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Background Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. Methods Patients with CKD stage 2-5 and aged 5-18 years with low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145 mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, which was escalated to 20 mg/day if LDL-C remained > 100 mg/dL and/or non-HDL-C > 120 mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C [less than or equal to] 100 mg/dL and non-HDL-C [less than or equal to] 120 mg/dL) and adverse events were assessed at 24 weeks. Results Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8-63.7%) at 24 weeks; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20 mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00-1.11) and older age (OR 36.5, 95% CI 2.57-519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20 mg/day. Conclusion Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target. Graphical abstract, Author(s): Punitha Lakxmi Ramesh [sup.1] , Priyanka Khandelwal [sup.1] , R. Lakshmy [sup.2] , Aditi Sinha [sup.1] , Arvind Bagga [sup.1] , Pankaj Hari [sup.1] Author Affiliations: (1) grid.413618.9, 0000 [...]

Background Coexisting genetic variants in patients with anti-factor H (FH)-associated atypical hemolytic uremic syndrome (aHUS) have implications for therapy. We estimated the prevalence of complement genetic variants in children with anti-FH aHUS from a prospective nationwide cohort and determined if significant genetic variants impact long-term kidney outcomes. Methods Of 436 patients in the database, 77 consecutive patients, 21 with a relapse and 9 with kidney failure and/or death were included. Targeted sequencing, using a 27-gene panel including CFH, CFI, CFB, C3, CD46, PLG, DGKE, and THBD and multiplex ligation-dependent probe amplification of CFH-CFHR region, was performed. The adverse outcome was eGFR < 30 ml/min/1.73 m.sup.2 or death. Results Patients had high anti-FH titers 5670 (2177-13,545) AU/ml, relapsing course (42.1%), and adverse outcomes (19.6%). Variants, chiefly of unknown significance, were found in 7 (6.5%; 95% CI 3.1-13.2%); a pathogenic variant was found in one patient. Homozygous deletion of CFHR1 was present in 91.6% compared to 9.8% in 184 healthy controls. Plasma exchanges and immunosuppression showed a trend of improving outcomes, independent of genetic defects (HR 0.32; P = 0.070). Meta-analysis of 18 studies (384 patients) showed that the pooled prevalence of pathogenic and likely pathogenic variants was 3% (95% CI 0-8%). Of 37 total variants in the meta-analysis, 7 (18.9%) each were pathogenic and likely pathogenic; others were variants of unknown significance. Conclusions Significant variants in complement regulatory genes are rare in patients with anti-FH-associated aHUS. Irrespective of genetic defects, plasma exchanges and immunosuppression showed a statistical trend to improved outcomes. Graphical abstract, Author(s): Priyanka Khandelwal [sup.1] , Aditi Joshi [sup.2] , Aradhana Mathur [sup.2] , Mamta Puraswani [sup.1] , Bahadur Singh Gurjar [sup.1] , Aditi Sinha [sup.1] , Pankaj Hari [sup.1] , [...]

Background Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support. Methods Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically. Results We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child's suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood). Conclusions Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Yifan Zhang [sup.1] , Talia Gutman [sup.1] [sup.2] , Allison Tong [sup.1] [sup.2] , Jonathan C. Craig [sup.3] , Aditi Sinha [sup.4] , Allison Dart [sup.5] , Allison A. [...]

Author(s): Aditi Sinha [sup.1] , Arvind Bagga [sup.1] Author Affiliations: (1) grid.413618.9, 0000 0004 1767 6103, Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, [...]

Background Rituximab and tacrolimus are therapies reserved for patients with frequently relapsing or steroid-dependent nephrotic syndrome who have failed conventional steroid-sparing agents. Given their toxicities, demonstrating non-inferiority of rituximab to tacrolimus may enable choice between these medications. Methods This investigator-initiated, single-center, open-label, pilot randomized controlled trial examined the non-inferiority of two doses of intravenous (IV) rituximab given one-week apart to oral therapy with tacrolimus (1:1 allocation), in maintaining sustained remission over 12 months follow-up, in patients with difficult-to-treat steroid-sensitive nephrotic syndrome, defined as frequently relapsing or steroid-dependent disease that had failed [greater than or equal to] 2 steroid-sparing strategies. Secondary outcomes included frequency of relapses, proportion with frequent relapses, time to relapse and frequent relapses, and adverse events (CTRI/2018/11/016342). Results Baseline characteristics were comparable for 41 patients randomized to receive rituximab (n = 21) or tacrolimus (n = 20). While 55% of patients in each limb were in sustained remission at 1 year, non-inferiority of rituximab to tacrolimus was not demonstrated (mean difference 0%; 95% CI - 30.8%, 30.8%; non-inferiority limit - 20%; P = 0.50). Frequent relapses were more common in patients administered rituximab compared to tacrolimus (risk difference 30%, 95% CI 7.0, 53.0, P = 0.023). Both groups showed similar reductions in relapse rates and prednisolone use. Common adverse events were infusion-related with rituximab and gastrointestinal symptoms with tacrolimus. Conclusions Therapy with rituximab was not shown to be non-inferior to 12-months treatment with tacrolimus in maintaining remission in patients with difficult-to-treat steroid-sensitive nephrotic syndrome. Frequent relapses were more common with rituximab. While effective, both agents require close monitoring for adverse events. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Georgie Mathew [sup.1] , Aditi Sinha [sup.1] , Aijaz Ahmed [sup.1] , Neetu Grewal [sup.1] , Priyanka Khandelwal [sup.1] , Pankaj Hari [sup.1] , Arvind Bagga [sup.1] Author Affiliations: [...]

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 m.sup.2; 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. Graphical abstract, Author(s): Priyanka Khandelwal [sup.1] , Sudarsan Krishnasamy [sup.1] , Srinivasavaradan Govindarajan [sup.1] , Manish Kumar [sup.2] , Binata Marik [sup.1] , Aditi Sinha [sup.1] , Pankaj Hari [sup.1] , Arvind [...]

Academic stress is the most common mental state that medical students experience during their training period. To assess academic stress, to find out its determinants, to assess other sources of stress and to explore the various coping styles against academic stress adopted by students. Methods: It was a cross sectional study done among medical students from first to fourth year. Standard self-administered questionnaires were used to assess academic stress and coping behaviour. Mean age of the 400 participants was 20.3 ± 1.5 years. 166(41.5%) of them were males. The academic stress was found to be of mild, moderate and severe level among 68(17%), 309(77.3%) and 23(5.7%) participants respectively. Overall coping with stress was found to be poor, average and good among 15(3.8%), 380(95%) and 5(1.2%) participants respectively. Passive emotional (p = 0.054) and passive problem (p = 0.001) coping behaviours were significantly better among males. Active problem coping behaviour (p = 0.007) was significantly better among females. Active emotional coping behaviour did not vary significantly between genders (p = 0.54). Majority of the students preferred sharing their personal problems with parents 211(52.7%) followed by friends 202(50.5%). Binary logistic regression analysis found worrying about future (p = 0.023) and poor self-esteem (p = 0.026) to be independently associated with academic stress. Academic stress although a common finding among students, the coping style to deal with it, was good only in a few. The coping behaviours were not satisfactory particularly among male participants. This along with other determinants of academic stress identified in this study need to be addressed during counselling sessions., Author(s): Nitin Joseph [sup.1] [sup.2] , Aneesha Nallapati [sup.2] [sup.3] , Mitchelle Xavier Machado [sup.2] [sup.3] , Varsha Nair [sup.2] [sup.3] , Shreya Matele [sup.2] [sup.3] , Navya Muthusamy [sup.2] [...]

Background Distal renal tubular acidosis (RTA) is typically caused by defects in ATP6V0A4, ATP6V1B1, and SLC4A1, accounting for 60-80% of patients. Genes recently implicated include FOXI1, ATP6V1C2, and WDR72, of which WDR72 is associated with dental enamel defects. Methods We describe 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Distal tubular acidification was evaluated by furosemide-fludrocortisone test, urine-to-blood PCO2 gradient and fractional excretion of bicarbonate. Exome sequencing was performed using a panel of genes implicated in human disease. Results Patients had polyuria, hypokalemia, hypercalciuria, and nephrocalcinosis, but metabolic acidosis varied in severity. Although all patients acidified urine to pH < 5.3 during furosemide-fludrocortisone test, urine-to-blood PCO.sub.2 gradient was < 20 mmHg during bicarbonate loading. All patients had transient proximal tubular dysfunction with urinary losses of phosphate and beta-2-microglobulin, and generalized aminoaciduria. Homozygous pathogenic truncating variants in WDR72 was detected in all probands. Conclusion Patients with WDR72 mutations show mild rate-dependent distal RTA with variable metabolic acidosis, and intact ability to acidify the urine on provocative testing. Concomitant proximal tubular dysfunction may be present. Mutations in WDR72 should be considered in patients with suspected distal RTA, especially if associated with dental defects., Author(s): Priyanka Khandelwal [sup.1] Mahesh V [sup.1] , Vijay Prakash Mathur [sup.2] , Sumantra Raut [sup.1] , Thenral S. Geetha [sup.3] , Sandhya Nair [sup.3] , Pankaj Hari [sup.1] , [...]

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]

Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given., Author(s): Agnes Trautmann [sup.1] , Marina Vivarelli [sup.2] , Susan Samuel [sup.3] , Debbie Gipson [sup.4] , Aditi Sinha [sup.5] , Franz Schaefer [sup.1] , Ng Kar Hui [sup.6] , [...]

Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality. [ABSTRACT FROM AUTHOR]

Background While patients with frequently relapsing nephrotic syndrome (FRNS) are initially treated with long-term alternate-day prednisolone, relapses and adverse effects are common. In an open-label randomized controlled trial, we compared the efficacy of therapy with low-dose daily to standard alternate-day prednisolone in reducing relapse rates over 12-month follow-up. Methods Consecutive patients, aged 2-18 years, with FRNS were included. Following therapy of relapse, prednisolone was tapered to 0.75 mg/kg on alternate days. Stratifying for steroid dependence, patients were randomly assigned to prednisolone at 0.2-0.3 mg/kg daily or 0.5-0.7 mg/kg alternate day for 12 months. Relapses were treated with daily prednisolone, followed by return to intervention. Primary outcome was the incidence of relapses. Proportion with therapy failure ([greater than or equal to] 2 relapses in any 6 months or significant steroid toxicity) and sustained remission, cumulative prednisolone intake and adverse events were evaluated. Results Patients receiving daily prednisolone (n = 30) showed significantly fewer relapses than those on alternate-day therapy (n = 31) (0.55 relapses/person-year versus 1.94 relapses/person-year; incidence rate ratio 0.28; 95% CI 0.15, 0.52). Daily therapy was associated with higher rates of sustained remission at 6 months (73.3 versus 48.4%) and 1 year (60 versus 31.6%; log rank p = 0.013), lower rates of treatment failure at 6 months (3.3 versus 32.8%) and 1 year (6.7 versus 57.4%; p < 0.0001), and lower prednisolone use (0.27 ± 0.07 versus 0.39 ± 0.19 mg/kg/day; p = 0.003). Three and two patients need to receive the study intervention to enable sustained remission and prevent treatment failure, respectively. Conclusions In patients with FRNS, daily administration of low-dose prednisolone is more effective than standard-dose alternate day therapy in lowering relapse rates, sustaining remission, and enabling steroid sparing., Author(s): Menka Yadav [sup.1] , Aditi Sinha [sup.1] , Priyanka Khandelwal [sup.1] , Pankaj Hari [sup.1] , Arvind Bagga [sup.1] Author Affiliations: (Aff1) 0000 0004 1767 6103, grid.413618.9, Division of [...]

Background Dyslipidemia is an important cardiovascular risk factor in steroid-resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of hyperlipidemia in children with SRNS is unclear. Methods This prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial enrolled 30 patients with SRNS, aged 5-18 years, with serum low-density lipoprotein cholesterol (LDL-C) levels between 130 and 300 mg/dl, to receive a fixed dose of atorvastatin (n = 15, 10 mg/d) or placebo (n = 15) by block randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12 months. Change in levels of other lipid fractions, carotid intima-media thickness (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events were also evaluated. Results At the end of 12 months, atorvastatin was not superior to placebo in reducing plasma LDL-C levels, median percentage reduction 15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in modified intention-to-treat analysis (P = 0.01) but not in the per-protocol analysis. There was no significant effect on other lipid fractions, cIMT and FMD. Adverse events were similar between groups. Change in serum albumin was negatively associated with change in serum LDL-C, very low-density lipoprotein cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P < 0.001), irrespective of receiving atorvastatin, age, gender, body mass index, and serum creatinine. Conclusions Atorvastatin, administered at a fixed daily dose of 10 mg, was not beneficial in lowering lipid levels in children with SRNS; rise in serum albumin was associated with improvement in dyslipidemia., Author(s): Pankaj Hari [sup.1] , Priyanka Khandelwal [sup.1] , Amit Satpathy [sup.1] , Smriti Hari [sup.1] , Ranjeet Thergaonkar [sup.1] , R Lakshmy [sup.2] , Aditi Sinha [sup.1] , Arvind [...]

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]

Author(s): Sudarsan Krishnasamy [sup.1] , Aditi Sinha [sup.1] , Arvind Bagga [sup.1] Author Affiliations: (1) grid.413618.9, 0000 0004 1767 6103, Division of Nephology, Department of Pediatrics, All India Institute of [...]