Epidemiology, clinical characteristics and outcomes of multisystem inflammatory syndrome in children.

BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia. METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes. RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement. CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.

Health-related quality of life amongst children with chronic kidney disease in Malaysia: performance of the Bahasa Melayu version of the PedsQL 3.0 ESRD Module : (PedsQL 3.0 VerBATIM: version in Bahasa Melayu. Translated for use in Malaysia).

BACKGROUND: The PedsQL 3.0 End Stage Renal Disease (ESRD) Module is a well-accepted instrument internationally but it is not available in the local language. We aimed to validate the Bahasa Melayu (Malay language) version and determine the health-related quality of life (HRQoL) scores amongst children with CKD in Malaysia. METHODS: The source questionnaire in English was translated into Bahasa Melayu. Linguistic validation guidelines by the MAPI Research Institute were followed. The already validated Bahasa Melayu PedsQL 4.0 Generic Core Scales was used for comparison. Sociodemographic data were collected during the interview. Statistical analyses were performed using SPSS version 25.0. RESULTS: Sixty-nine children aged 8 to 18 with CKD stages 4 and 5, with or without dialysis, and their caregivers were recruited. Mean age was 12.62 ± 2.77 (SD). Evaluation of the PedsQL 3.0 ESRD Module Bahasa Melayu version demonstrated good internal consistency (Cronbach alpha 0.82). There was good agreement between child self-report and parent proxy report in all domains; average intraclass correlation coefficients (ICC) were 0.78, 95% CI (0.71, 0.84). Scores obtained from Generic 4.0 scales correlated with the disease-specific ESRD 3.0 scale, Spearman's rho = 0.32, p = 0.007. The Kruskal-Wallis H test indicated that there were no significant differences between stages of CKD and their respective mean HRQoL score, χ2(2) = 2.88, p = 0.236. CONCLUSIONS: The PedsQL 3.0 ESRD Module Bahasa Melayu version is a reliable and feasible tool for cross-cultural adaptation. A longer prospective study may help better illustrate the quality of life in this group of children.

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.

Occult Kidney Dysfunction in Children With Transfusion-Dependent Thalassemia.

Background: Thalassemia is the commonest hemoglobinopathy in Southeast Asia. Kidney dysfunction is an underreported sequelae in children with thalassemia. We conducted a retrospective study to identify the prevalence of and predisposing factors for kidney dysfunction in children with transfusion-dependent thalassemia (TDT). Method: Abnormal kidney function was defined as children with a glomerular filtration rate (GFR) of <90 ml/min/1.73 m2 or a decline in GFR of >20 ml/min/1.73 m2 or presence of nephrotic range proteinuria within 3 years of commencing regular (every ≤6 weeks) red cell transfusion. Data analyzed were age at diagnosis of thalassemia, number of transfusion-years, iron chelation therapy, serum ferritin, and pre-transfusion hemoglobin levels. Results: Eighty-one children were studied. Mean age was 11.72 ± 5.275 years. Thirty out of 81 (37%) demonstrated abnormal kidney function. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit. This fraction was doubled [48/81 (59.3%)] when the cohort was tracked back by 3 years from the last clinic encounter. Age at diagnosis (RR, 1.157; 95% CI, 1.014-1.319; p = 0.03) and duration of receiving transfusions (RR, 0.984; 95% CI, 0.974-0.994; p = 0.001) were associated with increased risk of developing abnormal kidney function. Conclusion: Abnormal kidney function in children with TDT may be overlooked by medical personnel without active screening measures. Children receiving regular red cell transfusions require systematic surveillance to enable early detection of kidney dysfunction and timely implementation of appropriate therapeutic interventions.

Case Report: Severe Hyponatremia in Infants With Urinary Tract Infection.

Introduction: Many reports on investigations and treatments in UTI, however little, have been mentioned with regard to electrolyte abnormalities. Secondary pseudohypoaldosteronism (PHA) in UTI, though less common, is a known association. Features include hyponatremia and concomitant hyperkalemia. Objectives: We aim to highlight these uncommon sequelae in UTI to avoid incorrect diagnosis and unnecessary investigations. Study Design: Clinical data of patients admitted and referred to a pediatric nephrologist at the University Malaya Medical Center between May 2019 and October 2020 were collated and elaborated. Results and Discussion: We report three infants with hyponatremia and hyperkalemia during UTI episodes. Two infants were known to have posterior urethral valve (PUV) before the onset of UTI and one infant had UTI, which led to investigations confirming the diagnosis of bladder vaginal fistula. The electrolyte derangements were temporary and resolved within 48 to 72 h of treatment with intravenous fluid and appropriate antibiotic therapy. Out of three, only one had a hormonal study, which confirms PHA. Reduced aldosterone activity could be due to absolute reduction in aldosterone titer or lack of aldosterone responsiveness at tubular (other tissues) level. In the latter, aldosterone titer is elevated. The infant in our cohort who had hormonal evaluation had the mentioned electrolyte abnormalities with a markedly elevated aldosterone titer. This demonstrated defective action of the hormone at the level of mineralocorticoid receptor. Although the remaining two infants had no confirmatory hormonal study, all of them recovered within 48 h of hospital admission, after receiving appropriate management for the primary problem, which was UTI. We observed a slower recovery of hyponatremia in relation to hyperkalemia, but none of these infants required salt replacement upon discharge. Conclusion: Infants with severe UTI and deranged electrolytes should be screened for structural abnormality and vice versa. Not all infants require hormonal screening, but those who required prolonged salt replacement or showed involvement of other systems warrant further evaluation.

Assessing the hydration status of children with chronic kidney disease and on dialysis: a comparison of techniques.

Background: Fluid balance is pivotal in the management of children with chronic kidney disease (CKD) and on dialysis. Although many techniques are available to assess fluid status, there are only a few studies for children, of which none have been comparable against cardiovascular outcome measures. Methods: We performed a longitudinal study in 30 children with CKD5-5D and 13 age-matched healthy controls (71 measurements) to determine a correlation between optimal weight by bioimpedance spectroscopy (Wt-BIS) and clinical assessment (Wt-CA). The accuracy of Wt-BIS [relative overhydration (Rel-OH)] was compared against indicators of fluid status and cardiovascular measures. Results: There was poor agreement between Wt-CA and Wt-BIS in children on dialysis (P = 0.01), but not in CKD5 or control subjects. We developed a modified chart to plot Rel-OH against systolic blood pressure (SBP) z-score for the appropriate representation of volume status and blood pressure (BP) in children. In total, 25% of measurements showed SBP >90th percentile but not with concurrent overhydration. Rel-OH correlated with peripheral pulse pressure (P = 0.03; R = 0.3), higher N-terminal pro-brain natriuretic peptide (P = 0.02; R = 0.33) and left ventricular end-diastolic diameter (P = 0.05; R = 0.38). Central aortic mean and pulse pressure significantly associated with the left ventricular end-diastolic diameter (P = 0.03; R = 0.47 and P = 0.01; R = 0.50, respectively), but not with Rel-OH. SBP was positively associated with pulse wave velocity z-score (P = 0.04). In total, 40% of children on haemodialysis and 30% on peritoneal dialysis had increased left ventricular mass index. Conclusions: BIS provides an objective method for the assessment of hydration status in children on dialysis. We noted a marked discrepancy between BP and hydration status in children on dialysis that warrants further investigation.