Changes in renal hemodynamics and urodynamics in rats with chronic hyperoxaluria and after acute oxalate infusion: role of free radicals.
OBJECTIVE
The aim of this study was to evaluate possible changes in renal hemodynamic and urodynamic parameters in rats with chronic hyperoxaluria and after acute oxalate challenge. We also evaluated the possible association between free radical (FR) production, hyperoxaluria, and calcium oxalate (CaOx) calculi formation.


METHODS
Chronic hyperoxaluria was induced by adding 0.75% ethylene glycol (EG) to the drinking water of male Wistar rats. After 7, 21, and 42 days of treatment, urinary biochemistry, oxalate levels, and lipid peroxides were measured. Kidney calculi were examined by polarizing microscopy. In the second part of the experiments, 1, 10, 20, and 30 mg kg(-1) hr(-1) oxalate was infused, by means of an intrarenal arterial catheter (IRA), into normal rats sequentially. Superoxide dismutase (SOD) infusion by means of IRA, in addition to oxalate, was also performed to check its influence on the altered renal function after oxalate infusion. In both the acute and chronic groups, renal blood flow (RBF), cortical microvascular blood flow (CMVBF), glomerular filtration rate (GFR), urine flow (UV), and urinary sodium excretion (U(Na)V) were measured, and chemiluminescence (CL) was examined in the renal venous blood.


RESULTS
Levels of urinary lipid peroxides and enzymuria had increased since day 7, and increased the size of numbers of CaOx crystals in the kidney were noted beginning on day 21, but elevated CL was detectable only on day 7 after 0.75% EG treatment. Decreased UV and U(Na)V were noted in the 42-day EG group, although the 24-hr creatinine clearance values were normal in all experimental groups. On the other hand, RBF, GFR, and CMVBF were attenuated with elevated FR when the oxalate concentration was higher than 10 mg kg(-1) hr(-1) in the acute oxalate infusion group. With SOD pretreatment, the decreased RBF, GFR, and CMVBF could be reversed at 10 mg kg(-1) hr(-1) of oxalate, and be partially reversed at 20. FR also could be reduced significantly at 10 and 20 mg kg(-1) hr(-1) of oxalate.


CONCLUSIONS
Decreased urine flow and sodium excretion were the main renal functions affected by chronic hyperoxaluria. However, that only the 42-day EG group had a decreased tubular function cannot be fully explained by the persistent tubular enzymuria and increased lipid peroxides that began on day 7 after EG treatment. With acute oxalate infusion, the major insult to renal function was renal hemodynamics. Pretreated SOD could reverse the attenuated hemodynamics and reduce the elevated FR partly, which suggested that FR is responsible for oxalate toxicity.
Huang
Ho-Shiang
HS
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Ma
Ming-Chieh
MC
Chen
Jun
J
Chen
Chau-Fong
CF
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D019855:Ethylene Glycol; D005609:Free Radicals / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006959:Hyperoxaluria / Q000378:metabolism* / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008163:Luminescent Measurements; D008297:Male; D010070:Oxalates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery; D012079:Renal Circulation; D013482:Superoxide Dismutase / Q000494:pharmacology; D014563:Urodynamics
D005609:Free Radicals; D010070:Oxalates; D013482:Superoxide Dismutase; D019855:Ethylene Glycol