Dose effect of nitrendipine on urinary enzymes and microproteins following non-ionic radiocontrast administration

Although calcium-channel antagonists have been proposed as prophylaxis to prevent radiocontrast-induced nephropathy, the dose and dose interval to achieve a protective effect have not been quantified in humans.

In a randomized, double-blind protocol we studied urinary enzyme and microprotein excretion in 121 outpatients (mean age 65.3 +/- 9.3 years, 62% male) with normal renal function who were to undergo digital subtraction arteriography with iohexol or iopentol. The subjects were treated with a single dose of placebo (group 1) or nitrendipine 10 mg (group 2) or 20 mg (group 3) p.o. 1 h before the procedure. Blood and urine samples were collected 1 h before, 1 h after, and 24 h after contrast administration. Study variables included contrast volume and serum creatinine, and urinary creatinine, osmolality, albumin, alanylamino-peptidase (AAP, a brush border enzyme), N-acetyl-beta-glucosaminidase (NAG, a lysosomal enzyme), and alpha-1-microglobulin (alpha-1-micro, a filtered microprotein).

Serum values of creatinine remained unchanged during the study period. Albuminuria was not affected by contrast administration, whereas AAP, NAG, and alpha-1-micro increased significantly, all except AAP returning to baseline at 24 h. Pretreatment with nitrendipine did not reduce enzyme excretion, although AAP levels were lower in general in the group assigned to the 20-mg dose. Acute renal failure, defined as a 50% increase of serum creatinine 24 h after radiocontrast administration, was found in eight patients: four from group 1 (8.3%), three from group 2 (6.5%), and one from group 3 (3.7%).

Neither the course of enzyme excretion nor the incidence of acute renal failure following radiocontrast administration were affected by single doses of calcium antagonists. AAP levels were lower in general in subjects taking the 20-mg dose of nitrendipine. This study also indicates that a single low or normal dose of nitrendipine per os is not effective prophylaxis before radiocontrast administration. The designs of future studies investigating the "nephroprotective' effect of calcium-channel antagonists per os should incorporate (1) the use of repeated doses to saturate hepatic metabolic pathways, and (2) the control of confounding variables in the measurement of urinary enzymes.