Fibroblast Growth Factor 23 and Tubular Sodium Handling in Young Patients with Incipient Chronic Kidney Disease

Background: Experimental studies have shown fibroblast growth factor 23 FGF23)-mediated upregulation of the distal tubule sodium/chloride (NaCl) co-transporter leading to increased Na reabsorption, volume expansion and hypertension. However, data on the associations of FGF23 with renal Na regulation and blood pressure (BP) are lacking in young CKD patients.

Methods: FGF23 and other determinants of mineral metabolism, plasma renin activity (PRA), fractional excretion of Na (FENa) and BP, were analyzed at a single center in 60 patients aged 5-22 years with CKD Stages 1 ( = 33) and Stages 2-3 ( = 27) defined by cystatin C- and creatinine-based estimating equations (estimated glomerular filtration rate, eGFR). Associations between FGF23 and renal Na handling were explored by regression analysis.

Results: Median FGF23 levels were higher in CKD Stages 2-3 versus CKD 1 (119 versus 79 RU/mL; P < 0.05), with hyperparathyroidism [parathyroid hormone (PTH) >69 pg/mL] in only few subjects with CKD Stages 2-3. Median FENa was comparable in both subgroups, but with proportionally more values above the reference mean (0.55%) in CKD Stages 2-3 and 3-fold higher (1.6%) in CKD Stage 3. PRA was higher in CKD Stages 2-3 (P < 0.05). Meanwhile in CKD Stage 1, FGF23 did not associate with FENa, and in CKD Stages 2-3 FGF23 associated positively with FENa ( = 0.4; P < 0.05) and PTH ( = 0.45; P < 0.05), and FENa associated with FE of phosphate ( = 0.6; P < 0.005). Neither FGF23 nor FENa was associated with systolic or diastolic BP in either subgroup. The negative association of eGFR by cystatin with FENa remained the strongest predictor of FENa by multivariable linear regression in CKD Stages 2-3.

Conclusions: The elevated FGF23, FENa and PRA and the positive association of FGF23 with FENa do not suggest FGF23-mediated increased tubular Na reabsorption and volume expansion as causing hypertension in young patients with incipient CKD.