#1323 Kidney health in children with X-linked hypophosphatemia: lessons from the prospective multicenter study in Germany and Switzerland Article Swipe

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Ineke Böckmann , Maren Leifheit‐Nestler , Ulrike John , Oliver Metzing , Mirko Rehberg , Karl P. Schlingmann , Marcus Weitz , Elke Wühl , Giuseppina Spartà , Dirk Schnabel , Bernd Höppe , Dieter Haffner ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1093/ndt/gfae069.137

Background and Aims X-linked hypophosphatemia (XLH) is the most common genetic cause of hypophosphatemia. Mutations in the PHEX gene cause elevated circulating levels of fibroblast growth factor 23 (FGF23), phosphaturia, rickets and osteomalacia. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis and preclinical studies in mice have shown that a chronic high phosphate load causes proximal tubular injury and fibrosis. There is no detailed analysis on kidney health in XLH patients yet. Method We conduct a prospective observational multicenter study in Germany and Switzerland to evaluate kidney health in pediatric XLH patients. Patients receive conventional therapy or burosumab, a fully humanized anti-FGF23 antibody. Clinical and biochemical data, blood and urine samples are collected annually. Results To date, 137 patients (80 girls, mean age 10.5 years) from 40 centers are included. 22% of patients have been treated conventionally for 7.5 years, 78% of patients have received burosumab for 2.3 years with 3.7 years of conventional therapy beforehand. Children with XLH show increased systolic blood pressure and body mass index (BMI), and overweight (BMI >90th percentile) and hypertension (systolic blood pressure >95th percentile) were each found in 20% of patients. A reduced eGFR (<90 ml/min/1.73 m2) and/or nephrocalcinosis was noted in 7% and 28% of patients, respectively. Microalbuminuria is twice as prevalent in children with XLH as in healthy children (14% vs 7%). Urinary lithogenic substances (calcium, oxalate, glycolate) are increased in 1.8-22.8%, and citrate is decreased in 12.3% of XLH patients. Tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) are elevated in urine of children with XLH, Chitinase 3-like 1 (CHl3L1) is comparable to children with chronic kidney disease, while kidney injury molecule-1 (Kim-1), indicating proximal tubule cell injury, is within a normal range. The renal inflammation marker monocyte chemoattractant protein-1 (MCP-1) is elevated in children with XLH, and epidermal growth factor (EGF), a marker of tubular cell repair, is decreased compared to healthy adults. Conclusion Pediatric XLH patients on conventional or burosumab therapy show enhanced systolic blood pressure slightly associated with elevated BMI, and significant renal comorbidity, i.e. reduced eGFR, nephrocalcinosis, increased urinary lithogenic substances, elevated urinary markers of glomerular and tubular injury and inflammation. The impact of conventional versus burosumab treatment are still being investigated.

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Hypophosphatemia Medicine Political science Pediatrics Internal medicine

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Type: article
Language: en
Landing Page: https://doi.org/10.1093/ndt/gfae069.137
PDF: https://academic.oup.com/ndt/article-pdf/39/Supplement_1/gfae069-0137-1323/57791968/gfae069-0137-1323.pdf
OA Status: bronze
Cited By: 1
Related Works: 10
OpenAlex ID: https://openalex.org/W4398755931

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DOI: https://doi.org/10.1093/ndt/gfae069.137

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Title: #1323 Kidney health in children with X-linked hypophosphatemia: lessons from the prospective multicenter study in Germany and Switzerland

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Language: en

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Publication year: 2024

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Publication date: 2024-05-01

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Authors: Ineke Böckmann, Maren Leifheit‐Nestler, Ulrike John, Oliver Metzing, Mirko Rehberg, Karl P. Schlingmann, Marcus Weitz, Elke Wühl, Giuseppina Spartà, Dirk Schnabel, Bernd Höppe, Dieter Haffner

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Landing page: https://doi.org/10.1093/ndt/gfae069.137

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Concepts: Hypophosphatemia, Medicine, Political science, Pediatrics, Internal medicine

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Cited by: 1

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