Assessment of South Asian Pediatric Acute Kidney Injury: Epidemiology and Risk Factors (ASPIRE)-a prospective study on "severe dialysis dependent pediatric AKI".

BACKGROUND: Pediatric acute kidney injury (AKI) is a global health concern with an associated mortality risk disproportionately pronounced in resource-limited settings. There is a pertinent need to understand the epidemiology of pediatric AKI in vulnerable populations. Here, we proposed a prospective study to investigate the epidemiology and associated risk factors of "severe dialysis dependent AKI" in children among South Asian nations which would be the first and largest of its kind. METHODS: The ASPIRE study (part of PCRRT-ICONIC Foundation initiative) is a multi-center, prospective observational study conducted in South Asian countries. All children and adolescents ≤ 18 years of age who required dialysis for AKI in any of the collaborating medical centers were enrolled. Data collection was performed until one of the following endpoints was observed: (1) discharge, (2) death, and (3) discharge against medical advice. RESULTS: From 2019 to 2022, a total of 308 children with severe AKI were enrolled. The mean age was 6.17 years (63% males). Secondary AKI was more prevalent than primary AKI (67.2%), which predominantly occurred due to infections, dehydration, and nephrotoxins. Common causes of primary AKI were glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, and obstructive uropathy. Shock, need for ventilation, and coagulopathy were commonly seen in children with severe AKI who needed dialysis. The foremost kidney replacement therapy used was peritoneal dialysis (60.7%). The mortality rate was 32.1%. CONCLUSIONS: Common causes of AKI in children in South Asia are preventable. Mortality is high among these children suffering from "severe dialysis dependent AKI." Targeted interventions to prevent and identify AKI early and initiate supportive care in less-resourced nations are needed.

An open label non-inferiority randomized controlled trial evaluated alternate day prednisolone given daily during infections vs. levamisole in frequently relapsing nephrotic syndrome.

Initial therapies for children with frequently relapsing nephrotic syndrome include alternate-day prednisolone that is given daily during infections, or levamisole. In this open label, non-inferiority trial, 160 patients, 2 to 18-years-old with frequent relapses, were randomly assigned to receive either prednisolone (0.5-0.7 mg/kg/alternate-day, given daily during infections), or levamisole (2-2.5 mg/kg/alternate-days) for one-year. Patients with relapses on alternate day prednisolone at over 1 mg/kg, prior use of potent steroid-sparing therapies, eGFR under 60 ml/min/1.73 m2 and significant steroid toxicity were excluded. Primary outcome was the proportion of patients with frequent relapses, defined as three-relapses in one-year, or two-relapses within six-months if associated with significant steroid toxicity or loss to follow up. Eighty patients each were randomized to receive prednisolone and levamisole. Baseline features showed preponderance of young patients presenting within two-years of disease onset. On intention-to-treat analysis, frequent relapses were more common in patients administered prednisolone (40% versus 22.5%; risk difference 17.5%; 95% confidence interval 3.4-31.6%). Prednisolone was not non-inferior to levamisole in preventing frequent relapses. However, the two groups showed similar proportions of patients in sustained remission, comparable frequency of relapses, and low frequency of adverse events. The decline in steroid requirement from baseline was higher in the levamisole group. Per-protocol analysis showed similar results. These results have implications for choice of therapy for frequently relapsing nephrotic syndrome. Although therapy with alternate-day prednisolone was not non-inferior to levamisole in preventing frequent relapses, both therapies were effective in other outcome measures. Thus, levamisole was relatively steroid-sparing and may be preferred in patients at risk of steroid toxicity.

Correlation of renal length with anthropometric and demographic data in healthy children: A prospective cross sectional study.

Background: Renal size is an important parameter in the assessment of a child with renal disease. Renal size can be estimated by measuring renal length, renal volume, and cortical volume or thickness. Renal length depends on different factors, which include size, body mass index and gender. Ultrasonography is useful, non-invasive and easily available method for reliably performing the measurement of kidney length. This study was conducted to find out correlation between renal length and age and anthropometric variables in healthy children. This prospective cross sectional study was carried out with the following objectives: (a) To determine the anthropometric variable that correlated best with renal length in healthy children. (b) To develop a nomogram for renal length in healthy children. Methods: Five hundred healthy children were included in this study. Sonographic assessment of renal length was performed using real time mechanical sector scanner with 5 MHz and 8 MHz frequency. The renal length was correlated with somatic parameters like age, weight, height, body surface area and body mass index. Regression equations were derived for each pair of dependent and independent variables. Results: We performed the measurement of renal length in 500 healthy children. In our series, renal measuring parameters showed a good correlation with studied body parameters, height having the best correlation. Data from left and right kidneys are shown separately since there was small but statistically significant difference between them. Based on our study, using the height of the child, renal length may be calculated by using following equation: Left renal length (cm) = 0.052 × height (cm) + 1.042, Right renal length (cm) = 0.052 × height (cm) + 0.867. Conclusions: This study provides values of renal length (mean ± 2SD) in normal Indian children and its correlation with body parameters. Renal length may be easily calculated by derived linear regression equation. Nomograms of renal length with respect to age and height have been formulated. Renal Length was found to correlate best with height of the child.

Comparative analysis of blind vs real-time ultrasound-guided pediatric renal biopsies: A cross-sectional study.

Background: Renal biopsy has a definite role in the management of pediatric kidney diseases. Most centers have given up the earlier practice of performing blind biopsy using Tru-Cut needle and started doing real time ultrasound-guided renal biopsy with an automated spring-loaded gun, which has become standard of care in the last decade or so. Methods: We performed a cross-sectional analysis of the pediatric biopsies conducted at our center over the years by both methods to evaluate whether ultrasound-guided renal biopsy with a disposable automated spring-loaded gun was superior to blind biopsy with a disposable needle of the same size in terms of reduction of complications and improving the yield. We also reviewed the indications and the histopathological diagnosis of pediatric renal biopsies at our center. Results: A total of 45 native kidney biopsies were performed blind and 48 ultrasound-guided biopsies using the curvilinear probe (frequency 3-5 Hz) of GE Logiq P3 ultrasound machine with disposable spring-loaded automated guns. There was a significant increase in the yield of biopsy in terms of the number of glomeruli per pass. A significant increase in the mean number of glomeruli was noted when a biopsy was performed under ultrasound guidance (P < 0.0001). Gross hematuria was significantly reduced as compared to the earlier biopsies done blind i.e., without ultrasound (P » 0.03). Nephrotic syndrome was the commonest indication for biopsy in our patients during both time periods studied. The most common histopathological diagnosis was MesPGN among the children who underwent kidney biopsy from 2005 to 2007, while Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) were most frequently reported. Conclusion: Ultrasound guided kidney biopsies in pediatric age group have significant reduction in incidence of post gross hematuria and significant increase in the mean number of glomeruli per pass.

Clinicopathological spectrum and treatment outcome of idiopathic steroid-resistant nephrotic syndrome in children at a tertiary care center.

Background: Idiopathic steroid-resistant nephrotic syndrome (iSRNS) is a common problem in pediatric nephrology. About 10%-20% of children with nephrotic syndrome have iSRNS and almost 50 percent progress to end-stage renal disease. Very few studies have tried to study the histopathological spectrum, correlate clinical features, renal biopsy patterns and treatment outcome in children presenting with iSRNS in India. In this study, we compared the histopathologic distribution of different subtypes of glomerular morphologic patterns in iSRNS and the clinical and biochemical parameters at the time of diagnosis and outcome of patients after immunosuppressive therapy. Methods: It is a retrospective cross-sectional study involving review of records of all children with iSRNS presenting to our pediatric nephrology OPD who underwent renal needle biopsy and followed-up for a period of atleast six months post biopsy. Histopathological subtypes were correlated with clinical features (viz. age of onset, gender, oliguria, microscopic hematuria, hypertension, serum creatinine at presentation, serum total protein, serum albumin, 24 h urine protein, persistent proteinuria after 12 weeks of calcineurin inhibitor therapy, and progress to end stage renal disease (ERSD), if any, outcome. Result: It was found that minimal change disease (MCD) was overall the most common cause of iSRNS. These patients have a significantly greater incidence of remission with immunosuppression as compared with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy subgroup. Conclusion: Kidney biopsy is of prognostic value in children with iSRNS. The prognosis of children with SRNS owing to MCD is much better than with other nephropathy.

Clinical efficacy of mycophenolate mofetil versus levamisole therapy in frequently relapsing and steroid dependent childhood nephrotic syndrome - A retrospective comparative analysis.

BACKGROUND: Children with frequently relapsing (FR) or steroid dependent (SD) nephrotic syndrome (NS) often develop side effects of corticosteroids. Various steroid-sparing agents are in practice, but only a few studies exist so far which have compared the safety and efficacy of these two commonly used agents. METHODS: We did a retrospective medical records review of children with FRNS or SDNS who had levamisole or mycophenolate mofetil (MMF) as a steroid-sparing agent with a minimum follow-up period of 12 months. The aim was to compare the course of our patients on MMF and levamisole. Our primary objective was to determine the number of children in sustained remission and those with the infrequently relapsing course on levamisole and MMF and, the median time to relapse in months in the two groups. The secondary objective was to compare time to first relapse and number of relapses in FRNS and SDNS group children on MMF and levamisole. RESULTS: A total of 88 children (34% female) with diagnosis FR/SDNS (44 each) were included in the study. Thirty-nine patients took levamisole, while 49 received MMF therapy. The median age of presentation at the relapsing course was 4.2 years. The proportion of children with sustained remission or infrequent relapsing (IFR) course on MMF was 73.6%, compared to 48.71% on levamisole (p-value .015). In addition, the median time to first relapse was 12 months (24, 1.5) and 4.5 months (24, 1) on respective medications. CONCLUSION: Clinical outcome was superior in the MMF group than levamisole, especially in SDNS patients, and also MMF was more efficacious in maintaining sustained remission.

Infectious complications in children with nephrotic syndrome: Can they be prevented?

Background: Sixty percent of children with nephrotic syndrome have frequently relapsing or steroid-dependent course. Serious infections like peritonitis, cellulitis, pneumonia etc. and anasarca with reduced urine output and complications there of including acute kidney injury and thromboembolism contribute significantly to morbidity and mortality in these children. Methods: Questionnaire-based module to study infectious complications in children with nephrotic syndrome was circulated through survey monkey portal to paediatric nephrologists in our country. Twenty-two responded. Forty percent said that they saw patients with severe infections once a month. Fish bone analysis conducted on such patients reporting to our centre over next 3 months revealed that only 22% regularly monitored urine protein by dipstick. We proposed that reduction in time to report relapse by regularly monitoring urine protein could reduce complications in these children. Six urine protein dipsticks were handed over to patients who presented >7 days since relapse or with severe infection or anasarca in the last 1 year. These children were followed up for the next 1 year and given six more urine dipsticks every 3 months. Results: Twenty-three patients were given urine protein dipsticks. Nine of them had 12 severe complications in the previous 6 months. None had any serious infections/anasarca on follow-up. Sixteen new patients had 14 serious complications in this time. Conclusions: Early detection of relapse by home monitoring of urine protein by dipsticks was effective in significantly reducing the number of patients with severe infections and anasarca with reduced urine output.

Hemophagocytic lymphohistiocytosis in a child with chronic granulomatous disease: A rare complication of a rare disorder.

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder (PID) of phagocytic cells resulting in failure to eradicate catalase positive microorganisms like Staphylococci and fungal infections; due to deficiency or malfunction of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits in phagocytic leucocytes. We illustrate here one such case; a six year old girl who was admitted in our hospital with history of prolonged fever, non resolving bilateral otitis media and recurrent pneumonia. She was evaluated for an underlying PID and was found to have CGD based on Nitro blue Tetrazolium (NBT) Slide Test and flow cytometric Dihydrorhodamine (DHR) assay. The child was symptomatic despite initial treatment with first-line followed by second-line antibiotics. During the course of current systemic infection, she also developed infection-associated secondary Hemophagocytic Lympho Histiocytosis (HLH) as suggested by her clinical and laboratory parameters. Despite a thorough search, no microorganism could be isolated and so she was treated with empircal antibiotic therapy comprising of meropenem, linezolid and an antifungal. Fever resolved with gradual improvement of laboratory parameters and finally spontaneous resolution of HLH. We conclude that a high index of suspicion for PID is required in a child with recurrent infections. Identification of underlying infectious agent should be attempted to start targeted antimicrobial therapy; both to prevent as well as cure infection associated secondary HLH.

Utility of glomerular morphometry in diagnosing pediatric renal disease.

BACKGROUND: Morphometry has now become a useful adjunct to the diagnostic armamentarium of light, immunofluorescence, and electron microscopy, as it provides a deep insight into quantitative parameters of nephropathies. There has been a limited study on its utility especially in diagnosing pediatric renal diseases. This study is probably the first in India to assess the contribution of this diagnostic modality in pediatric renal disease to the best of authors' knowledge. METHODS: It's a retrospective cross-sectional study covering a period of 05 years at a tertiary care hospital. The study includes 28 cases of pediatric (age till 14 years) nephropathies. The diseases were divided into two groups-nephrotic presentation and nephritic presentation. Glomerular morphometry was performed and mean was calculated for Bowman's capsule area, glomerular capillary tuft area, and Bowman's space area; for the three groups, respectively. Renal parameters serum creatinine, blood urea, 24 h urine protein were studied along with hemoglobin and serum cholesterol for the cases. Data were analyzed using SPSS software, version 25, for one-way ANOVA comparing mean in the three groups. RESULTS: We found a positive and significant correlation between Bowman's capsule area with proteinuria, blood urea, and serum creatinine. There was positive and significant correlation between glomerular capillary tuft area and serum creatinine and Bowman's space area and proteinuria in both the groups. CONCLUSION: Glomerular morphometry may contribute to the diagnosis of some glomerulopathies and the association between glomerular morphometric parameters and laboratory data may promote better understanding of the prognosis of these patients.