Antineutrophil cytoplasmic antibody in children with nephrotic syndrome treated with levamisole: a cross-sectional cohort study.

BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.

Assessment of South Asian Pediatric Acute Kidney Injury: Epidemiology and Risk Factors (ASPIRE)-a prospective study on "severe dialysis dependent pediatric AKI".

BACKGROUND: Pediatric acute kidney injury (AKI) is a global health concern with an associated mortality risk disproportionately pronounced in resource-limited settings. There is a pertinent need to understand the epidemiology of pediatric AKI in vulnerable populations. Here, we proposed a prospective study to investigate the epidemiology and associated risk factors of "severe dialysis dependent AKI" in children among South Asian nations which would be the first and largest of its kind. METHODS: The ASPIRE study (part of PCRRT-ICONIC Foundation initiative) is a multi-center, prospective observational study conducted in South Asian countries. All children and adolescents ≤ 18 years of age who required dialysis for AKI in any of the collaborating medical centers were enrolled. Data collection was performed until one of the following endpoints was observed: (1) discharge, (2) death, and (3) discharge against medical advice. RESULTS: From 2019 to 2022, a total of 308 children with severe AKI were enrolled. The mean age was 6.17 years (63% males). Secondary AKI was more prevalent than primary AKI (67.2%), which predominantly occurred due to infections, dehydration, and nephrotoxins. Common causes of primary AKI were glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, and obstructive uropathy. Shock, need for ventilation, and coagulopathy were commonly seen in children with severe AKI who needed dialysis. The foremost kidney replacement therapy used was peritoneal dialysis (60.7%). The mortality rate was 32.1%. CONCLUSIONS: Common causes of AKI in children in South Asia are preventable. Mortality is high among these children suffering from "severe dialysis dependent AKI." Targeted interventions to prevent and identify AKI early and initiate supportive care in less-resourced nations are needed.

Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Morphometry and Morphology of the Acromion Process and Its Implications in Subacromial Impingement Syndrome.

Introduction Subacromial impingement syndrome (SIS) is a common shoulder disorder characterized by pain and limited range of motion in the shoulder joint. It is frequently attributed to the compression or impingement of the rotator cuff tendons and bursa between the humeral head and the acromion process of the scapula during arm elevation. Subacromial impingement syndrome may arise as a result of the morphology of the acromion process, a bony protrusion at the top of the scapula that is important in the biomechanics of the shoulder joint. In order to detect potential anatomical differences that can predispose people to subacromial impingement syndrome, medical professionals and researchers need to have a thorough understanding of the morphometry and morphology of the acromion process. Aims and objectives The aim of the present study was to measure the morphometric and morphological characteristics of the acromion process in dried human scapulae that belonged to the North Indian population. Materials and methods This was a cross-sectional study that was carried out on 120 undamaged adult human scapula, of which 52 belonged to the right side and 68 belonged to the left side. Our study focused on analyzing the morphology of the acromion process as well as determining its maximum length, maximum breadth, acromio-coracoid distance, acromio-glenoid distance, and thickness. A statistical analysis of the observed parameters was carried out using the chi-square test and independent t-test with the help of Statistical Package for the Social Sciences (SPSS, IBM Corp., Armonk, NY) 24.0. Statistical significance was set at 0.05 (if the P-value ≤ 0.05, it is significant). Results We observed that the quadrangular shape (51.67%) of the acromion process was most commonly reported in our study, while the tubular (9.99%) shape was the least common. The difference in the incidences of various shapes of the acromion process on the right and left sides of the scapula was found to be statistically significant (p-value ≤ 0.05). In this study, the curved or type II acromion process was the most common type (53.34%) observed, while the least common shape reported was the hooked type (18.33%). The average length of the right acromion process was 44.52±6.61 mm, and the left acromion process was 45.13±6.35 mm. For the breadth, the right acromion had an average value of 28.31±4.67 mm, while the left had an average of 28.34±4.92 mm. The thickness of the right acromion measured 7.10±1.73 mm, and the left acromion was 7.53±1.44 mm. The acromio-coracoid distance on the right side was 34.59 ± 6.47 mm, and the left side was 37.46±6.22 mm. The acromio-glenoid distance was measured to be 32.31±5.87 mm on the right side and 33.18±5.39 mm on the left side. Conclusions Planning and carrying out an acromioplasty require an understanding of the morphometric parameters of the acromion process. Although there is a paucity of research on its morphometric evaluation in the North Indian population, the surgeons would be able to use these data as a reference.

Geochemical evolution of dissolved trace elements in space and time in the Ramganga River, India.

Understanding the spatiotemporal dynamics of river water chemistry from its source to sinks is critical for constraining the origin, transformation, and "hotspots" of contaminants in a river basin. To provide new spatiotemporal constraints on river chemistry, dissolved trace element concentrations were measured at 17 targeted locations across the Ramganga River catchment. River water samples were collected across three seasons: pre-monsoon, monsoon, and post-monsoon between 2019 and 2021. To remove the dependency of trace element concentrations on discharge, we used molar ratios, as discharge data on Indian transboundary rivers are not publicly available. The dataset reveals significant spatiotemporal variability in dissolved trace element concentrations of the Ramganga River. Samples collected upstream of Moradabad, a major industrial city in western Uttar Pradesh, are characterized by ~ 1.2-2.5 times higher average concentrations of most of the trace elements except Sc, V, Cr, Rb, and Pb, likely due to intense water-rock interactions in the headwaters. Such kind of enrichment in trace metal concentrations was also observed at sites downstream of large cities and industrial centers. However, such enrichment was not enough to bring a major change in the River Ganga chemistry, as the signals got diluted downstream of the Ramganga-Ganga confluence. The average river water composition of the Ramganga River was comparable to worldwide river water composition, albeit a few sites were characterized by very high concentrations of dissolved trace elements. Finally, we provide an outlook that calls for an assessment of stable non-traditional isotopes that are ideally suited to track the origin and transformation of elements such as Li, Mg, Ca, Ti, V, Cr, Fe, Ni, Cu, Zn, Sr, Ag, Cd, Sn, Pt, and Hg in Indian rivers.

Presentation and outcome of pediatric lupus nephritis from a large single centre contemporary cohort in Eastern India.

BACKGROUND: We present clinical, biochemical, and histopathological characteristics and treatment outcomes of biopsy proven childhood lupus nephritis (LN) from a low/middle income setting treated in the current era of increased use of Mycophenolate Mofetil (MMF) and biologics. METHODS: Retrospective observational study of children (1-18 years) with biopsy proven LN treated from 01.01.2010 to 31.01.2020. RESULTS: 60 children met our inclusion criteria (80%, n = 48 were females). The median age at diagnosis was 11 (IQR: 9-12) years. The most common extra-renal manifestation was mucocutaneous (n = 54, 90%) and the most common kidney manifestation was edema (n = 50, 83.3%). The median 24-h urinary protein excretion was 1117.8 (IQR: 795.4-1941.7) mg/m2/day with 67% (n = 40) having nephrotic range proteinuria (>1000 mg/m2/day). 75% (n = 45) children had eGFR <90 mL/min/1.73 m2 (median eGFR = 71; IQR: 56-90 mL/min/1.73 m2). Anti-Nuclear Antibody was positive in all, both complement three and four were low in 82% (n = 49) and anti-double stranded DNA antibodies were positive in 63% (n = 38). 85% (n = 51) had proliferative LN with majority being class IV (57%, n = 34). All children received steroids for induction therapy. MMF was given as the sole induction agent in 48% (n = 29) and cyclophosphamide in 27% (n = 16). Rituximab was added in 17% (n = 10) as a rescue agent. Median follow up duration was 50 (IQR: 28-82) months. Six children (10%) died as a result of serious infections and none of them had shown complete response (CR). Out of the 52 children who had a follow up duration of at least 2 years, CR was achieved in 46 children (88%) and partial response (PR) or no response (NR) in three children (6%) each. Although children who were in CR/PR at last follow up had lower proteinuria, higher eGFR, and lower histopathology activity index at onset; low numbers in the NR group precluded us from subjecting them to any statistical correlation tests. 36% (n = 22) of children developed 36 episodes of renal flares with overall incidence of 0.14/person-year. CONCLUSION: Our study on a contemporary cohort of childhood LN highlights the importance of achieving CR and its feasibility.

Voiding Pressures in Boys: Pdetmax versus PdetQmax - Does it Make a Difference?

Introduction: Invasive urodynamics (UDS) is a standard investigation in children. Studies measuring voiding pressures in children use varied nomenclatures and quote a wide range of voiding pressures. Thus, voiding pressures in children are not considered reliable and they do not find any place in the pediatric diagnostic armamentarium. On the contrary, adult studies have well-defined nomograms and standard values which make voiding studies indispensable in the diagnosis of voiding dysfunctions in adults. The difference primarily lies in the uniformity of parameters assessed in adults and the contrasting heterogeneity in the pediatric literature. Objective: The objective of this study was to study the voiding parameters observed during UDS in boys. Study Design: We retrospectively reviewed the pressure flow data obtained during conventional invasive UDS in 106 neurologically normal boys (6 months-16 years) who had different indications for urodynamics. The values of Pdetmax and PdetQmax were analyzed and compared with the existing data of pressure flow studies in children. Results: Pdetmax decreased with age whereas PdetQmax was independent of age. The difference between the values of Pdetmax and PdetQmax was more in the younger kids. The wide range of voiding detrusor pressure (Pdet) in the existing pediatric literature is similar to the values of Pdetmax observed in our study, whereas the value of PdetQmax is much lower. Discussion: The values of Pdetmax observed in this study are similar to the values of "maximum Pdet during voiding" documented in previous studies and are determined by detrusor contractility and functional/dynamic contraction of outflow during voiding. PdetQmax has been documented in very few pediatric studies and is significantly less than Pdetmax. Further prospective studies are needed to corroborate UDS findings with radiologic/cystoscopic findings to create nomograms of voiding parameters in children. Conclusion: Existing literature on pediatric voiding studies mentions voiding pressures during variable phases of void (usually Pdetmax) and the values have been very heterogeneous, making voiding pressure-flow studies unreliable in children. PdetQmax values are much lower than values quoted as "standard" pressures and are age independent. The use of PdetQmax instead of PdetMax may make voiding pressures in children more reproducible and informative.

Single- versus Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children: An Open-Label RCT.

BACKGROUND: Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has resulted in variation in practice, with divided-dose prednisolone still commonly used. We conducted this open-label randomized control trial to compare HPA axis suppression between single-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome. METHODS: Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl. RESULTS: Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002. CONCLUSIONS: Among children with first episode of nephrotic syndrome, single-dose and/or divided-dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CTRI/2021/11/037940. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000216.mp3.

SARS-CoV-2 Infection in Children with Idiopathic Nephrotic Syndrome: A Multicentric Study.

A multicenter retrospective study was conducted to assess the clinical spectrum of 30 severe acute respiratory syndrome coronavirus (SARS-CoV-2)-positive children with idiopathic nephrotic syndrome. Difficult to treat nephrotic syndrome was found to be a high-risk group with a high incidence of acute kidney injury and mortality.

A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.

Incidence and risk factors of acute kidney injury among childhood nephrotic syndrome: a prospective cohort study.

Acute kidney injury (AKI) is a known independent risk factor for morbidity/mortality but there is scarcity of robust data on it among childhood nephrotic syndrome (NS). We assessed the incidence of AKI among hospitalized children with NS as well as looked for any significant risk factors. Prospective observational study conducted across two tertiary pediatric hospitals in Eastern India from September 2020 to August 2021. Children aged 1-18 years admitted with NS and without any nephritic features or pre-existing chronic kidney disease (CKD) were included. In 200 admissions (n = 176; 63% female, median age 4 years [IQR: 3-7]), AKI occurred in 36 (18%; 95% CI 13 to 36%). Two children required kidney replacement therapy and one death was recorded. In 27/36 (75%), AKI resolved within 48 h, 4 had persistent AKI, 3 acute kidney disease, and two progressed to CKD. On multivariate regression analysis: fractional excretion of sodium ≤ 0.2% (OR 12.77; 95% CI 3.5-46.4), male gender (OR 6.38; 95% CI 2.76-14.74), underlying infection (OR 5.44; 95% CI 2.4-11.86), nephrotoxic drugs (OR 4.83; 95% CI 2.21-10.54), and albumin ≤ 1.4 g/dl (OR 4.35; 95% CI 1.55-12.8) were associated with AKI. A predictive equation using these five variables on admission had high AUC (0.86) in correctly identifying 17 children who subsequently developed AKI.   Conclusion: In a low resource setting, AKI is common among hospitalized children with NS. Larger multi-center prospective studies are needed to refine prediction equations and test its utility in preventing AKI development. What is Known: • Acute Kidney Injury is a known independent risk factor for increased morbidity and mortality. • There are few studies to assess the incidence of Acute kidney injury in hospitalised cases of childhood nephrotic syndrome.. What is New: • This is the largest prospective cohort of children suffering from nephrotic syndrome, in India, proposing a novel algorithm for predicting the risk of AKI among hospitalised cases of childhood nephrotic syndrome.

Improving acute peritoneal dialysis outcome with use of soft peritoneal dialysis catheter (Cook Mac-Loc Multipurpose Drainage catheter®) among infants < 1500 g in a low resource setting.

BACKGROUND: Despite its utility, uncertainty exists on the feasibility of acute peritoneal dialysis (PD) and optimal PD catheter type for very low birth weight (VLBW < 1500 g) and extremely low birth weight (ELBW < 1000 g) infants. We hereby report our experience of acute PD among these high-risk infants and compare the outcome between stylet-based rigid catheter (SRC) and Cook Mac-Loc Multipurpose Drainage catheters® (CMMDC). METHODS: Case notes of infants < 1500 g undergoing PD between 2012 and 2021 in a network of five participating neonatal units supported by a tertiary paediatric nephrology centre in Kolkata, India, were retrospectively reviewed. PD was conducted either with SRC or after 2018 with CMMDC. Outcome parameters included complications, survival during PD, and survival to discharge. RESULTS: 24 infants (VLBW: n = 13 and ELBW: n = 11) underwent PD at median age 4.5 days (IQR 3-6) with either CMMDC (n = 14) or SRC (n = 10). Significant improvement in biochemical parameters and fluid removal was seen in both ELBW and VLBW infants. CMMDC was associated with significantly fewer PD-related complications 7/14 (50%) vs. 9/10 (90%) (p = 0.04) and higher survival during PD 13/14 (93%) vs. 5/10 (50%) (p = 0.02), without significant difference in survival to hospital discharge 8/14 (57%) vs. 3/10 (30%) (p = 0.25). CMMDC also enabled longer duration of PD, higher ultrafiltration, and better control of acidosis. Consumable cost was higher for CMMDC (USD$60) than SRC (USD$14). CONCLUSIONS: In a low resource setting, CMMDC had lower PD complications and superior short-term survival among ELBW/VLBW infants. A higher resolution version of the Graphical abstract is available as Supplementary information.

Deriving wetland-cover types (WCTs) from integration of multispectral indices based on Earth observation data.

The wetland cover is defined as the spatially homogenous region of a wetland attributed to the underlying biophysical conditions such as vegetation, turbidity, hydric soil, and the amount of water. Here, we present a novel method to derive the wetland-cover types (WCTs) combining three commonly used multispectral indices, NDVI, MNDWI, and NDTI, in three large Ramsar wetlands located in different geomorphic and climatic settings across India. These wetlands include the Kaabar Tal, a floodplain wetland in east Ganga Plains, Chilika Lagoon, a coastal wetland in eastern India, and Nal Sarovar in semi-arid western India. The novelty of our approach is that the derived WCTs are stable in space and time, and therefore, a given WCT across different wetlands or within different zones of a large wetland will imply similar underlying biophysical attributes. The WCTs can therefore provide a novel tool for monitoring and change detection of wetland cover types. We have automated the proposed WCT algorithm using the Google Earth Engine (GEE) environment and by developing ArcGIS tools. The method can be implemented on any wetland and using any multispectral imagery dataset with visible and NIR bands. The proposed methodology is simple yet robust and easy to implement and, therefore, holds significant importance in wetland monitoring and management.

Space-time dynamics of soil moisture and groundwater in an agriculture-dominated critical zone observatory (CZO) in the Ganga basin, India.

Space-time variability of soil moisture (SM) and ground water plays a fundamental role in shaping hydrology of terrestrial ecosystem, best represented as the Critical Zone (CZ), which extends from top of vegetation canopy to the bottom of groundwater table. In several parts of the world, a network of instrumented sites, known as Critical Zone Observatories (CZOs), have been set up to understand the hydrodynamics of soil-water system in particular reference to natural and anthropogenic forcings. Here, we employed the empirical orthogonal function (EOF), random combination, and temporal stability approach to understand the in-situ space-time dynamics of SM and depth to groundwater table (DTGT) over an agriculture-dominated CZO in the Ganga basin. Our results showed that both the components exhibit a constant temporal coefficient of variation, suggesting a consistent seasonal changing pattern. Around 91 % of the observed DTGT spatial variation are explained by first two spatial EOFs while the first five EOFs explain only 67 % of the total SM variability. On an annual basis, the spatial patterns of SM and DTGT are driven by topography and soil texture (% clay) while monsoon rainfall and post-monsoon crop cycle appear to be the leading factors for temporal variability of both components. Furthermore, we have demonstrated that randomly selected four sampling locations and three monitoring wells within the CZO could capture the mean spatial variability of SM (RMSE = 3 % vol/vol) and DTGT (RMSE = 0.7 mgbl) respectively. In addition, temporal stability analysis indicates that four representative sites and a single monitoring well can provide robust catchment mean with an absolute error of ±2 % vol/vol and 0.36 mgbl respectively. Overall, this study provides an insight to the hydrodynamics and controls of SM and groundwater in an agricultural landscape with significant implications for upscaling and efficient water resource management in such regions.