Effects of oral alkali drug therapy on clinical outcomes in pre-dialysis chronic kidney disease patients: a systematic review and meta-analysis.

BACKGROUND: Metabolic acidosis accelerates the progression of chronic kidney disease (CKD) and increases the mortality rate. Whether oral alkali drug therapy benefits pre-dialysis CKD patients is controversial. We performed a meta-analysis of the effects of oral alkali drug therapy on major clinical outcomes in pre-dialysis CKD patients. METHODS: We systematically searched MEDLINE using the Ovid, EMBASE, and Cochrane Library databases without language restriction. We included all eligible clinical studies that involved pre-dialysis CKD adults and compared those who received oral alkali drug therapy with controls. RESULTS: A total of 18 eligible studies, including 14 randomized controlled trials and 4 cohort studies reported in 19 publications with 3695 participants, were included. Oral alkali drug therapy led to a 55% reduction in renal failure events (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.25-0.82), a rate of decline in the estimated glomerular filtration rate (eGFR) of 2.59 mL/min/1.73 m2 per year (95% CI, 0.88-4.31). There was no significant effect on decline in eGFR events (RR: 0.34; 95% CI: 0.09-1.23), proteinuria (standardized mean difference: -0.32; 95% CI: -1.08 to 0.43), all-cause mortality events (RR: 0.90; 95% CI: 0.40-2.02) and cardiovascular (CV) events (RR: 1.03; 95% CI: 0.32-3.37) compared with the control groups. CONCLUSION: Based on the available and low-to-moderate certainty evidence, oral alkali drug therapy might potentially reduce the risk of kidney failure events, but no benefit in reducing all-cause mortality events, CV events, decline in eGFR and porteninuria.

Comparative efficacy and safety of oral anticoagulants for the treatment of venous thromboembolism in the patients with different renal functions: a systematic review, pairwise and network meta-analysis.

OBJECTIVES: To compare the efficacy and safety of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and different renal functions. DESIGN: Systematic review containing pairwise and Bayesian network meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: MEDLINE, EMBASE and Cochrane Library. ELIGIBILITY CRITERIA: RCTs reporting the efficacy and safety outcomes of DOACs in different creatinine clearance (CrCl) subgroups. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment were undertaken by two independent reviewers. Data were pooled using the DerSimonian-Laird method in pairwise meta-analysis. Network meta-analysis within a Bayesian framework was conducted. RESULTS: Data from 10 RCTs were included. In the treatment of acute VTE, DOACs did not significantly reduce recurrent VTE or VTE-related death (OR, 0.96; 95% CI, 0.82 to 1.11) but significantly reduced bleeding events (0.76, 0.68 to 0.90) compared with warfarin. In the extended treatment of VTE, DOACs produced significant benefits in recurrent VTE or VTE-related death (0.23, 0.16 to 0.29), but significantly increased bleeding events (1.86, 1.04 to 3.33) compared with placebo/aspirin. There were no significant differences in efficacy and safety of DOACs among the three CrCl stratified subgroups in acute and extended treatment of VTE (p for subgroup heterogeneity >0.1). Bayesian network meta-analysis suggested that apixaban 2.5 mg and 5 mg two times per day were associated with a lower risk of bleeding than dabigatran, rivaroxaban, warfarin and aspirin in the subgroup with CrCl >80 mL/min. CONCLUSIONS: For the treatment of acute VTE, DOACs are similar to warfarin in reducing recurrent VTE and VTE-related death but are significantly superior to warfarin in reducing the risk of bleeding. For the efficacy and safety of DOACs across different CrCl stratifications (30-50, 50-80 and more than 80 mL/min), no significant difference was found. In light of minimal evidence, apixaban might be associated with a lower risk of bleeding in patients with VTE and CrCl >80 mL/min. PROSPERO REGISTRATION NUMBER: CRD42018090896.

Oral Anticoagulant Agents in Patients With Atrial Fibrillation and CKD: A Systematic Review and Pairwise Network Meta-analysis.

OBJECTIVE: To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD). STUDY DESIGN: Systematic review and pairwise and Bayesian network meta-analysis. SETTING & STUDY POPULATIONS: Adult patients with AF and CKD stages 3-5D who received OACs. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR)<60mL/min. DATA EXTRACTION: Two reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE). ANALYTICAL APPROACH: Random-effects models using restricted maximum-likelihood methods were fit for the pairwise meta-analyses as well as a network meta-analysis within a Bayesian framework. RESULTS: Pairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct OACs (DOACs) were superior to warfarin in preventing thromboembolic events (hazard ratio [HR], 0.86 [95% CI, 0.78-0.95]), without heterogeneity (I2=10.5%), and in reducing the risk of bleeding events (HR, 0.81 [95% CI, 0.66-0.99]), with substantial heterogeneity (I2=69.8%), in patients with AF and a GFR of 15-60mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15-mg dose of edoxaban were superior to the other OAC regimens in reducing bleeding events. Dose-adjusted apixaban was more effective than edoxaban in preventing thromboembolic events for patients with AF and GFR in the range of 25-50 or 30-50mL/min. In dialysis recipients with AF, the use of OACs increased the risk of bleeding events by 28% (HR, 1.28 [95% CI, 1.03-1.60]) without significant beneficial effects versus not using anticoagulants. LIMITATIONS: Low SOE and heterogeneity in most comparisons. CONCLUSIONS: This study suggests that DOACs are superior to warfarin for the prevention of thromboembolic events and reduction in bleeding risk in patients with AF and mild to moderate kidney disease. However, the low SOE limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase bleeding risk without significant benefits in dialysis recipients with AF. REGISTRATION: Registered at PROSPERO with identification number CRD42018090896.

Effect of antiplatelet therapy on cardiovascular and kidney outcomes in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: The benefits and risks of antiplatelet therapy for patients with chronic kidney disease (CKD) remain controversial. We undertook a systematic review and meta-analysis to investigate the effects of antiplatelet therapy on major clinical outcomes. METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published before April 2019 without language restriction. We included rrandomized controlled trials that involved adults with CKD and compared antiplatelet agents with controls. RESULTS: Fifty eligible trials that included at least one event were identified, providing data for 27773patients with CKD, including 4518 major cardiovascular events and 1962 all-cause deaths. Antiplatelet therapy produced a 15% (OR, 0.85; 95% CI 0.74-0.94) reduction in the odds of major cardiovascular events (P = 0.002), a 48% reduction for access failure events (OR, 0.52; 95% CI, 0.31-0.73), but had no significantly effect on all-cause death (OR, 0.87; 95% CI, 0.71-1.01) or kidney failure events (OR, 0.87; 95% CI, 0.32-1.55). Adverse events were significantly increased by antiplatelet therapy, including major (OR, 1.33; 95% CI, 1.11-1.59) or minor bleeding (OR, 1.66; 95% CI, 1.27-2.05). Among every 1000 persons with CKD treated with antiplatelet therapy for 12 months, 23 major cardiovascular events will be prevented while nine major bleeding events will occur. CONCLUSIONS: Major prevention with antiplatelet agents (cardiovascular events and access failure), might outweigh the risk of bleeding, and there seemed to be an overall net benefit. Individual evaluation and careful monitoring are required.

Effect of diet protein restriction on progression of chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Dietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial. OBJECTIVE: We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease. METHOD: Ovid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI). RESULTS: Nineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: -1.85, P = 0.001), and for proteinuria (MD: -0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: -0.37, 95% CI: -0.5 to -0.24) and BMI (MD: -0.61, 95% CI: -1.05 to -0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: -0.51 to 0.97). CONCLUSIONS: Based on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution.

Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis.

BACKGROUND AND OBJECTIVES: The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used. RESULTS: Sixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31-64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17-62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50-1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86-6.35) and the standardized mean differences in the change in proteinuria or albuminuria (-0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, -0.43 to -0.04) were also statistically significant. CONCLUSIONS: Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.