Production and degradation of calcitriol in renal failure rats.
We studied the metabolism of calcitriol in renal failure achieved by nephrectomy in three groups of rats. Group 1 (n = 7) had sham operation of nephrectomy. Group 2 (n = 8) had unilateral nephrectomy. Group 3 (n = 7) had 5/6 nephrectomy. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied 3 wk after the surgery. Serum creatinine concentrations were increased after nephrectomy for groups 2 and 3. Endogenous plasma levels of calcitriol were not different between the rats with renal failure and the controls. MCR of calcitriol were decreased in renal failure rats compared with controls (group 1, 0.24 +/- 0.01; group 2, 0.20 +/- 0.01, P less than 0.01; group 3, 0.16 +/- 0.01 ml.min-1.kg-1, P less than 0.001). The MCR of calcitriol was correlated with the endogenous creatinine clearance by linear regression analysis (r = 0.72, P less than 0.001). The PR of calcitriol were also decreased in renal failure; however, the decreases were much less than the amount of renal tissue removed. We concluded that production of calcitriol is decreased in the remnant kidney. The decreased synthesis is associated with decreased degradation of calcitriol resulting in normal concentrations of calcitriol in mild to moderately severe renal failure.
Department of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor 48109.
C H
CH
Hsu
S
S
Patel
E W
EW
Young
R U
RU
Simpson
D000818:Animals; D001784:Blood Gas Analysis; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D010758:Phosphorus; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium