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IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in childhood with an incidence of 1.8 cases per 100 000 children in Germany. The treatment of the first episode implies two aspects: induction of remission and sustainment of remission. The recent Kidney Disease Improving Global Outcomes, American Academy of Pediatrics and German guidelines for the initial treatment of the first episode of a nephrotic syndrome recommend a 12-week course of prednisone. Despite being effective, this treatment is associated with pronounced glucocorticoid-associated toxicity due to high-dose prednisone administration over a prolonged period of time. The aim of the INTENT study (Initial treatment of steroid-sensitive idiopathic nephrotic syndrom in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial) is to show that an alternative treatment regimen with mycophenolic acid is not inferior regarding sustainment of remission, but with lower toxicity compared with treatment with glucocorticoids only.Methods and designThe study is designed as an open, randomised, controlled, multicentre trial. 340 children with a first episode of steroid-sensitive nephrotic syndrome and who achieved remission by a standard prednisone regimen will be enrolled in the trial and randomised to one of two treatment arms. The standard care group will be treated with prednisone for a total of 12 weeks; in the experimental group the treatment is switched to mycophenolate mofetil, also for a total of 12 weeks in treatment duration. The primary endpoint is the occurrence of a treated relapse within 24 months after completion of initial treatment.Ethics and disseminationEthics approval for this trial was granted by the ethics committee of the Medical Faculty of the University of Heidelberg (AFmu-554/2014). The study results will be published in accordance with the Consolidated Standards of Reporting Trials statement and the Standard Protocol Items: Recommendations for Interventional Trials guidelines. Our findings will be submitted to major international paediatric nephrology and general paediatric conferences and submitted for publication in a peer-reviewed, open-access journal.Trial registration numberDRKS0006547; EudraCT2014-001991-76; Pre-result.Date of registration30 October 2014; 24 February 2017.

BackgroundData on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients.MethodsWe therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5–30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant.ResultsChildren aged 5–11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m2, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100–1411 and > 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant.ConclusionA standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination.

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being “at risk” in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

As for other diseases of higher age low birth weight was expected to be a risk factor for an altered bone metabolism and osteoporosis. One the first glance this expectation appears to be confirmed by animal data: rats with intrauterine growth restriction following maternal protein malnutrition show a reduction of bone mineral density going in line with a decrease in serum vitamin D concentrations. However, the situation is less clear in newborns with low birth weight: Some studies show a relation of birth weight and bone mineral density whereas others don't. The older the former low birth weight patients the fainter the effect seems to be. In fact young adults with idiopathic short stature have a low bone mineral density than the low birth weight group irrespective of whether they have experienced catch-up growth or not. As a consequence low birth weight is can not be identified as a relevant risk factor for hip fractures in menopausal women. Postmenopausal women with low birth weight even show higher vitamin D concentrations than normal birth weight individuals. In conclusion, there is no consistent long term effect of low birth weight on bone mineral density or hip fracture risk later in life. Whether methodological weaknesses in the studies performed so far are causal or whether postnatal factors such as physical activity and nutrition are of higher importance can only be speculated upon at present.

The anti-CD20 antibody rituximab has been used successfully as a rescue therapy in some patients with therapy-refractory steroid-dependent nephrotic syndrome (SDNS), including both primary SDNS with minimal changes on biopsy and recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation. All patients showed remission from steroid dependency for at least 9 months concurring with the reappearance of B lymphocytes that had been eliminated by rituximab. The doses used so far vary between 375 mg/m 2 per dose at weekly intervals for 6 weeks and a single dose of 375 mg/m 2 . Until now, with the limited information available, no substantial adverse effects have been reported. However, a recommendation to use rituximab instead of any other established treatment, such as cyclophosphamide, in SDNS cannot be given before clinical studies have been conducted, especially as publication bias cannot be excluded.

All die Themen der aktuellen Ausgabe der Monatsschrift Kinderheilkunde stehen mehr oder weniger in Beziehung zu dieser groß angelegten Strukturreform, führt sie doch dazu, dass das Diagnosis-Related-Groups(DRG)-System, das für die Pflege in großen Teilen bereits Geschichte ist, durch die Einführung der Vorhaltekosten zu 60 % deutlich an Bedeutung verlieren wird.

Zusammenfassung Eine intrauterine Wachstumsrestriktion („intrauterine growth restriction“ [IUGR]) tritt in etwa 5–8 % aller Schwangerschaften auf und ist häufig auf eine intrauterine Mangelversorgung zurückzuführen. Entscheidend für die Diagnose ist nicht das Geburtsgewicht, sondern ein die Perzentilen kreuzendes, reduziertes intrauterines Wachstum. Da eine IUGR das Risiko für metabolische und nichtmetabolische Folgeerkrankungen erhöht, sollte die Diagnose nicht nur von der geburtshilflichen zur neonatologischen Station übergeben werden, sondern auch später behandelnden KollegInnen aus Allgemeinpädiatrie, Allgemeinmedizin und Innerer Medizin bekannt sein. Die tatsächliche Manifestation von Folgeerkrankungen hängt stark von weiteren Einflussfaktoren während des gesamten Lebens ab. Insbesondere in der postnatalen Entwicklungsphase können sich individuell angepasste Umweltbedingungen (z. B. Dauer der Stillzeit, Zusammensetzung der frühkindlichen Ernährung) langfristig präventiv auswirken. In der vorliegenden Übersichtsarbeit wird zunächst auf Ätiologie, Diagnostik und Management der IUGR eingegangen. Zudem werden epidemiologische und experimentelle Daten dargestellt, die den Zusammenhang zwischen IUGR und späterer metabolischer Erkrankung illustrieren. Hieraus abgeleitet werden die Möglichkeiten präkonzeptioneller und pränataler präventiver Maßnahmen diskutiert und Ansätze postnataler Strategien zur Prävention metabolischer Folgeerkrankungen erläutert.