%0 Journal Article
%T Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the Pathogenesis of Secondary Hyperparathyroidism
%A Kenneth R. Phelps
%J Archive of "Nutrients".
%D 2017
%R 10.3390/nu9050427
%X Chronic kidney disease (CKD) causes secondary hyperparathyroidism (SHPT). The cardinal features of SHPT are persistence of normocalcemia as CKD progresses and dependence of the parathyroid hormone concentration ([PTH]) on phosphate influx (IP). The tradeoff-in-the-nephron hypothesis integrates these features. It states that as the glomerular filtration rate (GFR) falls, the phosphate concentration ([P]CDN) rises in the cortical distal nephron, the calcium concentration ([Ca]CDN) in that segment falls, and [PTH] rises to maintain normal calcium reabsorption per volume of filtrate (TRCa/GFR). In a clinical study, we set GFR equal to creatinine clearance (Ccr) and IP equal to the urinary excretion rate of phosphorus (EP). We employed EP/Ccr as a surrogate for [P]CDN. We showed that TRCa/Ccr was high in patients with primary hyperparathyroidism (PHPT) and normal in those with SHPT despite comparably increased [PTH] in each group. In subjects with SHPT, we examined regressions of [PTH] on EP/Ccr before and after treatment with sevelamer carbonate or a placebo. All regressions were significant, and £¿[PTH] correlated with £¿EP/Ccr in each treatment cohort. We concluded that [P]CDN determines [PTH] in CKD. This inference explains the cardinal features of SHPT, much of the evidence on which other pathogenic theories are based, and many ancillary observations
%K chronic kidney disease
%K secondary hyperparathyroidism
%K phosphate
%K calcium
%K parathyroid hormone
%K cortical distal nephron
%K distal convoluted tubule
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452157/