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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical