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Background: The etiology of atypical hemolytic uremic syndrome (aHUS) is unknown in 30–40% of patients. Anti-factor B (FB) antibodies are reported in C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN), though not in aHUS. Methods: We screened patients < 18-year-old from cohorts of aHUS and C3G/idiopathic IC-MPGN. Anti-FB IgG antibodies were measured by ELISA and confirmed by Western blot. Normative levels were based on antibody levels in 103 healthy blood donors. Results: Prevalence of anti-FB antibodies was 9.7% (95% CI 6.1–14.5%; n = 21) in 216 patients with aHUS, including 11.5% (95% CI 6.4–18.5%; n = 14) in anti-FH associated aHUS and 11.8% (95% CI 4.4–23.9%; n = 6) in patients without a definitive genetic or autoimmune etiology. Patients with significant genetic variants did not show anti-FB antibodies. In patients with concomitant anti-FB and anti-FH antibodies, median anti-FH titers were higher (11,312 AU/mL vs. 4920 AU/mL; P = 0.04). Anti-FB antibody titer correlated with disease severity (hemoglobin and platelets; P < 0.05), declined following plasma exchange and increased during relapse. While 4/64 patients with C3G (6.3%) and 1/17 with IC-MPGN showed anti-FB antibodies, titers were higher in aHUS (544.8 AU/mL vs. 1028.8 AU/mL; P = 0.003). Conclusion: Anti-FB antibodies are present in 6–10% of patients with aHUS and C3G/IC-MPGN, with higher titers in the former. The diagnostic and therapeutic implication of anti-FB antibodies in aHUS needs confirmation and further studies. The study shows propensity for autoantibody generation and co-existence of multiple risk factors for aHUS in Indian children. [ABSTRACT FROM AUTHOR]

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7–10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3–5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Over the years, survival of children with chronic diseases has significantly improved and a large proportion of them now are entering into adulthood. Transition of Care (ToC) of such patients with having childhood onset of chronic diseases to the adult health care system is well organized in developed countries, although it is an emerging concept in India. In situations where the systems for ToC are not in place, such cases are fraught with unsatisfactory health outcomes. With proper ToC in place, these patients are likely to receive uninterrupted care by the adult care physicians and hence reach their full potential. This document highlights the need, rationale and way forward for ToC of youth with special health care needs (YSHCN) across the country. It also describes the standard operating procedures to develop the ToC at a hospital level for clinicians and administrators. [ABSTRACT FROM AUTHOR]

This article explores the option of restructuring a corporate debtor through sale as a going concern in liquidation, as opposed to the corporate insolvency resolution process. Although the existing insolvency law in India treats liquidation as a matter of last resort, this article argues that if sale as a going concern in liquidation entails a higher realisation for the creditors, it should be viewed as an equally viable and beneficial option for restructuring. However, this would necessitate overhauling the existing insolvency regime to allow the stakeholders to assess and select the best option for themselves and the corporate debtor. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of autoantibody generation in anti-factor H (FH) antibody associated atypical hemolytic uremic syndrome (aHUS) is unknown and is perhaps triggered by an infectious or environmental agent. We observed an unusual increase of patients with anti-FH antibody associated aHUS coinciding with the second pandemic wave in New Delhi and suspected that SARS-CoV-2 infection might be a potential trigger. Methods: We screened for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction (RT-PCR) and serology in 13 consecutive patients with anti-FH antibody associated aHUS during the past year in New Delhi. Results: We report 5 patients, 4–13 years old, who presented with a febrile illness without respiratory symptoms during the second pandemic wave. Of these, 3 patients presented with a relapse 25–85 months following the initial episode of aHUS. SARS-CoV-2 was detected by RT-PCR in 1 patient and by serology in 4 patients (median titer 47.1 cut-off index). Patients had high titers of anti-FH antibodies (median 2,300 AU/ml). Genetic studies, done in 3 of the 5 patients, showed homozygous CFHR1 deletion without other significant genetic abnormalities. Specific management comprised plasma exchanges and oral prednisolone, combined with either cyclophosphamide or mycophenolate mofetil. At median follow-up of 3.3 months, the estimated glomerular filtration rate in 4 patients ranged from 62 to 110 ml/min/1.73 m2; one patient was dialysis-dependent. Conclusion: Increased vigilance is required during the pandemic, especially in patients with anti-FH associated aHUS, who might relapse despite quiescent disease for a prolonged period. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) refers to numbness, tingling, and burning sensation caused by chemotherapy that can cause impairment in Quality of Life (QoL) of the patients. Study assesses severity, risk factors, and quality of life of patients associated with CIPN. A cross sectional descriptive study was conducted at day care ward, tertiary care hospital India. Total of 98 patients receiving paclitaxel for ≥4 months were enrolled by convenient sampling. Data regarding demographics and clinical characteristics, CIPN severity, risk factors, and QoL were collected by structured questionnaires. Study revealed that median score of autonomic symptoms was higher than sensory and motor symptoms. Mean score of FACT/GOG-Ntx sub-domain was 99.05 ± 20.87on a scale of 0 to 152. ECOG Performance status, current exercise behavior, and fruit and vegetable intake was found to be significantly (at p <.05) associated with sensory, motor, and autonomic symptom score. Therefore, CIPN was found to have debilitating effect on QoL. [ABSTRACT FROM AUTHOR]

Objective: Information on etiology of congenital nephrotic syndrome in non-Caucasian populations is limited. This study aimed to determine the genetic basis of congenital nephrotic syndrome in Indian patients. Methods: In this observational, cross-sectional study, whole exome sequencing was performed on samples from all children diagnosed with congenital nephrotic syndrome, presenting at centers collaborating in a nationwide registry and biorepository. Analysis was targeted to focus on reported or novel, pathogenic or likely pathogenic variants in 89 genes implicated in etiology of nephrotic syndrome. Sanger sequencing was used to confirm disease-causing variants in patients and allelic segregation of compound heterozygous variants in samples from parents. Inheritance of a shared haplotype was analyzed among ten individuals carrying the most common variant. Results: During 2017–2019, 34 patients with congenital nephrotic syndrome were screened. Consanguinity and similar illness in siblings were reported in eleven patients each. Homozygous or compound heterozygous, pathogenic or likely pathogenic variants were found in NPHS1 in 24 cases, including two novel variants. One patient each had homozygous pathogenic or likely pathogenic known or novel variant in NPHS2, PLCE1, OSGEP and LAMB2 genes. Patients with OSGEP and LAMB2 mutations had phenotype typical of Galloway Mowat and Pierson syndromes, respectively. Three variants in NPHS1 were common to 16 individuals. One reported variant in exon 19 (c.2600G>A; p.Gly867Asp) appears to share a common founder. Conclusion: A genetic cause was determined for 82.4% patients with congenital nephrotic syndrome. Variants in NPHS1 are most common in Indian patients and founder mutations might be present. [ABSTRACT FROM AUTHOR]

Background: Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. Methods: Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. Results: An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. Conclusions: Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima-media thickness (cIMT) and brachial artery flow-mediated dilation (FMD). Information on the association of these parameters with dyslipidemia in pre-dialysis pediatric CKD is limited. Methods: Eighty patients aged 9.9 ± 3.2 years, with estimated glomerular filtration rate of 38.8 ± 10.8 ml/1.73 m/min, and 42 pediatric controls underwent cross-sectional analysis of lipid profile, cIMT, and brachial artery FMD. Significant differences in these parameters between patients and controls were analyzed using Student's t test. Predictors of cIMT and dyslipidemia were assessed using linear and logistic regression respectively. Results: Patients had elevated blood levels of triglyceride and of total and LDL cholesterol than controls ( P ≤ 0.001); 73.8 % were dyslipidemic. Mean cIMT was higher (0.421 ± 0.054 mm vs 0.388 ± 0.036 mm, P = 0.001) and brachial artery FMD was reduced (10.6 ± 4.9 % vs 18.9 ± 4.1 %, P < 0.0001) in patients compared with controls. On multivariate analysis, hypertension (OR 3.68, P = 0.044) and male gender (OR 10.21, P = 0.004) were associated with dyslipidemia; cIMT was significantly associated with LDL cholesterol (β = 28.36, P = 0.033). Conclusion: Dyslipidemia was prevalent and cIMT significantly elevated in pre-dialysis pediatric CKD, indicating increased cardiovascular risk. Elevated LDL cholesterol predicted increased cIMT, strengthening the association between dyslipidemia and atherosclerosis in early CKD. [ABSTRACT FROM AUTHOR]

Background: Anti-complement factor H (anti-CFH) antibody-associated hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in Indian children. While management comprises plasma exchange and immunosuppression, information on the impact on serial antibody titers and outcomes is limited. Methods: This retrospective study included 45 patients with anti-CFH-associated HUS who were followed for ≥12 months. Following the initial plasma exchange sessions, patients received prednisolone and either intravenous (IV) cyclophosphamide ( n = 31) or IV rituximab ( n = 14), followed by maintenance immunosuppression. Results: The median anti-CFH antibody titers fell from 3,215.5 [interquartile range (IQR) 1,977.9-8,453.9 to 414.6 (IQR 251.6-1,368.2) AU/ml with plasma exchange therapy ( P < 0.0001), and the decline was similar with three, five, or seven plasma exchange sessions ( P = 0.08). Serial anti-CFH titers were similar in patients receiving IV cyclophosphamide- and rituximab-based regimens during the 12-month follow-up ( P = 0.63). Renal outcomes and relapse frequencies at the 15.4-month follow-up were comparable. Seven patients relapsed 6.5 (IQR 2.2-12.3) months from treatment onset. Patients with relapse had higher antibody titers during remission ( P = 0.017). Titers of ≥1,300 AU/ml at 6 months predicted subsequent relapses. Conclusions: Our patients with anti-CFH antibody-associated HUS showed a significant fall in antibody titers following daily plasma exchange sessions. Therapy with cyclophosphamide- or rituximab-based regimens was associated with similar outcomes and a comparable decline in antibody titers. [ABSTRACT FROM AUTHOR]

While studies show that prolonged initial prednisone therapy reduces the frequency of relapses in nephrotic syndrome, they lack power and have risk of bias. In order to examine the effect of prolonged therapy on frequency of relapses, we conducted a blinded, 1:1 randomized, placebo-controlled trial in 5 academic hospitals in India on 181 patients, 1-12 years old, with a first episode of steroid-sensitive nephrotic syndrome. Following 12 weeks of standard therapy, in random order, 92 patients received tapering prednisolone while 89 received matching-placebo on alternate days for the next 12 weeks. On intention-to-treat analyses, primary outcome of number of relapses at 1 year was 1.26 in the 6-month group and 1.54 in the 3-month group (difference −0.28; 95% confidence interval (CI) −0.75, 0.19). Relative relapse rate for 6- vs. 3-month therapy, adjusted for gender, age, and time to initial remission, was 0.70 (95% CI 0.47-1.10). Similar proportions of patients had sustained remission, frequent relapses, and adverse effects due to steroids. Adjusted hazard ratios for first relapse and frequent relapses with prolonged therapy were 0.57 (95% CI, 0.36-1.07) and 1.01 (95% CI, 0.61-1.67), respectively. Thus, extending initial prednisolone treatment from 3 to 6 months does not influence the course of illness in children with nephrotic syndrome. These findings have implications for guiding the duration of therapy of nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is characterized by acute- or subacute-onset encephalopathy with extrapyramidal, psychiatric, and epileptic manifestations. Diagnosis is confirmed by positive antibodies to NMDA receptor in cerebrospinal fluid and serum. Eleven pediatric cases presented over a 2-year period at a tertiary care teaching hospital in North India. The average age at presentation was 9 years (range: 2.5 to 18 years, median: 10 years) with a slight female predominance (1.2:1). The common modes of presentation were progressive extrapyramidal syndrome with global neuroregression in 45% (5 of 11), epileptiform encephalopathy in 27% (3 of 11), and an overlap between the 2 in 27% (3 of 11). Fifty-eight percent showed significant response to steroids and intravenous immunoglobulin. This entity should be considered in an acute- or subacute-onset encephalopathy if common infectious etiologies are ruled out and there are specific clinical pointers. Early diagnosis and treatment significantly improves the outcome. [ABSTRACT FROM PUBLISHER]

Background: Parkinson's disease is the second most common progressive neurodegenerative disorder. Knowledge plays a vital role in providing optimal care based on the different needs of a person with Parkinson's disease. Care givers are the primary care providers at home. Technological advances help the transition of care back to the home. Video-assisted teaching is an effective method, which improves the knowledge. Objective: The objective of the present study is to develop video-assisted teaching on home care management and to assess its effectiveness on the knowledge of the care givers and also to assess the patients' satisfaction regarding the care given by the care givers after delivering video-assisted teaching. Methods: Preexperimental one group; pretest--posttest design. The study was done on patients with PD and their care givers from a movement disorder clinic/neurology OPD of a tertiary care teaching hospital in India over the period September 2020--December 2020. The tools used for data collection were a self-structured knowledge questionnaire for care givers and a satisfaction scale for patients. Both tools were validated and found reliable. The video on home care management was locally developed and validated by subject experts. One-to-one video-assisted teaching was given by the nursing professional. Results: We included 45 patients and 45 corresponding care givers. Data were analyzed using descriptive and inferential statistics. In total, 47% of the care givers belong to the age group of 21--40 years, and 64% of the patients were in the age group of more than 60 years. Care givers knowledge scores improved from baseline (12.77 + 4.51) to (26.57 + 2.38, P < 0.001) immediately after intervention and 1 month after intervention (23.64 + 2.31, P < 0.001). Care givers demonstrate that variables did not correlate with knowledge. Patients significant improved from baseline (23.08 + 5.81) to (40.49 + 3.33, P < 0.001) after 1 month. Conclusion: The video-assisted teaching module on home care management improved the knowledge of care givers and enhanced the satisfaction of patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence and outcome of acute kidney injury (AKI) in hospitalized patients. Design: Prospective, observational. Setting: Tertiary care center in North India. Participants/patients: Inpatients, 1 month to 18-yr-old. Intervention: None. Main Outcome Measures: Incidence of AKI based on the serum creatinine criteria proposed by the AKI Network. Results: During February to September 2008, thirty nine of 108 (36.1%) critically ill patients and 34 of 378 (9.0%) patients who were not critically ill developed AKI ( P <0.001); the respective incidence densities were 45.1 and 11.7 cases/1000 patient days, respectively. The maximal stage of AKI was stage 1 in 48 (65.8%) patients, stage 2 in 13 (17.8%) and stage 3 in 12 (16.4%) patients; 11 (15.1%) required dialysis. Patients with AKI had a significantly longer duration of hospital stay (9 days vs 7 days, P<0.02) and higher mortality (37% vs 8.7%; hazard ratio, HR 2.73; 95% CI 1.64, 4.54). Independent risk factors for AKI were young age (HR 0.89; 95% CI 0.83, 0.95), shock (HR 2.65; 95% CI 1.32, 5.31), sepsis (HR 3.64; 95% CI 2.20, 6.01), and need for mechanical ventilation (2.18; 95% CI 1.12, 4.26). Compared to patients without AKI, the mortality was higher for AKI stage 2 (HR 5.18; 95% CI 2.59, 10.38) and stage 3 (HR 4.34; 95% CI 2.06, 9.16). Shock was an independent risk factor for mortality (HR 10.7; 95% CI 4.96, 22.98). Conclusions: AKI is common in critically ill children, especially younger patients with septicemia and shock, and results in increased hospital stay and high mortality. [ABSTRACT FROM AUTHOR]

Although therapy with intravenous (IV) rituximab and tacrolimus reduces the relapse rate in steroid-dependent nephrotic syndrome (SDNS), studies on comparative efficacy are lacking. We retrospectively reviewed the records of patients with difficult-to-treat SDNS who had previously received levamisole, cyclophosphamide and/or mycophenolate mofetil, then treated with either rituximab or tacrolimus and followed for 12 months. Between January 2009 and April 2010, ten patients received two to three doses of IV rituximab (375 mg/m/week) and 13 received tacrolimus (0.1-0.2 mg/kg/day) for 12 months; none had previously received either agent. Patients received tapering doses of alternate-day prednisolone; other immunosuppressive agents were discontinued. The mean age of the patients at treatment initiation with rituximab and tacrolimus was 12.2 ± 2.3 and 12.3 ± 3.0 years, respectively. The respective pre-treatment relapse rates (3.1 ± 1.1 and 3.5 ± 1.6 relapses per year) and cumulative prednisolone dose (137.2 ± 69.4 and 140.5 ± 59.0 mg/kg/year) were similar. Therapy resulted in a decline in relapse rate in both groups ( P < 0.001). The number of relapses in the rituximab and tacrolimus groups was similar at 6 months (0.3 ± 0.5 vs. 0.3 ± 0.6 episodes, respectively), 12 months (0.8 ± 1.0 vs. 0.9 ± 1.1 episodes) and last follow-up (1.2 ± 1.0 vs. 1.5 ± 1.3 episodes). There were no differences in relapse-free survival at 6, 12 and 18 months. Therapy resulted in a significant decline in the cumulative prednisolone dose (67.2% in the rituximab group and 43.6% in the tacrolimus group) and a reduced body mass index. These findings suggest that in our patients with difficult-to-treat SDNS, treatment with two to three doses of rituximab was as effective as 12 months of therapy with tacrolimus in terms of steroid sparing and reduction in the relapse rate. [ABSTRACT FROM AUTHOR]

Sinha A, Hari P, Guleria S, Gulati A, Dinda AK, Mehra NK, Srivastava RN, Bagga A. Outcome of pediatric renal transplantation in north India. Pediatr Transplantation 2010: 14:836-843. © 2010 John Wiley & Sons A/S. We report our experience and long-term outcome of pediatric renal transplantation at a referral center in New Delhi. During 1995-2008, 45 transplants were performed in 43 patients at a mean age of 13.3 ± 4.0 (range 3.8-18) yr. The chief causes for ESRD were reflux nephropathy, obstructive uropathy, vasculitis, renal dysplasia, and focal segmental glomerulosclerosis. Most (91.1%) donors were living related. Post-transplant immunosuppression comprised prednisolone, a calcineurin inhibitor and azathioprine or MMF. AR and CR were seen in 14 (31.1%) and 12 (26.7%) allografts, respectively. Predictors of CR were unsatisfactory compliance and multiple episodes of AR (p = 0.002 each). Urinary infections (n = 13), septicemia (4), tuberculosis (4), CMV disease (7), viral hepatitis (7), and pneumonia (3) were important causes of morbidity. Two patients each had lymphoproliferative disease and new-onset diabetes. There were eight (17.8%) graft losses and six (14%) deaths. The one-, five- and 10-yr graft survivals were 91.1%, 80.4% and 75.1%, respectively; the mean graft survival was 119.4 ± 8.38 months. The respective patient survivals were 95.3%, 87.9%, and 76.9% at one-, five- and 10 yr. Our results affirm that despite scarcity of resources and frequent infections, long-term outcomes of pediatric renal transplantation are highly satisfactory. [ABSTRACT FROM AUTHOR]

Background & objectives: Vitamin D deficiency with a resurgence of rickets and tetany are increasingly being reported in young infants from temperate regions, African Americans and also from India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. Therefore, we undertook this study to determine the prevalence of vitamin D deficiency and insufficiency [serum 25 hydroxyvitamin D (25OHD) ≤ 15 ng/ml and 15-20 ng/ml, respectively] among healthy term breastfed 3 month old infants and their mothers, evaluate for clinical and radiological rickets in those infants having 25OHD < 10 ng/ml, and check for seasonal variation and predictors of infants' vitamin D status. Methods: A total of 98 infants aged 2.5 to 3.5 months, born at term with appropriate weight and their mothers were enrolled: 47 in winter (November- January) and 51 in summer (April-June). Details of infants' feeding, vitamin D supplementation, sunlight exposure and mothers' calcium and vitamin D intake were recorded. Serum calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25OHD) and parathormone were estimated. Results: Vitamin D deficiency was found in 66.7 per cent of infants and 81.1 per cent of mothers; and insufficiency in an additional 19.8 per cent of infants and 11.6 per cent of mothers. Radiological rickets was present in 30.3 per cent of infants with 25OHD < 10 ng/ml. 25OHD did not show seasonal variation in infants but maternal concentrations were higher in summer [11.3 (2.5 - 31) ng/ml] compared to winter [5.9 (2.5-25) ng/ml, P=0.003]. Intake of vitamin supplement, sunlight exposure and mother's 25OHD were predictors of infants' 25OHD levels. Interpretation & conclusions: Prevalence of vitamin D deficiency and insufficiency was found to be high in breastfed infants and their mothers, with radiological rickets in a third of infants with 25OHD < l0 ng/ml in this study. Studies with large sample need to be done in different parts of the country to confirm these findings. [ABSTRACT FROM AUTHOR]

Guidelines recommend initiating supplemental enteral feeding through a nasogastric (NG) or gastrostomy tube (G-tube) in patients with chronic kidney disease who have inadequate oral intake despite repeated nutritional counseling. While G-tube placement is shown to improve both nutritional status and anthropometric indices of children with CKD in developed regions, information from developing countries is lacking. This retrospective report reviewed the impact of G-tube feeding on nutritional intakes and anthropometric parameters over a 1-y follow-up in 5 children with CKD-5D managed at one tertiary care center in India. Gastrostomy feeding facilitated significant increments in caloric and protein intake and was easy and safe. However, G-tube feeding led to additional expenses, and the changes in growth parameters were variable in the short term. A longer follow-up appears necessary to understand its impact on wasting, growth velocity, and stature., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India., Methods: The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database., Results: Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001)., Conclusion: The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: To describe the perspectives on life participation by young adults with childhood-onset chronic kidney disease (CKD)., Design: Semi-structured interviews; thematic analysis., Setting: Multiple centres across six countries (Australia, Canada, India, UK, USA and New Zealand)., Participants: Thirty young adults aged 18 to 35 years diagnosed with CKD during childhood., Results: We identified six themes: struggling with daily restrictions (debilitating symptoms and side effects, giving up valued activities, impossible to attend school and work, trapped in a medicalised life, overprotected by adults and cautious to avoid health risks); lagging and falling behind (delayed independence, failing to keep up with peers and socially inept); defeated and hopeless (incapacitated by worry, an uncertain and bleak future, unworthy of relationships and low self-esteem and shame); reorienting plans and goals (focussing on the day-to-day, planning parenthood and forward and flexible planning); immersing oneself in normal activities (refusing to miss out, finding enjoyment, determined to do what peers do and being present at social events); and striving to reach potential and seizing opportunities (encouragement from others, motivated by the illness, establishing new career goals and grateful for opportunities)., Conclusions: Young adults encounter lifestyle limitations and missed school and social opportunities as a consequence of developing CKD during childhood and as a consequence lack confidence and social skills, are uncertain of the future, and feel vulnerable. Some re-adjust their goals and become more determined to participate in 'normal' activities to avoid missing out. Strategies are needed to improve life participation in young adult 'graduates' of childhood CKD and thereby strengthen their mental and social well-being and enhance their overall health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues., Results: We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono- and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

Background: Infection with Plasmodium vivax, a common human parasite, is occasionally recognized to cause severe organ dysfunction similar to P. falciparum infection. Acute kidney injury (AKI) in malaria is attributed to acute tubular necrosis; thrombotic microangiopathy is not described., Methods: This observational study includes patients referred to a tertiary care center in North India during June to September 2011 with severe AKI, anemia, and thrombocytopenia following vivax malaria. Renal biopsies were processed by light, immunofluorescence, and electron microscopy., Results: Nine patients (including 5 children) had persistent AKI with thrombocytopenia and variable anemia following the diagnosis of malaria. Based on peripheral smear, eight patients were diagnosed with vivax malaria and had received antimalarial therapy prior to referral; a laboratory diagnosis of P. vivax infection was made for one patient at this center. Renal histology in all cases showed features of thrombotic microangiopathy, including fibrin thrombi, subendothelial widening, and mesangiolysis, along with variable tubulointerstitial nephritis and acute tubular or cortical necrosis. Ultrastructural examination confirmed endothelial injury and subendothelial widening. All patients required hemodialysis, and six were dialysis dependent at four weeks. Delayed presentation to the hospital (P = 0.019), hemolysis on peripheral smear (P = 0.083), and prolonged oligoanuria (P = 0.036) were associated with dialysis dependence., Conclusion: The association of anemia, thrombocytopenia, and renal histological evidence of thrombotic microangiopathy with vivax malaria is novel, and suggests the presence of severe endothelial injury. Further studies are necessary to confirm the association and examine the factors associated with its occurrence.

Objective: To review the disease course in patients with steroid sensitive nephrotic syndrome (SSNS) and the factors that determine outcome, Design: Retrospective, analytical, Setting: Pediatric Nephrology Clinic at referral center in North India, Participants/patients: All patients with SSNS evaluated between 1990 and 2005 INTERVENTION: None, Main Outcome Measures: Disease course, in patients with at least 1-yr follow up, was categorized as none or infrequent relapses (IFR), frequent relapses or steroid dependence (FR), and late resistance. Details on complications and therapy with alternative agents were recorded., Results: Records of 2603 patients (74.8% boys) were reviewed. The mean age at onset of illness and at evaluation was 49.7±34.6 and 67.5±37.9 months respectively. The disease course at 1-yr (n=1071) was categorized as IFR in 37.4%, FR in 56.8% and late resistance in 5.9%. During follow up, 224 patients had 249 episodes of serious infections. Alternative medications for frequent relapses (n=501; 46.8%) were chiefly cyclophosphamide and levamisole. Compared to IFR, patients with FR were younger (54.9±36.0 vs. 43.3±31.4 months), fewer had received adequate (=8 weeks) initial treatment (86.8% vs. 81.7%) and had shorter initial remission (7.5±8.6 vs. 3.1±4.8 months) (all P<0.001). At follow up of 56.0±42.6 months, 77.3% patients were in remission or had IFR, and 17.3% had FR., Conclusions: A high proportion of patients with SSNS show frequent relapses, risk factors for which were an early age at onset, inadequate initial therapy and an early relapse.

There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for idiopathic steroid-resistant nephrotic syndrome in children. To clarify this, we compared tacrolimus and intravenous cyclophosphamide therapy in a multicenter, randomized, controlled trial of 131 consecutive pediatric patients with minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis, stratified for initial or late steroid resistance. Patients were randomized to receive tacrolimus for 12 months or 6-monthly infusions of intravenous cyclophosphamide with both arms receiving equal amounts of alternate-day prednisolone. The primary outcome of complete or partial remission at 6 months, based on spot urine protein to creatinine ratios, was significantly higher in children receiving tacrolimus compared to cyclophosphamide (hazard ratio 2.64). Complete remission was significantly higher with tacrolimus (52.4%) than with cyclophosphamide (14.8%). The secondary outcome of sustained remission or steroid-sensitive relapse of nephrotic syndrome at 12 months was significantly higher with tacrolimus than cyclophosphamide. Treatment withdrawal was higher with cyclophosphamide, chiefly due to systemic infections. Compared to cyclophosphamide, 3 patients required treatment with tacrolimus to achieve 1 additional remission. Thus, tacrolimus and prednisolone are effective, safe, and preferable to cyclophosphamide as the initial therapy for patients with steroid-resistant nephrotic syndrome.

Background: Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma., Objective: To investigate the association of inducible nitric oxide synthases (iNOS) gene repeat polymorphisms with asthma., Methods: 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex., Results: A total of four repeats-a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)-were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p < 0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p < 0.001) and nitric oxide levels (p = 0.03)., Conclusion: This is the first study to identify the repeat polymorphisms in the iNOS gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis.