Moderate hyperuricemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency

Venla Kurra, Arttu Eräranta, Timo Paavonen, Teemu Honkanen, Juhani Myllymäki, Asko Riutta, Ilkka Tikkanen, Päivi Lakkisto, Jukka Mustonen, Ilkka Pörsti

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    Abstract

    Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham-operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine, and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and RT-PCR. Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/l. In remnant kidney rats, moderate hyperuricemia decreased glomerulosclerosis, tubulointerstitial damage, and kidney mast cell count, without influencing the fibrosis marker collagen I mRNA content. In both sham-operated and 5/6 nephrectomized rats, the mast-cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue COX-2 levels were decreased. To conclude, hyperuricemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.

    Original languageEnglish
    Pages (from-to)21-32
    JournalBasic and Clinical Pharmacology and Toxicology
    Volume132
    Issue number1
    Early online date11 Oct 2022
    DOIs
    Publication statusPublished - Jan 2023
    Publication typeA1 Journal article-refereed

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