Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease
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PROVIDER: S-EPMC10768787 | 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:(1) Background: it is unclear whether serum vitamin B12 and circulating methylmalonic acid (MMA) are related with a poor prognosis among individuals with chronic kidney disease (CKD); (2) Methods: this prospective cohort study included 2589 individuals with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, and from 2011 to 2014, respectively. Hazard ratios (HRs) and 95% Cis for the associations of MMA and vitamin B12 levels with the risk of all-cause and cardiovascular disease (CVD) mortality were calculated using multivariable Cox proportional hazards regression models. Restricted cubic spline analyses were used to examine the non-linear association of MMA levels with all-cause and CVD mortality. (3) Results: among the 2589 participants, we identified 1192 all-cause deaths and 446 CVD deaths, respectively, with a median follow-up of 7.7 years. Compared with participants with MMA < 123 nmol/L, those with MMA ≥ 240 nmol/L had an increased all-cause and CVD mortality in the multivariable-adjusted model [HR (95% CI), 2.01 (1.54-2.62) and 1.76 (1.18-2.63), respectively]; (4) Conclusions: higher circulating MMA levels were found to be strongly associated with an elevated all-cause and CVD mortality among individuals with CKD, while serum vitamin B12 levels were not associated.
| S-EPMC10343878 | biostudies-literature
Project description:Objectives This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. Methods This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: <2.5th, 2.5-25.0th, 25.0-50.0th, 50.0-75.0th, 75.0-97.5th, and >97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. Results Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (<2.5th: HR, 6.23; 95% confidence interval [CI], 1.16 to 33.56; >97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (<2.5th: HR, 1.37; 95% CI, 0.58 to 3.27; >97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). Conclusions We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.
| S-EPMC10248107 | biostudies-literature
Project description:Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.
| S-EPMC9259314 | biostudies-literature
Project description:Importance:Patients with rheumatoid arthritis (RA) are at high risk for cardiovascular (CV) mortality, attributed to chronic inflammation coupled with elevated circulatory homocysteine levels. Increasing the serum folate level reduces homocysteine, but the association of serum folate concentration with CV mortality in patients with RA has not been previously examined. Objective:To examine the association of serum folate concentration and CV mortality risk among patients with RA. Design, Setting, and Participants:A cohort study of the third National Health and Nutrition Examination Survey (1988-1994) and 2011 Linked Mortality File was performed. Adults aged 18 years or older with self-reported physician-diagnosed RA were included. Data analysis was performed between April 2019 and June 2019. Exposure:Serum folate level. Main Outcomes and Measures:All-cause and CV mortality risk estimated using Cox proportional hazards models, adjusted for the complex survey design and patient characteristics, including demographic characteristics, body mass index, C-reactive protein level, smoking, RA medication use, and comorbid conditions. Results:A total of 683 patients with RA (mean [SE] age, 55.9 [1.0] years; 225 [30.2%] men; 478 [87.0%] white) were classified into tertiles based on serum folate levels, as follows: tertile 1, folate levels less than 4.3 ng/mL (n = 239); tertile 2, folate levels 4.3 ng/mL to 8.2 ng/mL (n = 234); and tertile 3, folate levels greater than 8.2 ng/mL (n = 210). During a median (interquartile range) follow-up of 17.4 (10.0-19.4) years, a total of 392 all-cause deaths and 258 CV deaths occurred. Compared with tertile 1, patients in tertile 2 had lower all-cause mortality risk (hazard ratio [HR], 0.63; 95% CI, 0.47-0.85). The risk of CV mortality was lower among patients in tertile 2 (HR, 0.52; 95% CI, 0.30-0.92) and tertile 3 (HR, 0.44; 95% CI, 0.26-0.75) compared with those in tertile 1 (P for trend = .01). Findings for CV mortality were consistent in a sensitivity analysis that estimated 10-year risk; patients in tertile 2 (HR, 0.31; 95% CI, 0.17-0.57) and tertile 3 (HR, 0.39; 95% CI, 0.22-0.69) had lower CV mortality risk compared with those in tertile 1 (P for trend = .04). Conclusions and Relevance:Among patients with RA, a serum folate level of at least 4.3 ng/mL was associated with lower CV mortality risk. Further research is needed to examine whether a causal relationship exists between serum folate and CV risk among patients with RA.
| S-EPMC7137687 | biostudies-literature
Project description:Despite reported evidence on the relationship between higher serum aluminum levels and poor outcomes in patients on chronic hemodialysis (CHD), the acceptable cutoff value of serum aluminum for mortality remains unclear. A retrospective observational cohort study with 636 Taiwanese patients on CHD was conducted to investigate the impact of serum aluminum levels on mortality. The predictors were bivariate serum aluminum level (<6 and ≥6 ng/mL) and the Outcomes were all-cause and cardiovascular (CV) mortality. During the mean follow-up of 5.3 ± 2.9 years, 253 all-cause and 173 CV deaths occurred. Crude analysis showed that a serum aluminum level of ≥6 ng/mL was a significant predictor of all-cause [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.40-2.23] and CV (HR, 1.84; 95% CI, 1.36-2.50) mortality. After multivariable adjustment, the serum aluminum level of ≥6 ng/mL remained a significant predictor of all-cause mortality (HR, 1.37, 95% CI, 1.05-1.81) but became insignificant for CV mortality (HR, 1.29; 95% CI, 0.92-1.81). Therefore, our study revealed that a serum aluminum level of ≥6 ng/mL was independently associated with all-cause death in patients on CHD, suggesting that early intervention for aluminum level in patients on CHD might be beneficial even in the absence of overt aluminum toxicity.
| S-EPMC6233210 | biostudies-literature
Project description:BACKGROUND:Serum uric acid (UA) level has been reported to be associated with chronic allograft nephropathy and graft failure in patients who undergo kidney transplantation (KT). However, the role of serum UA level in renal graft survival remains controversial. OBJECTIVE:This study aimed to investigate the effect of mean serum UA level during two different post-KT periods on long-term renal graft outcomes in a large population cohort in which living donor KT prevails. MATERIAL AND METHODS:A retrospective cohort study was performed using KT data prospectively collected at a single institution. Patients (n = 2,993) were divided into low-, normal-, and high-UA groups according to the mean serum UA level within the first year (1-YR) and 1-5 years (5-YR) after transplantation. RESULTS:In the 1-YR Cox proportional hazards analysis, the low- and high-UA groups had a significantly decreased and increased risk, respectively, for overall graft failure (OGF), death-censored graft failure (DCGF), and composite event (return to dialysis, retransplantation, death from graft dysfunction, and 40% decline in estimated glomerular filtration rate) compared with the normal-UA group. Similarly, in the 5-YR analysis, the low-UA group had a significantly reduced risk of DCGF compared with the normal-UA group, whereas the high-UA group had a significantly increased risk of all three graft outcomes. In a marginal structural model, hyperuricemia had a significant causal effect on worsening graft outcomes, with consideration of all confounding variables (OGF: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.33-3.78; DCGF: HR 2.38, 95% CI 1.09-4.9; composite event: HR 3.05, 95% CI 1.64-5.49). CONCLUSIONS:A low-to-normal serum UA level within the first year and 1-5 years after KT is an independent factor for better renal allograft outcomes in the long-term follow-up period rather than high serum UA level.
| S-EPMC6294369 | 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:Background and Objectives: Soluble alpha Klotho (s.Klotho) is an emerging marker for chronic kidney disease (CKD) prognosis. The objective was to study the association between s.Klotho and CKD-related decrease in glomerular filtration rate (GFR), bone and vascular damage. Method: A total of 118 patients with CKD stage 2-4 were enrolled and 107 patients continued in the study. Clinical and laboratory parameters were recorded at time of enrollment and 12 months. A double sandwich ELISA for s.Klotho was recorded in controls (n = 25) and patients' serum samples at 6 months (n = 107) and 12 months (n = 102). Primary endpoints like 40% or more fall in GFR, a requirement for renal replacement therapy (RRT), and death with different grades of s.Klotho deficiency were studied. Results: Of the 107 patients (80 male and 27 female), mean s.Klotho was 3.46 ng/mL (02.3-04.2). The GFR fall was significantly different (p value < 0.0001) in the different grades of s.Klotho deficiency with Grade 4 s.Klotho deficiency (0.1-2.99 ng/mL) having the maximum fall of GFR at 9.2 mL/min/1.73 m2 (04.8-12.0) and minimum in Grade 2 (3-5.99 ng/mL) at 1.35 mL/min/1.73 m2 (03.0-02.75). The Ankle Brachial Pressure Index positively correlated with s.Klotho and the correlation coefficient was 0.536 (0.382-0.662) (p < 0.001). The carotid intimal medial thickness negatively correlated with s.Klotho and the correlation coefficient was -0.712 (95% CI: -0.797--0.601, p < 0.001). All five deaths had s.Klotho Grade 4 (severe) deficiency. The event-free survival rate was maximum (100%) in Grade 2 Klotho deficiency and lowest (55%) in Grade 4 s.Klotho deficiency. Conclusions: s.Klotho levels decreased significantly in patients with progressive kidney failure. s.Klotho levels significantly correlated with the presence of vascular disease. Death and need for RRT were significantly more in patients with severe s.Klotho deficiency.
| S-EPMC11563715 | biostudies-literature
Project description:Background and objectivesIn patients with CKD, elevated plasma parathyroid hormone (PTH) levels are associated with greater cardiovascular morbidity and mortality. However, the reference method for PTH measurement is disputed. It has been argued that measurement of nonoxidized PTH better reflects biologically active PTH than measurements with conventional assays.Design, setting, participants, & measurementsPTH and nonoxidized PTH levels were measured at study baseline in 535 patients with CKD with an eGFR range between 89 and 15 ml/min per 1.73 m2. Patients were followed over 5.1 years for the occurrence of acute heart failure, atherosclerotic events, CKD progression (doubling of serum creatinine or initiation of RRT), or all-cause death.ResultsAtherosclerotic events, acute heart failure, CKD progression, and deaths from any cause occurred in 116, 58, 73, and 85 patients, respectively. In Kaplan-Meier analyses, patients at the highest PTH and nonoxidized-PTH tertile (79-543 and 12-172 pg/ml, respectively) showed a higher rate of atherosclerotic events, acute heart failure, CKD progression, and death from any cause. After adjustment for eGFR and albuminuria, nonoxidized PTH was no longer associated with atherosclerotic events (hazard ratio third versus first tertile, 1.04 [95% confidence intervals, 0.62-1.75]), acute heart failure (hazard ratio third versus first tertile, 1.24 [95% confidence intervals, 0.59-2.62]), CKD progression (hazard ratio third versus first tertile, 0.93 [95% confidence intervals, 0.46-1.90]), and death from any cause (hazard ratio third versus first tertile, 1.23 [95% confidence intervals, 0.66-2.31]), and PTH lost its association with atherosclerotic events (hazard ratio third versus first tertile, 0.80 [95% confidence intervals, 0.46-1.38]) and CKD progression (hazard ratio third versus first tertile, 0.99 [95% confidence intervals, 0.46-2.10]), although it remained associated with acute heart failure (hazard ratio third versus first tertile, 2.76 [95% confidence intervals, 1.11-6.89]) and all-cause death (hazard ratio third versus first tertile, 2.35 [95% confidence intervals, 1.13-4.89]). After further adjustment for cardiovascular and kidney risk factors, PTH remained associated with all-cause death (hazard ratio third versus first tertile, 2.79 [95% confidence intervals, 1.32-5.89]), but with no other end point.ConclusionsIn a cohort of patients with CKD, PTH was associated with all-cause mortality; there was no association of nonoxidized PTH with any of the clinical outcomes examined.
| S-EPMC5968904 | biostudies-literature