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Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

ABSTRACT: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD).Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria.XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m²; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m²; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria.XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.

SUBMITTER: Pisano A

PROVIDER: S-EPMC5713253 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

Pisano Anna A Cernaro Valeria V Gembillo Guido G D'Arrigo Graziella G Buemi Michele M Bolignano Davide D

International journal of molecular sciences 20171031 11

<h4>Background</h4>Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD).<h4>Methods</h4>Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. ...[more]

PMID: 29088122

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Project description:BackgroundDetermining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions.MethodsMEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors.ResultsTwenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) -0.21, 95% confidence interval (CI) -0.34, -0.09] and triglycerides (MD -9.98, 95% CI -19.47, -0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD -0.54, 95% CI -0.96, -0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD -2.06, 95% CI -3.79, -0.32) and tumor necrosis factor-α (MD -2.65, 95% CI -3.91, -1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD -0.66, 95% CI -1.23, -0.09) and high-sensitivity C-reactive protein (MD -2.01, 95% CI -3.87, -0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08).ConclusionThe results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.

Project description:Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear. Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function. Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) >300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR<60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58-0.83], I2 = 0.00%) and by 43% in patients with UACR > 300 mg/g (HR 0.57, [95% CI 0.48-0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR<60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51-1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38-0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR > 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR<60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47-1.38], I2 = 0.00%; UACR > 300 mg/g: HR 0.66, [95% CI 0.41-1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48). Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.

Dataset Information

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

Publications

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

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