Elke Wühl

Burosumab is effective in improving rickets in children with X-linked hypophosphatemia (XLH). Predictors of health-related quality of life (HRQoL) in pediatric XLH patients treated with burosumab are unknown. In this cross-sectional analysis of a prospective binational observational study, we investigated HRQoL in 64 pediatric XLH patients (36 female) on burosumab treatment, using the KIDSCREEN-52 questionnaire and qualitative interviews. Associations between HRQoL and clinical findings were analysed using multiple regression and receiver operating characteristics (ROC) curve analyses. Median age at investigation and duration of burosumab treatment were 13.1 (IQR 10.4; 14.8) and 2.8 (IQR 1.4; 3.8) years, respectively; 54.7% of patients received secondary burosumab treatment following prior active vitamin D and phosphate. Overall, HRQoL scores were comparable to national reference values. Caregivers rated Physical Well-Being, Moods & Emotions, and Bullying lower than the patients themselves. Burosumab dose was significantly associated with Physical Well-Being, Psychological Well-Being, and Self-Perception in self-report, and with total T-values and Physical Well-Being in proxy questionnaires. The duration of prior treatment with active vitamin D and phosphate was significantly associated with the dimension of Autonomy in self-report and proxy reports. A burosumab dosage above 0.6 mg/kg was associated with a good Physical Well-Being (above the mean of the general population) with a sensitivity and specificity of 75% and 70% in self-report, and 67% and 70% in proxy questionnaires, respectively. In this real-world study, HRQoL in burosumab-treated children with XLH was comparable to that of the general population and associated with burosumab dosage.

Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in CTNS, which encodes cystinosin, a H⁺/cystine symporter that mediates cystine efflux from lysosomes. Defective cystinosin leads to accumulation of cystine in lysosomes and the formation of cystine crystals in most tissues. In its more severe and frequent form, infantile nephropathic cystinosis, patients present with renal Fanconi syndrome in the first 2 years of life, which progresses to chronic kidney disease. Since the 1970s, cysteamine therapy and improvements in dialysis and transplantation have substantially improved patient outcomes, and currently most patients survive into adulthood. Consequently, the diagnosis and management of extra-renal complications that develop later in life have become increasingly important. In addition to the kidneys, commonly affected organs include the eyes, the musculoskeletal system, the central nervous system, exocrine glands and endocrine organs. Cystinosis therefore requires integrated care that involves multiple medical specialties and a structured transition plan from paediatric to adult care. Herein, we present evidence-based and expert opinion-based clinical practice recommendations, developed by a team of international specialists and patient representatives following the GRADE methodology, to improve the diagnosis and management of cystinosis in children and adults.

BACKGROUND: Office blood pressure (BP) trajectories may help assess hypertension progression and the effects of antihypertensive treatment in children with chronic kidney disease. METHODS: Analysis of antihypertensive treatment and BP slopes in 320 patients from the 4C study (Cardiovascular Comorbidity in Children with Chronic Kidney Disease) cohort with chronic kidney disease before renal replacement therapy, based on a minimum of 3 individual observations and 2 years of follow-up. RESULTS: At enrollment, 70 (22%) patients had uncontrolled or untreated hypertension, 130 (41%) patients had controlled hypertension, and 120 (37%) patients had normotension without antihypertensive treatment. Antihypertensive treatment medication was prescribed for 53% of patients at baseline and initiated or added for 91 patients (AHT-I [group with intensification of antihypertensive treatment] group, 28%) during follow-up. Overall BP SD score remained stable over time in the cohort (β=−0.037±0.034, P =0.34 and −0.029±0.348, P =0.093 per year for systolic and diastolic BP SD score). In the AHT-I group, systolic and diastolic BP SD scores were higher at baseline and decreased significantly during follow-up (−0.22±0.07, P P =0.01). Only 8 of 70 (11%) patients from the previously untreated/uncontrolled group remained untreated at the last observation, while 31 (44%) were controlled during follow-up. Of the 120 normotensive patients at baseline, 60% remained normotensive while 40% progressed to uncontrolled/untreated (n=23, 19%) or controlled (n=24, 20%) hypertension. CONCLUSIONS: Although the overall BP of the population remained stable over time, individual patterns of BP management showed considerable variability. BP control improved significantly with intensified antihypertensive therapy; however, a significant number of previously normotensive individuals developed new-onset hypertension during the observation period.

Rationale To investigate blood pressure (BP) trajectories, and the impact of pharmacological intervention in children with chronic kidney disease (CKD). Methods Analysis of antihypertensive treatment (AHT) and BP slopes in 320 patients of the 4C Study cohort with CKD prior to renal replacement therapy, based on a minimum of three individual observations and two years of follow-up. Results At enrollment, 70 patients (22%) had uncontrolled or untreated hypertension, 130 patients (41%) had controlled hypertension, and 120 patients (37%) had normotension without antihypertensive treatment. AHT medication was prescribed in 53% of patients at baseline and initiated or added in 91 patients (AHT-I, 28%) during follow-up. Overall BP standard deviation score (SDS) remained stable over time in the cohort (ß= -0.037±0.034, p=0.34 and -0.029± 0.348, p=0.093 per year for systolic and diastolic BP SDS). In the AHT-I group, systolic and diastolic BP SDS was higher at baseline and decreased significantly during follow-up (−0.22±0.07, p<.003 and -0.12±0.05 SDS per year, p=0.01). Only 8/70 (11%) patients of the previously untreated/uncontrolled group remained untreated at the last observation, while 31 (44%) were controlled during follow-up. Of the 120 normotensive patients at baseline, 60% remained normotensive while 40% progressed to uncontrolled/untreated (n=23, 19%) or controlled (n=24, 20%) hypertension. Conclusions The study provides comprehensive real-world evidence on long-term management of blood pressure in children with CKD from the 4C Study. Although blood pressure control improved significantly with the intensification of antihypertensive therapy, a notable proportion of previously normotensive patients developed de novo hypertension over the observation period.

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