RESUMO
Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals.
Assuntos
Suplementos Nutricionais , Hiperuricemia/induzido quimicamente , Hiperuricemia/prevenção & controle , Rim/efeitos dos fármacos , Rim/lesões , Ácido Oxônico/efeitos adversos , Probióticos/farmacologia , Animais , Citoproteção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Rim/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Projetos Piloto , Ratos , Ratos Wistar , Ácido Úrico/metabolismoRESUMO
INTRODUCTION: Uremic syndrome consists of nitrogenous waste retention, deficiency in kidney-derived hormones, and reduced acid excretion, and, if untreated, may progress to coma and eventual death. Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4. This report presents preliminary data from a pilot study. METHODS: This was a 6-month prospective, randomized, double-blind, placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries, at five institutions, on 46 outpatients with CKD stages 3 an nd 4: USA (n=10), Canada (n=113), Nigeria (n=115), and Argentina (n=8). Outcomes were compared using biochemical parameters:blood urea nitrogen (BUN), serum creatinine, and uric acid. General well-being was assessed as a secondary parameter by a quality of life (QQOL) questionnaire on a subjective scale of 1-10. RESULTS: Oral ingestion of probiotics (90 billion colony forming units [CFUs]/day) was well tolerated and safe during the entire trial period at all sites. BUN levels decreased in 29 patients (63%, P<0.05), creatinine levels decreased in 20 patients (43%, no statistical significance), and uric acid levels decreased in 15 patients (33%, no statistical significance). Almost all subjects expressed a perceived substantial overall improvement in QOL (86%, P<0.05). CONCLUSION: The main outcomes of this preliminary trial include a significant reduction of BUN, enhanced well-being, and absence of serious adverse effects, thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction. QOL and BUN levels showed statistically significant differences in outcome (P<0.05) between placebo and probiotic treatment periods at all four sites (46 patients). A major limitation of this trial is the small sample size nd elated inconsistencies.