Markus J. Kemper’s research while affiliated with Asklepios Klinik Nord and other places

X-linked hypophosphatemia (XLH) is the most common inherited form of hypophosphatemic rickets. Children with XLH have an increased risk of obesity, which may promote high blood pressure, but data on blood pressure in XLH are inconclusive. We aimed to assess blood pressure and its determinants in pediatric XLH patients. We conduct a prospective, multicenter observational study of children with XLH in Germany and Switzerland. Office blood pressure and body mass index (BMI) were annually measured in 128 pediatric XLH patients with a median follow-up of 2 years (range 1–6). Potential predictors of blood pressure were investigated by Spearman correlation. Seventeen percent of patients were treated with phosphate supplements and active vitamin D for a median of 8 years, 83% of patients received burosumab for 2.3 years with 3.1 years of prior treatment with phosphate supplements and active vitamin D. Median systolic (0.75 z-score) and diastolic (0.32 z-score) blood pressure and BMI (0.72 z-score) were increased compared to healthy children (each p < 0.01). The prevalence of obesity (9.8% vs. 3%), arterial hypertension (26.2% vs. 5%), and high-normal blood pressure (22.9% vs. 5%) was higher in the XLH cohort compared to the general pediatric population (each p < 0.001). Spearman rank correlation analysis revealed significant associations between both systolic (r = 0.24; p < 0.01) and diastolic (r = 0.20; p < 0.05) blood pressure with BMI, while the mode of treatment, i.e. burosumab versus phosphate supplements and active vitamin D, was no significant correlate. Children with XLH present with elevated office blood pressure values, associated with elevated BMI.

Background Primary hyperoxaluria type 1 (PH 1) is a rare genetic condition due to mutations in the AGXT gene. This leads to an overproduction of oxalate in the liver. Hyperoxaluria often causes kidney stones, nephrocalcinosis, and chronic kidney disease. Lumasiran is a recently approved drug that reduces the hepatic oxalate production by mRNA interference. Methods In this multicenter study, we evaluated the response to lumasiran treatment in PH 1 patients ( n = 8) with a median age of 10.9 years (range 1.2–17.9 years), including two patients on hemodialysis. We retrospectively analyzed the reduction of urinary and plasma oxalate levels as well as changes in kidney stone events, nephrocalcinosis, and kidney function. Results In patients without kidney failure, the median reduction of urinary oxalate was 64% (range 10–80%) and 71% (61–86%) at 6 and 12 months, respectively. However, only one patient reached urinary oxalate levels within the age-specific normal range. Two patients did not respond to lumasiran and treatment was stopped. In one of the two patients on hemodialysis, the frequency of sessions could be reduced. The only notable side effects were injection site reactions. Conclusion There was a variable response to lumasiran in PH 1. Despite a reduction of hyperoxaluria in many patients with PH 1, only one patient reached normal values and 2 of 8 patients did not respond. Regular monitoring of urinary oxalate values and registry data collection seems mandatory to monitor the efficacy and the long-term outcome of PH 1 treated with lumasiran. Graphical Abstract

Ciliopathies are heterogeneous, genetically determined diseases often involving different organ systems. Patients with polycystic kidney disease frequently show extrarenal involvement, e.g. congenital liver fibrosis, choledochal cysts or Caroli’s syndrome. The most frequent polycystic kidney diseases include autosomal recessive (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) and the nephronophthisis-related ciliopathies (NPHP-RC), which can all show extrarenal symptoms. In ARPKD congenital liver fibrosis with portal hypertension is always present, in ADPKD liver cysts are typical and in patients with nephronophthisis in addition to fibrosis and cyst formation, hepatic pruritus is also frequently present. In addition, there are diverse rare syndromic diseases from the group of ciliopathies, which can show renal and also hepatic phenotypes. In patients with polycystic kidney disease and hepatobiliary involvement interdisciplinary management should be the standard as other organ systems can frequently be affected. The portal hypertension with the formation of varices can lead to severe complications. Hepatic pruritus can severely impair the quality of life of these patients. Apart from symptomatic treatment, liver transplantation can be considered an option in individual patients.

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

Background Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients’ clinical and morphological presentation over the past decades have not yet been thoroughly investigated. Methods Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016). Results In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z -score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z -score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients. Conclusions Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear. Graphical Abstract

Background: Kidney transplantation (KTx) from small donors is associated with inferior graft survival in registry studies, whereas single-center studies show favorable results. Methods: We compared 175 pediatric KTx from small donors ≤20 kg (SDKTx) with 170 age-matched recipients from adult donors (ADKTx) from 20 centers within the Cooperative European Paediatric Renal Transplant Initiative registry. Graft survival and estimated glomerular filtration rate (eGFR) were analyzed by Cox regression and mixed models. Detailed data on surgical and medical management were tested for association with graft survival. Results: One-year graft survival was lower after SDKTx compared with ADKTx (90.9% versus 96.5%; odds ratio of graft loss, 2.92; 95% confidence interval [CI], 1.10-7.80; P = 0.032), but 5-y graft survival was comparable (90.9% versus 92.7%; adjusted hazard ratio of graft loss 1.9; 95% CI, 0.85-4.25; P = 0.119). SDKTx recipients had an annual eGFR increase of 8.7 ± 6.2 mL/min/1.73 m² compared with a decrease of 6.9 ± 5.7 mL/min/1.73 m² in ADKTx recipients resulting in a superior 5-y eGFR (80.5 ± 25.5 in SDKTx versus 65.7 ± 23.1 mL/min/1.73 m² in ADKTx; P = 0.008). At 3 y posttransplant, eGFR after single SDKTx was lower than after en bloc SDKTx (86.6 ± 20.4 versus 104.6 ± 35.9; P = 0.043) but superior to ADKTx (68.1 ± 23.9 mL/min/1.73 m²). Single-kidney SDKTx recipients had a lower rate of hypertension at 3 y than ADKTx recipients (40.0% versus 64.7%; P = 0.008). Conclusions: Compared with ADKTx, 5-y graft function is superior in SDKTx and graft survival is similar, even when performed as single KTx. Utilizing small donor organs, preferably as single kidneys in experienced centers, is a viable option to increase the donor pool for pediatric recipients.

Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS. Data of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111). Patients in the VE group had a significant relative median weight gain compared to HC (7.8% (3.4–11.3) vs. 1.2% (− 0.7–3.9), p < 0.0001) 48 h after admission. The need for dialysis was not reduced by VE (VE 21/38 (55.3%) vs. HC 64/111 (57.7%), p = 0.8). However, central nervous system involvement (impairment of consciousness, seizures, focal neurological deficits, and/or visual disturbances) was significantly reduced (VE 6/38 (15.8%) vs. HC 38/111 (34.2%), p = 0.039). None of the patients in the VE group died or developed chronic kidney disease (CKD) stage 5, whereas in the HC group, three patients died and three patients had CKD stage 5 at discharge. This study suggests that volume expansion may be associated with the mitigation of the acute course of STEC-HUS, especially severe neurological involvement and the development of CKD. Prospective trials should lead to standardized protocols for volume expansion in children with STEC-HUS. A higher resolution version of the Graphical abstract is available as Supplementary information

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.