An examination of multiple explanations for secondary hyperparathyroidism

Aims: Seven theories address the evolution of secondary hyperparathyroidism (SHPT) as chronic kidney disease (CKD) progresses. The tradeoff-in-the-nephron hypothesis states that the plasma parathyroid hormone ([PTH]) concentration rises because an increased phosphate concentration in the cortical distal nephron ([P](CDN)) reduces the ionized calcium concentration in that segment. In the present study, we compared this hypothesis to its predecessors. Materials and methods: We studied 30 patients with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m(2) (mean 29.5). To examine historic theories, we performed regressions of [PTH] on plasma concentrations of ionized calcium, phosphorus, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and fibroblast growth factor 23, and on calcium excreted per volume of filtrate (E-Ca/C-cr). To assess the tradeoff-in-the-nephron hypothesis, we examined regressions of [PTH] on 100/eGFR and phosphorus excreted per volume of filtrate (E-P/C-cr). Results: Regressions pertinent to historic theories yielded significant direct relationships between [PTH] and both E-Ca/C-cr and [FGF23], but neither association supported the theory to which it pertained. [PTH] varied directly with 100/eGFR and with E-P/C-cr, a surrogate for [P](CDN). E-P/C-cr correlated strongly with 100/eGFR. Conclusions: The only theory of SHPT that our data support is the tradeoff-in-the-nephron hypothesis. Other theories are not supported.