The long-term outcome of childhood nephrotic syndrome in Germany: a cross-sectional study.

BACKGROUND: Long-term outcomes of children with nephrotic syndrome have not been well described in the literature. METHODS: Cross-sectional study data analysis of n = 43 patients with steroid-sensitive (SSNS) and n = 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30 years after onset, there was the longest follow-up period to date. RESULTS: The mean age at FUV was 33.6 years (14.4-50.8 years, n = 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8 years (1.2-14.5 years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were "frequent relapsers" (25.6%) and four patients still had relapses beyond the age of 18 years. Except of cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (< 4 years) was a risk factor for frequent relapses. An early relapse (within 6 months after onset) was a risk factor and a low birth weight was not a significant risk factor for a complicated NS course. The mean age of patients with SRNS at onset was 4.6 ± 4.4 years and 27.5 ± 9.9 years at FUV. Three patients received kidney transplantations. CONCLUSIONS: The positive long-term prognosis of SSNS can reduce the concern of parents about the probability of the child developing a chronic renal disease during the clinical course after onset.

Clinical course & management of childhood nephrotic syndrome in Germany: a large epidemiological ESPED study.

BACKGROUND: Nephrotic syndrome (NS) is one of the most frequent occurring chronic kidney diseases in childhood, despite its rarely occurrence in the general population. Detailed information about clinical data of NS (e.g. average length of stay, complications) as well as of secondary nephrotic syndrome (SNS) is not well known. METHODS: A nationwide ESPED follow-up study presenting the clinical course and management of children with NS in Germany. RESULTS: In course of 2 years, 347 children developed the first onset of NS, hereof 326 patients (93.9%) had a primary NS, and 19 patients had a SNS (missing data in 2 cases), the majority due to a Henoch-Schönlein Purpura. Patients with steroid-resistant NS (SRNS) stayed significantly longer in hospital than children with steroid-sensitive NS (25.2 vs. 13.3 d, p <  0.001). Patients with bacterial/viral infections stayed longer in hospital (24.9 d/19.5d) than children without an infection (14.2 d/14.9 d; p <  0.001; p = 0.016). Additionally, children with urinary tract infections (UTI) (p < 0,001), arterial hypertension (AH) (p < 0.001) and acute renal failure (ARF) (p < 0,001) stayed significantly longer in hospital. Patients with SRNS had frequent complications (p = 0.004), such as bacterial infections (p = 0.013), AH (p < 0.001), UTI (p < 0.001) and ARF (p = 0.007). Children with a focal segmental glomerulosclerosis (FSGS) had significantly more complications (p = 0.04); specifically bacterial infections (p = 0.01), UTI (p = 0.003) and AH (p < 0,001). Steroid-resistance was more common in patients with UTI (p < 0.001) and in patients with ARF (p = 0.007). Furthermore, steroid-resistance (p < 0.001) and FSGS (p < 0.001) were more common in patients with AH. CONCLUSIONS: This nationwide, largest German study presents results on the clinical course of children with NS considering a diverse range of complications that can occur with NS. The establishment of a region-wide and international pediatric NS register would be useful to conduct further diagnostic and therapy studies with the aim to reduce the complication rate and to improve the prognosis of NS, and to compare the data with international cohorts.

[Interviewing children in cases of suspected child endangerment: pitfalls and quality assurance]. / Befragung des Kindes bei Verdacht auf Kindeswohlgefährdung: Fallstricke und Qualitätssicherung.

Doctors and especially paediatricians in clinics and private practices are often the first professionals to be confronted with the suspicion of a child endangerment (sexual abuse, physical abuse, neglect, Munchausen-by-proxy syndrome). They thus play a key role in the early assessment and clarification of suspicion and setting the course for the further interdisciplinary procedure.The clinical investigation of a suspicion is a diagnostic and communicative challenge. The procedure includes biomedical diagnostics, structured medical history based on standardized questionnaires and a forensic (investigative) interview of caregivers and especially of the affected child.The child's statements are subject to various risks of bias. The mental processing of events can modulate and distort the scope and quality of the report in many ways. Expectations on how the professionals will use this information and the consequences that may arise for the family as well as the resulting conflicts of loyalty are superimposed on the child's willingness to talk and to provide valid statements. On the part of the interviewer too, motivational, affective and cognitive processes pose risks for a suggestive influence on the child as well as for the objectivity in carrying out the interview and the interpretation of the findings. Complex pitfalls endanger the validity and forensic usability of the interview results. In order to assure the quality of their findings, interviewers are therefore required to carefully register and reflect on their own motivational tendencies and implicit hypotheses, to know and avoid suggestive question formulations and to make use of standardized interview protocols whenever possible.

[Structured interviewing of children in suspected child endangerment cases: The German version of the revised NICHD Investigative Interview Protocol]. / Strukturierte Befragung von Kindern bei Kindeswohlgefährdung: Die deutsche Version des NICHD-Interviewprotokolls in seiner revidierten Fassung.

Interviewing a child of a suspected abuse (physical abuse, sexual abuse, neglect, Munchausen-by-proxy syndrome) is subject to complex risks of suggestion and distortion. The use of a standardized interview protocol as part of the investigation can significantly increase the scope and validity of the child's report in different settings (for example, pediatrics, child welfare services, court).In this paper, the interview protocol provided by the National Institute of Child Health and Human Development (NICHD) in its revised and complete version is presented in German and made available for free clinical use in the Appendix. The NICHD interview protocol is the most prominent and most carefully evaluated tool. It is currently considered as a reference for the assessment of child abuse. The protocol follows certain guiding principles. At the beginning of the interview, basic rules are explained to the child (e. g. telling the truth, correct the interviewer if necessary). The focus is placed on detailed exploration of critical abusive episodes. Open questions are asked instead of closed questions. A good rapport has to be established before moving to the actual interview topic.In addition to a technically correct application of the protocol, further competencies of the interviewer are essential to ensure the validity of the findings, such as: sensitive contact with the child; knowledge of the typical sources of bias and suggestion; awareness and control of personal impulses, motives and implicit assumptions; a hypothesis-led approach; and developmentally appropriate interpretation and evaluation of the child's report.

The incidence of the nephrotic syndrome in childhood in Germany.

BACKGROUND: The incidence of childhood nephrotic syndrome (NS) in Germany is not well known. METHODS: An ESPED-based nationwide collection of epidemiological data of children in 2005 and 2006. RESULT: The mean age of NS at onset was 5.5 ± 3.7 years. The gender ratio of boys to girls was 1.8:1. The average length of stay was 15.5 ± 11.2 days, with younger children remaining significantly longer in hospital. Steroid-resistance was more common in children ≥8 years (p = 0.023). Focal-segmental glomerulosclerosis (FSGS) was more common in children >10 years (p = 0.029). The ratio of males to females with FSGS was 1:1.9, thus the FSGS risk for girls at onset was 3.3-times greater. Considering the available data, the incidence of NS in Germany is 1.2/100,000 in the population <18 years, of which 1.0/100,000 are steroid-sensitive. CONCLUSION: Compared with international data, which primarily focused on regional and small populations, this is the largest study about the incidence of the childhood NS.

Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria.

Alpha-aminoadipic and alpha-ketoadipic aciduria is an autosomal recessive inborn error of lysine, hydroxylysine, and tryptophan degradation. To date, DHTKD1 mutations have been reported in two alpha-aminoadipic and alpha-ketoadipic aciduria patients. We have now sequenced DHTKD1 in nine patients diagnosed with alpha-aminoadipic and alpha-ketoadipic aciduria as well as one patient with isolated alpha-aminoadipic aciduria, and identified causal mutations in eight. We report nine novel mutations, including three missense mutations, two nonsense mutations, two splice donor mutations, one duplication, and one deletion and insertion. Two missense mutations, one of which was reported before, were observed in the majority of cases. The clinical presentation of this group of patients was inhomogeneous. Our results confirm that alpha-aminoadipic and alpha-ketoadipic aciduria is caused by mutations in DHTKD1, and further establish that DHTKD1 encodes the E1 subunit of the alpha-ketoadipic acid dehydrogenase complex.

Beta-trace protein--a marker of kidney function in children: "Original research communication-clinical investigation".

OBJECTIVES: To determine the pediatric reference interval for serum beta-trace protein (beta-TP) and to compare beta-TP with established LMW markers of GFR, i.e., cystatin C (CysC) and beta(2)-microglobulin (beta(2)-M). DESIGN AND METHODS: All three LMW markers were measured immunonephelometrically. In 106 children above the age of 2 years without evidence of kidney disease, non-parametric reference intervals were calculated. The relative rise of the GFR marker concentrations above the upper reference was studied in 107 samples from 96 patients covering the entire GFR range. RESULTS: Above 2 years, the reference range of beta-TP was constant at 0.43-1.04 mg/L. With decreasing Schwartz-GFR, there was a comparable rise in beta-TP and beta(2)-M, while CysC rose less in the group with GFR below 30 mL/min/1.73 m(2) (278+/-49% [CysC] versus 336+/-65% [beta-TP] and 342+/-76% [beta(2)-M]; p=0.043 and 0.027, respectively). CONCLUSIONS: These data confirm the potential of ss-TP as an endogenous GFR marker in children.

Novel OCRL1 mutations in patients with the phenotype of Dent disease.

BACKGROUND: Dent disease is an X-linked tubulopathy frequently caused by mutations affecting the voltage-gated chloride channel and chloride/proton antiporter ClC-5. A recent study showed that defects in OCRL1, encoding a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ocrl) and usually found mutated in patients with Lowe syndrome, also can provoke a Dent-like phenotype (Dent 2 disease). METHODS: We investigated 20 CLCN5-negative males from 17 families with a phenotype resembling Dent disease for defects in OCRL1. RESULTS: In our complete series of 35 families with a phenotype of Dent disease, a mutation in the OCRL1 gene was detected in 6 kindreds. All were novel frameshift (Q70RfsX88 and T121NfsX122, detected twice) or missense mutations (I257T and R476W). None of our patients had cognitive or behavioral impairment or cataracts, 2 classic hallmarks of Lowe syndrome. All patients had mild increases in lactate dehydrogenase and/or creatine kinase levels, which rarely is observed in CLCN5-positive patients, but frequently found in patients with Lowe syndrome. To explain the phenotypic heterogeneity caused by OCRL1 mutations, we performed extensive data-bank mining and extended reverse-transcriptase polymerase chain reaction analysis, which provided no evidence for yet unknown (tissue-specific) alternative OCRL1 transcripts. CONCLUSION: Mutations in the OCRL1 gene are found in approximately 23% of kindreds with a Dent phenotype. Defective protein sorting/targeting of Ocrl might be the reason for mildly elevated creatine kinase and lactate dehydrogenase serum concentrations in these patients and a clue to suspect Dent disease unrelated to CLCN5 mutations. It remains to be elucidated why the various OCRL1 mutations found in patients with Dent 2 disease do not cause cataracts.

Impact of prenatal urinomas in patients with posterior urethral valves and postnatal renal function.

OBJECTIVE: Posterior urethral valves (PUV) are a common cause of lower urinary tract obstruction. Renal failure occurs in approximately one third of the cases. It is debated whether urinoma formation is a protective mechanism to reduce pressure-related impairment of renal function. The aim of our study was to determine if urinoma formation is able to preserve renal function on the side of the urinoma. METHODS: Five male patients diagnosed with posterior urethral valves and uni- or bilateral urinoma formation were reviewed. Renal function was assessed by serum creatinine level at days 4-7 and at two months, in addition to dimercaptosuccinylacid (DMSA) scintigraphy at 4-6 weeks postnatal age. RESULTS: Impaired renal function occurred unilaterally in four patients, two had bilateral urinoma formation, and the other two boys presented with unilateral urinoma, one with preserved renal function ipsilateral to the urinoma and the other on the contralateral side. Urinary ascites was detected in three patients, all underwent antenatal centesis. CONCLUSIONS: No association was found between renal function and urinoma formation in patients with PUV.

Perforating colonic duplication as rare cause of renal abscess in children.

Renal abscess is uncommon in children. In a few cases, ascending infection and/or hematogenous spread have been outlined as pathophysiologic mechanisms in published studies. We report on a 7-month-old female infant who was hospitalized with a high fever. Ultrasonography revealed a hypoechogenic mass in the left kidney. The diagnosis of a renal abscess was confirmed by computed tomography. Because antibiotic treatment had only a transient effect, an open operative procedure was performed. Intraoperatively, a perforating colonic duplication with broad contact to the kidney was found that had destroyed major parts of the kidney's parenchyma. After nephrectomy and complete resection of the colonic duplication, the patient recovered uneventfully.