Is 1,25-dihydroxy-cholecalciferol harmful to renal function in patients with chronic renal failure?

Seventeen undialysed adult patients with chronic renal failure took part in a controlled study of the effects of 1,25(OH)2D3 and D3. After a 6-month observation period the patients were allocated at random to two groups for 6 months of treatment with either 1,25(OH)2D3 (mean dose 0.5 microgram daily) or D3 (dose 100 microgram daily). Treatment was then discontinued and the patients were studied for a further 6 months. Serum iPTH was decreased in both groups but most markedly in the 1,25(OH)2D3 group in which the iPTH values became normal. Serum creatinine increased during treatment in both groups. In the group receiving 1,25(OH)2D3 this was coupled to an increase in serum calcium within the normal range. Our data demonstrate that 1,25(OH)2D3 treatment in patients with chronic renal failure leads to a further reduction in renal function, which may be partially reversible. Physicians should therefore be reluctant to give vitamin D analogues to patients with chronic renal failure unless they have severe symptomatic renal osteodystrophy.

Decreased renal function in association with administration of 1,25-dihydroxyvitamin D3 to patients with stable, advanced renal failure.

A controlled study of the effects of 1,25-dihydroxycholecalciferol (1,25[OH]2D3) and vitamin D3 (D3) was performed in 18 non-dialyzed patients with chronic renal failure (CRF) (creatinine clearance below 35 ml/min) and mild renal osteodystrophy. After 6 months observation of the spontaneous course, the patients were randomly allocated to 6 months oral treatment with either 1,25(OH)2D3 or D3 in initial daily doses of 1 and 100 microgram, respectively, combined with 0.5 g calcium (Calcium Sandoz). 1,25(OH)2D3 had a fast normalizing effect on the biochemical changes of calcium metabolism. D3 had similar, but less pronounced effects. The percent fall in creatinine clearance was greater during than before treatment in all patients on 1,25(OH)2D3 (p less than 0.01) and in 7 of 9 patients on D3 treatment (n.s.). Deterioration of renal function is a major limitation to clinical use of 1,25(OH)2D3 (and D3) in non-dialyzed patients with CRF. In fact, the decreased formation of 1,25(OH)2D3 seen in CRF might protect renal function through the abnormalities in mineral metabolism.

Deterioration of renal function during treatment of chronic renal failure with 1,25-dihydroxycholecalciferol.

A controlled study of the effects of the potent vitamin-D metabolite, 1, 25-dihydroxycholecalciferol (1,25[OH]2D3), and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure (C.R.F.). Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected. After 6 months' observation of the spontaneous course the patients were randomly allocated to 6 months' oral treatment with either 1, 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U., respectively, combined with 0.5 g calcium. 1,25(OH)2D3 quickly corrected hypocalcaemia, reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone, and more than doubled the urinary excretion rate of calcium. D3 had similar, but less pronounced effects. 7 out of 8 patients on 1,25(OH)2D3, developed hypercalcaemia which necessitated a reduction in dosage. None of the patients on D3 treatment developed hypercalcaemia. The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1, 25 (OH)2D3 (P less than 0.01) and in 7 of 9 patients on vitamin D3 treatment (though the group change here was not significant). Deterioration of renal function is a major limitation of the clinical use of 1, 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact, the decrased formation of 1, 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism.