ESPE2023 Free Communications Bone, Growth Plate and Mineral Metabolism (6 abstracts)
A real-world study in Germany and Switzerland regarding renal health in children with X-linked hypophosphatemia
Ineke Böckmann 1 , Maren Leifheit-Nestler 1 , Ulrike John 2 , Oliver Metzing 2 , Mirko Rehberg 3 , Karl Peter Schlingmann 4 , Markus Kemper 5 , Ludwig Patzer 6 , Marcus Weitz 7 , Elke Wühl 8 , Clemens Freiberg 9 , Giuseppina Sparta 10 , Olaf Hiort 11 , Dirk Schnabel 12 , Bernd Hoppe 13 & Dieter Haffner 1
1Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. 2Department of Pediatric Nephrology and Endocrinology, University Children’s Hospital, Jena, Germany. 33Department of Pediatrics, University of Cologne, Cologne, Germany. 4Department of General Pediatrics, Pediatric Nephrology, University Children’s Hospital, Münster, Germany. 5Asklepios Children’s Hospital Hamburg-Heidberg, Hamburg, Germany. 6St. Elisabeth and St. Barbara Children’s Hospital, Halle/Saale, Germany. 7Pediatric Nephrology, University Children’s Hospital, Tübingen, Germany. 8Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany. 9Department of Pediatrics, University Medicine Göttingen, Göttingen, Germany. 10Pediatric Nephrology, University Children's Hospital Zurich, Zurich, Germany. 11University Children’s Hospital Lübeck, Lübeck, Germany. 12Center for Chronically Sick Children, Pediatric Endocrinology, University Medicine, Charité, Berlin, Germany. 13Department of Pediatric Nephrology, Children's Hospital of the University of Bonn, Bonn, Germany
Purpose: X-linked hypophosphatemia (XLH) is the most common hereditary cause of hypophosphatemic rickets. Elevated circulating levels of fibroblast growth factor 23 (FGF23) caused by mutations in the PHEX gene lead to renal phosphate wasting and rickets. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis in XLH patients. Mice on a high phosphate diet develop proximal tubular injury. Detailed analysis on kidney health and contributing factors in XLH are lacking.
Methods: To investigate the long-term outcome and its contributing factors in children with XLH we are conducting a prospective observational multicenter study in Germany and Switzerland. Patients are treated with conventional therapy or burosumab, a fully humanized anti-FGF23 antibody. Clinical and biochemical data as well as urine samples are annually obtained. Lithogenic substances and biomarkers for kidney health and their associations e.g. with estimated glomerular filtration rate (eGFR) and nephrocalcinosis are examined.
Results: Currently, 103 patients (62 girls, mean age 13 years) from 32 centers are included in the study. 14% of patients have been treated conventionally for 9.7 years, and 86% of patients have received burosumab for an average of 4.1 years with 4.5 years of conventional therapy beforehand. A reduced eGFR (<90 ml/min/1.73 m2) and/or nephrocalcinosis was noted in 9% and 29.4% of patients, respectively. Microalbuminuria is twice as prevalent in children with XLH as in healthy children (14% vs 7%). The excretion of lithogenic substances (calcium, oxalate, glycolate) is increased in 1.8-22.8%, and the excretion of citrate is decreased in 12.3% of XLH patients when compared to healthy children. The urinary tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) are elevated in children with XLH compared to healthy individuals, and chitinase 3-like 1 (CHl3L1) is comparable to that in children with chronic kidney disease. The renal inflammation marker monocyte chemoattractant protein-1 (MCP-1) is elevated in children with XLH and epidermal growth factor (EGF) preserving the capacity of tubular cells to recover is decreased compared to healthy children. Children with XLH showed increased mean z-scores for systolic blood pressure and body mass index (BMI), but blood pressure values were not associated with BMI z-scores.
Conclusions: First analyses show considerable renal comorbidity in children with XLH, including reduced eGFR, nephrocalcinosis, elevated urinary lithogenic substances and increased urinary kidney injury markers as well as elevated blood pressure independent of BMI. A comparison between conventional and burosumab treatment needs to be conducted.
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