Browsing by Author "Metzing, Oliver"

Abstract Context Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents is lacking. Objective To assess the effects of 12 months burosumab treatment on mineral metabolism in children (aged < 12 years) and adolescents (aged 12-18 years) with XLH. Design Prospective national registry. Setting Hospital clinics. Patients 93 XLH patients (65 children, 28 adolescents). Main outcome measures Z-scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months. Results At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD) and elevated ALP (2.7 SD, each p < 0.001 versus healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH, and a steady decline in serum ALP (each p < 0.001 versus baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27% and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared to children (0.72 versus 1.06 mg/kg, p < 0.01). Conclusion In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children.

Abstract Background X-linked hypophosphatemia (XLH) is a rare inherited phosphate-wasting disorder associated with bone and dental complications. Health-related quality of life (HRQoL) is reduced in XLH patients on conventional treatment with phosphate supplements and active vitamin D, while information on patients treated with burosumab is rare. Methods HRQoL was assessed in 63 pediatric XLH patients participating in a prospective, observational study and patient registry in Germany using the KIDSCREEN-52 survey instrument and standardized qualitative interviews. Results The median age of the XLH patients was 13.2 years (interquartile range 10.6 – 14.6). At the time of the survey, 55 (87%) patients received burosumab and 8 (13%) conventional treatment. Forty-six patients (84%) currently being treated with burosumab previously received conventional treatment. Overall, HRQoL was average compared to German reference values (mean ± SD: self-report, 53.36 ± 6.47; caregivers’ proxy, 51.33 ± 7.15) and even slightly above average in some dimensions, including physical, mental, and social well-being. In general, XLH patients rated their own HRQoL higher than their caregivers. In qualitative interviews, patients and caregivers reported that, compared with conventional therapy, treatment with burosumab reduced stress, bone pain, and fatigue, improved physical health, and increased social acceptance by peers and the school environment. Conclusions In this real-world study in pediatric XLH patients, HRQoL was average or even slightly above that of the general population, likely due to the fact that the vast majority of patients had their treatment modality switched from conventional treatment to burosumab resulting in improved physical health and well-being. Graphical abstract

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens.