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Hyperparathyroidism and 1,25-Dihydroxyvitamin D Deficiency in Mild, Moderate, and Severe Renal Failure^*

THOMAS O. PITTS, BETH H. PIRAINO, ROBERT MITRO, TAI C. CHEN, GINO V. SEGRE, ARTHUR GREENBERG and JULES B. PUSCHETT

Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 90033
the Endocrine Unit, Massachusetts General Hospital Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Thomas O. Pitts, M.D., Department of Medicine, Division of Nephrology, Los Angeles County/University of Southern California Medical Center, 2025 Zonal Avenue, Los Angeles, California 90033.

It has been postulated that hyperparathyroidism in chronic renal failure results from hypocalcemia, occurring, in part, from phosphate retention and/or deficient 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] synthesis. However, many studies have failed to demonstrate hyperphosphatemia or low 1,25-(OH)₂D levels in patients with mild renal failure. We measured creatinine clearance (C_Cr), fractional excretion of phosphorus (FEP), and serum phosphorus, ionized calcium, and plasma N-terminal PTH, and 1,25-(OH)₂D concentrations in 21 normal subjects and 51 patients with renal failure. Patients with mild renal failure (C_cr, >40 mL/min·1.73 m²) had normal mean serum phosphorus and ionized calcium and decreased mean 1,25-(OH)₂D levels compared with those in normal subjects. In patients with moderate renal failure (C_Cr, 20–40), the mean ionized calcium level was normal, plasma PTH levels and FEP were elevated, and the decrement in 1,25-(OH)₂D was more pronounced. The mean ionized calcium level was decreased only in the group of patients with severe renal failure (C_Cr, <20). The 1,25-(OH)₂D values correlated positively with CCr and negatively with the log of plasma PTH and serum phosphorus concentrations. Log of plasma PTH correlated negatively with C_Cr and positively with FEP. The ionized calcium concentration correlated very weakly with C_Cr and the log of the plasma PTH level. These data demonstrate the presence of hyperparathyroidism, normocalcemia, and 1,25-(OH)₂D deficiency in renal failure and are consistent with a role for 1,25-(OH)₂D in the suppression of parathyroid activity through as yet unidentified mechanisms.

^* Portions of this work were presented to the 17th Annual Meeting of the American Society of Nephrology, Washington, D.C., December 1984, and have appeared in abstract form (Kidney Int 27:123, 1985). This work was supported in part by the U.S.V.A.

During portions of the tenure of this work, Dr. T. O. Pitts was a fellow of the National Kidney Foundation and a recipient of a career development award from the U.S.V.A.

Received December 2, 1987.

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