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Author(s): Nicholas Ware [sup.1] , Neil J. Sebire [sup.1] , W. K. Chong [sup.1] , Rajesh Krishnan [sup.2] , Stephen D. Marks [sup.1] Author Affiliations: (1) 0000 0004 0426 7394grid.424537.3Department [...]

Introduction Nephrotic syndrome (NS) which appears early in life provides a diagnostic and management challenge to pediatric nephrologists[1]. It is caused by heterogeneous glomerular diseases, and the diagnosis is based [...], Background Nephrotic syndrome (NS) presenting early in life is caused by heterogeneous glomerular diseases. We retrospectively evaluated whether histological diagnosis in children presenting with NS in the first year of life predicts remission or progression to end-stage kidney disease (ESKD). Methods This is a single centre retrospective review of all children diagnosed with NS before one year of age between 1990 and 2009. All subjects had a renal biopsy, which was independently blindly reviewed by a single renal pathologist for the purpose of this study. Results Forty-nine children (25 female) who presented at 0.1-11.6 (median 1.6) months were included with 31 presenting within the first three months of life. Histopathological review diagnostic categories were; 13 Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic complications of the biopsy. Eight children achieved remission (four MesGN, one Finnish type changes, one FSGS, one MCD and one membranous) with patient and renal survival of 73% and 43%, respectively, at follow-up duration of 5-222 (median 73) months (with five lost to follow-up). All children with Finnish-type histopathological changes presented within five months of age. Due to the historical nature of the cohort, genetic testing was only available for 14 children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1 and one ITGA3) with none of these nine children achieving remission. All of them had presented within four months of age and required renal replacement therapy, and two died. Conclusions Histopathological findings are varied in children presenting with NS early in life. Whilst groups of histological patterns of disease are associated with differing outcomes, accurate prediction of disease course in a specific case is difficult and more widespread genetic testing may improve the understanding of this group of diseases and their optimal management Keywords Congenital nephrotic syndrome * Infantile nephrotic syndrome * Histopathology * Genetics * Outcome

Although early survival of preterm infants has improved, late-onset septicemias or severe complications such as necrotizing enterocolitis (NEC) have increased as causes of mortality and long-term morbidity (4-6). Yet relatively [...], In spite of their precipitous encounter with the environment, newborn infants cannot readily mount T helper type 1 ([T.sub.H].1) cell antibacterial and antiviral responses. Instead, they show skewing toward [T.sub.H].2 responses, which, together with immunoregulatoiy functions, are thought to limit the potential for inflammatory damage, while simultaneously permitting intestinal colonization by commensals (1-3). However, these collective capabilities account for relatively few T cells. Here we demonstrate that a major T cell effector function in human newborns is interleukin-8 (CXCL8) production, which has the potential to activate antimicrobial neutrophils and γδ T cells. CXCL8 production was provoked by antigen receptor engagement of T cells that are distinct from those few cells producing [T.sub.H]1, [T.sub.H]2 and [T.sub.H]17 cytokines, was co-stimulated by Toll-like receptor signaling, and was readily apparent in preterm babies, particularly those experiencing neonatal infections and severe pathology. By contrast, CXCL8-producing T cells were rare in adults, and no equivalent function was evident in neonatal mice. CXCL8 production counters the widely held view that T lymphocytes in very early life are intrinsically anti-inflammatory, with implications for immune monitoring, immune interventions (including vaccination) and immunopathologies. It also emphasizes qualitative distinctions between infants' and adults' immune systems.

Introduction C1q nephropathy (C1qN) is a histologically defined disease entity defined by immune deposits in the mesangium and diffuse mesangial staining with C1q on immunofluorescence (IF) or immunohistochemical staining (IHC) [...], Background C1q nephropathy has been suggested as a separate disease entity. C1q positivity has also been described in association with nephrotic syndrome (NS) as a potential marker for worse outcome. The aims of this study were to describe the clinical characteristics, laboratory parameters and outcomes of 35 children whose renal histology revealed predominant mesangial C1q deposition and to investigate if the experience at our institution supports the above hypothesis. Method Clinical and pathological characteristics of all children whose kidney biopsies showed positive C1q staining were retrospectively recorded. The outcome of children with minimal change nephrotic syndrome (MCNS) and predominant mesangial C1q deposition based on C1q staining was compared with that of a concurrent group of children with MCNS with no such immune staining. Results The median age of the patient cohort was 4.5 years (range 6 months to 16 years), 69% were boys and 88% presented with nephrotic syndrome (NS). Children with C1q staining and MCNS had more relapses (p = 0.001) and shorter relapse-free periods (p = 0.033) than those with negative immunostaining, but the long-term outcomes were similar in both groups. Conclusion Our data do not support C1q nephropathy as a separate diagnostic category. Children with MCNS and mesangial C1q deposition (staining) showed more relapses but no difference in long term renal outcome. Keywords C1q staining * C1q nephropathy * Minimal change nephropathy * Nephrotic syndrome * Outcome