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.

Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study.

BACKGROUND: The aim of the study was to determine the prevalence of congenital anomalies of the kidney and urinary tract (CAKUT) in the neonatal intensive care unit (NICU) and to evaluate risk factors associated with worse outcomes. We hypothesized that infants with CAKUT with extra-renal manifestations have higher mortality. METHODS: This is a cohort study of all inborn infants who were diagnosed with any form of CAKUT discharged from NICUs managed by the Pediatrix Medical Group from 1997 to 2018. Logistic and linear regression models were used to analyze risk factors associated with in-hospital mortality. RESULTS: The prevalence of CAKUT was 1.5% among infants hospitalized in 419 NICUs. Among the 13,383 infants with CAKUT analyzed, median gestational age was 35 (interquartile range [IQR] 31-38) weeks and median birth weight was 2.34 (IQR 1.54-3.08) kg. Overall in-hospital mortality for infants with CAKUT was 6.8%. Oligohydramnios (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 2.2-9.1, p < 0.001), extra-renal anomalies (aOR 2.5, 95% CI 2.0-3.1, p < 0.001), peak SCr (aOR 1.02, 95% CI 1.01-1.03, p < 0.001) and exposure to nephrotoxic medications (aOR 1.4, 95% CI 1.1-1.7, p = 0.01) were associated with increased mortality, while a history of urological surgery or intervention was associated with lower mortality (aOR 0.6, 95% CI 0.4-0.7, p < 0.001). CONCLUSIONS: Infants hospitalized in the NICU who have CAKUT and the independent risk factors for mortality (e.g., oligohydramnios and presence of extra-renal anomalies) require close monitoring, minimizing of exposure to nephrotoxic drugs, and timely urological surgery or intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.

Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review.

Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8-dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11-year-old brother and his 14-year-old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere-like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.

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.

Desmopressin therapy in children and adults: pharmacological considerations and clinical implications.

PURPOSE: This review aims to provide prescribing clinicians a deeper appreciation of desmopressin's clinical indications and formulation types, to better balance efficacy and safety through proper formulation selection. BACKGROUND: Since its discovery 50 years ago, desmopressin's antidiuretic properties have been used for central diabetes insipidus, primary monosymptomatic nocturnal enuresis and adult nocturnal polyuria, while its coagulant effects are useful for mild hemophilia A and von Willebrand Disease. During this time, newer formulations of desmopressin have also been introduced to the market raising questions on interchangeability, dose conversion and safety. The wide array of clinical indications and variable pharmacokinetic properties of different desmopressin preparations raises the possibility of medication error, especially the risk of hyponatraemia. METHODOLOGY: A narrative review to explore clinically relevant aspects of desmopressin therapy, synthesising information obtained from searches of published literature. RESULTS: We identified that the risk factors for developing hyponatremia include extremes of age, existing comorbidity, drug interaction, intranasal formulations and intercurrent illness. We describe the dose equivalence between all formulations to facilitate conversion. We highlight that in view of inter-subject variability, close monitoring is recommended when switching preparations. We found that paediatric data remains limited, leading to recent proposals for age- and weight-based dosing regimens. CONCLUSION: The risk of hyponatremia, albeit small, can be reduced by adhering to the indication-specific doses and taking steps to govern the safe prescription of the drug. Further paediatric clinical trials are awaited to expand the evidence base of childhood desmopressin therapy.

Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore. METHODS: We performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs). RESULTS: We attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change - 87.9, 95% CI - 89.3 to - 86.3, p < 0.001) and gastrointestinal infections (% change - 72.4, 95%CI - 75.9 to - 68.4, p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change - 40.0, 95%CI - 44.3 to - 35.3, p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change - 73.9, 95%CI - 75.9 to - 71.7, p < 0.001). CONCLUSIONS: We highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.

Investigating urinary characteristics and optimal urine white blood cell threshold in paediatric urinary tract infection: A prospective observational study.

Introduction: While the definitive diagnosis of urinary tract infection (UTI) requires a positive urine culture, the likelihood of UTI can be determined by urinalysis that includes white blood cell (WBC) count. We aimed to determine the optimal urine WBC threshold in urinalysis to predict UTIs in children presenting at the emergency department (ED). Method: We performed a prospective observational study in the ED at KK Women's and Children's Hospital for children below 18 years old who underwent both urine microscopy and urine cultures, between 10 January and 7 November 2022. We assessed the various urine WBC thresholds associated with culture-proven UTIs using sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and area under receiver operating characteristic curve. Results: We found a culture-proven UTI rate of 460/1188 (38.7%) among all patients analysed, and 278/998 (27.9%) among those with nitrite-negative urine samples. Among all patients, a urinalysis WBC threshold of 100/µL had a sensitivity of 82.2% (95% confidence interval [CI] 78.4-85.5) and negative predictive value of 86.2% (95% CI 83.6-88.4). Among those who were nitrite-negative, a WBC threshold of ≥100/µL resulted in a potential missed rate of 48/278 (17.3%). By lowering the WBC threshold to ≥10/µL, the potential missed cases reduced to 6/278 (2.2%), with an estimated increase in 419 urine cultures annually. Conclusion: A urine microscopy WBC threshold of ≥100/µL results in a clinically significant number of missed UTIs. Implementation of various thresholds should consider both the potential missed UTI rate and the required resource utilisation.

Dilated aorta in CNOT3 -related neurodevelopmental disorder: 'expanding' the phenotype.

INTRODUCTION: Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child's development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype-phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management. METHODS: In this study, we report a case of a patient with CNOT3 -related NDD who presented with progressive aortic dilatation, a feature not reported previously. RESULTS: Our patient presented with intellectual disorder, dysmorphic facial features, and cardiac anomalies, notably progressive aortic dilatation - a novel finding in CNOT3 -related NDD. Genetic testing identified a de novo 6.3 kbp intragenic deletion in CNOT3 , providing a possible genetic basis for her condition. CONCLUSION: This study presents the first case of CNOT3 -related NDD in Southeast Asia, expanding the phenotype to include progressive aortic dilatation and suggesting merit in cardiac surveillance of patients with CNOT3 -related NDD. It also emphasizes the importance of genetic testing in diagnosing complex NDD cases as well as reanalysis of 'negative' cases using advanced sequencing technologies to uncover potential hidden genetic etiologies in undiagnosed NDDs.

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.

Outcome of boys with posterior urethral valves from a single tertiary hospital in Singapore.

INTRODUCTION: Posterior urethral valve (PUV) is the most common congenital cause of bladder outflow obstruction in male infants. Despite timely treatment, renal damage can still occur in the long-term leading to chronic kidney disease (CKD). METHODS: A retrospective review of all PUV patients in a single tertiary institution between April 1998 and July 2019 was conducted to analyze their presentations, management and outcomes. Long-term renal function, radiologic scans and somatic growth were evaluated. RESULTS: A total of 16 patients were included in this study. Two patients who defaulted all follow-ups were excluded. Seven patients (43.7%) presented in the antenatal period; four patients (25%) presented in the neonatal period and five patients (31.3%) presented in the post-neonatal period. Primary transurethral fulguration of valves was done in 13 patients, while three had vesicostomies as the primary procedure. Three patients had associated anterior urethral valves (AUV), which were treated endoscopically. Nine boys had additional procedures for diversion and undiversion, VUR, non-functioning kidney and clean intermittent catheterization. Ten patients had urodynamic studies performed, of which eight patients received anticholinergic therapy. Eleven patients had DMSA scans, of which three patients had a normal study and eight patients showed unilateral reduced function. Four patients were diagnosed with CKD on long-term follow-up duration over 5 years. All patients were shown to have good somatic growth. CONCLUSION: Patients with PUV can suffer from complications despite primary treatment. In our small cohort, a quarter of our patients developed CKD on follow-up. Thus, patients need long-term follow-up to optimize bladder and renal function.

Epidemiology and Management of Children with Hypertensive Crisis: A Single-Center Experience.

Most children who present with hypertensive crisis have a secondary cause for hypertension. This study describes the epidemiology and management of children with hypertensive crisis. A retrospective cohort study was done in a tertiary pediatric hospital from 2009 to 2015. Thirty-seven patients were treated for hypertensive crisis. Twelve (32.4%) patients were treated for hypertensive emergency. The majority of our patients (33 [89.1%]) had a secondary cause of hypertension. The most common identifiable cause of hypertension was a renal pathology (18/37 [48.6%]). Oral nifedipine (23 [62.1%]) was the most frequently used antihypertensive, followed by intravenous labetalol (8 [21.6%]). There were no mortalities or morbidities. Hypertensive crisis in children is likely secondary in nature. Oral nifedipine and intravenous labetalol are both effective treatments.

Prevention of Acute Kidney Injury in Children Undergoing Cardiac Surgery: A Narrative Review.

Children undergoing cardiac surgery are at risk of developing acute kidney injury (AKI). Preventing cardiac surgery-associated AKI (CS-AKI) is important as it is associated with increased early- and long-term mortality and morbidity. Targeting modifiable risk factors (eg, avoiding poor renal perfusion, nephrotoxic drugs, and fluid overload) reduces the risk of CS-AKI. There is currently no strong evidence for the routine use of pharmacological approaches (eg, aminophylline, dexmedetomidine, fenoldopam, and steroids) to prevent CS-AKI. There is robust evidence to support the role of early peritoneal dialysis as a nonpharmacologic approach to prevent CS-AKI.

Obstructive uropathy and severe acute kidney injury from renal calculi due to adenine phosphoribosyltransferase deficiency.

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is an uncommon genetic cause of chronic kidney disease due to crystalline nephropathy. METHODS: A case of a Chinese boy with APRT deficiency presenting with severe acute kidney injury secondary to obstructive uropathy from multiple renal calculi was reviewed. RESULTS: The patient underwent staged removal of the calculi. Infrared spectrometry of the renal calculi showed 2,8-dihydroxyadenine. APRT deficiency was confirmed with abolished APRT enzyme activity in red blood cells. He was started on allopurinol and low purine diet with complete resolution of the residual calculi. CONCLUSION: APRT deficiency should be considered in patients with multiple radiolucent renal calculi.