Influence of glomerular filtration rate on non-(I-84) parathyroid hormone (PTH) detected by intact PTH assays

Background Commercial intact parathyroid hormone (I-PTH) assays detect mole cular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino aci d native molecule. These molecular form(s) accumulate in hemodialyzed patie nts. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. Methods: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided accordi ng to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL . min(-1) . 1.73 m(-2), 12 with a GFR between 30 and 60 mL . min (-1) . 1.73 m(-2), and 8 with a GFR between 5 and 30 mL . min(-1) . 1.73 m( -2). We evaluated indicators of calcium and phosphorus metabolism and creat inine clearance (CrCl) in the progressive renal failure groups, and the HPL C profile of I-PTH and C-terminal PTH in all groups. Results: Only patients with a GFR <30 mL . min(-1) . 1.73 m-2 and hemodialy zed patients had decreased Ca2+ and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca2+ (r = -0.66; P < 0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvi tamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the compos ition of I-PTH increased with each GFR decrease, being 21% in healthy indiv iduals, 32% in progressive renal failure patients with a GFR <30 mL . min(- 1) . 1.73 m(-2), and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. Conclusions: As I-PTH increases progressively with GFR decrease, part of th e increase is associated with the accumulation of non-(1-84) PTH, particula rly when the GFR is <30 mL min-1 1.73 m-2. Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of rena l failure. (C) 2000 American Association for Clinical Chemistry.