Use of sevelamer to examine the role of intraluminal phosphate in the pathogenesis of secondary hyperparathyroidism

作者：Phelps Kenneth R^*; Stote Kim S; Mason Darius

来源：Clinical Nephrology, 2014, 82(3): 191-201.

DOI：10.5414/CN108227

• chronic kidney disease
• secondary hyperparathyroidism
• phosphate
• sevelamer carbonate
• tubular calcium reabsorption

Aims: Parathyroid hormone (PTH) promotes calcium reabsorption in the cortical distal nephron (CDN). The phosphate concentration ([P](f)) rises in that segment in chronic kidney disease (CKD); in theory, high [P](f) could reduce availability of calcium for reabsorption and necessitate a compensatory rise in [PTH]. With assumptions, [P](f) is proportional to phosphate excreted/volume of filtrate (E-P/GFR). We therefore hypothesized that [PTH] would correlate with E-P/GFR in CKD, and A[PTH] would correlate with Delta E-P/GFR after sevelamer therapy. Methods: We conducted a 4-week, placebo-controlled trial of sevelamer carbonate in patients with CKD. [PTH] 1-84 and parameters of phosphate homeostasis were measured before and after treatment. GFR was assumed to equal creatinine clearance (C-cr). Pertinent linear regressions were performed. Results: Phosphate excretion fell in the sevelamer group only. Decrements in [PTH] with sevelamer differed from increments with placebo. With either treatment, [PTH] correlated with Ep/C-cr and A[PTH] correlated with Delta E-P/Ccr. Changes in [PTH] were minimal in some sevelamer recipients despite reductions in Ep/Cer; calcium excreted/volume of filtrate was low in these subjects. Conclusions: Phosphate influx affected [PTH] in CKD by determining [P](f) in the CDN. In some patients, low calcium influx may have blunted the effect of sevelamer on [PTH].

• 出版日期2014-9