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Nutrients 2017, 9(5), 427; doi:10.3390/nu9050427

Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the Pathogenesis of Secondary Hyperparathyroidism

1
Research Service, Stratton Veterans’ Affairs Medical Center, Albany, NY 12208, USA
2
Department of Medicine, Division of Nephrology, Albany Medical College, Albany, NY 12208, USA
Received: 27 February 2017 / Revised: 10 April 2017 / Accepted: 17 April 2017 / Published: 26 April 2017
(This article belongs to the Special Issue Nutrition and Chronic Kidney Disease)
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Abstract

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. View Full-Text
Keywords: chronic kidney disease; secondary hyperparathyroidism; phosphate; calcium; parathyroid hormone; cortical distal nephron; distal convoluted tubule chronic kidney disease; secondary hyperparathyroidism; phosphate; calcium; parathyroid hormone; cortical distal nephron; distal convoluted tubule
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Phelps, K.R. Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the Pathogenesis of Secondary Hyperparathyroidism. Nutrients 2017, 9, 427.

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