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Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical and genetic data of 60/62 children who participated in the EARLY PRO-TECT Alport trial were analyzed. Genetic variants were interpreted according to current guidelines and criteria. Genetically solved patients with X-linked inheritance were then classified according to the severity of their COL4A5 variant into less-severe, intermediate, and severe groups and disease progress was compared. Almost 90% of patients were found to carry (likely) pathogenic variants and classified as genetically solved cases. Patients in the less-severe group demonstrated a borderline significant difference in disease progress compared to those in the severe group (p = 0.05). While having only limited power according to its sample size, an obvious strength is the precise clinical and genetic data of this well ascertained cohort. As in published data differences in clinical progress were shown between patients with COL4A5 less-severe and severe variants. Therefore, clinical and segregational data are important for variant (re)classification. Genetic testing should be mandatory allowing early diagnosis and therapy of AS.

BackgroundVariable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far.MethodsIn a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n=42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.23.8years, for whom ambulatory blood pressure monitoring (ABPM) data were available.ResultsIn the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM >1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p=0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p<0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p=0.014) and to 14.3% of control (p=0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p=0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change.Conclusions Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m(2). uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m(2), and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m(2), or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.

Objectives It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents' lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process. Setting In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed. Results This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition. Conclusions While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.

Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process. Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed. Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition. Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge. Trial registration: number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).

Growth restriction and retarded bone age are common findings in children with chronic kidney disease (CKD). We compared the automated BoneXpert (TM) method with the manual assessment of an X-ray of the non-dominant hand. In this retrospective multicenter study, 359 patients with CKD stages 2-5, aged 2-14.5 (girls) or 2.5-17 years (boys) were included. Bone age was determined manually by three experts (according to Greulich and Pyle). Automated determination of bone age was performed using the image analysis software BoneXpert (TM). There was a strong correlation between the automatic and the manual method (r = 0.983, p < 0.001). The automatic method tended to generate higher bone age values (0.64 +/- 0.73 years) in the younger patients (4-5 years) and to underestimate retardation or acceleration of bone age. The so-called bone health index (BHI) was reduced in comparison to the reference population. Bone health index standard deviation score (BHI-SDS) was not related to the stage of CKD, but weakly negatively correlated with plasma PTH concentrations (r = 0.12, p = 0.019). BoneXpert (TM) allows an objective, time-saving, and in general valid bone age assessment in children with CKD. Possible underestimation of retarded or accelerated bone age should be taken into account. Validation of the BHI needs further study.