Attenuated Rise of 1,25 (OH) ₂ Vitamin D ₃ in Response to Parathyroid Hormone in Patients with Incipient Renal Failure

Despite elevated parathyroid hormone (PTH) levels, low normal or diminished serum 1,25(OH)₂D₃concentrations are found in patients with incipient renal failure. To further assess (indirectly) the reserve capacity of renal production of 1,25(OH)₂D₃ we studied 9 patients with incipient or moderate renal failure (inulin clearance 31–68ml/min/1.73 m2) and 9 controls, using a novel stimulation test. We measured 1,25 (OH)₂D₃ levels, free 1,25(OH)₂D₃ index, cAMP excretion, calciuria and phosphaturia before and after infusion of 2 × 400 U of human (h) PTH (1–38). Baseline 1,25(OH)₂D₃ levels were not significantly different in patients (42.5 pg/ml, 21.6–51.1) compared with controls (45.0 pg/ml, 37.4–67.3). After infusion of hPTH(l-38), however, median increase in 1,25(OH)₂D₃ was only + 25% versus + 86% in controls, despite a greater proportional increase in cAMP/GF ratio. The data suggest subnormal stimulation of renal 1,25(OH)₂D₃ production in response to exogenous PTH in most patients with incipient renal failure. This may reflect partial exhaustion of biosynthetic reserve capacity.