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Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

ABSTRACT: Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE^®, EMBASE^® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m²; 95% CI 1.3?4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9?4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

SUBMITTER: Hu MK

PROVIDER: S-EPMC6406285 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Hu May Khei MK Witham Miles D MD Soiza Roy L RL

Journal of clinical medicine 20190207 2

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examin ...[more]

PMID: 30736428

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Project description:ObjectiveTo analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).DesignMeta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).Study selectionRandomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.Data extraction and analysisTwo reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.ResultsFifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference -42.28 mg/dl (1.10 mmol/l), 95% confidence interval -47.25 to -37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; -43.12 mg/dl (1.12 mmol/l), -47.85 to -38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; -0.73 g/24 hour, -0.95 to -0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), -2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.ConclusionStatins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.

Project description:BackgroundPharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking.MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106.Findings25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores (I2 = 78.0%) and pain scores (I2 = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin (I2 = 66.8%), tamsulosin and levofloxacin versus tamsulosin (I2 = 93.3%), and tamsulosin versus placebo (I2 = 83%).InterpretationPharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS.FundingDr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).

Project description:ObjectiveTo define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.DesignCollaborative prospective meta-analysis of randomised trials.Data sources and eligibilityParticipating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm.Main outcome measuresMajor cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death.Participants26 trials (152,290 participants), including 30,295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2).Data extractionIndividual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model.ResultsCompared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity).ConclusionsBlood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

Project description:BackgroundChronic kidney disease with metabolic acidosis is common in older people, but the effectiveness of oral sodium bicarbonate therapy in this group is unclear. We tested whether oral sodium bicarbonate provides net health benefit for older people with advanced chronic kidney disease and serum bicarbonate concentrations < 22 mmol/L.MethodsPragmatic multicentre, parallel group, double-blind, placebo-controlled randomised trial. We recruited adults aged ≥ 60 years with estimated glomerular filtration rate of < 30 mL/min/1.73 m2, not receiving dialysis, with serum bicarbonate concentration < 22 mmol/L, from 27 nephrology and geriatric medicine departments in the UK. Participants received oral sodium bicarbonate (up to 3 g/day) or matching placebo given for up to 2 years, randomised in a 1:1 ratio. The primary outcome was between-group difference in the Short Physical Performance Battery (SPPB) at 12 months, adjusted for baseline values, analysed by intention to treat. Secondary outcomes included generic and disease-specific quality of life (EQ-5D and KDQoL tools), anthropometry, renal function, walk distance, blood pressure, bone and vascular health markers, and incremental cost per quality-adjusted life year gained.ResultsWe randomised 300 participants between May 2013 and February 2017, mean age 74 years, 86 (29%) female. At 12 months, 116/152 (76%) participants allocated to bicarbonate and 104/148 (70%) allocated to placebo were assessed; primary outcome data were available for 187 participants. We found no significant treatment effect for the SPPB: bicarbonate arm 8.3 (SD 2.5) points, placebo arm 8.8 (SD 2.2) and adjusted treatment effect - 0.4 (95% CI - 0.9 to 0.1, p = 0.15). We found no significant treatment effect for glomerular filtration rate (0.6 mL/min/1.73 m2, 95% CI - 0.8 to 2.0, p = 0.39). The bicarbonate arm showed higher costs and lower quality of life as measured by the EQ-5D-3L tool over 1 year (£564 [95% CI £88 to £1154]); placebo dominated bicarbonate under all sensitivity analyses. Adverse events were more frequent in those randomised to bicarbonate (457 versus 400).ConclusionsOral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.Trial registrationEuropean Clinical Trials Database (2011-005271-16) and ISRCTN09486651; registered 17 February 2012.

Project description:OBJECTIVE:Randomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients' preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined. DESIGN:Systematic review and meta-analyses. DATA SOURCES:MEDLINE, Embase, PsycINFO and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:RPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed. RESULTS:In total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%-100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%-99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI -0.178 to 0.364, p=0.502). CONCLUSIONS:Patients' preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs. PROSPERO REGISTRATION NUMBER:CRD42019094438.

Project description:ObjectiveGut flora imbalance characterizes patients with chronic kidney disease (CKD). Although biotic supplementation has been proposed to lessen inflammation and oxidative stress and, thus, reduce the risk of progressive kidney damage and cardiovascular disease, the effects remain controversial. We conducted a meta-analysis to assess the therapeutic benefits of biotics in CKD.MethodsPubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials that evaluated any biotic (prebiotic, probiotic, synbiotics) supplements in patients with CKD (CKD, stage 3-4 to end-stage renal disease). Primary endpoints included changes in renal function, markers of inflammation, and oxidative stress. Secondary endpoints included changes in levels of uremic toxins and variations in lipid metabolism.ResultsTwenty-three eligible studies included 842 participants. In a pooled-analysis, biotics did not change estimated glomerular filtration rate (mean difference [MD] = 0.08, P = .92) or serum albumin (MD = -0.01, P = .86), although prebiotics reduced serum creatinine (standardized mean difference [SMD] = -0.23, P = .009) and blood urea nitrogen (MD = -6.05, P < .00001). Biotics improved total antioxidative capacity (SMD = 0.37, P = .007) and malondialdehyde (SMD = -0.96, P = .006) and reduced the inflammatory marker interleukin-6 (SMD = -0.30, P = .01) although not C-reactive protein (SMD = -0.22, P = .20). Biotic intervention reduced some uremic toxins, including p-cresol sulfate (SMD = -2.18, P < .0001) and indoxyl sulfate (MD = -5.14, P = .0009), which decreased in dialysis-dependent patients. Another toxin, indole-3-acetic acid (MD = -0.22, P = .63), did not change. Lipids were unaffected by biotic intervention (total cholesterol: SMD = -0.01, P = .89; high-density lipoprotein: SMD = -0.08, P = .76; low-density lipoprotein: MD = 3.54, P = .28; triglyceride: MD = -2.26, P = .58).ConclusionThe results highlight the favorable influence of biotics on circulating markers of creatinine, oxidant stress (malondialdehyde, total antioxidative capacity), inflammation (interleukin-6), and uremic toxins (p-cresol sulfate) in patients with CKD. Biotics did not affect estimated glomerular filtration rate, albumin, indole-3-acetic acid, or lipids in either predialysis or dialysis patients.

Project description:BACKGROUND:Colchicine is a widely used drug to treat inflammatory diseases. Due to its long historical use in medicine, controlled clinical trials have been small and there remains some caution with the use of this drug in patients with co-morbidities. The aim of the study is to systematically examine the side effect profile of colchicine in controlled clinical trials across all published indications. METHODS:A systematic review was conducted in accordance with PRISMA methodology. The Cochrane Library, MEDLINE and EMBASE were searched for double-blind controlled trials of oral colchicine in adult patients that reported adverse event data. Meta-analyses were used to determine the relative risk (RR) of adverse events in colchicine users compared to comparator groups. RESULTS:A total of 4915 studies were initially identified and after exclusions, 35 randomised controlled trials with placebo (n =?35) or active comparators (n =?5) were included. The most common diseases studied were gout, liver cirrhosis and pericarditis. There were a total of 8659 pooled participants, 4225 participants were randomised to receive colchicine, 3956 to placebo and 411 to an active comparator. Diarrhoea was reported in 17.9% of colchicine users versus 13.1% in comparator groups (RR 2.4, 95% confidence interval (CI) 1.6, 3.7). Any gastrointestinal event was reported in 17.6% of colchicine users and 13.1% of comparators (RR 1.7, 95% CI 1.3, 2.3). Adverse liver events were reported in 1.9% of colchicine users versus 1.1% in the comparator groups (RR 1.6, 95% CI 0.9, 3.0). Muscle events were reported in 4.2% of colchicine users and 3.3% in the comparator groups (RR 1.3, 95% CI 0.8, 1.9). Haematology events were reported in 0.6% of colchicine users and 0.4% of comparator groups (RR 1.34 (0.64, 2.82). No study reported neuropathy events. Other sensory events were reported in 1.1% of colchicine users and 1.5% of comparator groups (RR 1.4, 95% CI 0.3, 6.7). Infectious events were reported in 0.4% of colchicine users and 2.1% of comparator groups (RR 1.0, 95% CI 0.7, 1.5). No study reported death as an adverse event. CONCLUSION:Colchicine increases the rate of diarrhoea and gastrointestinal adverse events but does not increase the rate of liver, sensory, muscle, infectious or haematology adverse events or death.

Project description:BackgroundCalcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting.Methods and findingsCochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89-1.05]), had imprecise effect on cardiovascular mortality (0.67 [0.16-2.87]), and prevented parathyroidectomy (0.49 [0.40-0.59]) and hypercalcemia (0.23 [0.05-0.97]), but increased hypocalcemia (6.98 [5.10-9.53]), nausea (2.02 [1.45-2.81]), and vomiting (1.97 [1.73-2.24]). Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients.ConclusionsCinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population.

Dataset Information

Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

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Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

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