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BackgroundData on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited.MethodsIn this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged <18-years with C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n = 51), tacrolimus (n = 11), and/or IV cyclophosphamide (n = 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRcr < 15 mL/min/1.73 m2 or death) were evaluated.ResultsA total of 92 patients were classified as DDD (n = 48, 52.2%), C3GN (n = 26, 28.3%), and IC-MPGN (n = 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3 years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset < 2.5 g/dL (HR = 0.29, P = 0.005) and persistently low serum C3 (HR = 0.34, P = 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P = 0.006). Presentation as rapidly progressive GN (HR = 11.2, P < 0.001), age > 10 years at onset (HR = 4.0, P = 0.004), and DDD (HR = 4.2, P = 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P < 0.001).ConclusionOutcome in patients with C3 glomerulopathy and IC-MPGN was unsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.

Children with steroid-resistant nephrotic syndrome (SRNS) are exposed to multiple cardiovascular risk factors predisposing them to accelerated atherosclerosis. This risk is negligible in steroid-sensitive nephrotic syndrome, but a substantial proportion of children with SRNS progress to chronic kidney disease, exacerbating the already existing cardiovascular risk. While dyslipidemia is an established modifiable risk factor for cardiovascular disease in adults with NS, it is uncertain to what extent analogous risks exist for children. There is increasing evidence of accelerated atherosclerosis in children with persistently high lipid levels, especially in refractory NS. Abnormalities of lipid metabolism in NS include hypertriglyceridemia and hypercholesterolemia due to elevated apolipoprotein B-containing lipoproteins, decreased lipoprotein lipase and hepatic lipase activity, increased hepatic PCSK9 levels, and reduced hepatic uptake of high-density lipoprotein. Existing guidelines for the management of dyslipidemia in children may be adapted to target lower lipid levels in children with NS, but they will most likely require both lifestyle modifications and pharmacological therapy. While there is a lack of data from randomized controlled trials in children with NS demonstrating the benefit of lipid-lowering drugs, therapies including statins, bile acid sequestrants, fibrates, ezetimibe, and LDL apheresis have all been suggested and/or utilized. However, concerns with the use of lipid-lowering drugs in children include unclear side effect profiles and unknown long-term impacts on neurological development and puberty. The recent introduction of anti-PCSK9 monoclonal antibodies and other therapies targeted to the molecular mechanisms of lipid transport disrupted in NS holds promise for the future treatment of dyslipidemia in NS.

A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56–1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28–0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29–0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56–1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21–0.69).Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions. What is Known: • Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance. • Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults.What is New: • Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract. • Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population.

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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

BackgroundDistal 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.MethodsWe 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.ResultsPatients 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 PCO2 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.ConclusionPatients 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.

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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required. Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year ( = 317) were compared to before ( = 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity ( = 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset. Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank = 0.022). Mean anti-FH titers stayed 700-1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission [Generalized estimating equations (GEE), = 0.001]; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3; = 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23; = 0.024), time to PEX ≥14 days (HR 2.09; = 0.071) and PEX for <14 days (HR 2.60; = 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37; = 0.026); maintenance therapy reduced risk of relapses (HR 0.11; < 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively. Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.

Background miRNAs are non-coding RNA that are recognized as biomarkers of kidney disorders. There is limited information on the differential expression of miRNA and their target genes in idiopathic nephrotic syndrome of childhood. Methods We enrolled patients, 2–18 years old, with steroid-sensitive nephrotic syndrome, either at onset or during relapse, and steroid-resistant disease, at diagnosis of steroid-resistance. Patients with steroid-sensitive disease were off immunosuppressive medications, while those with steroid-resistance were on therapy with prednisolone at enrollment. Controls were healthy children attending the hospital for vaccinations or for minor non-infectious, non-kidney ailments. Following RNA extraction from whole blood, differential expression of 2549 miRNAs was examined to identify differentially expressed miRNA, defined as those with absolute log 2 fold change > 2 and adjusted P  < 0.05. Target genes, predicted using miRNet, were compared against the genes for nephrotic syndrome in the NCBI database, and the ontology of selected genes was examined using DAVID. Results Comparison of miRNA expression in 36 patients and 12 controls led to the identification of 62 and 12 differentially expressed miRNA in patients with steroid-sensitive and steroid-resistant disease, respectively. Of 76 miRNAs that were differentially regulated between the two disease categories, 26 were unique to steroid-sensitive disease and 11 to steroid-resistance. Of 5955 and 2813 genes targeted by the miRNAs specific to steroid-sensitive and steroid-resistant nephrotic syndrome, respectively, 79 were relevant in context of the disease. Conclusion Steroid-sensitive and steroid-resistant nephrotic syndrome have distinct miRNA expression profiles, which can be examined as biomarkers and in pathogenetic pathways.

Objective: Surgical site infections (SSIs) owing to nontuberculous Mycobacteria (NTM) have emerged as an important cause of hospital-acquired SSI leading to great morbidity and mortality. Among NTM, Mycobacterium abscessus is reported in these sites. Epidemiology and transmission of M. abscessus in humans is noticing crux changes. Case report: We hereby describe a case of SSI after lower segment cesarean section (LSCS), presenting as a skin and soft tissue infection (SSTI) owing to a NTM. Conclusion: Clinicians should be aware of the possibility of infections caused by M. abscessus in patients who develop SSIs, particularly if they do not respond to conventional first-line antimicrobial therapy.

Background The benefits of long-term low-dose antibiotics in preventing urinary tract infection (UTI) and renal damage in children with primary vesicoureteric reflux (VUR) are unclear. Methods Children aged between 1 and 12 years with VUR grade I–IV and a microbiologically proven UTI were randomized into two groups to receive either antibiotic prophylaxis [2 mg/kg trimethoprim + sulfamethoxazole (TMP-SMX)] daily or placebo, respectively, for 12 months. Primary outcome was microbiologically confirmed symptomatic UTI. Intention-to-treat analysis using time-to-event data was performed. Results A total of 93 children (66.7 % boys) with a median age of 4.6 years were enrolled in this study; VUR grade III–IV was present in 73.1 % of these children. At least one symptomatic UTI occurred in ten (21.3 %) patients receiving antibiotic prophylaxis and in three (6.5 %) patients receiving placebo [hazard ratio in antibiotic group 3.9; 95 % confidence interval (CI) 1– 14; log rank test P  = 0.02). Compared to the group receiving placebo, the antibiotic group had a 14.8 % increased risk for developing UTI (95 % CI 1–28; P  = 0.03). Of the total number of episodes of UTI, 58.3 % of those in the antibiotic group were caused by TMP-SMX-resistant bacteria compared to 20 % in the placebo group ( P  = 0.15). A renal scan at 12 months revealed that six of 37 (16.2 %) patients in the antibiotic group and seven of 43 (16.3 %) patients in the placebo group had new or worsening of pre-existing scar. Conclusions Long-term antibiotic prophylaxis with TMP-SMX is associated with increased risk of symptomatic UTI compared to placebo in children with grade I–IV VUR.