Chronic kidney disease, proteinuria, and mortality risk in patients with Parkinson’s disease: a 12-year longitudinal study

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.

Prospective randomized clinical trials show that implantable cardioverter defibrillators (ICDs) can reduce the risk of total mortality in select populations. However, data regarding patients with chronic kidney disease (CKD) are inconclusive. The aim of this study was to evaluate if ICDs affect total mortality in CKD patients at high risk of sudden cardiac death. Two separate meta-analyses were performed to (i) assess the effect of ICD on all-cause mortality in CKD patients at high risk of sudden cardiac death and (ii) assess the effect of CKD on all-cause mortality in patients who already had an ICD for primary or secondary prevention purposes. Medline and EMBASE were searched from 1966 to 2013. A manual search by cross-referencing was performed. Five observational studies with 17 460 CKD patients considered at high risk of sudden cardiac death were included to evaluate the effect of ICDs on patients with severe CKD. Patients with ICD implants had a reduction in all-cause mortality (adjusted hazard ratio (HR) = 0.65, 95% confidence interval (CI) = 0.47-0.91, P < 0.05) compared with a matched control group. Based on 15 observational studies with 5233 patients as part of our second comparison that evaluated the effect of CKD on patients who received an ICD, CKD was associated with higher mortality risk (HR = 2.86, 95% CI = 1.91-4.27, P < 0.05) despite an ICD. The meta-analysis indicates that for patients undergoing ICD implant, CKD is associated with greater risk of dying. However, ICD placement reduces mortality in CKD patients at high risk of sudden cardiac death.

The loss of skeletal muscle mass and muscle strength is common in patients suffering from chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing dialysis. The purpose of this study was to conduct a meta-analysis to explore the relationship between physical functional performance and all-cause mortality in CKD and ESRD patients undergoing dialysis. A systematic literature search was conducted on an electronic database up to January 2022, and all data were analyzed using RevMan5 (version 5.3). Totally, 19 studies involving 6908 patients were enrolled for analysis. Patients with poor physical functional performance in the handgrip strength (HGS) (hazard ratio [HR] = 1.99, P < 0.00001), gait speed (HR = 2.45, P = 0.0005), 6m walk test (HR = 2.94, P < 0.01), and timed up and go test (HR = 1.69, P = 0.02) showed increased risk of all-cause mortality than those with good physical functional performance. In continuous analyses, both per 1kg increase in HGS (95% CI 0.94-0.98; P < 0.00001; I2 = 47%) and per 1 SD increase in HGS (HR = 0.47 95% CI 0.35-0.64; P < 0.0001; I2 = 35%) were significantly associated with lower all-cause mortality. The present meta-analysis demonstrated that poor physical function outcomes, including grip strength, gait speed, 6MWT, and TUG test, were significantly associated with high all-cause mortality in patients with CKD and ESRD.

Medullary thyroid carcinoma (MTC) is a malignancy with a high mortality rate and a wide age range. However, there are relatively few studies on the relationship between age and all-cause mortality in patients with MTC. As one of the important factors influencing cancer prognosis, the association between age and all-cause mortality in MTC patients needs to be further investigated. The aim of this study was to investigate the relationship between age and all-cause mortality in MTC patients, especially whether there is an inverse L-shaped curve relationship, in order to provide new insights for clinical management and prognostic assessment. A detailed retrospective cohort analysis of 1291 MTC patients diagnosed between 2000 and 2021 was included in this study using the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression modelling, curve fitting, Kaplan-Meier (KM) survival curves and subgroup analyses were used to assess the association between age and all-cause mortality in MTC patients. Potential confounders, including patient sex, race, Summary stage, surgery, Lymph.node.dissection, tumour size and lymph node metastasis (LNM), were rigorously controlled. The risk of all-cause mortality in MTC patients increased by 6% per 1-year increase in age (hazard ratio HR=1.06, 95% confidence interval CI: 1.05-1.06, p<0.001). Further analysis revealed a significant inverse L-shaped relationship between age and all-cause mortality in MTC patients. Specifically, before the age of 50 years, the hazard ratio increased slowly with age (HR=1.024, 95% CI: 0.991-1.059) and the difference was not statistically significant (p=0.1616). After the age of 50 years, the hazard ratio accelerated with increasing age (HR=1.066, 95% CI: 1.051-1.081) and the difference was statistically significant (p<0.001). The results of this study confirm that there is an inverse L-shaped relationship between age and all-cause mortality in MTC patients. The risk of all-cause mortality in MTC patients increased significantly with age after age >50 years. This finding provides new insights into understanding the complex relationship between age and all-cause mortality in MTC, which may help inform clinical management and prognostic assessment.

Chronic kidney disease (CKD) is a global health concern associated with an elevated risk of cardiovascular (CV) and all-cause mortality. The ankle-brachial index (ABI), a noninvasive diagnostic tool, is widely recognized for detecting peripheral arterial disease. This meta-analysis aims to assess whether abnormally low or high ABI values independently predict CV and all-cause mortality in CKD patients, including those on hemodialysis. A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using PubMed, Cochrane, and Google Scholar databases through September 2024 to identify studies on abnormal ABI and mortality outcomes in CKD patients with or without hemodialysis. Data was analyzed with random-effects models, and subgroup analyses evaluated variations by patient characteristics, region, sample size, and follow-up duration. The analysis included 10 cohort studies comprising 13,378 participants. ABI values between 0.9 and 1.3 were defined as normal. Individuals with abnormally low ABI (<0.9) demonstrated a significantly higher incidence in CV mortality [hazard ratio (HR) = 2.23; confidence interval (CI), 1.75-2.83) and all-cause mortality (HR = 1.78; CI, 1.55-2.05). Those with high ABI ≥1.3 were associated with a 2.77-fold increase in CV mortality (HR = 2.77; CI, 1.74-4.41) and a 1.49 higher risk of all-cause mortality (HR = 1.49; CI, 1.09-2.02). Overall, abnormal ABI values were linked to a 1.74 higher risk of all-cause mortality (HR = 1.74; CI, 1.54-1.96) and a 2.34-fold increase in CV mortality (HR = 2.34; CI, 1.93-2.85). Subgroup analyses revealed higher mortality risks in hemodialysis patients compared with nondialysis CKD patients and in studies conducted in Asia. Abnormal ABI values show a U-shaped relationship with mortality, serving as strong predictors of CV and all-cause mortality in CKD patients, particularly those on hemodialysis. Since CV and all-cause mortality are high in CKD patients, these findings suggest that ABI measurement is a useful screening technique to assist in prognosticating such patients. Further studies are warranted to validate these findings and to better understand the prognostic utility of ABI across different CKD stages, including both dialysis-dependent and nondialysis CKD patients.

Background Studies have yielded conflicting findings on the association of asymmetric dimethylarginine (ADMA) level with cardiovascular or all-cause mortality in patients with chronic kidney disease (CKD). This meta-analysis sought to evaluate the association of blood ADMA level with cardiovascular or all-cause mortality in CKD patients. Materials and methods PubMed and Embase databases were comprehensively searched until September 9, 2020 for studies investigating the association of ADMA level with cardiovascular or all-cause mortality in CKD patients. Results Data were collected from nine prospective studies involving 6553 patients. The pooled adjusted risk ratio (RR) of all-cause mortality was 2.06 (95% confidence interval [CI] 1.43–2.96) for the highest versus the lowest ADMA level. Each 0.20 μmol/L ADMA increase was associated with 21% (95% CI 1.09–1.35) higher risk of all-cause mortality but not cardiovascular mortality (RR 1.07; 95% CI 0. 99–1.16). Subgroup analysis showed that each 0.20 μmol/L ADMA increase was significantly associated with all-cause mortality in end-stage renal disease (ESRD) patients (RR 1.22; 95% CI 1.05–1.41) but not in patients with stage 3 to 4 CKD (RR 1.16; 95% CI 0.86–1.56). Conclusions Elevated ADMA level is independently associated with higher risk of all-cause mortality in ESRD patients.

Background Although 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. Methods Data 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. Results A 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. Conclusion A 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.

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.

Background:Some studies have found that hypomagnesemia is associated with vascular calcification, atherosclerosis, and cardiovascular disease, which may lead to increased mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) who need to maintain hemodialysis (HD). However, the conclusion of these studies remain controversial.Methods:Relevant literature was retrieved from the database of Cochrane library, PubMed, EMBASE, and CNKI until December 2020, without any language restrictions. The data was analyzed using the Stata 12.0 software.Results:A total of 31 studies were included, involving 205436 participants. The results showed that after multivariable adjusted, hypomagnesemia was significant associated with the risk of all-cause mortality in patients with CKD and end-stage renal disease (ESRD) (hazard ratios [HR] 1.955; 95% confidence interval (95% CI) 1.511-2.528; P = .000; hypomagnesemia vs normal magnesium or hypermagnesemia). In contrast, in patients with CKD and ESRD, hypermagnesemia was negatively correlated with all-cause mortality (HR 0.873; 95% CI 0.793-0.960; P = .005) (per unit increase). Moreover, in the adjusted model, it was observed that hypermagnesemia was significantly associated with a reduced risk of cardiovascular death (HR 0.598; 95% CI 0.094-1.102, P = .020). In addition, subgroup analysis found that hypomagnesemia was closely related to the increase of all-cause mortality in HD patients (HR 1.799; 95% CI 1.375-2.354; P = .000) (hypomagnesemia vs normal magnesium or hypermagnesemia).Conclusion:Our results show that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in maintenance HD patients. Further studies should be conducted to evaluate the benefits of magnesium correction in maintenance dialysis patients with hypomagnesemia.

Although some previous meta-analyses have demonstrated a relationship between statin therapy and all-cause mortality in patients with chronic kidney disease (CKD), conflicting results have been reported. Thus, we performed an umbrella review to understand the strength of evidence and validity of the claimed associations between statin use and all cause and cardiovascular mortality in CKD patients, including patients on dialysis (CKD stage 5D) and transplant recipients. We comprehensively re-analyzed the data of 14 meta-analyses of observational studies and randomized controlled trials on associations between statin use and different CKD groups - CKD, CKD stage 5D, and kidney transplant recipients. We also assessed the strength of evidence of the re-analyzed outcomes, which were determined from the criteria, including the statistical significance of the p-value of random-effects, as well as fixed-effects meta-analyses, small-study effects, between-study heterogeneity, and a 95% prediction interval. For CKD patients, statin use showed suggestive evidence for an association with reduced all-cause mortality [relative risk (RR) 0.77, 95% confidence interval (0.69-0.87)]. For kidney transplant recipients, statin use showed suggestive evidence for an association with reduced cardiovascular mortality [RR 0.67, 95% CI (0.50-0.90)]. However, for patients on dialysis, statins showed neither cardiovascular [RR 0.93, 95% CI (0.86-1.01)] nor all-cause mortality [RR 0.98, 95% CI (0.89-1.08)] benefits. Our finding indicates that statin could improve all-cause and cardiovascular mortality in patients with non-dialysis CKD.

High-density lipoprotein cholesterol to apolipoprotein A1 ratio and all-cause mortality among incident peritoneal dialysis patients

Studies have shown that low serum albumin (Salb) levels are associated with a high risk of mortality among patients on maintenance hemodialysis (MHD); however, the impact of Salb variability on short-term cardiovascular mortality remains unclear. Herein, we investigated the association between Salb levels and Salb variability on short-term all-cause and cardiovascular-related mortality in patients on MHD.Eligible patients on MHD at Chongqing General Hospital between June 2017 and June 2020 were recruited in this study. Patients were grouped by Salb levels (normal Salb, ≥3.8 g/dL; low Salb, 3.4–3.8 g/dL; and lower Salb, 2–3.4 g/dL) and Salb variability (decreased, >5% loss; increased, >5% gain; and steady, 5% loss to 5% gain). Associations between Salb levels, Salb variability, and all-cause and cardiovascular-related mortality were analyzed using Cox regression models. A survival analysis was performed using the Kaplan–Meier analysis.We enrolled a total of 181 patients on MHD with an average age of 65 years (interquartile range [IQR], 53–75 years). The mean Salb level was 3.8 ± 0.6 g/dL (IQR 2.9–4.4 g/dL), and the median Salb variability was 2.6% per year (IQR, −4.1 to 6.5). Fifty-two (29%) patients died, including 31 (17%) patients who died due to cardiovascular-related causes. Compared with the other groups, the lower Salb group had higher all-cause mortality (P < .01). Cox regression analyses revealed that lower Salb levels and decreased Salb variability were independently associated with all-cause mortality (hazard ratio [HR] = 1.95, 95% confidence interval [CI] 1.103–3.452; HR = 2.245, 95% CI 1.084–4.650), whereas increased Salb variability was independently associated with cardiovascular-related mortality (HR = 2.919, 95% CI 1.178–7.234; P < .05).Lower Salb levels were an independent predictor of all-cause mortality in patients on MHD. Increased Salb variability was strongly associated with cardiovascular-related mortality in the same population, especially in the short-term and in patients with normal Salb levels. Significantly elevated Salb variability should be evaluated to reduce cardiovascular-related mortality.

Although the effect of vitamins on the risk of mortality in diabetic patients has been reported, most studies focus on individual vitamins. However, humans are often exposed to multiple vitamins simultaneously in daily life. Therefore, it is worth exploring the effects of co-exposure to multiple vitamins on the risk of mortality in diabetic patients. This study included diabetic patients aged ≥20WD years who participated in NHANES from 2003 to 2006. An unsupervised K-means clustering method was used to cluster eight vitamins in serum into several patterns of co-exposure to multiple vitamins, and the Cox proportional hazards model was used to evaluate the impact of different patterns of co-exposure to multiple vitamins on the risk of all-cause mortality in diabetic patients. Three patterns of co-exposure to multiple vitamins were generated based on K-means clustering, namely, low-level, moderate-level, and high-level. Among the 484 diabetic patients, with a median follow-up of 13.7 years, a total of 211 deaths occurred. After adjusting for covariates, the individual vitamins had varying effects on the risk of all-cause mortality in diabetic patients. Compared to the low-level group of co-exposure to multiple vitamins, the high-level group significantly reduced the risk of all-cause mortality in diabetic patients, with a HR of 0.42 (95% CI: 0.20, 0.87). Subgroup analysis demonstrated that high levels of co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in males, individuals aged ≥ 60 years, and non-Hispanic White people with diabetes compared to the low-level group, with HR of 0.42 (95% CI: 0.18, 0.98), 0.53 (95% CI: 0.26, 0.98), and 0.26 (95% CI: 0.12, 0.58) respectively. While individual vitamins had different effects on the risk of all-cause mortality in patients with diabetes, high-level co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in patients with diabetes, with differences observed among genders, ages, and race. This suggests that when developing vitamin intervention strategies for patients with diabetes, consideration should be given not only to the dosage of individual vitamins but also to the variations between different population groups.

Background: Studies have shown inconsistent results regarding the association between circulating osteoprotegerin (OPG) levels and all-cause mortality in patients with chronic kidney disease (CKD). The aim of this meta-analysis is to investigate the association between circulating OPG levels and all-cause mortality in patients with CKD.Methods: The PubMed, EMBASE and Cochrane Library databases were searched for eligible studies investigating the association between circulating OPG levels and all-cause mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using a random effects model.Results: In all, 13 studies that included 2,895 patients with CKD were included in this analysis. According to the meta-analysis, patients with the highest circulating OPG level had a significantly higher risk of all-cause mortality (7 studies; the adjusted HR, 1.88; 95% CI, 1.45 - 2.44) compared with patients with the lower circulating OPG level. An increase of 1 pmol/L in the circulating OPG level was associated with a 6% increased risk of all-cause mortality (7 studies; the adjusted HR, 1.06; 95% CI, 1.03-1.10). A subgroup analysis by dialysis methods suggested that an elevated circulating OPG level was independently associated with all-cause mortality in the HD only population.Conclusion: Elevated circulating OPG levels independently predict an increased risk of all-cause mortality in patients with CKD, especially in the HD only population.