DISTAL TUBULAR-ACIDOSIS INDUCED BY FK506

This study was designed to investigate the effect of tacrolimus (FK506 ) and of cyclosporine (CsA) on tubular function in renal graft recipie nts. Patients were randomised after renal transplantation to immunosup pressive treatment with FK506 (n = 8) or CsA (n = 8), Patients had a m ean age of 45.7 +/- 3.4 yr; there was no difference in age, sex, HLA s tatus or CMV mismatches. Neither was there any difference in the frequ ency of episodes of acute kidney failure between the groups, nor was t here a significant difference in the frequency of episodes of kidney r ejection within the first year. The mean FK506 level at the time lay a t 14.7 +/- 14.4 ng/mL whole blood, and the mean CsA level at the time of study was 162 +/- 25 ng/mL whole blood. We performed renal function studies 6 months after transplantation: C-In, C-PAH, NaHCO3 loading, and Na2SO4 loading. There was no significant impairment of GFR in pati ents treated with FK506 with 53.6 +/- 2.5 mL/min as compared to 58 +/- 6 mt in group 2. Plasma renin activity (0.6 +/- 0.4 ng/mL vs 2.3 +/- 3; p < 0.01) and aldosterone (69 +/- 17 vs 157 +/- 28.2 pg/mL; p < 0.0 5) were significantly decreased during treatment with FK506. Fractiona l HCO3 excretion was low in both groups, indicating that bicarbonate r eabsorption in the proximal nephron was unimpaired. Distal renal tubul ar acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2. Potassium levels were slightly increased in patients treated with FK506 (5.4 +/- 0.2 mmoL/L) as compared to cyclosporine (4.9 +/- 0.3 mmoL/L; p < 0.05). Distal hydrogen ion secretion, evaluated by the ability to increase urinary pCO(2) in a highly alkaline urine, was im paired in patients treated with FK506 (U-B pCO(2): 16.1 +/- 4 vs 36 +/ - 5.8; p < 0.05) as compared to patients treated with CsA. The maximum acidification capability (NAE) was slightly lowered during therapy wi th FK506 (67.5 +/- 11.8 versus 86.6 +/- 16.5 mu mol/min, ns). We concl ude that FK506 administration results in a decrease in the rate of hyd rogen ion secretion by the collecting tubules. This defect was disclos ed by the finding of a subnormal pCO(2) in a highly alkaline urine. Th ese results show that FK506 is able to induce distal tubular acidosis. Distal tubular acidosis is part of FK506 induced nephrotoxicity, the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be furt her elucidated.