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]) 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 (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/C). To assess the tradeoff-in-the-nephron hypothesis, we examined regressions of [PTH] on 100/eGFR and phosphorus excreted per volume of filtrate (E/C).

RESULTS

Regressions pertinent to historic theories yielded significant direct relationships between [PTH] and both E/C and [FGF23], but neither association supported the theory to which it pertained. [PTH] varied directly with 100/eGFR and with E/C, a surrogate for [P]. E/C 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.