IgA nephropathy in children: before and after the start of COVID-19.

BACKGROUND: We describe the clinical course of children with IgA nephropathy (IgAN), diagnosed before and after the emergence of COVID-19. We hypothesized that COVID-19 vaccination and/or infection resulted in more children with IgAN to present clinically. METHODS: We conducted a retrospective cohort study of children with IgAN diagnosed on kidney biopsy from 2014-2020 (Period 1) and 2021-2022 (Period 2). Baseline characteristics, clinical presentation, investigations and treatments were compared between patients diagnosed in Period 1 and Period 2, as well as between patients with and without chronic changes on kidney biopsy. Continuous variables were compared using the Wilcoxon rank sum test. Categorical variables were compared using χ2 or Fisher exact tests. RESULTS: Nineteen children with IgAN were diagnosed by kidney biopsy, with 10 during Period 1 and 9 patients during Period 2 (an average of 1-2 patients/year and 4-5 patients/year in Periods 1 and 2, respectively). The most common indication for kidney biopsy is proteinuria with urine protein/creatinine ratio 1.4 (interquartile range [IQR] 1.2-9.0) vs. 0.8 (IQR 0.6-1.5) g/g (p = 0.064) at time of kidney biopsy for patients in Period 1 and 2, respectively. Clinical course was similar in both periods. No patient required acute or chronic kidney replacement therapy. CONCLUSIONS: The rate of diagnosing children with IgAN was higher since the emergence of COVID-19, suggesting that COVID-19 may trigger an immune response responsible for IgAN, similar to other mucosal infections.

Stakes of Assessments in Residency: Influence on Previous and Current Self-Regulated Learning and Co-Regulated Learning in Early Career Specialists.

Introduction: Assessments drive learning but the influence of the stakes of the assessments on self-regulated (SRL) during and after residency are unknown. As early career specialists (ECS) must continue learning independently, the answer to this is important as it may inform future assessments with the potential to promote life-long learning after graduation. Methods: We utilized constructivist grounded theory to explore the perspectives of eighteen ECS on the influence of stakes of assessments within residency on their SRL during training and in current practice. We conducted semi-structured interviews. Results: We initially set out to examine the influence of the stakes of assessments on SRL during residency and after graduation. However, it was apparent that learners increasingly engaged with others in co-regulated learning (CRL) as the perceived stakes of the assessments increased. The individual learner's SRL was embedded in CRL in preparation for the various assessments in residency. For low-stakes assessments, the learner engaged in less CRL, taking less cues from others. As stakes increased, the learner engaged in more CRL with peers with similar intellectual level and supervisors to prepare for these assessments. SRL and CRL influenced by assessments in residency had a knock-on effect in clinical practice as ECS in: 1) developing clinical reasoning, 2) improving doctor-patient communication and negotiation skills, and 3) self-reflections and seeking feedback to deal with expectations of self or others. Discussion: Our study supported that the stakes of assessments within residency reinforced SRL and CRL during residency with a continued effect on learning as ECS.

Risk factors for imaging abnormalities after the first febrile urinary tract infection in infants ≤3 months old: a retrospective cohort study.

OBJECTIVES: To assess the association of clinical factors and investigation results (blood and urine) with imaging abnormalities (ultrasound of the kidneys, ureters and bladder; dimercaptosuccinic acid scan; and/or micturating cystourethrogram) and recurrent urinary tract infections (UTIs) in infants ≤3 months old presenting with their first febrile UTI. METHODS: We conducted a retrospective cohort study of infants ≤3 months old with first febrile UTI admitted from 2010 to 2016. Multivariable logistic regression model was used to analyse the association of imaging abnormalities and recurrent UTI with covariates selected a priori: age at presentation, maximum temperature, duration of illness at presentation, interval between start of antibiotics and fever resolution, C-reactive protein, total white cell count on the full blood count, bacteraemia, white cell count on the urinalysis and non-Escherichia coli growth in the urine culture (non-E. coli UTI). RESULTS: There were 190 infants but 12 did not undergo any imaging. Median age at presentation was 63 days (IQR 41-78). Twenty-four patients had imaging abnormalities. Non-E. coli UTI (adjusted OR (aOR) 5.01, 95% CI 1.65 to 15.24, p=0.004) was independently associated with imaging abnormalities, while bacteraemia (aOR 4.93, 95% CI 1.25 to 19.43, p=0.022) and non-E. coli UTI (aOR 5.06, 95% CI 1.90 to 13.48, p=0.001) were independently associated with recurrent UTI. CONCLUSION: Non-E. coli UTI at the first febrile UTI in infants ≤3 months old may be useful in predicting imaging abnormalities while bacteraemia and non-E. coli UTI may be useful to predict recurrent UTI.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Salmonella Renal Abscess in an Immunocompetent Child: Case Report and Literature Review.

We describe a case of a 10-year-old immunocompetent girl with a left renal abscess due to Group C Salmonella (Salmonella serovar Oranienburg). Percutaneous drainage of the abscess was done. She also received 2 weeks of intravenous ceftriaxone, followed by 4 weeks of oral co-trimoxazole with resolution seen on ultrasound. A review of pediatric Salmonella renal abscesses is also presented.

A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features.

PURPOSE: The endoplasmic reticulum membrane complex (EMC) is a highly conserved, multifunctional 10-protein complex related to membrane protein biology. In seven families, we identified 13 individuals with highly overlapping phenotypes who harbor a single identical homozygous frameshift variant in EMC10. METHODS: Using exome, genome, and Sanger sequencing, a recurrent frameshift EMC10 variant was identified in affected individuals in an international cohort of consanguineous families. Multiple families were independently identified and connected via Matchmaker Exchange and internal databases. We assessed the effect of the frameshift variant on EMC10 RNA and protein expression and evaluated EMC10 expression in normal human brain tissue using immunohistochemistry. RESULTS: A homozygous variant EMC10 c.287delG (Refseq NM_206538.3, p.Gly96Alafs*9) segregated with affected individuals in each family, who exhibited a phenotypic spectrum of intellectual disability (ID) and global developmental delay (GDD), variable seizures and variable dysmorphic features (elongated face, curly hair, cubitus valgus, and arachnodactyly). The variant arose on two founder haplotypes and results in significantly reduced EMC10 RNA expression and an unstable truncated EMC10 protein. CONCLUSION: We propose that a homozygous loss-of-function variant in EMC10 causes a novel syndromic neurodevelopmental phenotype. Remarkably, the recurrent variant is likely the result of a hypermutable site and arose on distinct founder haplotypes.

Clinical characteristics and mortality risk prediction in critically ill children in Malaysian Borneo.

INTRODUCTION: Mortality risk prediction scores are important for benchmarking quality of care in paediatric intensive care units (PICUs). We aimed to benchmark PICU outcomes at our hospital against the Pediatric Index of Mortality 2 (PIM2) mortality risk prediction score, and evaluate differences in diagnosis on admission and outcomes between Malaysian and immigrant children. METHODS: We prospectively collected demographic and clinical data on paediatric medical patients admitted to the PICU of Sabah Women's and Children's Hospital in Kota Kinabalu, Sabah, Malaysia. The PIM2 risk score for mortality was tabulated. RESULTS: Of the 131 patients who met the inclusion criteria, data was available for 115 patients. The mean age of the patients was 2.6 ± 3.8 years, with 79% of the cohort aged less than five years. Patients were mainly of Kadazan (38%) and Bajau (30%) descent, and 26% of patients were non-citizens. Leading diagnoses on admission were respiratory (37%), neurological (18%) and infectious (17%) disorders. Out of the 29 patients who died, 23 (79%) were Malaysians and the main mortality diagnostic categories were respiratory disorder (22%), septicaemia (22%), haemato-oncological disease (17%) and neurological disorder (13%). Calculated standardised mortality ratios (SMRs) were not significantly > 1 for any patient category for variables such as age and admission diagnosis. However, infants less than two years old with comorbidities were significantly worse (SMR 2.61, 95% confidence interval 1.02-6.66). CONCLUSION: The patient profile at our centre was similar to that reported from other PICUs in Asia. The PIM2 score is a useful mortality risk prediction model for our population.

Urological anomalies and chronic kidney disease in children with anorectal malformations.

BACKGROUND: This study aims to predict risk factors for urological anomalies in children with anorectal malformations (ARM) and describes the clinical features of patients who have developed chronic kidney disease. METHODS: We retrospectively reviewed infants with ARM who received surgery and were followed at the Sabah Women and Children's Hospital, Malaysia, from 1986 to 2010. RESULTS: One hundred and twenty-two children with anorectal malformations were studied, after excluding 24 children with incomplete data. Three factors were significant as predictors of the presence of a urological anomaly: high ARM lesion (OR 3.12, 95%CI 1.1-8.9), the presence of genital abnormality (OR 2.95, 95%CI 1.10-7.91) and cloacal anomaly in girls (OR 8.27, 95% CI 1.91-35.6). The most common anomalies were vesicoureteric reflux, single kidney and neurogenic bladder. Chronic kidney disease (CKD) was noted in 5.7%, in children who had recurrent urinary tract infections, neurogenic bladder or complex renal tract pathology; end-stage renal failure was seen in only 0.8% of children with ARM. CONCLUSION: Urological anomalies were seen in 23% of patients, but the overall incidence of CKD and end-stage renal disease is low. Early identification of infants with ARM at risk of renal failure may be important for renal survival.