Abbreviated protocol of plasma exchanges for patients with anti-factor H associated hemolytic uremic syndrome.

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.

Etiology and Outcome of Community-Acquired Acute Kidney Injury in Pediatric Inpatients.

OBJECTIVE: To estimate the etiology, outcome, and risk factors for mortality in children with community-acquired acute kidney injury (CA-AKI). METHODS: Between October, 2020 and December, 2021, consecutive hospitalized children aged 2 mo-12 years with a minimum 24 hours of stay, and at least one serum creatinine level measured at or within 24 hours of hospitalization were prospectively enrolled. CA-AKI was labelled in children with an elevated serum creatinine level at admission and subsequent fall during hospitalization. RESULTS: Of 2780 children, 215 were diagnosed as CA-AKI (7.7%, 95% CI 6.7-8.6). Diarrhea with dehydration (39%) and sepsis (28%) were the most common causes of CA-AKI. 24 children (11%) died during hospitalization. Requirement of inotropes was an independent predictor of mortality. Out of 191 children discharged, 168 (88%) had complete renal recovery. At 3 months, out of 22 children without complete renal recovery, 10 progressed to chronic kidney disease (CKD), with 3 becoming dialysis dependent. CONCLUSION: CA-AKI is common in hospitalized children, and is associated with increased risk of progression to CKD, especially in those with incomplete renal recovery.

Identification of Probable Urinary Tract Infection in Children Using Low Bacterial Count Thresholds in Urine Culture.

OBJECTIVE: To assess the proportion of children, symptomatic for urinary tract infection (UTI), with urine culture showing single bacterial species >104 CFU/mL, and to compare patient and disease characteristics between children having low counts (from >104-105 CFU/mL) and those with counts >105 CFU/mL. METHODS: Prospective observational study, enrolling symptomatic children aged 1 month to 12 years. Mid-stream clean-void or catheter collected urine were cultured. Children with single species >104 CFU/mL were scheduled for imaging studies, following age criteria of Indian Society of Pediatric Nephrology guidelines. The main outcome was proportion with single bacterial species >104 CFU/mL in urine culture. RESULTS: Of 216 children (132 males) with median (IQR) age of 24 (12, 48) months, 38 (17.6%) showed single species growth >104 CFU/mL. Of these, 29 (13.4%) were diagnosed as UTI at cutoff >105 CFU/mL, and an additional 9 (4.2%) were found to have 'probable low-count UTI' (from >104 to 105 CFU/mL). One child in the latter group had bilateral hydroureteronephrosis, vesico-ureteral reflux and renal scarring. There was largely no difference in parameters between children with low counts and those with counts >105 CFU/mL. CONCLUSIONS: An additional proportion of symptomatic children with probable urinary tract infection and possible underlying urological abnormalities may be identified by lowering bacterial colony count cutoff to >104 CFU/mL, in clean-voided and catheter-based urine samples.

SARS-CoV-2 infection in children with chronic kidney disease.

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.

Clinico-Etiologic Profile of Macroscopic Hematuria in Children: A Single Center Experience.

OBJECTIVE: To study the demographic, clinical and etiological profile of macroscopic hematuria in children presenting to a tertiary care hospital. METHODS: This prospective observational study, conducted between January, 2018 and December, 2019, enrolled children aged 3 months to 12 years, presenting with gross hematuria. RESULTS: Of the 62 children (44 males) enrolled, (mean (SD) age of 7.3 (2.6) years), glomerular hematuria was seen in 59.7%. Post-infectious glomerulonephritis was the commonest etiology of glomerular hematuria; hypercalciuria and renal calculi predominated among non-glomerular hematuria. After a median (IQR) follow up of 8 (6,14.2) months, microscopic hematuria persisted in 10 (7, glomerular hematuria) children. The median time to resolution of gross as well as microscopic hematuria tended to be longer in glomerular etiologies. CONCLUSION: Majority of children with gross hematuria had glomerular etiologies, thus requiring monitoring and follow-up.

Publication Ethics.

Publications in the field of medical literature are a matter of prestige and fame for doctors. While genuine research contributes to the existing scientific knowledge, fraudulent data make publication unreliable, demeans the credibility of the author and reduces faith in science. Research misconduct includes the three cardinal sins fabrication, falsification and plagiarism. To promote highest standards in publication ethics, Committee on Publication Ethics provides advice and guidance to journals and publishers. Investigators should abide by ethical norms during the conduct of the research. Journals also maintain editorial standards and have well-defined policies for responding to misconduct. With an increase in medical publications over the years, it is important for all stakeholders to abide by publication ethics, in order to uphold the sanctity of research and credence in science.

Low-dose versus conventional-dose prednisolone for nephrotic syndrome relapses: a randomized controlled non-inferiority trial.

BACKGROUND: Reduction of steroid exposure in relapses of steroid-sensitive nephrotic syndrome (SSNS) is under-researched. METHODS: In this randomized controlled non-inferiority trial, 1-12-year-old children with relapse of SSNS were randomized to receive prednisolone 1 mg/kg/day (low dose) or 2 mg/kg/day (standard dose) until disease remission or day 15, whichever was earlier. Therapy was switched to 2 mg/kg/day in children in low-dose group not in remission by day 15. Primary outcome was days to remission, and secondary outcome being pattern of subsequent relapse(s) over 1 year. Estimating time to remission of 8 ± 2.5 days with standard-dose therapy, non-inferiority margin of 2 days, 90% power, and α-0.05, 60 patients were randomized. RESULTS: Of the 60 children (30 in each group) enrolled, 4 (one in low-dose group) failed remission by day 15. Time to remission was comparable between low-dose and standard-dose groups [9.0 ± 2.2 vs. 8.6 ± 2.2 days; mean difference (95% CI) 0.4 (- 0.79 to 1.59) days; p = 0.49], thus establishing non-inferiority of low dose. Median time to subsequent relapse was 86 (IQR 74.8, 97.2) and 150 (IQR 59.0, 240.9) days, in low- versus standard-dose groups, respectively (log rank p = 0.39). In follow-up, proportion of children having relapses, frequency of relapses, proportion with frequent relapse/steroid dependent (FR/SD), and cumulative corticosteroid dose taken were comparable between groups. CONCLUSIONS: This study shows that time to achieve remission after treatment of a relapse with low-dose prednisolone is non-inferior to that after treatment with conventional dose in children with SSNS. The proportion of children achieving remission, further course, and pattern of relapses was comparable between both groups.

Steroid Sensitive Nephrotic Syndrome: Revised Guidelines.

JUSTIFICATION: Steroid sensitive nephrotic syndrome (SSNS) is one of the most common chronic kidney diseases in children. These guidelines update the existing Indian Society of Pediatric Nephrology recommendations on its management. OBJECTIVE: To frame revised guidelines on diagnosis, evaluation, management and supportive care of patients with the illness. PROCESS: The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by review of literature and evaluation of evidence by experts in two face-to-face meetings. RECOMMENDATIONS: The initial statements provide advice for evaluation at onset and follow up and indications for kidney biopsy. Subsequent statements provide recommendations for management of the first episode of illness and of disease relapses. Recommendations on the use of immunosuppressive strategies in patients with frequent relapses and steroid dependence are accompanied by suggestions for step-wise approach and plan of monitoring. Guidance is also provided regarding the management of common complications including edema, hypovolemia and serious infections. Advice on immunization and transition of care is given. The revised guideline is intended to improve the management and outcomes of patients with SSNS, and provide directions for future research.

Reliable cerebrospinal fluid cytology reporting over an extended period: Is it possible by adding formol saline and ethylenediaminetetraacetic acid as cell preservative?

BACKGROUND: Reporting cerebrospinal fluid (CSF) cytology within a narrow time frame is crucial as it is often indicated in critically ill patients and moreover, the cells in CSF are highly labile and tend to decline rapidly on standing. However, due to various logistic issues, delay in reporting is inevitable at times, especially if ancillary tools are required. In this study, we examine the effect of using formol saline and ethylenediaminetetraacetic acid (EDTA) as a preservative on the cellular composition of CSF at 18, 24, and 48 hours of preservation. METHODS: Thirty CSF specimens were examined within 2 hours of collection and this reading was recorded as time zero reading. The CSF specimens were then divided in three tubes with: (a) preservative:CSF ratio of 1:1; (b) preservative:CSF ratio of 1:5; and (c) no preservative. Total and differential leucocyte counts and immunocytochemistry were performed on the three specimens at 18, 24, and 48 hours and were compared with the readings at 0 hour. RESULTS: Preserved CSF (in the ratio of 1:5) showed no significant decrease in the number of cells at 18 hours (P = .4), 24 hours (P = .3), and 48 hours (P = .1). Cellularity decreased by 8.5%, 22%, and 40% at 18, 24, and 48 hours, respectively. Cell morphology and antigenicity were well preserved at all the three time intervals. CONCLUSION: Formol saline and EDTA, when mixed with the CSF in the ratio of 1:5, can preserve significant cellularity for up to 24 hours.

Prediction of Severe Acute Kidney Injury using Renal Angina Index in a Pediatric Intensive Care Unit.

OBJECTIVE: To determine the proportion of children in a pediatric intensive care unit with a positive Day 0 Renal angina index who develop severe acute kidney injury (AKI) on Day 3; and to compare the predictive ability of the index with that of individual markers of renal injury, for the development of severe acute kidney injury. DESIGN: Observational study. SETTING: Pediatric intensive care unit of a tertiary-care hospital. PARTICIPANTS: Consecutive children, 1 month to 12 years, admitted in Level 3 pediatric intensive care unit for a minimum of 8 hours, having weight and intake-output records, were eligible. Children known to have chronic kidney disease or already in stage 2/3 acute kidney injury/dialysis were excluded. PROCEDURE: Day 0 Renal angina index was calculated from the product of Risk Group score (Pediatric intensive care admission/Ventilation and inotropy) and Renal Injury score (fluid overload over previous 8 hours or the % fall in estimated creatinine clearance from baseline). Renal angina index ³8 was considered positive. MAIN OUTCOME MEASURE: The proportion of children with positive Day 0 Renal angina index who develop severe AKI (Kidney Disease Improving Global Outcomes (KDIGO) ≥ Stage 2) on Day 3. RESULTS: Of 162 enrolled children (median (IQR) age 10.5 (3,39) months), 86 (53%) had positive Renal angina index. On Day 3, a higher proportion of children with positive index developed severe AKI, compared to negative group (RR 95.5; 95% CI 21.7,420.5; P<0.001). Day 0 positive Renal angina index had a sensitivity, specificity, positive predictive value and negative predictive value of 96.9%, 75.5%, 72% and 97.4% respectively, for predicting severe AKI on Day 3. The Receiver Operating Characteristic curve of Day 0 renal angina scores showed AUC of 0.90 (95% CI 0.85, 0.95), better than the AUC obtained from either Day 0 serum creatinine or Day 0 percent fall in estimated creatinine clearance from baseline. CONCLUSIONS: Day 0 Renal angina index positivity is a promising tool to identify critically ill children with impending severe AKI.

Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks.

JUSTIFICATION: In view of easy availability and increasing trend of consumption of fast foods and sugar sweetened beverages (fruit juices and drinks, carbonated drinks, energy drinks) in Indian children, and their association with increasing obesity and related non-communicable diseases, there is a need to develop guidelines related to consumption of foods and drinks that have the potential to increase this problem in children and adolescents. OBJECTIVES: To review the evidence and formulate consensus statements related to terminology, magnitude of problem and possible ill effects of junk foods, fast foods, sugar-sweetened beverages and carbonated drinks; and to formulate recommendations for limiting consumption of these foods and beverages in Indian children and adolescents. PROCESS: A National Consultative group constituted by the Nutrition Chapter of the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines and policy regulations. Detailed review of literature was circulated to the members, and the Group met on 11th March 2019 at New Delhi for a day-long deliberation on framing the guidelines. The consensus statements and recommendations formulated by the Group were circulated to the participants and a consensus document was finalized. CONCLUSIONS: The Group suggests a new acronym 'JUNCS' foods, to cover a wide variety of concepts related to unhealthy foods (Junk foods, Ultra-processed foods, Nutritionally inappropriate foods, Caffeinated/colored/carbonated foods/beverages, and Sugar-sweetened beverages). The Group concludes that consumption of these foods and beverages is associated with higher free sugar and energy intake; and is associated with higher body mass index (and possibly with adverse cardiometabolic consequences) in children and adolescents. Intake of caffeinated drinks may be associated with cardiac and sleep disturbances. The Group recommends avoiding consumption of the JUNCS by all children and adolescents as far as possible and limit their consumption to not more than one serving per week. The Group recommends intake of regional and seasonal whole fruits over fruit juices in children and adolescents, and advises no fruit juices/drinks to infants and young children (age <2y), whereas for children aged 2-5 y and >5-18 y, their intake should be limited to 125 mL/day and 250mL/day, respectively. The Group recommends that caffeinated energy drinks should not be consumed by children and adolescents. The Group supports recommendations of ban on sale of JUNCS foods in school canteens and in near vicinity, and suggests efforts to ensure availability and affordability of healthy snacks and foods. The Group supports traffic light coding of food available in school canteens and recommends legal ban of screen/print/digital advertisements of all the JUNCS foods for channels/magazines/websites/social media catering to children and adolescents. The Group further suggests communication, marketing and policy/taxation strategies to promote consumption of healthy foods, and limit availability and consumption of the JUNCS foods.

Hemolytic uremic syndrome in a developing country: Consensus guidelines.

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

Profile of Acute Kidney Injury in Hospitalized Children with Idiopathic Nephrotic Syndrome.

OBJECTIVE: To determine the incidence, risk factors and outcome of acute kidney injury (AKI) in hospitalized children with nephrotic syndrome. METHODS: All consecutive hospitalized children (aged 1-14 years) with diagnosis of nephrotic syndrome between February 2016 and February 2017 were enrolled for the study. Children (aged 1-14 years) with features of nephritis, underlying secondary causes of nephrotic syndrome as well as children admitted for diagnostic renal biopsy and intravenous cyclophosphamide or rituximab infusion were excluded. RESULTS: A total of 73 children (81 admissions) were enrolled; incidence of AKI was 16% (95% CI, 9-23). On multivariate logistic regression analysis, furosemide infusion was observed as an independent risk factor for acute kidney injury (OR 23; 95% CI, 3-141; P<0.001). Out of 13 children with AKI, three died. CONCLUSIONS: Acute kidney injury in hospitalized children with nephrotic syndrome has high risk of mortality. Children receiving furosemide infusion should be closely monitored for occurrence of acute kidney injury.

Predictors of poor outcome in children with steroid sensitive nephrotic syndrome.

BACKGROUND AND OBJECTIVE: Nearly 50% of the children with steroid sensitive nephrotic syndrome (SSNS) have a frequently relapsing (FR) or steroid dependent (SD) course, experiencing steroid toxicities and complications of immunosuppression. The study aimed to compare parameters between children with infrequent relapsing (IFR) and FR/SD nephrotic syndrome and to identify the factors associated with a FR/SD course. METHODS: A retrospective analysis of medical records from 2009 to 2014, of children with SSNS attending the pediatric nephrology clinic in a tertiary care medical college and hospital. RESULTS: Out of 325 children (226 males) with SSNS, 213 were IFR and 112 were FRNS/SDNS. The median age of onset was 34 (IQR 24-48) months. The median time to the first relapse was 4 (IQR 3-7) months and 6 (IQR 4-12) months in FR/SD and IFR group respectively. Multivariate logistic regression analysis showed "adequate treatment (≥12 weeks) of the first episode" (odds ratio 0.56, 95% CI 0.34-0.91; p value=0.02) and "shorter median time to the first relapse" (odds ratio 1.04, 95% CI=1.01-1.08; p value=0.04) to be independent predictors of FR/SD course. An ROC curve was constructed which showed that time to first relapse <5.5 months was associated with a sensitivity of 69% and specificity of 60% in predicting a FR/SD course. CONCLUSION: Adequate treatment of the first episode is associated with less chance of an FR/SD course. After treatment of first episode, the first relapse occurring within 5.5 months may predict a frequently relapsing or steroid dependent course.

Isotonic versus Hypotonic Parenteral Maintenance Fluids in Very Severe Pneumonia.

OBJECTIVE: To compare the risk of hyponatremia between hypotonic and isotonic parenteral maintenance solutions (PMS) administered to children with very severe pneumonia, admitted in the general pediatric ward. METHODS: A randomized controlled open label trial was conducted in the pediatrics department of a tertiary care medical college hospital including euvolemic children 2 mo to 5 y of age, fulfilling the WHO clinical definition of very severe pneumonia and requiring PMS. They were randomized to receive either isotonic PMS (0.9% saline in 5% dextrose and potassium chloride 20 meq/L) or hypotonic PMS (0.18% saline in 5% dextrose and potassium chloride 20 meq/L) at standard rates for next 24 h. RESULTS: A total of 119 children were randomized (59: Isotonic; 60: Hypototonic PMS). Nine (15%) children in the isotonic PMS group and 29 (48%) in the hypotonic PMS group developed hyponatremia during the study period, (p <0.001) with a relative risk being 3.16 (95% CI 1.64 to 6.09). Mean serum sodium was significantly lower in the hypotonic group compared to the isotonic group (p < 0.001 each at 6, 12 and 24 h). The difference in mean change in serum sodium from baseline was also significant at 12 and 24 h (5.4 and 5.8 meq/L respectively; p < 0.001 each). CONCLUSIONS: This study demonstrates the rationality of the use of isotonic PMS in children with respiratory infections, a condition regularly encountered by most pediatricians.

The impact of pediatric nephrotic syndrome on parents' health-related quality of life and family functioning: an assessment made by the PedsQL 4.0 family impact module.

The multi-dimensional impact on the quality of life (QOL) of families of children with the nephrotic syndrome (NS) has not been studied sufficiently in the literature. We aimed to study this aspect and the predictors of poor QOL among Indian families having children with NS. A cross-sectional study was conducted to compare the parents of children with chronic NS on treatment for at least one year with parents of a matched healthy control group. The parents of both groups were asked to complete the standard self-administered multi-dimensional questionnaire of Pediatric Quality of Life Inventory 4 (PedsQL TM ) Family Impact Module (FIM). Descriptive and analytical statistics were performed to compare scores between the two groups. Possible predictors of poor outcome in each of the summary scales among the cases were assessed by both univariate and multivariate analysis. The parents of 61 cases and 72 controls completed the PedsQL TM FIM questionnaire. The scores in each of the categories, namely FIM Total Scale Score, Parent HRQOL Summary Score, Family Functioning Summary Score and eight individual domains, were found to be significantly higher among controls. Female gender of the affected child was an independent risk factor for poor Family Functioning Summary Score. Also, presence of serious complications during the course of the disease independently predicted poor Total FIM and Parent HRQOL Summary Scores. Even a relatively benign and potentially curable chronic disorder in children, like the NS, can disturb the QOL of parents in multiple domains of functioning.