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

Abstract

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 brosis and in ammation, but some studies have shown nephroprotective effects probably due to alleviated oxidative stress. We studied the in uence 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 in ammation and brosis were evaluated using RT-PCR and immunohistochemistry.Results: Oxonic acid diet increased plasma uric acid levels by >80 µmol/l without in uencing 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 in uence the brosis marker collagen I mRNA content. In both hyperuricemic groups, the mast-cell product 11-epi-prostaglandin-F 2α 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 in ammation. Thus, moderately increased plasma uric acid had bene cial effects on the kidney in this low-renin model of experimental chronic renal insu ciency.

Optimization of the extraction process and metabonomics analysis of uric acid-reducing active substances from Gymnadenia R.Br. and its protective effect on hyperuricemia zebrafish

“…Adenosine is oxidized to inosine by adenosine deaminase, which is further broken down to hypoxanthine, then converted to xanthine by XO, and xanthine is then converted to UA by XO. The whole process is catalyzed (102). To evaluate the hypouricemic effect of the two Gym ethanolic extracts, we further constructed an acute HUA zebrafish model by combining PO and XSS.…”

“…The change in renal function can be reflected in the level of BUN. When the BUN level is increased, it may indicate impaired renal function, decreased glomerular filtration rate, and increased CRE level ( 102 ). To evaluate the hypouricemic effect of the two Gym ethanolic extracts, we further constructed an acute HUA zebrafish model by combining PO and XSS.…”