Challenges in Estimating Renal Function in X-linked Hypophosphatemia Because of Formula Overestimation and FGF23 Effects.

Abstract

In X-linked hypophosphatemia (XLH), phosphate and vitamin D analogs increase the risk of nephrocalcinosis and renal impairment. Kidney function assessment is challenging, as creatinine-based estimated glomerular filtration rate (eGFR) may overestimate GFR because of reduced muscle mass. Cystatin C alternatively may be used. Moreover, fibroblast growth factor 23 (FGF23) has been suggested to potentially impact GFR, leading to hyperfiltration and complicating kidney function assessment. We conducted a single-center retrospective study on adults with XLH to compare eGFR formulas (CKD-EPIcreat, CKD-EPIcyst) with true measured GFR (mGFR). Bias, precision, and accuracy were calculated. In a subgroup, mGFR changes after burosumab initiation were assessed. Finally, we analyzed the FGF23/GFR relationship in a pediatric cohort in whom FGF23 was also hypersecreted (fibrous dysplasia) to support our hypothesis that FGF23 leads to hyperfiltration. We included 20 patients (17 females, median age 35 years). None had nephrocalcinosis or hypercalciuria, but 8 had secondary hyperparathyroidism. Median mGFR was 90 (85-107) mL/min/1.73 m², significantly lower than CKD-EPIcreat (125 [114-121]) and CKD-EPIcyst (103 [118]) (respectively P < .0001 and P = .01). Bias was significantly greater with CKD-EPIcreat (-22 [-29 to -13]) than CKD-EPIcyst (-13 [-19 to -4]), with lower accuracy (25% vs 93%). In 5 patients with XLH, mGFR decreased from 98 to 84 mL/min/1.73 m² after burosumab introduction. FGF23 moderately correlated with eGFR in 14 fibrous dysplasia patients (R = 0.62, P = .02). eGFR overestimates GFR in XLH, increasing CKD misclassification risk. Annual cystatin C measurement is recommended if CKD is suspected. FGF23 impact on GFR should also be considered in burosumab-treated patients.