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Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis.
J Nephrol. 2021 Dec; 34(6):1805-1817.JN

Abstract

INTRODUCTION

Accumulation of protein-bound uremic toxins, including indoxyl sulfate and p-cresyl sulfate, are associated with increased cardiovascular disease and mortality in chronic kidney disease (CKD). We performed a systematic review and meta-analysis to synthesize the available strategies for lowering protein-bound uremic toxin levels in CKD patients.

METHODS

We conducted a meta-analysis by searching the databases of MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials for observational studies and randomized controlled trials (RCTs) that examined the effect of dietary protein restrictions, biotic supplements (including prebiotics, probiotics, and synbiotics), AST-120, dialysis techniques, and the outcome of preservation of residual renal function (RRF) on indoxyl sulfate and p-cresyl sulfate levels. Random-effect model meta-analyses were used to compute changes in the outcomes of interest.

RESULTS

A total of 38 articles (2,492 patients), comprising 28 RCTs, 8 single-arm or prospective cohort studies, and 2 cross-sectional studies were included in this meta-analysis. When compared with placebo, prebiotics, synbiotics, and AST-120 provided significantly lower levels of both serum indoxyl sulfate and p-cresyl sulfate. There were no significant reductions in serum indoxyl sulfate and p-cresyl sulfate levels in patients receiving probiotics. Preservation of RRF in dialysis patients resulted in lower levels of both of the protein-bound uremic toxins. When compared with conventional hemodialysis, hemodiafiltration significantly decreased serum p-cresyl sulfate alone, whereas a significant change in serum indoxyl sulfate levels was observed only in studies with long-term observation periods. Very low protein diet (VLPD) and other oral medications yielded insignificant differences in protein-bound uremic toxins.

CONCLUSIONS

The present meta-analysis demonstrated that prebiotics, synbiotics, and AST-120 can effectively reduce both serum indoxyl sulfate and p-cresyl sulfate in CKD patients when compared with placebo. Preservation of RRF was associated with lower serum indoxyl sulfate and p-cresyl sulfate levels. The effect of biotic supplements was detected only in dialysis patients. For non-dialysis CKD patients, the results were limited due to the small number of studies. Further studies are needed to determine the efficacy in these populations.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand. pesancerinus@hotmail.com. Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. pesancerinus@hotmail.com.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

33484425

Citation

Takkavatakarn, Kullaya, et al. "Protein-bound Uremic Toxin Lowering Strategies in Chronic Kidney Disease: a Systematic Review and Meta-analysis." Journal of Nephrology, vol. 34, no. 6, 2021, pp. 1805-1817.
Takkavatakarn K, Wuttiputinun T, Phannajit J, et al. Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis. J Nephrol. 2021;34(6):1805-1817.
Takkavatakarn, K., Wuttiputinun, T., Phannajit, J., Praditpornsilpa, K., Eiam-Ong, S., & Susantitaphong, P. (2021). Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis. Journal of Nephrology, 34(6), 1805-1817. https://doi.org/10.1007/s40620-020-00955-2
Takkavatakarn K, et al. Protein-bound Uremic Toxin Lowering Strategies in Chronic Kidney Disease: a Systematic Review and Meta-analysis. J Nephrol. 2021;34(6):1805-1817. PubMed PMID: 33484425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis. AU - Takkavatakarn,Kullaya, AU - Wuttiputinun,Thunyatorn, AU - Phannajit,Jeerath, AU - Praditpornsilpa,Kearkiat, AU - Eiam-Ong,Somchai, AU - Susantitaphong,Paweena, Y1 - 2021/01/23/ PY - 2020/06/10/received PY - 2020/12/27/accepted PY - 2021/1/24/pubmed PY - 2022/1/29/medline PY - 2021/1/23/entrez KW - Chronic kidney disease KW - Indoxyl sulfate KW - Protein-bound uremic toxins KW - p-Cresyl sulfate SP - 1805 EP - 1817 JF - Journal of nephrology JO - J Nephrol VL - 34 IS - 6 N2 - INTRODUCTION: Accumulation of protein-bound uremic toxins, including indoxyl sulfate and p-cresyl sulfate, are associated with increased cardiovascular disease and mortality in chronic kidney disease (CKD). We performed a systematic review and meta-analysis to synthesize the available strategies for lowering protein-bound uremic toxin levels in CKD patients. METHODS: We conducted a meta-analysis by searching the databases of MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials for observational studies and randomized controlled trials (RCTs) that examined the effect of dietary protein restrictions, biotic supplements (including prebiotics, probiotics, and synbiotics), AST-120, dialysis techniques, and the outcome of preservation of residual renal function (RRF) on indoxyl sulfate and p-cresyl sulfate levels. Random-effect model meta-analyses were used to compute changes in the outcomes of interest. RESULTS: A total of 38 articles (2,492 patients), comprising 28 RCTs, 8 single-arm or prospective cohort studies, and 2 cross-sectional studies were included in this meta-analysis. When compared with placebo, prebiotics, synbiotics, and AST-120 provided significantly lower levels of both serum indoxyl sulfate and p-cresyl sulfate. There were no significant reductions in serum indoxyl sulfate and p-cresyl sulfate levels in patients receiving probiotics. Preservation of RRF in dialysis patients resulted in lower levels of both of the protein-bound uremic toxins. When compared with conventional hemodialysis, hemodiafiltration significantly decreased serum p-cresyl sulfate alone, whereas a significant change in serum indoxyl sulfate levels was observed only in studies with long-term observation periods. Very low protein diet (VLPD) and other oral medications yielded insignificant differences in protein-bound uremic toxins. CONCLUSIONS: The present meta-analysis demonstrated that prebiotics, synbiotics, and AST-120 can effectively reduce both serum indoxyl sulfate and p-cresyl sulfate in CKD patients when compared with placebo. Preservation of RRF was associated with lower serum indoxyl sulfate and p-cresyl sulfate levels. The effect of biotic supplements was detected only in dialysis patients. For non-dialysis CKD patients, the results were limited due to the small number of studies. Further studies are needed to determine the efficacy in these populations. SN - 1724-6059 UR - https://www.unboundmedicine.com/medline/citation/33484425/Protein_bound_uremic_toxin_lowering_strategies_in_chronic_kidney_disease:_a_systematic_review_and_meta_analysis_ L2 - https://dx.doi.org/10.1007/s40620-020-00955-2 DB - PRIME DP - Unbound Medicine ER -