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.

Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study.

BACKGROUND: Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology. METHODS: This was a multicenter descriptive study wherein children (< 18 years) with clinically suspected tubular disorders were recruited for molecular testing through WES. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were done when required. Variants were classified as per American College of Medical Genetics 2015 guidelines and pathogenic (P)/likely pathogenic (LP) variants were considered causative. RESULTS: There were 77 index cases (male =73%). Median age at diagnosis was 48 months (IQR 18.5 to 108 months). At recruitment, the number of children in each clinical group was as follows: distal renal tubular acidosis (dRTA) = 25; Bartter syndrome = 18; isolated hypophosphatemic rickets (HP) = 6; proximal tubular dysfunction (pTD) = 12; nephrogenic diabetes insipidus (NDI) = 6; kidney stone/nephrocalcinosis (NC) = 6; others = 4. We detected 55 (24 novel) P/LP variants, providing genetic diagnoses in 54 children (70%). The diagnostic yield of WES was highest for NDI (100%), followed by HP (83%; all X-linked HP), Bartter syndrome (78%), pTD (75%), dRTA (64%), and NC (33%). Molecular testing had a definite impact on clinical management in 24 (31%) children. This included revising clinical diagnosis among 14 children (26% of those with a confirmed genetic diagnosis and 18% of the overall cohort), detection of previously unrecognized co-morbidities among 8 children (sensorineural deafness n = 5, hemolytic anemia n = 2, and dental changes n = 1) and facilitating specific medical treatment for 7 children (primary hyperoxaluria n = 1, cystinosis n = 4, tyrosinemia n = 2). CONCLUSION: WES is a powerful tool in the diagnosis and management of children with inherited tubulopathies in the Indian population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Snake bite associated with acute kidney injury.

Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.

Risk factors and outcome of acute kidney injury in children with snake envenomation.

Our study evaluates the risk factors of acute kidney injury (AKI) in children with snake envenomation. Out of 145 cases, 54 (37%) developed AKI. Unsurprisingly, the mortality increased with oliguria and higher levels of creatinine. Bleeding manifestations were also more common among the AKI group.

Cardiorenal syndrome in the pediatric population: A systematic review.

The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS, there is a paucity of information on the understanding of its pathophysiology and management, increasing both morbidity and mortality for patients. This review summarizes the existing conceptual pathophysiology of different types of CRS and delves into the associated therapeutic modalities with a focus on pediatric cases. Prospective or retrospective observational studies, comparative studies, case reports, case-control, and cross-sectional studies that include pediatric patients with CRS were included in this review. Literature was searched using PubMed, EMBASE, and Google Scholar with keywords including "cardio-renal syndrome, type," "reno-cardio syndrome," "children," "acute kidney injury," and "acute decompensated heart failure" from January 2000 to January 2021. A total of 14 pediatric studies were ultimately included and analyzed, comprising a combined population of 3608 children of which 32% had CRS. Of the 14 studies, 57% were based on type 1 CRS, 14% on types 2 and 3 CRS, and 7% were on types 4 and 5 CRS. The majority of included studies were prospective cohort, although a wide spectrum was observed in terms of patient age, comorbidities, etiologies, and treatment strategies. Commonly observed comorbidities in CRS type 1 were hematologic, oncologic, cardiology-related side effects, muscular dystrophy, and pneumonia/bronchiolitis. CRS, particularly type 1, is prevalent in children and has a significant risk of mortality. The current treatment regimen primarily involves diuretics, extracorporeal fluid removal, and treatment of underlying etiologies and comorbidities.

Impact of rituximab on anthropometric indices among childhood steroid-dependent nephrotic syndromes.

BACKGROUND: There is scarcity of data on impact of rituximab on anthropometrical parameters (weight, height and body mass index i.e. BMI SD score (SDS)) among children with steroid-dependent nephrotic syndromes (SDNS). METHODS: Multicentre retrospective review. RESULTS: 102 children with SDNS (male: 63%; n=64), median age 7 (IQR: 4.3-9.6) years, received a total of 217 rituximab infusions (total 110 cycles). At median follow-up of 2.1 (IQR: 1.3-2.8) years, 58 (57%) children were off steroids and a significant fall in steroid threshold for relapse was noted (median 0.6; IQR 0.4-0.9 to median 0.3; IQR 0.12 - 0.5 mg/kg/alternate day, p=0.005). Anthropometric parameters (BMI SDS: 0.92±1.8 to 0.25±1.47, p=0.003; weight SDS: 0.20±1.6 to -0.11±1.3, p=0.01; and height SDS: -0.93±1.88 to -0.45±1.54, p=0.04) as well as obesity (38% to 20%, p=0.003) and short stature (11% to 3%, p=0.02) improved. Results remained significant even when analysis was restricted to children ≤12 years (n=88), (BMI SDS: 0.97±1.98 to 0.25±1.5, p=0.001; weight SDS: 0.33±1.6 to 0.02±1.2, p=0.01; and height SDS: -0.67±1.84 to -0.186±1.42, p=0.001). CONCLUSIONS: Use of rituximab resulted in significant steroid sparing effect with an improvement in both growth and obesity parameters.

Use of rituximab in paediatric nephrology.

Rituximab is a chimeric monoclonal antibody capable of depleting B cell populations by targeting the CD20 antigen expressed on the cell surface. Its use in oncology, initially in B cell lymphoma and post-transplant lymphoproliferative disorders, predates its current utility in various fields of medicine wherein it has become one of the safest and most effective antibody-based therapies. It was subsequently found to be effective for rheumatological conditions such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Over the past decade, rituximab has generated a lot of interest in nephrology and has become an emerging or accepted therapy for multiple renal conditions, including systemic lupus erythematosus, lupus nephritis, vasculitis, nephrotic syndrome and in different scenarios before and after kidney transplantation. This review outlines its current use in paediatric nephrology practice, focusing on the knowledge required for general paediatricians who may be caring for children prescribed this medication and reviewing them on a shared care basis.

Genetic Characteristics of Rotavirus Acute Gastroenteritis Among Hospitalized Children of Odisha in Eastern India.

OBJECTIVE: To generate epidemiological data of rotavirus diarrhea among hospitalized children less than 5 y of age and to characterize the circulating rotavirus genotypes post introduction of rotavirus vaccine in Universal Immunization Program (UIP). METHODS: This prospective study was conducted from April 2016 to July 2019 at Sardar Vallabhbhai Patel Post Graduate Institute of Paediatrics & SCB Medical College, Cuttack, Odisha among hospitalized children with acute gastroenteritis (AGE) under five years of age. Stool samples collected were tested for rotavirus by a commercial enzyme immunoassay and strains were characterized by reverse-transcription polymerase chain reaction (PCR). The data was analysed using a chi-square test with 95% confidence interval and risk ratio. RESULTS: Rotavirus diarrhea was seen in 715 (36.4%) of the 1963 samples tested. The peak incidence of rotavirus diarrhea was during the winter season, i.e., from the month of December to February. Most of the infections were in children between 6 mo to 2 y of age, affecting boys and girls equally. The commonest genotypes were G3P[8] (50.34%) followed by G1P[8] (17.46%). CONCLUSION: This study highlights the high prevalence of rotavirus diarrhea among children which emphasize the need for continued rotavirus vaccination. The changing patterns of genotype distribution stress the need for continued surveillance post introduction of vaccines to understand the effect of vaccines on strain evolution over a longer period and detect emergence of new genotypes.

Clinical Profile, Risk-Factors, and Outcome of Rotaviral Diarrhea and Non-rotaviral Diarrhea Among Under-Five Children at Cuttack, Odisha, India.

OBJECTIVE: To understand the prevalence of rotavirus diarrhea and its associated clinical and socio-demographic characteristics. METHODS: The prospective hospital-based study was conducted at SVP Post Graduate Institute of Pediatrics and SCB Medical College, Odisha, India among children under-five years of age from April 2016 to July 2019. From all eligible children admitted at hospital, a case-report form containing information on clinical and socio-demographic characteristics was collected and an attempt was made to collect stool sample. A simple logistic regression method was used to assess factors associated with rotavirus diarrhea. RESULTS: Of the 1963 children, median (IQR) age was 12 (8-19) mo with a female/male ratio was 1:2.05. The prevalence of rotavirus diarrhea was 36.4% (95% CI, 34.2%-38.6%). Children in the age group of 6-11 (OR 1.64, 95% CI, 1.24-2.18), 12-23 (OR 1.73, 95% CI, 1.31-2.29) mo had higher odds of getting rotavirus diarrhea, compared to those in that of 24-59 mo. The prevalence of wasting, stunting, underweight among children with rotavirus diarrhea was 25.2% (95% CI, 22%-28.4%), 2.1% (95% CI, 1.1%-3.1%), 9.0% (95% CI, 6.8%-11.2%), respectively. CONCLUSION: The results of this study confirmed that diarrhea remains an important cause of hospitalization in children. Further studies are required in the community for Rotavirus and its genotyping.

Childhood Intussusception after Introduction of Indigenous Rotavirus Vaccine: Hospital-Based Surveillance Study from Odisha, India.

OBJECTIVE: To study the epidemiology of intussusception in children < 2 y of age, postintroduction of Rotavac® (an indigenous oral rotavirus vaccine). METHODS: A multicenter hospital-based surveillance was conducted in Odisha from February 2016 to June 2019. The cases were diagnosed according to Brighton level-1 criteria. Data were collected regarding the time of onset, signs and symptoms, radiological diagnosis, management, complications, and outcome (discharged/died). RESULTS: One hundred and twenty children < 2 y of age were enrolled. The median age was 7 mo (M:F ratio = 2:1). The most common clinical feature was abdominal distention and blood in stool. The most common method for treatment was hydrostatic/pneumatic reduction. Median time (days) between symptom onset and admission was 2. Median (IQR) duration (days) of hospitalization was 5. Most common location of intussusceptions was ileo-colic. CONCLUSIONS: Hydrostatic/pneumatic reduction was possible in the majority presenting ≤ 48 h of symptom onset, and those presenting > 48 h mostly required surgical reduction. Intestinal resection was required in some cases presenting on day 5 of symptom onset. Majority of cases were managed by surgical reduction in Government facility.

Congenital Nephrotic Syndrome in India in the Current Era: A Multicenter Case Series.

BACKGROUND: There is a paucity of information on epidemiology, diagnosis, and treatment outcomes of congenital nephrotic syndrome (CNS) in developing countries. METHODS: Retrospective (2012-2017) review of case records undertaken across 12 Indian pediatric nephrology centers. RESULTS: Sixty-five children (58% male, median birth weight 2.4 kg [interquartile range (IQR) 2.1-2.86]) were identified with CNS. Nearly half (45%) were preterm with previous history of fetal loss/sibling death in 22% and history of consanguinity in a third. No infective etiology was confirmed. Genetic reports available for 15 (23%) children identified causal mutations in 10 (8 in NPHS1 [1 novel variant], 1 in WT 1 [novel variant], and 1 in PLCE-1 gene). In addition, 1 child was clinically diagnosed as Galloway Mowat syndrome. Next-generation sequencing showed 80% yield and Sanger sequencing 20%. Albumin infusion and angiotensin-converting enzyme inhibitors were used initially in around two-third of cohort, while only 12% of children received indomethacin. Totally, 22 (34%) children were lost to follow-up after initial visit, and among the rest median follow-up was 69 days (IQR 20-180) with 18 (42%) deaths. Eight children showed partial response (including 2 with NPHS1 compound mutation), 1 complete response, and all of them were alive at last follow-up in contrast to 53% mortality among nonresponders, p = 0.004. CONCLUSION: This largest reported series on CNS from India revealed suboptimal management with poor outcome as well as low number of CNS being subjected to genetic evaluation.

Spectrum of clinico-pathological profile and treatment response in children with nephrotic immunoglobulin a nephropathy.

Immunoglobulin A nephropathy (IgAN) is one of the most common types of primary glomerulonephritis in the world. Nephrotic syndrome is an uncommon presentation of IgAN. To evaluate the clinico-pathological features and treatment response of nephrotic IgAN, we prospectively studied 20 nephrotic children with biopsy-proven IgAN at our center from August 2009 to December 2012. The histopathological characterization of IgAN was carried out with the HAAS classification. The demographic profile, clinical presentation, initial laboratory, biopsy findings and treatment response were analyzed. The mean age was 6.7 years. The most common indication of renal biopsy was steroid-dependent nephrotic syndrome associated with microscopic hematuria (65%) and hypertension (25%). The majority of cases were classified as HAAS-III stage. Fifteen cases responded to oral cyclosporine-A, four cases to oral cyclophosphamide and one to mycophenolate mofetil. Complete remission of the nephrotic syndrome was achieved in 90% (18/20) cases within 3 months of initiation of therapy. Two cases that had partial remission were in the HASS-II and III stages. We conclude that the majority of children with nephrotic IgAN responded to oral cyclosporine-A. However, a larger cohort and longer duration follow-up are required to confirm our results.