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Background Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk. Methods Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17 years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models. Results Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6 years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17 years). Conclusion Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. Graphical abstract, Author(s): Sophia Müller [sup.1] , Rika Kluck [sup.1] , Celina Jagodzinski [sup.1] , Malina Brügelmann [sup.1] , Katharina Hohenfellner [sup.2] , Anja Büscher [sup.3] , Markus J. Kemper [sup.4] , [...]

[english] Since 1986 medical students at the University Children’s Hospital Essen are trained as peers in a two week intensive course in order to teach basic paediatric examination techniques to younger students. Student peers are employed by the University for one year. Emphasis of the peer teaching program is laid on the mediation of affective and sensomotorical skills e.g. get into contact with parents and children, as well as manual paediatric examination techniques. The aim of this study is to analyse whether student peers are able to impart specific paediatric examination skills as good as an experienced senior paediatric lecturer. 123 students were randomly assigned to a group with either a senior lecturer or a student peer teacher. Following one-hour teaching-sessions in small groups students had to demonstrate the learned skills in a 10 minute modified OSCE. In comparison to a control group consisting of 23 students who never examined a child before, both groups achieved a significantly better result. Medical students taught by student peers almost reached the same examination result as the group taught by paediatric teachers (21,7±4,1 vs. 22,6±3,6 of 36 points, p=0,203). Especially the part of the OSCE where exclusively practical skills where examined revealed no difference between the two groups (7,44±2,15 vs. 7,97±1,87 of a maximum of 16 points, p=0,154). The majority of students (77%) evaluated peer teaching as stimulating and helpful. The results of this quantitative teaching study reveal that peer teaching of selected skills can be a useful addition to classical paediatric teaching classes. [german] An der Universitäts-Kinderklinik Essen werden seit 1986 studentische Tutoren in einem vierzehntägigen Intensivkurs ausgebildet, um im Blockpraktikum Pädiatrie Studierende des 3. und 4. Klinischen Semesters am Krankenbett in basalen pädiatrischen Untersuchungstechniken zu unterrichten („peer-to-peer-teaching“). Die Tutoren werden für ein Jahr als studentische Hilfskräfte in der Klinik eingestellt. Der Schwerpunkt der Tutorenausbildung liegt auf der Vermittlung affektiver und sensomotorischer Fertigkeiten, wie zum Beispiel Kontaktaufnahme zu Eltern und Kindern, sowie auditive und manuelle Fertigkeiten. In dieser prospektiven Studie sollte untersucht werden, ob die Tutoren ausgewählte pädiatrische Untersuchungstechniken ähnlich gut vermitteln können, wie ein erfahrener pädiatrischer Dozent. Einhundertdreiundzwanzig Studierende wurden auf zwei Gruppen verteilt, die entweder einem pädiatrischen Dozenten oder einem studentischen Tutor zugeteilt wurden. Nach einer einstündigen Unterrichtseinheit mussten die erlernten manuellen und verbalen Fertigkeiten im Rahmen einer 10minütigen OSCE-Prüfung demonstriert werden. Gegenüber einer Kontrollgruppe von 23 Studierenden, die bisher an keinem Unterricht teilgenommen hatte, erzielten beide Untersuchungsgruppen ein signifikant besseres Prüfungsergebnis. Die Studierenden, die von einem Tutor unterrichtet wurden erreichten dabei im direkten Vergleich eine ähnliche Gesamtpunktzahl, wie die Gruppen, die von einem pädiatrischen Dozenten ausgebildet wurden (21,7±4,1 vs. 22,6±3,6 von 38 Punkten, p=0,203). Insbesondere in der Teilaufgabe, in der ausschließlich praktische Fertigkeiten geprüft wurden, zeigte die Gruppe der von einem Dozenten unterrichteten Studierenden keinen punktwerten Vorteil (7,44±2,15 vs. 7,97±1,87 von maximal 16 Punkten, p=0,154). Die Mehrzahl der Studierenden (77%) gab an, dass sie den Unterricht mit den Tutoren als lernförderlich angesehen haben. Die Ergebnisse der quantitativen Untersuchung können belegen, dass der Einsatz von studentischen Tutoren im klinischen Unterricht sinnvoll und lernförderlich ist, wenn diese ausgewählte Lernziele vermitteln sollen.

Background Secondary hyperparathyroidism (SHPT) may persist after renal transplantation (RTx), inducing hypophosphatemia and hypercalcemia that precludes the use of vitamin D analogs. The calcimimetic cinacalcet improved plasma calcium and parathyroid hormone (PTH) levels in randomized controlled trials in adults after RTx, but pediatric data are scarce. Methods In this retrospective study, we analyzed 20 pediatric patients from the Cooperative European Paediatric Renal TransplAnt Initiative (CERTAIN) Registry who received cinacalcet after RTx. The results are presented as median and interquartile range (25th-75th percentile). Results At 13.7 (11.0-16.5) years of age, 20 pediatric patients received a renal allograft. Cinacalcet was introduced at 0.4 (0.3-2.7) years post-transplant at an estimated glomerular filtration rate (eGFR) of 50 (34-66) mL/min/1.73 m.sup.2, plasma calcium of 2.58 (2.39-2.71) mmol/L, age-standardized (z score) phosphate of - 1.7 (- 2.7-- 0.4), and PTH of 136 (95-236) ng/L. The starting dose of cinacalcet was 0.5 (0.3-0.8) mg/kg per day, with a maximum dose of 1.1 (0.5-1.3) mg/kg per day. With a follow-up of 3.0 (1.5-3.6) years on cinacalcet therapy, eGFR remained stable; PTH levels decreased to 66 (56-124) ng/L at the last follow-up (p = 0.015). One patient displayed hypocalcemia (1.8 mmol/L). Cinacalcet was withdrawn in three patients (hypocalcemia, parathyroidectomy, incompliance). Nephrocalcinosis of the graft was not reported. Conclusions This pilot study suggests that cinacalcet as off-label therapy for SHPT after pediatric RTx is efficacious in controlling post-transplant SHPT with acceptable tolerability. Continuing cinacalcet even with normal PTH can lead to dangerous life-threatening hypocalcemia. Therefore, at each subsequent visit, the need to continue cinacalcet must be assessed., Author(s): Julie Bernardor [sup.1] [sup.2] , Claus Peter Schmitt [sup.3] , Jun Oh [sup.4] , Anne-Laure Sellier-Leclerc [sup.1] , Anja Büscher [sup.5] , Luca Dello Strologo [sup.6] , Gurkan Genc [...]

Background Previous studies on renal oligohydramnios (ROH) report highly variable outcome and identify early onset of ROH and presence of extrarenal manifestations as predictors of adverse outcome in most cases. Data on termination of pregnancy (TOP) and associated parental decision-making processes are mostly missing, but context-sensitive for the interpretation of these findings. We provide here a comprehensive analysis on the diagnosis, prenatal decision-making and postnatal clinical course in all pregnancies with ROH at our medical centre over an 8-year period. Methods We report retrospective chart review data on 103 consecutive pregnancies from 2008 to 2015 with a median follow-up of 554 days. Results After ROH diagnosis, 38 families opted for TOP. This decision was associated with onset of ROH (p < 0.001), underlying renal disease (p = 0.001) and presence of extrarenal manifestations (p = 0.02). Eight infants died in utero and 8 cases were lost to follow-up. Of the 49 liveborn children, 11 received palliative and 38 underwent active care. Overall survival of the latter group was 84.2% (n = 32) corresponding to 31% of all pregnancies (32 out of 103) analysed. One third of the surviving infants needed renal replacement therapy during the first 6 weeks of life. Conclusions Over one third of pregnancies with ROH were terminated and the parental decision was based on risk factors associated with adverse outcome. Neonatal death was rare in the actively treated infants and the overall outcome promising. Our study illustrates that only careful analysis of the whole process, from prenatal diagnosis via parental decision-making to postnatal outcome, allows sensible interpretation of outcome data., Author(s): Katrin Mehler [sup.1] , Ingo Gottschalk [sup.2] , Kathrin Burgmaier [sup.3] , Ruth Volland [sup.4] , Anja K. Büscher [sup.5] , Markus Feldkötter [sup.6] , Titus Keller [sup.1] , [...]

Background In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton. Methods We report a family with 14 affected individuals (autosomal-dominant mode of inheritance), most of whom presented with nephrotic-range proteinuria, hypertension, and progressive renal failure. Four members received a kidney transplant without disease recurrence. Two patients underwent renal biopsy with the result of minimal-change glomerulopathy and IgA nephropathy respectively. We performed mutational analysis of ACTN4, CD2AP, COQ6, INF2, LAMB2, NPHS1, NPHS2, PLCE1, TRPC6, and WT1 in the index patient by next-generation sequencing. Additionally, in 6 affected and 2 unaffected family members target diagnostics were performed. Results We identified a novel heterozygous mutation c.490G>C (p.(Ala164Pro) in exon 3 of the INF2 gene in the index patient and 6 additionally examined affected family members. In silico analysis predicted it as 'probably damaging'. Additionally, three patients and 2 unaffected relatives harbored a novel heterozygous variant in ACTN4 (c.1149C>G, p.(Ile383Met)) with uncertain pathogenicity. Conclusion Mutations in INF2 are associated with familial proteinuric diseases - irrespective of the presence of FSGS and in the case of rapid disease progression. Therefore, mutational analysis should be considered in patients with renal histology other than FSGS and severe renal phenotype., Author(s): Anja K. Büscher [sup.1] , Nora Celebi [sup.2] , Peter F. Hoyer [sup.1] , Hanns-Georg Klein [sup.3] , Stefanie Weber [sup.4] , Julia Hoefele [sup.5] Author Affiliations: (1) Pediatric [...]

Background Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). Methods A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM). Results Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM. Conclusions Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight., Author(s): Bianca Borchert-Mörlins [sup.1] , Daniela Thurn [sup.1] , Bernhard M. W. Schmidt [sup.2] , Anja K. Büscher [sup.3] , Jun Oh [sup.4] , Tanja Kier [sup.3] , Elena Bauer [...]