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Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis
Kullaya Takkavatakarn1, Thunyatorn Wuttiputinun1, Jeerath Phannajit1
1Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
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.
Insights
Prebiotics, synbiotics, and AST-120 effectively lower uremic toxins in chronic kidney disease (CKD) patients. Preserving residual renal function (RRF) also reduces these toxins, particularly in dialysis patients.
Area of Science:
- Nephrology
- Biochemistry
- Clinical Medicine
Background:
- Protein-bound uremic toxins like indoxyl sulfate and p-cresyl sulfate are linked to cardiovascular disease and mortality in chronic kidney disease (CKD).
- Effective strategies for reducing these toxins in CKD patients are crucial for improving outcomes.
Purpose of the Study:
- To systematically review and meta-analyze strategies for lowering protein-bound uremic toxin levels in CKD patients.
- To evaluate the efficacy of dietary protein restriction, biotic supplements, AST-120, and dialysis techniques on toxin reduction.
Main Methods:
- A meta-analysis of 38 articles (2,492 patients) including RCTs and observational studies.
- Searched MEDLINE, Scopus, and Cochrane Central Register for studies on indoxyl sulfate and p-cresyl sulfate levels.
- Used random-effect models to compute changes in outcomes related to toxin levels and residual renal function (RRF).
Main Results:
- Prebiotics, synbiotics, and AST-120 significantly reduced both indoxyl sulfate and p-cresyl sulfate compared to placebo.
- Probiotics did not show significant reductions. Preservation of RRF was associated with lower toxin levels.
- Hemodiafiltration reduced p-cresyl sulfate more than conventional hemodialysis; VLPD and other oral medications had insignificant effects.
Conclusions:
- Prebiotics, synbiotics, and AST-120 are effective in reducing serum indoxyl sulfate and p-cresyl sulfate in CKD patients.
- Preservation of RRF is linked to lower levels of these toxins, especially in dialysis patients.
- Further research is needed to confirm the efficacy of biotic supplements in non-dialysis CKD patients due to limited data.
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