Early Control of PTH and FGF23 in Normophosphatemic CKD Patients

Abstract

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4.Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n ‫؍‬ 19) or sevelamer hydrochloride (n ‫؍‬ 21).Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients.Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes.

Phosphate Binders in CKD

“…17 Serum phosphorus is highly fluctuating when measured in a nonfasted state, as was the case in the present study. It is good to know that phosphate binders do effectively chelate phosphate and remove it from the bowel even in CKD patients not yet on dialysis, as they do in those on dialysis.…”

“…Sevelamer-HCl reduces serum FGF23, whereas calcium acetate does not. 17 Finally, the effects of various types of phosphate binders on the progression of vascular calcification and on hard patient outcomes probably also differ, although this remains a matter of debate 13,18 . Such differences were also suggested by subgroup analyses in the study by Block et al, with calcium-and non-calcium-containing phosphate binders exerting differential effects on PTH, FGF23, and mineralization of the bone and vasculature.…”

Fibroblast Growth Factor-23 in Early Chronic Kidney Disease

“…Furthermore, our data are in favor of the new paradigm for the pathogenesis of secondary hyperparathyroidism according to which a reduced phosphate excretion capacity is the principal abnormality that initiates this complication. A clinical implication of our study is that measures to restrict phosphate loading (diet and phosphate binder therapy) should be considered at an earlier stage than is currently practiced (57).…”

FGF-23: estado da arte

“…Only in the sevelamer group, a reduction in serum FGF-23 levels was observed. 59 That result has important clinical implications. Similarly to the trade off theory 13,14 proposed to PTH, mild elevations in FGF-23 could prevent hyperphosphatemia in the early stages of CKD.…”

“…63 The mechanism involved in reducing FGF-23 levels by using P binders, specifically sevelamer, is unknown. 59 Sevelamer is believed to decrease oxidative stress and inflammatory markers because of its pleiotropic effects on the vascular endothelium of patients with CKD. 64,65 That effect could result from the sevelamer's property of chelating endotoxins in the intestine, thus preventing intestinal uptake of substances that stimulate inflammatory response.…”