Moderate hyperuricaemia ameliorated kidney damage in a low‐renin model of experimental renal insufficiency

Autor: Venla Kurra, Arttu Eräranta, Timo Paavonen, Teemu Honkanen, Juhani Myllymäki, Asko Riutta, Ilkka Tikkanen, Päivi Lakkisto, Jukka Mustonen, Ilkka Pörsti
Přispěvatelé: HUS Abdominal Center, Department of Medicine, Clinicum, Medicum, Helsinki University Hospital Area, University of Helsinki, Nefrologian yksikkö, HUSLAB, Department of Clinical Chemistry and Hematology, Tampere University, Clinical Medicine, Department of Internal medicine
Rok vydání: 2022
Předmět:
Zdroj: Basic & Clinical Pharmacology & Toxicology. 132:21-32
ISSN: 1742-7843
1742-7835
Popis: Background: Hyperuricemia may predispose to renal damage, but in end-stage renal disease lower uric acid concentrations have been associated with higher mortality. In experimental studies, uric acid has promoted renal fibrosis and inflammation, but some studies have shown nephroprotective effects probably due to alleviated oxidative stress. We studied the influence of moderate hyperuricemia on kidney morphology in 5/6 nephrectomized rats.Methods: Three weeks after subtotal nephrectomy or sham-operation, rats were put on 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Blood pressure was monitored using tail-cuff. At close of the study, blood, urine, and kidney samples were taken, and renal histology, mast cell count, and oxidative stress markers were determined. Kidney tissue inflammation and fibrosis were evaluated using RT‑PCR and immunohistochemistry.Results: Oxonic acid diet increased plasma uric acid levels by >80 µmol/l without influencing blood pressure. Creatinine clearance was reduced by ~60% in both remnant kidney groups, and by ~30% in hyperuricemic sham-operated rats. In remnant kidney rats with suppressed plasma renin activity, moderate hyperuricemia decreased glomerulosclerosis, tubulointerstitial damage, and kidney mast cell count, but did not influence the fibrosis marker collagen I mRNA content. In both hyperuricemic groups, the mast-cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue COX‑2 levels were decreased.Conclusions: Hyperuricemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately increased plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental chronic renal insufficiency.
Databáze: OpenAIRE
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