Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria.

Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 +/- 36 to 70 +/- 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 +/- 8.1% to 61.9 +/- 7.7%, and 24-h urinary Ca excretion declined from 7.6 +/- 1.4 to 5.7 +/- 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonresponders, despite reduction of 1,25-(OH)2D from 122 +/- 36 to 84 +/- 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 +/- 8.2% to 72.1 +/- 10.6%) or 24-h urinary Ca excretion (7.3 +/- 1.3 to 7.2 +/- 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recommended because of its generalized effects in inhibiting steroid synthesis.

Duke Scholars

Author Glenn Michael Preminger Urology