The effect of calcitriol on fasting urine calcium loss and renal tubular reabsorption of calcium in patients with mild renal failure--actions of a permissive hormone.

AIM

Renal production of 1,25-dihydroxycholecalciferol is attenuated in early renal failure. Renal tubular reabsorption of calcium is diminished in moderate renal failure and we wished to see if this were true in the early stages and whether supplementary calcitriol would bring about correction. We were interested in the idea of 1,25-dihydroxycholecalciferol being a permissive agent, operating indirectly.

METHODS

We measured calcium-related variables, including calculated ultrafiltrable serum calcium, before and after calcitriol 0.5 microg daily for six days in 34 subjects with stable mild renal failure.

RESULTS

The mean serum creatinine was 0.21 (+/- 0.08) mmol/l. The mean serum Ca++ was normal (1.18 mmol/l) but nine patients had values outside the normal range and in six cases, with low-normal serum Ca++ levels, there was a diminished tubular reabsorption. In five cases, basal serum Ca++ was mildly elevated. The coefficient of variation for serum Ca++ was 4.4%. PTH (1-84) levels were mildly elevated and 1,25-dihydroxycholecalciferol levels low-normal. The urine Ca/Cr, representing net bone resorption, was elevated in six cases. After calcitriol, the mean serum Ca++ level rose slightly and the coefficient of variation decreased to 3.6%. Changes in Ca++ whether upward or downward were accounted for by minor alterations in tubular reabsorption and a tendency to less net bone resorption. The initial Ca++ predicted (negatively) the magnitude of the correction. Neither the prevailing PTH nor the 1,25-dihydroxycholecalciferol levels explained any of the observed changes.

CONCLUSION

In early renal failure, there may be impaired regulation of serum Ca++. Despite elevated PTH, mild hypocalcemia may exist in the presence of increased net bone resorption relative to GFR. Hypocalcemia was accounted for by reduced renal tubular reabsorption of calcium which corrected after calcitriol. Net bone resorption tended to fall after calcitriol. Mild hypercalcemia, when present, was corrected by a reduction in tubular reabsorption. Calcitriol did not have a simple unidirectional effect but instead contributed to efficiency of the homeostatic mechanisms controlling the serum Ca++ set-point.