of all-cause and CVD mortality in participants with CKD (P < 0.001, P = 0.001). When extreme quartiles of serum lycopene concentrations were compared, the multivariable-adjusted HR (95% CI) was 0.778 (0.714-0.848) for all-cause mortality (P < 0.001), and 0.791 (0.692-0.905) for CVD mortality (P < 0.001). Specifically, higher serum lycopene decreased the risk of all-cause and CVD mortality at both CKD stage 1-2 and stage 3-5. Further subgroup analyses and sensitivity analyses supported the current results. Higher serum lycopene was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD. These findings suggested that maintain serum lycopene concentrations could lower mortality risk in CKD patients.
| S-EPMC9760801 | biostudies-literature
Project description:This study aimed to assess the correlation between estimated pulse wave velocity (ePWV) and mortality rates related to all-cause and cardiovascular disease (CVD) among individuals diagnosed with chronic kidney disease (CKD) in the United States. A total of 4669 participants with CKD were identified from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. We calculated the incidence of CKD using an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. Our study examined the association between ePWV and mortality risk based on weighted Kaplan-Meier plots and multivariate Cox regression. Linear testing between ePWV and mortality from all causes and CVD was performed using restricted cubic splines and Cox regression. This study included 4669 patients with CKD from the NHANES, representing 37 million Americans with CKD. There was a mean age of 71.9 years, and 48.1% of participants were male. With every increase of 1 m/s in ePWV measurement, there is a corresponding 31% (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.28-1.34) increase in the rate of mortality from all causes and a 32% (HR: 1.32, 95% CI: 1.27-1.37) increase in the rate of mortality from CVD. A significantly higher rate of cardiovascular and all-cause mortality was observed in patients with CKD with elevated ePWV than in those with lower ePWV, as shown in the weighted Kaplan-Meier plots. Patients with CKD have a significant relationship between ePWV and all-cause and cardiovascular mortality.
| S-EPMC11771810 | biostudies-literature
Project description:BackgroundAlthough handgrip strength is associated with all-cause mortality in patients with chronic kidney disease (CKD), whether this relationship is dose-related is unknown. Therefore, we examined dose-response relationships between handgrip strength and all-cause mortality in CKD patients based on previous studies by meta-analysis.MethodsData sources included three electronic databases (PubMed, Web of Science, and Embase) from inception through October 2023. The included cohort was a CKD population not limited to disease stage, and their handgrip strength was objectively measured. Two researchers independently screened studies, extracted data, and assessed the risk of bias. We utilized estimates of handgrip strength categories using robust-error meta-regression (REMR), pooled study-specific estimates, and established dose-response relationships. Outcomes of interest included only all-cause mortality.ResultsA total of 18 studies with 4810 participants (aged 47-71 years) were included. REMR modeling showed a U-shaped trend of association between handgrip strength and all-cause mortality in patients with CKD. Higher handgrip strength values, from 10 kg to approximately 28 kg, were associated with lower mortality risk. After that, the risk of death increased slightly.ConclusionA U-shaped association exists between handgrip strength and all-cause mortality risk in CKD patients. Future studies with quantitative measurements for each CKD stage will help to determine precise relative risk estimates between handgrip strength and mortality risk in patients with different stages of CKD.
| S-EPMC10810645 | biostudies-literature
Project description:BackgroundTrimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.MethodPubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.ResultsThe risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, p = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, p = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, p = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, p = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, p = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (r= -0.49; 95% CI= -0.75, -0.24; p < 0.001) and inflammatory markers (r = 0.43; 95% CI= 0.03, 0.84; p = 0.036) in non-dialysis patients.ConclusionsIncreased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.
| S-EPMC10228303 | biostudies-literature
Project description:BACKGROUND:Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD. METHODS:SAA concentration was measured in serum samples obtained at the start of follow-up. Multivariate proportional hazards models were employed to examine the magnitude of the risk of ESRD or death across tertiles of SAA concentration after adjustment for traditional risk factors. The C statistic was used to assess the additional predictive value of SAA relative to traditional risk factors. RESULTS:Of 256 participants (mean ± SD glomerular filtration rate [iothalamate] = 148 ± 45 mL/min, and median [interquartile range] urine albumin/creatinine = 39 [14-221] mg/g), 76 developed ESRD and 125 died during a median follow-up period of 15.2 and 15.7 years, respectively. After multivariable proportional hazards regression, participants in the 2 highest SAA tertiles together exhibited a 53% lower risk of ESRD (hazard ratio [HR] 0.47, 95% CI 0.29-0.78), and a 30% lower risk of death (HR 0.70, 95% CI 0.48-1.02), compared with participants in the lowest SAA tertile, although the lower risk of death was not statistically significant. Addition of SAA to the ESRD model increased the C statistic from 0.814 to 0.815 (p = 0.005). CONCLUSIONS:Higher circulating SAA concentration is associated with a reduced risk of ESRD in American Indians with type 2 diabetes.
| S-EPMC5654688 | biostudies-literature
Project description:BackgroundTo evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MethodsPubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ2 and I2 statistics.ResultsTotally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I2 = 79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I2 = 87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients.ConclusionsMetformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
| S-EPMC7575818 | biostudies-literature
Project description:BackgroundThe association between serum uric acid (SUA) and all-cause and cardiovascular disease (CVD) mortality in peritoneal dialysis (PD) patients is controversial. Therefore, we aimed to determine the relationship between SUA and all-cause and CVD mortality in PD patients.MethodWeb of Science, EMBASE, PubMed and the Cochrane Library databases were searched from their inception to 7 April 2021. Effect estimates were presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs) and pooled using random effects model.ResultThirteen cohort studies with 22418 patients were included in this systematic review, of which 9 were included in the meta-analysis. Before switching the reference group, pooled result for the highest SUA category was significantly greater than the median for all-cause mortality (HR = 2.41, 95% CI: 1.37-4.26). After switching the reference group, the highest SUA category did not demonstrate an increased all-cause (HR = 1.40, 95% CI: 0.95-2.05) or CVD (HR = 1.30, 95% CI: 0.72-2.34) mortality compared with the lowest SUA category. Dose-response analysis suggested a nonlinear association between SUA and all-cause mortality risk (Pnonlinearity = 0.002).ConclusionThis meta-analysis didn't find the relationship between SUA levels and all-cause and CVD mortality risk in PD patients. More rigorously designed studies are warranted in the future.
| S-EPMC8863225 | biostudies-literature