FGF23 Neutralizing Antibody Ameliorates Abnormal Renal Phosphate Handling in Sickle Cell Disease Mice

Endocrinology. 2023 Nov 16:bqad173. doi: 10.1210/endocr/bqad173. Online ahead of print.ABSTRACTWe assessed the involvement of FGF23 in phosphaturia in sickle cell disease (SCD) mice. Control and SCD mice were treated with FGF23 neutralizing antibody (FGF23Ab) for 24 hours. Serum ferritin was significantly increased in SCD mice and was significantly reduced in female but not male SCD mice by FGF23Ab. FGF23Ab significantly reduced increased erythropoietin in SCD kidneys. Serum intact FGF23 (iFGF23) was significantly increased in SCD female mice and was markedly increased in SCD male mice, however, FGF23Ab significantly reduced iFGF23 in both genotypes and sexes. Serum carboxy-terminal-fragment FGF23 (cFGF23) was significantly reduced in SCD-IgG male mice and was markedly but not significantly reduced in SCD-IgG female mice. FGF23Ab significantly increased cFGF23 in both sexes and genotypes. Serum 1,25-dihydroxyvitamin D3 was significantly increased in SCD-IgG and was further significantly increased by FGF23Ab in both sexes and genotypes. Significantly increased BUN in SCD was not reduced by FGF23Ab. Urine phosphate/creatinine ratio was significantly increased in SCD in both sexes and was significantly reduced by FGF23Ab. Increased SCD kidney damage marker KIM1 was rescued, but sclerotic glomeruli, increased macrophages, and lymphocytes were not rescued by short-term FGF23Ab. FGF23Ab significantly reduced increased pFGFR1, αKlotho, pERK, pSGK1, pNHERF-1, pJAK3, and pSTAT3 in SC...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research