{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:13:03Z","timestamp":1773148383283,"version":"3.50.1"},"reference-count":101,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T00:00:00Z","timestamp":1493164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u2206[PTH] correlated with \u2206EP\/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.<\/jats:p>","DOI":"10.3390\/nu9050427","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T13:42:06Z","timestamp":1493214126000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the Pathogenesis of Secondary Hyperparathyroidism"],"prefix":"10.3390","volume":"9","author":[{"given":"Kenneth","family":"Phelps","sequence":"first","affiliation":[{"name":"Research Service, Stratton Veterans\u2019 Affairs Medical Center, Albany, NY 12208, USA"},{"name":"Department of Medicine, Division of Nephrology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1210\/jcem-67-5-876","article-title":"Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure","volume":"67","author":"Pitts","year":"1988","journal-title":"J. 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