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.

An international, multi-center study evaluated rituximab therapy in childhood steroid-resistant nephrotic syndrome.

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival. Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome.

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.

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.

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.

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.

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.

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.

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.

Correction of hypernatremic dehydration in neonates with supervised breast-feeding: A cross-sectional observational study.

BACKGROUND: Hypernatremic dehydration is an uncommon but a serious cause of readmission in neonates especially in the ones on exclusive breast-feeding. The management of such neonates is challenging as serious complications can occur both because of hypernatremic dehydration and its rapid correction. The aim was to study the clinical profile of neonates with hypernatremic dehydration and determine the outcome of these neonates after appropriate management. METHODS: This is a prospective cross-sectional observational study of neonates readmitted with hypernatremic dehydration in a tertiary care hospital in a 12-month period from March 2017 to February 2018. The inclusion criterion was as follows: all neonates with serum sodium >145 mEq/l. The exclusion criteria were as follows: neonates with hypoglycemia, positive sepsis screen and any other congenital diseases. Neonates with serum sodium between 145 and 160 mEq/l were treated with supervised quantified oral feeds at 150 ml/kg/day, unless they had features of shock. Neonates who had serum sodium ≥160 mEq/l were given intravenous (IV) fluids initially. RESULTS: A total of 2412 deliveries took place during the study period. Hypernatremic dehydration was reported in 46 (1.9%) of them, which required admission. We found that all these neonates were exclusively breast-fed, with 81.3% neonates born to primigravidae. One neonate presented with seizures, and one, with metabolic acidosis. More than 50% neonates had acute kidney injury (AKI) on admission. No neonates in our study developed central nervous system (CNS) complications such as cerebral venous thrombosis, convulsions or intracranial haemorrhage, and complete recovery from AKI was documented in all neonates. CONCLUSION: Hypernatremic dehydration can be a serious problem even in term healthy neonates especially in exclusively breast-fed neonates born to primiparous women. Our study shows that quantified oral feeding is effective in successful management of hypernatremic dehydration and not associated with the dreaded CNS complications due to rapid correction.

Acute kidney injury in the pediatric intensive care unit at a tertiary care hospital of the Armed Forces: a cross-sectional observational study.

BACKGROUND: Acute kidney injury (AKI) is shown to be the commonest complication in critically ill children admitted to the pediatric intensive care unit (PICU). Kidney Disease: Improving Global Outcomes (KDIGO) classification and definition are now used universally. We undertook prospective observational study to study the etiology and maximum stage of AKI as defined by KDIGO and its complications and outcomes. METHODS: All children admitted to the PICU were included in the study. The diagnosis of sepsis and multiorgan dysfunction syndrome (MODS) was made according to the standard international guidelines. The patients were followed up till discharge/death. All children were screened for AKI at admission and subsequently using serum creatinine measured by modified Jaffe's method and urine output measurement. RESULTS: A total of 197 children were admitted to the PICU. 38 (19.28%) developed AKI, and 6 (15.78%) developed stage III AKI. Malignancies, serious neurological and renal disorders, and postsurgery complications accounted for most of the cases with AKI. Six were admitted with primary renal condition. Sepsis with or without MODS was seen in 12 patients with AKI and in 8 without AKI. Twenty-one children with AKI and 3 children without AKI were exposed to nephrotoxic drugs. Twenty-three children with AKI required inotropic support. The average length of stay (ALOS) of children with AKI in the PICU was 9.86 days, whereas ALOS of children without AKI was 6.23 days. Eighteen children with AKI (47.36%) and 36 (21.38%) with no AKI died. CONCLUSIONS: AKI in children in the PICUs of referral hospitals in the armed forces have varied etiologies and presentations. These children require early identification and management with close monitoring to prevent long-term renal morbidity and mortality.

Umbilical cord blood plasma vitamin A levels in low birth weight (LBW) babies.

BACKGROUND: Role of vitamin A in reducing the mortality in infants more than six months of age is well known. Supplementing newborn infants with vitamin A within 48 hours of birth reduces infant mortality by almost a quarter, with the greatest benefit to those of low birth weight (LBW). Studies that could highlight deficiency states in neonates, particularly LBW babies by objective measurement of vitamin A levels would help in formulating the recommendations to supplement these babies with vitamin A. METHODS: Cord blood plasma vitamin A levels of 154 LBW babies with birth weight in the range of 1505-2455 were analysed for plasma vitamin A (retinol) levels by HPLC method. Samples of 55 babies with normal birth weight were also analysed. LBW babies were divided into two subgroups of preterm LBW and LBW-term small for gestational age (SGA). RESULTS: Of the 154 babies with LBW, 92 were preterm LBW and 52 were LBW-term SGA. Mean cord blood plasma vitamin A levels were significantly lower in the preterm LBW group (n = 92) compared to levels observed in babies with normal birth weight (n = 55) and LBW-term SGA subgroups (n = 62). There was no significant difference in the mean vitamin A values between the normal birth weight babies and LBW-term SGA group. There was significant positive correlation of cord blood vitamin A levels with birth weight in the entire set of (n = 154) LBW babies (r=0.37, P < 0.0001). CONCLUSION: This study revealed significantly lower cord blood vitamin A levels in the preterm LBW babies. The level of vitamin A in LBW babies also correlated with their birth weight. There are enough evidence to support causative association between vitamin A deficiency state and neonatal morbidity. Simple interventions like vitamin A supplementation during a crucial stage of an infant's life may be beneficial in the long run. There is a need to establish norms for vitamin A levels and seriously examine the role of vitamin A supplementation for LBW babies during the immediate postnatal period.

Primary Sjogren's syndrome manifesting with distal renal tubular acidosis and severe metabolic bone disease.

Sjogren's syndrome (SS) is a chronic, autoimmune, inflammatory disorder affecting primarily the salivary and lacrimal glands with potential for systemic involvement. The disease predominantly occurs in women in the age group of 35-45 years and is relatively rare in children. It mainly affects salivary and lacrimal glands with potential for systemic involvement. Children presenting with the severe metabolic bone disease at the very outset has not been reported in the paediatric literature. We report a 13-year-old girl who presented with pain in multiple large joints with predominant involvement of hip joints leading to difficulty in walking for the past 6 months and unintentional weight loss of the same duration. Investigations revealed distal renal tubular acidosis with severe metabolic bone disease as an extra-glandular manifestation of primary SS.

Type B lactic acidosis due to Warburg effect in a child presenting with T cell acute lymphoblastic leukaemia: a milder phenotype.

Lactic acidosis (LA) is characterised by persistently increased blood lactate >5 mmol/L. Type A LA due to anaerobic glycolysis is frequently seen during management of haematological malignancies. A rare form of LA known as type B LA, which occurs as a result of metabolic dysregulation at cellular level has been described recently. This has been reported to be because of Warburg effect (WE) or aerobic glycolysis, which is seen in cancerous cells as they rely on aerobic glycolysis rather than oxidative phosphorylation for energy generation. Presence of type B LA at initial presentation of haematological malignancies is a poor prognosticating factor and has rarely been reported in children. We present a child with T cell acute lymphoblastic leukaemia with mild phenotype of type B LA due to WE. She responded dramatically to definitive chemotherapy and tolerated intensive phase of chemotherapy without any significant morbidity.