Comparison of Urinary Beta-2 Microglobulin Levels in Children with SSNS and Calcineurin Inhibitor-Treated SRNS.

Background: While the utility of beta-2 microglobulin (ß2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary ß2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission. Materials and Methods: This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary ß2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit. Results: Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary ß2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 mg/ml, P < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary ß2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 mg/ml, P = 0.03). Median ß2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 mg/ml). Conclusion: Urinary ß2M levels were higher in SRNS compared to SSNS disease in remission, and ß2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS.

Adrenocortical suppression in children with nephrotic syndrome treated with corticosteroids.

BACKGROUND: Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: This cross-sectional study enrolled children (2-18 years) both with steroid sensitive nephrotic syndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. RESULTS: Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. CONCLUSIONS: A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.

Serum apolipoproteins (apoA-1, apoB, and apoB/apoA-1 ratio) for early identification of dyslipidemia in children with CKD.

BACKGROUND: Dyslipidemia in children with chronic kidney disease (CKD) is identified based on lipid profile parameters; however, changes in lipoprotein quality precede quantitative changes. METHODS: A cross-sectional study was done from January to October 2021; overweight, obese children, known cases of diabetes mellitus, hypothyroidism or on steroid therapy, or lipid lowering drugs were excluded. Clinical details were elicited and examinations done. Besides hemogram, kidney function tests, liver function tests, total cholesterol, low density lipoproteins (LDL), triglycerides, high density lipoproteins (HDL), and apolipoproteins A-1 and B were estimated to identify dyslipidemia. Relevant tests of significance were applied, and ROC curves were drawn for apoA-1, apoB, and apoB/apoA-1 ratios. RESULTS: A total of 76 (61 M:15 F) children with median (IQR) age 7 (3.25-11) years were enrolled; cause of CKD was CAKUT in 82.3% patients. Dyslipidemia (alteration of 1 or more lipid parameters) was seen in 78.9% with a prevalence of 71.7% in early and 95.7% in later stages of CKD (P = 0.02); most had elevated serum triglyceride levels. The median (IQR) values of apoB, apoA-1, and apoB/apoA-1 ratio were 78 (58-110) mg/dl, 80 (63-96.75) mg/dl, and 0.88 (0.68-1.41), respectively; apoB, apoA-1, and apoB/apoA-1 ratio had a sensitivity of 26.67%, 86.67%, and 70%, respectively, and specificity of 87.5%, 62.5%, and 62.5%, respectively, for diagnosis of dyslipidemia. The ROC for apoB, apoA-1, and apoB/apoA-1 ratio showed AUC of 0.66, 0.68, and 0.74 (P = 0.4, 0.02, < 0.01), respectively. CONCLUSIONS: The prevalence (78.9%) of dyslipidemia was high in patients with CKD especially in those with later stages. The ratio of apoB/apoA-1 was altered early and appears to be promising for early detection.

Effect of Daily Vitamin D Supplementation on Serum Vitamin D Levels in Children with Epilepsy Receiving Sodium Valproate Monotherapy: A Randomized, Controlled Trial.

OBJECTIVES: To compare the change in serum vitamin D levels and to compare the changes in serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone in vitamin D supplemented and unsupplemented groups after 3 mo. METHODS: In this randomized, parallel group, nonblinded, controlled trial, 40 children, 2-12 y of age with newly diagnosed epilepsy, and vitamin D sufficient status, and started on valproate monotherapy, were randomized into the intervention group (n = 20), which was given daily oral 600 IU vitamin D supplementation, and the control group (n = 20), which was not given any supplementation. Changes in the biochemical parameters was measured in the two groups after 3 mo. RESULTS: There was a significant reduction in the median (IQR) vitamin D levels in the control group as compared to an increase seen in the intervention group [-6.64 (-8.4, -2.65) vs. 5.66 (1.81, 7.12); p < 0.001]. In the control group, 37.5% children developed vitamin D insufficiency and 12.5% developed deficiency whereas only 5% of the intervention group developed vitamin D insufficiency (p = 0.005). There was a significant decrease in ionized calcium (p = 0.02), increase in serum phosphate (p = 0.02), and alkaline phosphatase level (p = 0.003) in the unsupplemented group as compared to the supplemented group. CONCLUSION: Vitamin D supplementation can reduce the valproate-associated decline in vitamin D levels and the negative impact on other markers of bone mineral metabolism. TRIAL REGISTRATION: TCTR20200621002, 19.06.2020, retrospectively registered.

Childhood Steroid-resistant Nephrotic Syndrome: Long-term Outcomes from a Tertiary Care Center.

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is a rare condition that accounts for about 10% to 20% of all nephrotic syndromes in children. While calcineurin inhibitors induce remission in the majority, the data on long-term outcomes are limited. This retrospective study aimed to look at the clinical profile, biopsy findings, and long-term treatment outcomes in children with SRNS. Methods: The records of all children (1-18 years) with SRNS with biopsy findings of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangioproliferative glomerulonephritis, who received treatment for a minimum period of 12 months and were in follow-up during the years 2007-2018 at a tertiary care teaching hospital were retrieved. The clinical, histopathological, and biochemical factors and treatment outcomes were recorded and analyzed. Results: Ninety-one (72 boys) children with a median (interquartile range [IQR]) age of onset of nephrotic syndrome as 48 (24-87) months were included. MCD and FSGS were the most common histopathological types (57.1% and 36.3%, respectively) and 62 (68.1%) patients had late steroid resistance. Calcineurin inhibitors (CNIs) were used in 86.8% of the children, and response rates with cyclosporine and tacrolimus for complete remission (CR) were 80% and 73.7%, respectively, with median (IQR) time to response being 3 (2-4) months. The presence of MCD on histology and the use of CNIs were significantly associated with CR (P < 0.01). At a median (IQR) follow-up of 5 (3-7) years, 76 (83.5%) children had either CR or partial remission, four (4.4%) developed chronic kidney disease and five (5.5%) died (three due to end-stage renal disease and two of infective complications). Conclusion: SRNS children with MCD on biopsy, late resistance, and response to CNIs have better long-term outcomes. Most patients respond to CNIs within the first 6 months of use and need therapy for at least 24 to 36 months.

Diet, Fluid Intake, Urine Output and Urinary Sodium/Potassium Ratios in Children With Urolithiasis.

We performed a cross-sectional study on 25 children (17 boys) with urolithiasis with normal glomerular functions at a tertiary care teaching hospital between March, 2018 to March, 2019. Dietary assessment showed that caloric intake was below recommended dietary allowance (RDA) in 68% patients while the median protein intake was 34.3% more. The fluid intake was below the recommended standards in 56%, and 48% of the children had urine output below 1.5 mL/kg/hour. The urinary sodium was elevated in 96% of the children, urinary potassium was low in 40%, and hypercalciuria was seen in 28%. While metabolic causes predominate in childhood urolithiasis, other factors like dietary changes, liberal fluid and low sodium intake are advised for prevention of recurrences as they have a contributory role too.

Chronic Kidney Disease and COVID-19: Outcomes of hospitalised adults from a tertiary care centre in North India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel disease caused by the SARS-CoV-2 virus and has emerged as a deadly pandemic affecting countries all over the world. Here we share our experience of managing adults with chronic kidney disease (CKD) and concomitant COVID-19 infection jointly managed by pediatric and adult nephrology teams. METHODS: This retrospective study was done on patient admissions (>18 years) between 20th June- 30th October 2020 with previously diagnosed CKD and hospitalised with COVID-19 infection. The demographic details, underlying comorbidities, clinical presentation, medications, laboratory, radiological profile and outcomes were studied. RESULTS: A total of 213 adults (62% males) with CKD were admitted during this period with a median (IQR) age of 52 (42, 60) years; 75 (35.2%) had associated diabetes mellitus, 83.1% hypertension, 5.2% hypothyroidism and 7% coronary artery disease. 165 (77.5%) were on maintenance haemodialysis (MHD), and 72.8% had arteriovenous fistula as vascular access at presentation. Most (84.5%) patients were symptomatic for COVID-19, and about 2/3 diarrhoea had moderate to severe disease. Oxygen therapy was needed in 62.9%, and medications used were hydroxychloroquine in 84.5%, azithromycin in 21.6%, ivermectin in 82.6%, steroids in 63.8% and Low molecular weight heparin in 59.2%. A further comparison of patients with CKD5D and CKDND revealed similar parameters except for a higher incidence of diarrhoea, acute kidney injury (AKI) and a shorter period to RTPCR negativity (12.5 vs 15 days; P = 0.038) in CKDND. The overall mortality was 24.4%, with similar mortality rates in both groups (P = 0.709) and 20.7% needed ICU transfer. CONCLUSIONS: Adults with CKD especially on haemodialysis, are prone to more severe COVID-19 infection and take a longer time for viral clearance (>2 weeks); the mortality too is higher in these patients.

Detection of Mycoplasma pneumoniae by two polymerase chain reactions and role of Mycoplasma pneumoniae in pediatric community-acquired lower respiratory tract infections.

PURPOSE: The study was conducted to evaluate the role of Mycoplasma pneumoniae (M. pneumoniae) in children with community-acquired lower respiratory tract infections (LRTIs). METHODS: Seventy five children aged 2 months -12 years with community-acquired LRTIs were investigated for M. pneumoniae etiology employing paired serum samples to assay M. pneumoniae antibodies. Nasopharyngeal aspirates were obtained for the detection of M. pneumoniae by using polymerase chain reaction(PCR) and nested PCR. RESULTS: M. pneumoniae infection was positive in 24(85.71%) children aged <5 years and 4 (14.29%) â€‹≥ â€‹5-12 years and the difference was statistically insignificant (P â€‹= â€‹0.18). Difference in prevalence of M. pneumoniae infection across male and female groups was statistically insignificant (P â€‹= â€‹0.69). Clinical and radiological profiles across M. pneumoniae positive and negative cases were comparable except bronchopneumonia which was statistically significant (P â€‹= â€‹0.04). Serological evidence of M. pneumoniae infection was observed in 26(33%); PCR was positive in 9 (12%) and nested PCR in 10 (13.33%) children. Together, serology, PCR and nested PCR diagnosed M. pneumoniae infection in 28(37.33%) patients. Sensitivity of serology was 77.78%: specificity 68.18%; positive predictive value 25.00% and negative predictive value at 95.74%. CONCLUSIONS: Serological and molecular methods in combination is useful for detection of M. pneumoniae. Our data underline the role of M. pneumoniae in community-acquired LRTIs in children of all ages.

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.

Effectiveness of a Low Dose Prednisolone Regimen for Treatment of Relapses in Children with Steroid Sensitive Nephrotic Syndrome.

Introduction: There may be a role of reducing the total steroid doses for the treatment of relapses of nephrotic syndrome in children with milder and more stable disease. The primary objective of this study was to compare the effectiveness of a low-dose prednisolone regimen with standard therapy for the treatment of relapses in steroid-sensitive nephrotic syndrome (SSNS) at the end of treatment, the secondary objectives being time to remission and sustained remission after 3 months. Methods: This randomized controlled trial included a total of 40 children (20 in each group) with SSNS (presently infrequently relapsing course) and with a relapse. Both groups received prednisolone at a dose of 2 mg/kg/day until remission; subsequently, the patients in the study group received 1 mg/kg, and the control group participants received 1.5 mg/kg prednisolone on alternate days for 4 weeks. The patients were followed up till 3 months after stopping the therapy. Results: The median (IQR) age of children enrolled was 7.5 (range: 5-9.65) years, and the age at onset of nephrotic syndrome was 4 (range: 2.3-5.5) years. The median time to achieve remission was 9 days (comparable in low dose vs. standard therapy group; P = 0.14). All patients were in remission at the end of therapy; 85% of patients were in the low-dose group and 90% in the standard therapy group after 1 month (P = 0.32). At the end of 3 months, 60% continued to be in remission in the low-dose group and 65% with standard therapy (P = 0.37). Hazard ratios for relapse at the end of 1, 2, and 3 months were 1.05, 1.08, and 1.13, respectively. Patients who were infrequently relapsing (79%) from the onset of nephrotic syndrome had higher remission rates at the end of 3 months (80% in the low-dose group vs. 76.9% in the standard therapy group). Hazard ratios for relapse in these patients at the end of 1, 2, and 3 months were 1.01, 1.03, and 1.08, respectively. Conclusions: Lower doses of prednisolone can be used for the treatment of relapse of steroid sensitive nephrotic syndrome, with an infrequently relapsing course.

Chronic Hepatitis B and Nephrotic Syndrome in Children: Treatment Outcomes.

Hepatitis B-related glomerulonephritis (GN) is an uncommon but important cause of renal morbidity in children. While immunosuppressive therapy has been tried along with antivirals for treatment, some children may undergo spontaneous remission or achieve remission with antivirals alone. We retrospectively studied the outcomes of children with nephrotic syndrome (NS) and chronic hepatitis B infection treated at our nephrology clinic over a five years period; seven children were included of which six (86%) presented with NS and one with nephritic syndrome. Renal biopsy (done in 5 children) showed membranous GN in two (40%), membranoproliferative GN in one (20%), and focal segmental glomerulosclerosis in two (40%). Entecavir therapy was started in 6/7(86%) and four (57%) achieved remission after a median period of 2.7 months and achieved hepatitis B e-antigen seroconversion after mean duration of 1.2 years of treatment with entecavir; the remaining achieved remission with immunosuppression with calcineurin inhibitors.

Nephrotic Syndrome with Central Retinal Artery Occlusion: A Unique Presentation.

Childhood nephrotic syndrome is associated with significant morbidity because of recurrent relapses, infections, and episodes of thromboembolism. Thromboembolism in nephrotic syndrome may involve any major blood vessel. Timely recognition of symptoms and early initiation of anticoagulation therapy are important to avoid end-organ damage. We present here a case of a child with steroid-resistant nephrotic syndrome (SRNS) with bilateral central retinal artery occlusion (CRAO), whose vision improved with anticoagulation therapy.

Seroprotection for Diphtheria, Pertussis, Tetanus and Measles in Children With Nephrotic Syndrome.

OBJECTIVE: To determine seroprotective titres for diphtheria, pertussis, tetanus and measles in children with nephrotic syndrome who had received essential immunization. METHODS: Children (2-18 years) with steroid sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome (SRNS) who were in disease remission and had received essential childhood immunization were included. Anti-diphtheria, anti-pertussis, anti-tetanus and anti-measles antibody titres were measured. RESULTS: Seventy-six (40 with SSNS; 36 with SRNS) children with mean (SD) age 7.54 (3.96) years were enrolled. The time elapsed since last vaccination was >5 years in 68.4% patients. The seroprotection rates for diphtheria, tetanus, pertussis, and measles were 86.8%, 93.4%, 31.6% and 77.6% respectively; lower in SRNS subjects compared to SSNS. Robust seroprotection titers (1.0 IU/mL) for diphtheria were seen in 23.8% SSNS and 17.9% SRNS; P=0.04, and for tetanus in 69.3% SSNS and 43.8% of SRNS subjects; P=0.03, respectively. CONCLUSIONS: Children with nephrotic syndrome especially those with SRNS have lower seroprotective titers for diphtheria, tetanus, pertussis and measles, necessitating a booster dose of DPT/DT/Td and MR/MMR.

Consensus Guidelines on Management of Steroid-Resistant Nephrotic Syndrome.

JUSTIFICATION: The management of steroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management. OBJECTIVE: To frame revised guidelines on diagnosis and evaluation, treatment and follow up, 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 systematic review of literature, evaluation of evidence by experts and two face-to-face meetings. RECOMMENDATIONS: Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.

Acute kidney injury in children hospitalized with a relapse of nephrotic syndrome: A short-term outcome study.

Children with nephrotic syndrome (NS) have a number of potential risk factors for the development of acute kidney injury (AKI) including intravascular volume depletion, infection, exposure to nephrotoxic medication, and renal interstitial edema. This study was aimed to determine the incidence of AKI in children hospitalized with a relapse of NS and its short-term outcome. This prospective observational study was conducted from February 2017 to January 2018 at a tertiary care teaching hospital. A total of 54 children and adolescents (1-18 years) hospitalized with a diagnosis of NS and relapse with/or without other complications were enrolled. Clinical data and examination were recorded. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria and Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (p-RIFLE) classification. Children who developed AKI during the first two weeks of hospitalization were followed up till recovery or six weeks whichever was earlier to determine the outcome and factors predisposing to AKI. The mean age of the study population was 59.5 months and 35 (64.8%) patients were male. Of the 54 patients hospitalized, 42 (77.8%) were admitted with infection-associated relapses while 22.2% of children had relapse alone. Diarrhea and spontaneous bacterial peritonitis were the most common infections (26.1% each) followed by urinary tract infections in 19% and pneumonia in 14.3%. Twenty-three (42.6%) children developed AKI according to the KDIGO definition and 27 (50%) using the pRIFLE classification. Fourteen (60.9%) had stage 2 AKI while 21.7% had stage 3 AKI. Infections [odds ratio (OR) 1.24] and use of angiotensin-converting enzyme inhibitors (ACEI) (OR 2.3) were the most common predisposing factors for AKI. The mean recovery time for AKI was 7.34 days. Development of AKI was associated with prolonged hospital stay (12.57 vs.8.55 days P <0.01) and delayed recovery. At the end of follow-up all children recovered from AKI. The incidence of AKI in children hospitalized with complications of NS is high. While the occurrence of these AKI episodes may appear transient, a recurrence of such episodes may be detrimental to the long-term outcome of children with NS. Infections and the use of ACEI during relapses are risk factor for the occurrence of AKI.

Mucormycosis with Severe Acute Respiratory Syndrome Coronavirus-2 Patients on Hemodialysis: A Case Series with Review of Literature.

Coronavirus disease-2019 (COVID-19) emerged as a pandemic with varied clinical presentations. Patients with an underlying comorbidity such as diabetes and chronic kidney diseases (CKDs) had an increased risk of developing secondary bacterial and fungal coinfections which was further accentuated by the use of steroids during the management and with prolonged intensive care unit stay. This case series describes the clinical course of two patients with CKD who developed acute respiratory syndrome coronavirus-2 infection and mucormycosis.