Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the Pathogenesis of Secondary Hyperparathyroidism.
Nutrients
; 9(5)2017 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-28445401
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.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Fosfatos
/
Hiperparatireoidismo Secundário
/
Néfrons
Tipo de estudo:
Clinical_trials
/
Etiology_studies
Limite:
Humans
Idioma:
En
Revista:
Nutrients
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos