Abstract
To define the onset of the rise in intact parathyroid hormone (PTH) levels in renal insufficiency, we conducted a cross-sectional study of parameters of mineral metabolism in patients with varying degrees of renal impairment. Using an immunoradiometric assay to measure intact PTH levels, we found elevations in intact PTH levels as creatinine clearance approaches 60 ml/minute (serum creatinine near 1.8) and a significant inverse relationship between indices of renal function and intact PTH levels (r=-0.60, P<0.001 for intact PTH and creatinine clearance). Calcium and phosphate levels correlate less strongly with the degree of hyperparathyroidism (r=-0.39, P<0.001 for total calcium; r=0.31, P<0.05 for phosphate). As a group, only patients with severe renal failure (creatinine clearance <20 ml/minute) had 1,25-dihydroxyvitamin D levels below normal (11±4 [SEM] pg/dl, normal range 15–60). Intact and n-terminal PTH measurements correlate well in this patient population with varying degrees of renal insufficiency (r=0.9, P<0.001). Intact PTH can be elevated in patients with mild to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.
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Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nosawa-Ung K, Kim LY, Keufmann HT, Wang CA, Potts JT, Segre GV (1987) Highly sensitive two-site immunoradiometric assay of parathryn and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 33:1364–1367
Freidag J, Martin KJ, Hruska KA, Anderson C, Conrades M Ladenson J, Klahr S, Slatopolsky E (1978) Impaired parathyroid hormone metabolism in patients with chronic renal failure. N Engl J Med 298:29–32
Segre GV, D'Amour P, Hulton A, Potts JT Jr (1981) Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat. J Clin Invest 67:439–448
Martin KJ, Hruska KA, Freitag JJ, Klahr S, Slatopolsky E (1979) The peripheral metabolism of parathyroid hormone. N Engl J Med 301:1092–1098
Felsenfeld AJ, Llach F (1993) Parathyroid gland function in chronic renal failure. Kidney Int 43:771–789
Grunbaum D, Wexler M, Antos M, Gascon-Barre M, Goltzman D (1984) Bioactive parathyroid hormone in canine progressive renal insufficiency. Am J Physiol 247:E442-E448
Goltzman D, Gomolin H, DeLean A, Wexler M, Meakins JL (1984) Discordant disappearance of bioactive and immunoreactive parathyroid hormone after parathyroidectomy. J Clin Endocrinol Metab 58:70–75
Solal MC, Sebert JL, Boutilliez B, Marie A, Moriniere P, Gueris J, Boillon R, Fournier A (1991) Comparison of intact, midregion, and carboxyterminal assays of parathyroid hormone for the diagnosis of bone disease in hemodialized patients. J Clin Endocrinol Metab 73:516–524
Quarles LD, Davidai GA, Schwab SJ, Bartholomay DW, Lobaugh B (1988) Oral calcitriol and calcium: efficient therapy for uremic hyperparathyroidism. Kidney Int 34:840–844
Dunlay R, Rodriguez M, Felsenfeld AJ, Llach F (1989) Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis. Kidney Int 36:1093–1098
Pitts TO, Pirano PH, Mitro R, Chen TC, Segre GV, Greenberg A, Puschett JB (1988) Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate and severe renal failure. J Clin Endocrinol Metab 67:876–881
Reichel H, Deibert B, Schmidt-Gayk H, Ritz E (1991) Calcium metabolism in chronic renal failure: implications for the pathogenesis of hyperparathyroidism. Nephrol Dial Transplant 6:162–169
Blind E, Schmidt-Gayk H, Ambruster EP, Stadler A (1987) Measurement of intact human parathrin by an extracting twosite immunoradiomatric assay. Clin Chem 33:1376–1381
Dilena BA, White GH (1989) Interference with measurement of intact parathrin in serum from renal dialysis patients. Clin Chem 35:1543–1544
Brent GA, LeBoff MS, Seely EW, Conlin PR, Brown EM (1988) Relationship between the concentration and rate of change of calcium and serum intact parathyroid hormone levels in normal humans. J Clin Endocrinol Metab 67:944–950
Conlin PR, Fajtova VF, Mortensen RM, LeBoff MS, Brown EM (1989) Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper- and hypocalcemia in normal humans. J Clin Endocrinol Metab 69:593–599
SAS Institute (1985) SAS user's guide: statistics, 5th ed. SAS Institute, Cary, North Carolina, pp 433–506
Vincenti FV, Haffner R, Armond W, Feduska N, Duca R, Salvatiera O (1991) Decreased secondary hyperparathyroidism in diabetic patients receiving hemodialysis. JAMA 245:930–933
Schwarz P, Sorensen HA, Momsen G, Friis T, Transbal I, McNair P (1992) Hypocalcemia and parathyroid hormone responsiveness in diabetes mellitus: a trisodium-citrate clamp study. Acta Endocrinol (Copenh) 126:260–263
Portale AA, Booth BE, Halloran BP, Morris RC Jr (1984) Effect of dietary phosphorus on circulating concentrations of 1,21-dihydroxy vitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest 73:1580–1589
Wilson L, Felsenfeld A, Dresner MK, Llach F (1985) Altered ion metabolism in early renal failure: role of 1,25(OH)2D. Kidney Int 27:563–573
Llach F, Massry SG (1985) On the mechanism of secondary hyperparathyroidism in moderate renal insufficiency. J Clin Endocrinol Metab 61:601–606
Tessitore N, Venturi A, Adami S, Roncari C, Rugiu C, Cognati A, Bonucci E, Maschio G (1987) Relationship between serum vitamin D metabolites and dietary intake of phosphate in patients with early renal failure. Miner Electrol Metab 13:38–43
Silver J, Russell J, Sherwood LM (1985) Regulation by vitamin D metabolites of messenger RNA for pre-proparathyroid hormone in isolated bovine parathyroid cells. Proc Natl Acad Sci USA 82:4270–4273
Russell J, Lettieri D, Sherwood LM (1986) Suppression by 1,25(OH)2D3 of transcription of the parathyroid hormone gene. Endocrinology 119:2864–2866
Ruttman JR, Buurman CJ, Dakam E, Vissor TJ, Birkenhager JC (1981) Serum concentrations of metabolites of vitamin D in patients with chronic renal failure (CRF): consequences for the treatment with 1-α-hydroxy-derivatives. Clin Endocrinol 14:225–236
Korker AB (1987) Reduced binding of [3H]1,25-dihydroxy vitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 316:1573–1577
Quarles LD, Lobaugh B, Murphy G (1992) Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseus abnormalities in uremia. J Clin Endocrinol Metab 75:145–150
el-Hajj Fuleihan G, Chen CJ, Rivkees SA, Marynick SP, Stock J, Pallotta JA, Brown EM (1989) Calcium-dependent release of N-terminal fragments and intact immunoreactive parathyroid hormone by human pathological parathyroid tissue in vitro. J Clin Endocrinol Metab 69:860–867
Bauer JH, Brooks CS, Burch RN (1982) Clinical appraisal of creatinine clearance as a measurement of glomerular filtration rate. Am J Kidney Dis 2:337–346
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Fajtova, V.T., Sayegh, M.H., Hickey, N. et al. Intact parathyroid hormone levels in renal insufficiency. Calcif Tissue Int 57, 329–335 (1995). https://doi.org/10.1007/BF00302067
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DOI: https://doi.org/10.1007/BF00302067