Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy

Abstract

Fibroblast growth factor 23 (FGF-23) rises progressively in chronic kidney disease and is associated with adverse cardiovascular outcomes. FGF-23 putatively induces volume retention by upregulating the sodium-chloride cotransporter (NCC). We studied whether, conversely, interventions in volume status affect FGF-23 concentrations.We performed a post hoc analysis of 1) a prospective saline infusion study with 12 patients with arterial hypertension who received 2 L of isotonic saline over 4 hours, and 2) a randomized controlled trial with 45 diabetic nephropathy (DN) patients on background angiotensin-converting enzyme -inhibition (ACEi), who underwent 4 6-week treatment periods with add-on hydrochlorothiazide (HCT) or placebo, combined with regular sodium (RS) or low sodium (LS) diet in a cross-over design. Plasma C-terminal FGF-23 was measured by ELISA (Immutopics) after each treatment period in DN and before and after saline infusion in hypertensives.The patients with arterial hypertension were 45 ± 13 (mean ± SD) years old with an estimated glomerular filtration rate (eGFR) of 101 ± 18 mL/min/1.73 m2. Isotonic saline infusion did not affect FGF-23 (before infusion: 68 median [first to third quartile: 58–97] relative unit (RU)/mL, after infusion: 67 [57–77] RU/mL, P = 0.37). DN patients were 65 ± 9 years old. During ACEi + RS treatment, eGFR was 65 ± 25 mL/min/1.73 m2 and albuminuria 649 mg/d (230–2008 mg/d). FGF23 level was 94 (73–141) RU/mL during ACEi therapy. FGF-23 did not change significantly by add-on HCT (99 [74–148] RU/mL), LS diet (99 [75–135] RU/mL), or their combination (111 [81–160] RU/mL, P = 0.15).Acute and chronic changes in volume status did not materially change FGF-23 in hypertensive patients and DN, respectively. Our data do not support a direct feedback loop between volume status and FGF-23 in hypertension or DN.

Effect of Salt Intervention on Serum Levels of Fibroblast Growth Factor 23 (FGF23) in Chinese Adults: An Intervention Study

“…However, a recent study tried to figure out whether acute and chronic volume intervention influenced the concentrations of FGF23 in hypertensive and diabetic nephropathy patients. Acute saline infusion did not change FGF-23 concentrations, nor did six-week hydrochlorothiazide and/or low salt diet [ 20 ]. Low salt diet also failed at changing serum FGF23 in nondiabetic proteinuric CKD patients [ 10 ].…”

Fibroblast growth factor 23 is related to profiles indicating volume overload, poor therapy optimization and prognosis in patients with new-onset and worsening heart failure

“…It is noteworthy that in a recent study FGF23 did not markedly change in response to volume interventions that may suggest that FGF23 is a cause rather than a consequence of volume overload. [28] Plasma FGF23 levels were only measured at baseline in our study, and therefore we were not able to determine changes in plasma FGF23 in relation to the changes of signs of congestion and volume overload. Several studies showed an inverse relationship between renal function and FGF23 levels, consistent with our findings in worsening heart failure.…”

Fibroblast Growth Factor 23 and Adverse Clinical Outcomes in Type 2 Diabetes: a Bitter-Sweet Symphony

“…In addition to the regulation of phosphate reabsorption, a higher FGF23 level may also increase renal sodium uptake, leading to volume expansion and hypertension [59][60][61]. Although these data are not entirely consistent, it may at least partly explain the role of FGF23 in cardiovascular disease as observed in epidemiological studies.…”

“…Interventions aiming to optimize renin-angiogensin-aldostero system (RAAS)-blockade efficacy, such as low-sodium diet or the addition of a thiazide diuretic, may not affect FGF23 levels in diabetic nephropathy [61]. The aforementioned strategies were mostly performed on CKD patients, and thus these strategies have yet to be studied specifically in patients with type 2 diabetes.…”