Renal Phosphate Wasting Disorders

The regulation of phosphate handling in the kidney is established in great detail. The balance between the respective rates of glomerular filtration and tubular reabsorption determines the net renal handling of phosphate. Fibroblast growth factor 23 (FGF23) is the key regulator factor of serum phosphate. Its activity on kidney cells is dramatically increased when its cofactor αKlotho is present. Together with PTH and vitamin D metabolism, FGF23 belongs to a complex bone-kidney-parathyroid biological tightly balanced to ensure skeletal mineralization and growth, prevention of ectopic calcifications as well as adjustments of energy metabolism. Abnormal production, action, or regulation of FGF23 leads to renal phosphate wasting disorders. They share similar clinical and biochemical features including rickets and low serum phosphate. Clinical features of hypophosphatemia reflect the widely varying metabolic processes requiring phosphate. They are often vague and nonspecific, and diagnosis is, thus, often delayed. Chronic sustained hypophosphatemia manifests as osteomalacia, rickets, and associated skeletal deformities. Diagnosis is established through medical history, physical examination, biochemical tests, and radiographs. The most common cause of phosphate wasting is X-linked hypophosphatemia (XLH). Additional disorders of FGF23 excess include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, and tumor-induced osteomalacia. Treatment of XLH is challenging; it involves the association of calcitriol with multiple daily phosphate supplements. Different from a simple dietary supplementation, careful monitoring to avoid toxicity is required. Recently, an antiFGF23 was developed using a neutralizing antibody for FGF23 to counteract pathologic systemic and skeletal FGF23 effects; initial results from clinical trials support an important role for this agent in the therapeutic strategy of FGF23-mediated disorders. Multidisciplinary care is essential for the follow-up of children affected with rickets involving experts in bone diseases, endocrinologists, nephrologists, rheumatologists, dentists, dieticians, and physiotherapists. In this chapter, we describe the different causes and therapies of phosphate wasting disorders in children rickets, supported by the recent progress in genetics and development of novel molecules such as anti-FGF23 antibody.