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Background: Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA)., Methods: Our study enrolled children diagnosed with WDR72-dRTA below 18 years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored., Results: We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76 mL/min/1.73 m 2 , respectively, after 11.3-16 years of follow-up. No specific genotype-phenotype correlation could be established., Conclusions: WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study aimed to describe the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals., Study Design: Qualitative study., Settings & Participants: 120 children with CKD (aged 8-21 years), 250 parents, and 445 health professionals from 53 countries participated in 16 focus groups, two consensus workshops, and a Delphi survey., Analytical Approach: A thematic analysis of all qualitative data concerning growth from the Standardized Outcomes in Nephrology - Children and Adolescents (SONG-Kids) initiative., Results: We identified five themes: diminishing psychological wellbeing (compared to and judged by peers, tired of explaining to others, damaging self-esteem), constrained life participation and enjoyment (deprived of normal school experiences, excluded from sports or competing at a disadvantage, impaired quality of life in adulthood); grappling with impacts of symptoms and treatment (difficulty understanding short stature and accessing help, lack of appetite, uncertainty regarding bone pains, medication side effects, burden of growth hormone treatment); facilitating timely interventions and optimizing outcomes (early indicator of disease, assessing management, maximizing transplant outcomes, minimizing morbidity); and keeping growth and health priorities in perspective (quality of life and survival of utmost priority, achieved adequate height)., Limitations: Only English-speaking participants were included., Conclusions: Impaired growth may diminish psychological wellbeing, self-esteem, and participation in daily activities for children with CKD. Balancing different treatments that can affect growth complicates decision-making. These findings may inform the psychosocial support needed by children with CKD and their caregivers to address concerns about growth., (Copyright © 2024. Published by Elsevier Inc.)

The study focused on Syzygium cumini Leaf Extract (SCLE) loaded into Carboxymethylcellulose (CMC) film via Solution casting. Phytochemical screening revealed carbohydrates, and HPLC analysis identified quercetin, known for promoting wound healing. FT-IR spectroscopy confirmed various functional groups. X-Ray diffraction (XRD) determined the crystallite size to be 14.58 nm. Field Emission Scanning Electron Microscopy (FESEM) showed the dispersion of extracts, and Energy Dispersive X-ray (EDX) analysis detailed the weight percentages of components. Antibacterial activity tests revealed zones of inhibition for S. aureus (15 mm) and E. coli (11 mm). The film exhibited 63.11 % antioxidant activity at 517 nm with DPPH at a 750 μl sample concentration. Drug release kinetics were also studied. In-vitro wound healing using the L929 cell line showed 83 % healing at a 100 μl concentration. Over 14 days, the treatment group's wounds healed completely within 7 days, unlike the control groups which showed no recovery after 14 days. These findings indicate that the SCLE-CMC film is highly effective in promoting wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: There is a paucity of pooled synthesized data on the epidemiology of neonatal acute kidney injury (AKI). Our objective with this study is to systematically assess the worldwide incidence of AKI in neonates., Methods: We searched 3 electronic databases (Embase, PubMed, Web of Sciences) from January 2004 to December 2022 without language restrictions. We included cohort and cross-sectional studies that reported the incidence of AKI or associated mortality in neonates. Eligible studies had at least 10 participants and used standard criteria (Acute Kidney Injury Network/Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE)/ Kidney Disease Improving Global Outcomes) to define AKI. Two authors independently retrieved data on demographic characteristics, clinical setting, and outcomes (incidence and AKI-associated mortality) using a semi-structured proforma and assessed the risk of bias. We used a random-effects meta-analysis to calculate pooled estimates with 95% confidence intervals., Results: We included 201 studies (98 228 participants) from 45 countries. The incidence of any stage AKI was 30% (95% confidence interval 28-32), and that of severe AKI was 15% (14-16). Overall, AKI-associated mortality was 30% (27-33). The odds of mortality were higher (odds ratio 3.4; 2.9-4.0) in neonates with AKI compared with those without AKI. We found that perinatal asphyxia, sepsis, patent ductus arteriosus, necrotizing enterocolitis, and nephrotoxic medications were significant risk factors for AKI. Significant heterogeneity in the pooled estimates was a limitation of this study., Conclusions: AKI was observed in one-third of the neonates and was associated with increased risk of mortality. The incidence of AKI was almost similar in neonates with perinatal asphyxia and sepsis, but mortality was higher in the former group., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Plasma exchanges (PEX) and immunosuppression are the cornerstone of management of anti-factor H (FH) antibody-associated atypical hemolytic uremic syndrome (aHUS), particularly if access to eculizumab is limited. The duration of therapy with PEX for anti-FH aHUS is empirical., Methods: We compared the efficacy of abbreviated PEX protocol (10-12 sessions) in a prospective cohort of patients diagnosed with anti-FH aHUS (2020-2022), to standard PEX protocol (20-22 sessions) in a historical cohort (2016-2019; n = 65). Efficacy was defined as 70% decline in anti-FH titers or fall to ≤ 1300 AU/ml at 4 weeks. Patients in both cohorts received similar immunosuppression with oral prednisolone, IV cyclophosphamide (5 doses) and mycophenolate mofetil. Outcomes included efficacy, rates of hematological remission and adverse kidney outcomes at 1, 3 and 6 months., Results: Of 23 patients, 8.2 ± 2.1 years old enrolled prospectively, two were excluded for significant protocol deviation. PEX was abbreviated in 18/21 (86%) patients to 11.5 ± 3.3 sessions. Abbreviation failed for lack of hematological remission by day 14 (n = 2) and persistent neurological manifestations (n = 1). All patients in whom PEX was abbreviated achieved > 70% reduction in anti-FH titers at day 28. The percentage fall in anti-FH titers was similar for the abbreviated vs. standard PEX protocols at 1, 3 and 6 months. At last follow-up, at median 50 months and 25 months for standard and abbreviated cohorts, the estimated GFR was similar at 104.8 ± 29.1 vs. 93.7 ± 53.4, respectively (P = 0.42)., Conclusion: Abbreviation of the duration of PEX is feasible and efficacious in reducing anti-FH titers. Short-term outcomes were comparable in patients managed by abbreviated and standard PEX protocols., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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.

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 > 10 4 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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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 m 2 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., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited., Methods: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated., Results: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy., Conclusions: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Saliva components combine with oral cavity microorganisms, blood cells, and airway secretions after entering the oral cavity via salivary ducts; these factors provide relevant information about persons' health state, quality of life, and lifestyle, in addition to their age and gender due to which salivary microbiome has emerged as a subject of significant interest in the forensic domain. This study aims to provide an extensive review of the possible applications of the salivary microbiome in characterizing the habit-specific microbiomes. Thirty-three relevant articles were selected for inclusion in this study. The study highlighted the influence of habits on the salivary microbiome suggesting smokers have distinct bacteria like Synergistetes, Streptococcus, Prevotella, and Veillonella in relation to age; people of higher age have more Prevotella; further, dental plaque can be corelated with Streptococci and Actinomycetes. Likewise, dietary habits, alcoholism, and consumption of coffee also affect bacteria types in oral cavities. The study underscores the added benefits of salivary microbiome profiling in forensics, as it is evident that microbial DNA profiling holds substantial promise for enhancing forensic investigations; it enables the characterization of an individual's habits, such as smoking, alcohol consumption, and dietary preferences; bacteria specific to these habits can be identified, thereby helping to narrow down the pool of potential suspects. In conclusion, the salivary microbiome presents a valuable avenue for forensic science, offering a novel approach which not only enhances the prospects of solving complex cases but also underscores the rich potential of microbiome analysis in the realm of forensic investigation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: 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., Main Part: 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., Conclusion: 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.

Idiopathic nephrotic syndrome is the most common glomerular disease in children. Corticosteroids are the cornerstone of its treatment, and steroid response is the main prognostic factor. Most children respond to a cycle of oral steroids, and are defined as having steroid-sensitive nephrotic syndrome. Among the children who do not respond, defined as having steroid-resistant nephrotic syndrome, most respond to second-line immunosuppression, mainly with calcineurin inhibitors, and children in whom a response is not observed are described as multidrug resistant. The pathophysiology of nephrotic syndrome remains elusive. In cases of immune-mediated origin, dysregulation of immune cells and production of circulating factors that damage the glomerular filtration barrier have been described. Conversely, up to a third of cases of steroid-resistant nephrotic syndrome have a monogenic origin. Multidrug resistant nephrotic syndrome often leads to kidney failure and can cause relapse after kidney transplant. Although steroid-sensitive nephrotic syndrome does not affect renal function, most children with steroid-sensitive nephrotic syndrome have a relapsing course that requires repeated steroid cycles with significant side-effects. To minimise morbidity, some patients require steroid-sparing immunosuppressive agents, including levamisole, mycophenolate mofetil, calcineurin inhibitors, anti-CD20 monoclonal antibodies, and cyclophosphamide. Close monitoring and preventive measures are warranted at onset and during relapse to prevent acute complications (eg, hypovolaemia, acute kidney injury, infections, and thrombosis), whereas long-term management requires minimising treatment-related side-effects. A subset of patients have active disease into adulthood., Competing Interests: Declaration of interests MV provides scientific advice or participates in sponsored clinical trials for Novartis, Travere, Apellis, Roche, Biocryst, Chemocentrix, Bayer, Alexion, GlaxoSmithKline, and Purespring. OB provides scientific advice or participates in sponsored clinical trials for Alexion, Alnylam, Biocodex, Bristol-Myers Squibb, GlaxoSmithKline, Purespring, Roche, Sanofi, Takeda, and Travere/Vifor. KG provides scientific advice or receives research support for Travere, Aurinia, and Genentech. AS declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited., Methods: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5., Results: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel., Conclusions: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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 ≤ 100 mg/dL and non-HDL-C ≤ 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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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 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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenia purpura (TTP) are rare diseases sharing a common pathological feature, thrombotic microangiopathy (TMA). TMA is characterized by microvascular thrombosis with consequent thrombocytopenia, microangiopathic hemolytic anemia and/or multiorgan dysfunction. In the past, the distinction between HUS and TTP was predominantly based on clinical grounds. However, clinical presentation of the two syndromes often overlaps and, the differential diagnosis is broad. Identification of underlying pathogenic mechanisms has enabled the classification of these syndromes on a molecular basis: typical HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS); atypical HUS or complement-mediated TMA (aHUS/CM-TMA) associated with genetic or acquired defects leading to dysregulation of the alternative pathway (AP) of complement; and TTP that results from a severe deficiency of the von Willebrand Factor (VWF)-cleaving protease, ADAMTS13. The etiology of TMA differs between pediatric and adult patients. Childhood TMA is chiefly caused by STEC-HUS, followed by CM-TMA and pneumococcal HUS (Sp-HUS). Rare conditions such as congenital TTP (cTTP), vitamin B12 metabolism defects, and coagulation disorders (diacylglycerol epsilon mutation) present as TMA chiefly in children under 2 years of age. In contrast secondary causes and acquired ADAMT13 deficiency are more common in adults. In adults, compared to children, diagnostic delays are more frequent due to the wide range of differential diagnoses. In this review we focus on the three major forms of TMA, STEC-HUS, aHUS and TTP, outlining the clinical presentation, diagnosis and management of the affected patients, to help highlight the salient features and the differences between adult and pediatric patients which are relevant for management., Competing Interests: Declaration of Competing Interest RD has received honoraria from Alexion Pharmaceuticals for contributing to a publishing project. MN has received honoraria from Alexion Pharmaceuticals for giving lectures and for participating in advisory boards, and she has received research grants from Omeros, Gemini, Novartis and BioCryst Pharmaceuticals. GR has consultancy agreements with AbbVie, Alexion Pharmaceuticals, Novartis Pharma and BioCryst Pharmaceuticals., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We received a call from a transplant coordinator about the availability of a consented deceased donor. En-bloc kidneys with the aorta and IVC (inferior vena cava) were harvested from a toddler weighing 8 kg. The recipient was of early childhood weighing 14 kg who had been on haemodialysis for the last 3 years for end-stage kidney disease. He received anti-thymocyte globulin as an induction immunosuppressant. The kidneys were transplanted en bloc in the right lower quadrant retroperitoneal region; an anastomosis was performed to the recipient's aorta and IVC, and two separate neocystoureterostomies were created. His serum creatinine reached 0.5 mg/dL on the seventh postoperative day, following a few days of delayed graft function. In this study, we describe the surgical and non-surgical challenges that we faced while performing en-bloc kidney transplant to the youngest recipient and how a multidisciplinary team approach helped us overcome them., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute kidney injury (AKI) is common in critically ill patients, affecting almost one in four critically ill children and one in three neonates. Higher stages of AKI portend worse outcomes. Identifying AKI timely and instituting appropriate measures to prevent and manage severe AKI is important, since it is independently associated with mortality. Methods to predict severe AKI should be applied to all critically ill patients. Assessment of volume status to prevent the development of fluid overload is useful to prevent adverse outcomes. Patients with metabolic or clinical complications of AKI need prompt kidney replacement therapy (KRT). Various modes of KRT are available, and the choice of modality depends most on the technical competence of the center, patient size, and hemodynamic stability. Given the significant risk of chronic kidney disease, patients with AKI require long-term follow-up. It is important to focus on improving awareness about AKI, incorporate AKI prevention as a quality initiative, and improve detection, prevention, and management of AKI with the aim of reducing acute and long-term morbidity and mortality., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations., (© 2023. The Author(s).)

Objectives: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children., Methods: Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5 th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography., Results: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died., Conclusions: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

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.)

Background: Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome., Methods: We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs)., Results: Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy., Conclusions: Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Objectives: To provide up-to-date information on the use of long-term ventilation (LTV) in the UK paediatric population and to compare the results with data collected 10 and 20 years previously., Design: A single timepoint census completed by LTV centres in the UK, carried out via an online survey., Setting and Patients: All patients attending paediatric LTV services in the UK., Results: Data were collected from 25 LTV centres in the UK. The total study population was 2383 children and young people, representing a 2.5-fold increase in the last 10 years. The median age was 9 years (range 0-20 years). Notable changes since 2008 were an increase in the proportion of children with central hypoventilation syndrome using mask ventilation, an increase in overall numbers of children with spinal muscular atrophy (SMA) type 1, chronic lung disease of prematurity and cerebral palsy being ventilated, and a 4.2-fold increase in children using LTV for airway obstruction. The use of 24-hour ventilation, negative pressure ventilation and tracheostomy as an interface had declined. 115 children had received a disease-modifying drug. The use of ataluren and Myozyme did not influence the decision to treat with LTV, but in 35% of the children with SMA type 1 treated with nusinersin, the clinician stated that the use of this drug had or may have influenced their decision to initiate LTV., Conclusion: The results support the need for national database for children and young people using LTV at home to inform future recommendations and assist in resource allocation planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The present paper reports 10 patients (9 families) with Fanconi-Bickel syndrome managed during 2010-2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, β 2 -microglobinuria, urinary phosphate wasting, and hypercalciuria were present in all patients; 3 patients had nephrocalcinosis. Other metabolic abnormalities included hypertriglyceridemia (n = 5/6), fasting hypoglycemia (n = 5/8), and postprandial hyperglycemia (n = 3/6). Genetic analysis showed 7 homozygous or compound heterozygous variants in SLC2A2. A pathogenic variant c.952G>A, common to 4 patients (3 families), might be a potential hotspot. At a median follow-up of 43 mo, 4 patients died at a median of 25 mo; short stature persisted in all except one patient who showed catch-up growth with uncooked corn-starch diet. The present findings suggest that the Fanconi-Bickel syndrome has a severe phenotype with an unsatisfactory outcome. A high index of suspicion for diagnosis and efforts for facilitation of dietary therapy are necessary., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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.)

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 ≥ 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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

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 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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Advances in kidney genomics in the past 20 years has opened the door for more precise diagnosis of kidney disease and identification of new and specific therapeutic agents. Despite these advances, an imbalance exists between low-resource and affluent regions of the world. Individuals of European ancestry from the United States, United Kingdom, and Iceland account for 16% of the world's population, but represent more than 80% of all genome-wide association studies. South Asia, Southeast Asia, Latin America, and Africa together account for 57% of the world population but less than 5% of genome-wide association studies. Implications of this difference include limitations in new variant discovery, inaccurate interpretation of the effect of genetic variants in non-European populations, and unequal access to genomic testing and novel therapies in resource-poor regions. It also further introduces ethical, legal, and social pitfalls, and ultimately may propagate global health inequities. Ongoing efforts to reduce the imbalance in low-resource regions include funding and capacity building, population-based genome sequencing, population-based genome registries, and genetic research networks. More funding, training, and capacity building for infrastructure and expertise is needed in resource-poor regions. Focusing on this will ensure multiple-fold returns on investments in genomic research and technology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale & Objective: Clinical decision-making priorities may differ among children, their parents, and their clinicians. This study describes clinicians' perspectives on shared decision making in pediatric chronic kidney disease (CKD) and identifies opportunities to improve shared decision making and care for children with CKD and their families., Study Design: Semistructured interviews., Setting & Participants: Fifty clinicians participated, including pediatric nephrologists, nurses, social workers, surgeons, dietitians, and psychologists involved in providing care to children with CKD. They worked at 18 hospitals and 4 university research departments across 11 countries (United States of America, Canada, Australia, People's Republic of China, United Kingdom, Germany, France, Italy, Lithuania, New Zealand, and Singapore)., Analytical Approach: Interview transcripts were analyzed thematically., Results: We identified 4 themes: (1) striving to blend priorities (minimizing treatment burden, emphasizing clinical long-term risks, achieving common goals), (2) focusing on medical responsibilities (carrying decisional burden and pressure of expectations, working within system constraints, ensuring safety is foremost concern), (3) collaborating to achieve better long-term outcomes (individualizing care, creating partnerships, encouraging ownership and participation in shared decision making, sensitive to parental distress), and (4) forming cumulative knowledge (balancing reassurance and realistic expectations, building understanding around treatment, harnessing motivation for long-term goals)., Limitations: Most clinicians were from high-income countries, so the transferability of the findings to other settings is uncertain., Conclusions: Clinicians reported striving to minimize treatment burden and working with children and their families to manage their expectations and support their decision making. However, they are challenged with system constraints and sometimes felt the pressure of being responsible for the child's long-term outcomes. Further studies are needed to test whether support for shared decision making would promote strategies to establish and improve the quality of care for children with CKD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Monogenic lupus is a subset of lupus caused by single-gene disorders, integrating the paradoxical combination of autoimmunity and immunodeficiency. Pulmonary manifestations with recurrent pneumonia and bronchiectasis have rarely been described as the predominant presentation of juvenile lupus and may suggest an alternate differential like primary immunodeficiency, especially in early childhood. We describe a case of 10-year girl who presented with a history of recurrent pneumonia, arthritis, alopecia, and poor weight gain for the past 2 years. On examination, she had respiratory distress, bilateral diffuse crackles and arthritis of the small joints of hands. Lab investigations showed pancytopenia, low complement levels and high titers of ANA and anti-dsDNA antibodies. The patient was diagnosed with juvenile lupus. Imaging studies revealed evidence of multiple lobar collapse and consolidation with bronchiectasis. She was started on steroids, HCQ and supportive measures for bronchiectasis. The child reported relief in initial symptoms of lupus on follow-up but developed recurrent thrombocytopenia requiring IVIG and escalating the doses of oral steroids. The young age and atypical presentation prompted a screening for monogenic lupus, and clinical exome sequencing revealed a novel homozygous missense variation in exon 20 of the C4Agene with clinically reduced C4 levels, consistent with the diagnosis of C4A deficiency., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nutritional vitamin D deficiency is the most frequent cause of rickets followed by genetic causes, that include entities like classic hypophosphatemic rickets (FGF23 related), Dent disease, Fanconi syndrome, renal tubular acidosis, and vitamin D dependent rickets. Hypophosphatemia is a feature in all these forms. The diagnosis relies on a combination of clinical, biochemical and radiological features, but genetic testing is required to confirm the diagnosis. We screened 66 patients with hypophosphatemic rickets referred to this center between May 2015 and July 2019 using whole exome sequencing (WES) in addition to the measurement of their intact serum fibroblast growth factor 23 (FGF23) levels. WES revealed 36 pathogenic and 28 likely pathogenic variants in 16 different genes (PHEX, FGF23, DMP1, ENPP1, CLCN5, CTNS, SLC2A2, GATM, SLC34A1, EHHADH, SLC4A1, ATP6V1B1, ATP6V0A4, CYP27B1, VDR and FGFR1) in 63 patients which helped differentiate between the various forms of hypophosphatemic rickets. Intact serum FGF23 levels were significantly higher in patients with variations in PHEX, FGF23, DMP1 or ENPP1 genes. The major genetic causes of rickets were classic hypophosphatemic rickets with elevated FGF23 levels, distal renal tubular acidosis, and vitamin D dependent rickets. Based on the present results, we propose a customized gene panel for targeted exome sequencing, which will be useful for confirming the diagnosis in most patients with hypophosphatemic rickets., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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.

Craniopagus conjoined twins are extremely rare, reported 1 in 2.5 million live births. To date, 62 separation attempts in 69 well-documented cases of craniopagus twins have been made. Of these, 34 were performed in a single-stage approach, and 28 were attempted in a multistage approach. One or both twins died of massive intraoperative blood loss and cardiac arrest in 14 cases. We report our surgical experience with conjoined craniopagus twins (JB) with type III total vertical joining and shared circumferential/circular sinus with left-sided dominance. A brief review of the literature is also provided. In our twins, the meticulous preoperative study and planning by the multidisciplinary team consisting of 125-member, first-staged surgical separation consisted of creation of venous conduit to bypass part of shared circumferential sinus and partial hemispheric disconnection. Six weeks later, twin J manifested acute cardiac overload because of one-way fistula development from blocked venous bypass graft necessitating emergency final separation surgery. Unique perioperative issues were abnormal anatomy, hemodynamic sequelae from one-way fistula development after venous bypass graft thrombosis, cardiac arrest after massive venous air embolism requiring prolonged cardiopulmonary resuscitation, and return of spontaneous circulation at 15 minutes immediately after separation. This is the first Indian craniopagus separation surgery in a complex total vertical craniopagus twin reported by a single-center multidisciplinary team. Both twins could be sent home, but one remained severely handicapped. Adequate perioperative planning and multidisciplinary team approach are vital in craniopagus twin separation surgeries., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema., Methods: Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5-1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy., Results: A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8-1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia., Conclusion: The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status., (© 2021. Dr. K C Chaudhuri Foundation.)

Background: More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care., Methods: Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology-Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8-21 years) and caregivers (of children ages 0-21 years) pertaining to blood pressure., Results: Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects)., Conclusions: For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

A previously healthy boy of preschool age was brought to the emergency department by ambulance with respiratory distress following the accidental inhalation of food contact dust (cake decorating powder). Prehospital oxygen saturations were 80% in room air. Initial treatment was with oxygen, nebulised salbutamol, oral dexamethasone and intravenous amoxicillin/clavulanic acid. Treatment was escalated to nasal high flow oxygen therapy and high dependency care within 8 hours. Lung fields on his initial chest X-ray were clear but the following day showed perihilar infiltrates extending into the lower zones in keeping with inflammation. He was treated with intravenous methylprednisolone, followed by a weaning dose of oral prednisolone over 14 days.He required oxygen therapy for 9 days and remained in hospital for 11 days. Outpatient follow-up, 24 days after the inhalation took place was reassuring with the child showing no signs of abnormal respiratory symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Information on the course of SARS-CoV-2 infection in children with chronic kidney disease (CKD) is limited., Methods: We retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in patients with CKD followed at any of the four pediatric nephrology centers in New Delhi from April 2020 to June 2021. Outcomes, including cardiopulmonary and renal complications, were reported in relation to underlying disease category and illness severity at presentation., Results: Underlying illness in 88 patients included nephrotic syndrome (50%), other CKD stages 1-4 (18.2%), CKD 5D (17%), and CKD 5T (14.8%). Thirty-two of 61 patients with symptomatic COVID-19 and 9/27 asymptomatic patients were admitted for median 10 (interquartile range 7-15) days. Seventeen (19.3%) patients developed moderate or severe COVID-19. Systemic complications, observed in 30 (34.1%), included acute kidney injury (AKI, 34.2%), COVID-19 pneumonia (15.9%), unrelated pulmonary disease (2.3%), and shock (4.5%). Nineteen (21.6%) had severe complications (AKI stage 2-3, encephalopathy, respiratory failure, shock). Eight (11%) of twelve (16.4%) patients with severe AKI required dialysis. Three (3.4%) patients, two with steroid-resistant nephrotic syndrome in relapse and one with CKD 1-4, died due to respiratory failure. Univariate logistic regression indicated that patients presenting with nephrotic syndrome in relapse or moderate to severe COVID-19 were at risk of AKI (respective odds ratio, 95%CI: 3.62, 1.01-12.99; 4.58, 1.06-19.86) and/or severe complications (respective odds ratio, 95%CI: 5.92, 1.99-17.66; 61.2, 6.99-536.01)., Conclusions: Children with CKD presenting with moderate-to-severe COVID-19 or in nephrotic syndrome relapse are at risk of severe complications, including severe AKI and mortality. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. IPNA.)