Analysing The Excretion Of Uric Acid In Peritoneal Dialysis Patients And A Clinical Trial On Regulating Uric Acid By Prebiotics Intervention

Uric acid(UA)is excreted two-thirds by the kidneys,while the remaining one-third is excreted through the gut in healthy individuals.Peritoneal dialysis(PD)has been widely used in the treatment of end-stage renal disease(ESRD)as an economical and effective renal replacement therapy.Intestinal tract is the most important excretory organ for UA except the kidneys.The degradation of UA by a large number of gut microbiota plays an important role in regulating the UA levels.The gut microbiota may become a new target for lowering UA levels.However,the evidence from human clinical trials is still lacking.Objective:To explore the time trend for serum UA and excretion of UA in PD patients.To compare the excretion of UA between PD patients and healthy controls,and compare the different characteristics of gut microbiota between hyperuricemia and normouricemia patients.To examine the effect of inulin-type prebiotics on serum UA in PD patients and evaluate the role of gut microbiota composition in regulating UA levels.Methods:Firstly,a single-center cohort study based on continuous ambulatory peritoneal dialysis(CAPD)patients in central China was conducted from 2013 to 2020 year.Baseline datas were collected at the first visit after the fisrt PD therapy,and participants were followed up every three months with medical information.Secondly,the case-controlled studies were conducted based on 15 CAPD patients and 15 healthy volunteers,or hyperuricemia and normouricemia patients.Thirdly,PD patients were recruited to a randomized,double-blind,placebo-controlled,crossover trial with 12-week inulin-type prebiotics(10 g/day).Result:(1)Cohort study:A total of 266 PD patients were recruited in this study.The daily excretion of UA from urine and dialysate was approximate 200.0 mg/day.During the median follow-up of 31.7 months,the serum UA level increased with time.The hazard ratio for per 1-mg/dL increase in serum UA was 1.23(1.05-1.45).(2)Case control studies:The renal excretion of UA decreased significantly(205.69 ± 73.17 vs 481.20 ± 61.38 mg/day,P<0.001).The abundance of Bacteroidetes was significantly decreased in comparison to healthy controls(21.0%vs 49.2%,P<0.01),and the ratio of Firmicutes/Bacteroidetes(F/B)was significantly increased(P<0.05)in PD patients.The abundance of Proteobacteria in PD patients was significantly increased(15.4%vs 1.7%,P<0.05).Pseudomona and Erysipelatoclostridium were enriched in normouricemia groups.(3)Randomized clinical trial:Of 16 participants completed the whole trial,and a total of 64 samples were included in analysis.The average concentration of serum UA decreased from 6.54 to 6.09 mg/dL after inulin-type prebiotics intervention(P=0.077),and this reduction was significant in comparison to placebo(pre-placebo vs post-placebo:6.61 ± 1.40 mg/dL vs 6.81 ± 1.26 mg/dL(P=0.441),P for Δ prebiotics vs Δplacebo=0.047).Prebiotics significantly enhanced the fecal degradation of UA(0.59 ±0.14 mg/g vs 0.68 ± 0.18 mg/g,P=0.031)which was negatively associated with serum UA level(rrm=-0.342,P=0.016).The ratio of Firmicutes/Bacteroidetes(F/B)significantly increased in prebiotics intervention(P=0.032).Additionally,prebiotics intervention increased the concentration of acetic acid(1.86±0.47 μg/mg vs 2.16±0.46 μg/mg,P=0.055)and butyric acid(0.62±0.29 μg/mg vs 1.02±0.32 μg/mg,P<0.001).Moreover,we found 6 bacterial species involved in purine degradation(obtained from KEGG functional annotation)significantly enriched in prebiotics treatment in comparison to placebo(P<0.05).Conclusions:Serum UA increased over time in PD patients and the higher UA levels are associated with a higher risk for PD technique failure.Compared to healthy individuals,the elimination of UA via renal pathway is limited in PD patients,and the intestinal microecology was seriously disturbed.The abundance of bacteria degrading UA increased in normouricemia patients.Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA level in ESRD patients,and this urate-lowering effect was highly likely attributed to the modulation of gut microbiota.