BACKGROUND:Prognostic factors and outcome are incompletely known in childhood mesangiocapillary glomerulonephritis (MCGN). This study aimed to correlate renal outcome with clinical and histopathological variables. METHODS:We conducted a two-centre retrospective analysis of children with MCGN. RESULTS:Fifty-three children presented at a mean age of 8.8 years (range: 13 months-15 years). They were followed for a median of 3.5 years (range: 0-17 years). Histological classification identified 31 type 1, 14 type 2, two type 3 and six undetermined type. Mean renal survival [time to end-stage renal failure (ESRF)] was projected to be 12.2 years [confidence interval (CI): 9.7-14.6 years]. Five and 10 year renal survival was 92% (CI: 88-100%) and 83% (CI: 74-92%), respectively. Those with nephrotic syndrome at presentation had mean renal survival of 8.9 years (CI: 7.1-10.7 years) vs 13.6 years for those without (CI: 10.8-16.5 years) (P = 0.047). The mean estimated glomerular filtration rate (eGFR) at 1 year in those who progressed to ESRF was 52 vs 98 ml/min/1.73 m2 in those who did not (P < 0.001). Chronic damage scored on the first biopsy in 31 children (one centre) was positively associated with adverse renal outcome at 5 years: <20% was associated with 100% and > or =20% with 71% 5-year renal survival (P = 0.006). In 29 children treated with steroid there was a higher proportion (76%) with reduced eGFR at presentation and a significantly higher incidence of nephrotic syndrome (P = 0.002) and hypertension (P = 0.037). There were no significant differences in outcome eGFR, hypertension or proteinuria. CONCLUSIONS:Nephrotic syndrome at presentation and subnormal eGFR at 1 year were adverse features. The finding that structural disease at onset predicted poor renal outcome at 5 years has implications for the design of therapeutic trials. Treatment of MCGN was variable and not evidence-based.

Haemolytic uraemic syndrome (HUS) is a clinicalsyndrome characterized by microangiopathic haemo-lytic anaemia and thrombocytopaenia, often com-plicated by acute renal failure. Typically, it followsa diarrhoeal illness (dþ HUS), the most well knownprecipitating organism being the toxin-producingEscherichia coli serotype 0157. Less typical formsof HUS are associated with pregnancy, malignan-cies, transplant-associated illness and drug regimensincluding cyclosporin, mitomycin and the oral con-traceptive pill. Familial HUS [1] exists in patterns ofboth autosomal dominant and recessive inheritance.Familial HUS with hypocomplementaemia has beenwell recognized and an association has been foundwith abnormalities of Factor H, a factor involved inthe alternative pathway of the complement cascade.Recently, the gene for Factor H has been isolated onchromosome 1q32 and mutations of this gene havebeen seen in families with HUS. We report a familywith two generations affected by HUS in whom therewere persistently very low levels of C3 but normalC4 suggesting alternative pathway dysregulation, butwithout demonstrable abnormalities of Factor H. Inthe first generation, the morphology of the renal lesionover 20 years after the initial presentation was that ofmembranoproliferative glomerulonephritis (MPGN)type I, suggesting an aetiological relationship betweenthis entity and HUS, with shared mechanisms relatingto the alternative pathway of complement, and maybe the basis of an autosomal dominant inheritancepattern.

Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5–15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.

Thrombotic microangiopathy is an uncommon complication of cyclosporin immunosuppression following renal transplantation. We present a 15-year-old girl who developed clinical features of acute rejection, but in whom an early biopsy revealed thrombotic microangiopathy, allowing a change to FK506 immunosuppression resulting in excellent graft recovery.

Detailed antenatal sonography was performed on 18766 pregnant women between 1990 and 1994. Antenatal hydronephrosis, defined as an antero-posterior diameter of the renal pelvis (APPD) greater than 5 mm, was detected in 100 cases (0.59%). Sixty four infants had postnatal hydronephrosis at one and/or six weeks after delivery; 21 of these had urological anomalies. Twelve infants had vesico-ureteric reflux. In all refluxing units the APPD of the renal pelvis was less than 10 mm. Three patients had obstruction at the pelviureteric junction (PUJ); all required surgery. Vesico-ureteric reflux is emerging as the most common urological finding in infants with antenatal hydronephrosis and is likely to be missed if kidneys with APPD of less than 10 mm are not further investigated. In contrast, pelvi-ureteric junction obstruction may be overdiagnosed, based only on drainage patterns of dynamic renogram studies.

Continuous arteriovenous haemodiafiltration was used successfully to achieve controlled correction of hypernatraemia in the presence of renal failure, when peritoneal dialysis was contraindicated, in a 4 year old girl.

Summary Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase–ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection, induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung, and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, while PKR activation is evident in iAT2 and iCM. In SARS-CoV-2 infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however activation of OAS-RNase L and PKR is observed. This is in contrast to MERS-CoV, which effectively inhibits IFN signaling as well as OAS-RNase L and PKR pathways, but similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, both OAS-RNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OAS-RNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2. Significance SARS-CoV-2 emergence in late 2019 led to the COVID-19 pandemic that has had devastating effects on human health and the economy. Early innate immune responses are essential for protection against virus invasion. While inadequate innate immune responses are associated with severe COVID-19 diseases, understanding of the interaction of SARS-CoV-2 with host antiviral pathways is minimal. We have characterized the innate immune response to SARS-CoV-2 infections in relevant respiratory tract derived cells and cardiomyocytes and found that SARS-CoV-2 activates two antiviral pathways, oligoadenylate synthetase–ribonuclease L (OAS-RNase L), and protein kinase R (PKR), while inducing minimal levels of interferon. This in contrast to MERS-CoV which inhibits all three pathways. Activation of these pathways may contribute to the distinctive pathogenesis of SARS-CoV-2.

Two sisters of Asian origin showed typical clinical and biochemical features of primary somatomedin C (SM-C) deficiency (Laron dwarfism). Abnormalities of SM-C binding proteins were observed, one sister lacking the high molecular weight (150 Kd) protein.

Two children with hypoglycaemia secondary to hyperinsulinaemia were treated with diazoxide. They suffered serious side effects of cardiac failure and truncal ataxia.

Twelve children who have had chronic renal failure since infancy and underwent early dialysis (mean age 18 months) and early transplantation (mean age 28 months) were studied. Although head circumference in all was within the normal range at birth, by 1 year it was greater than 2 SD below the mean in nine, including six in whom it was greater than 3 SD below the mean. Developmentally, eight children were functioning in the subnormal range; four of these were moderately and one severely mentally retarded. It was not possible to determine whether the unfavorable neurologic-developmental outcome was the result of the toxic effects of uremia, malnutrition, or the associated psychosocial and experiential deprivation related to chronic, severe illness. Even minor insults at this vulnerable stage of brain development may produce permanent damage, and institution of therapy as early as possible may be crucial in obtaining a more favorable outcome.

We present two cases of acute renal failure associated with a microangiopathic haemolytic anaemia following pneumococcal infections. In both children there was evidence of red cell T-poly-agglutinability (being manifest initially as discrepant A80 blood grouping). In one child pneumococci were isolated from the blood whilst in the other there was antigenic evidence of a recent pneumococcal infection. Both children had a period of oliguric renal failure requiring dialysis. Prostaglandin metabolism was shown to be normal in both children. Renal biopsy in one case showed evidence of exposure of the T antigen on the renal glomeruli, tubules and red cell casts. Pneumococci are known to produce the enzyme neuraminidase which has been implicated in T-activation. We suggest that T-activation following pneumococcal infection should be included in the spectrum of the Haemolytic Uraemic Syndrome.

Subcutaneous emphysema is usually the result of trauma or surgery. We report an unusual case of a disturbed adolescent who presented with cervicofacial emphysema as a result of self abuse.