Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism

Studies in the past showed elevated immunoreactive parathyroid hormone (PTH) serum values in early renal failure, but the assays used in these studies could not discriminate between bioinactive fragments of the PTH peptide and biologically active hormone. The availability of a sensitive PTH assay, which quantitates intact hormone, now allows the analysis of biologically active PTH in renal failure. To characterise more precisely the point of onset of hyperparathyroidism in the course of chronic renal failure and its relation to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured plasma intact PTH and vitamin D metabolite serum values in 63 non-nephrotic uraemic patients (male n = 35, female n = 28, age 31-78 years) with incipient (GFR 60-90 ml/min per 1.73 m3, n = 19) mild (GFR 40-60, n = 22) and moderate (GFR 20-40, n = 22) renal failure, and in 22 age-matched healthy control subjects. Intact PTH concentrations were negatively correlated with GFR (r = -0.57, P less than 0.001). Median plasma intact PTH values (normal range 1.2-6 pmol/l) were 5.6 (range 2.2-13.0) in incipient, 8.1 (2.9-24.0) in mild, and 13.0 (5.4-59.0) in moderate renal failure. Intact PTH values in incipient renal failure were significantly greater than in 22 age-matched control subjects (P less than 0.01). The decline of GFR was paralleled by a progressive decrease in 1,25(OH)2D3 serum values (r = 0.44, P = 0.001). Median values of the hormone (normal range 35-90 pg/ml) were 32 (range 20-66) in incipient (P less than 0.01 vs. age-matched control subjects), 34 (22-74) in mild, and 26 (17-39) in moderate renal failure. In all three groups, mean serum phosphate and total calcium concentrations (corrected for serum protein) were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)