Steroid-resistant Nephrotic Syndrome In Children Research Articles

The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading contributor to chronic kidney disease (CKD), and calcineurin inhibitors (CNIs) or monoclonal antibodies are currently the best identified therapy. Meanwhile, some developing countries still use alkylating agents (AA) such as cyclophosphamide (CPA) to treat SRNS due to economic reasons. Objectives: This study aims to determine the employability of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker for monitoring therapy in SRNS children and compare the clinical improvement with those treated with an AA and CNIs. Methods: This was a retrospective cohort study conducted at Hasan Sadikin Hospital, Indonesia. The data was collected from July 2019 to July 2020 from 70 children with FSGS. Clinical signs were evaluated monthly, and serum suPAR level was measured at the third and sixth months following therapy. Two-way repeated measures ANOVA was carried out to compare the differences in suPAR level at baseline with the third and sixth months in SRNS patients who received AA and CNIs. Results: The mean age was nearly similar between the two groups based on the t-test (P = 0.140). Steroid-resistant nephrotic syndrome was more frequent in boys than in girls (P = 0.020), according to the Chi-square test. Baseline serum suPAR level was not significantly different between the two groups. In the third month, the daily urinary protein level was higher in SRNS patients that received the AA compared to the CNIs group (P < 0.001). There was a significant interaction between time and treatment (F(2,138) = 7.203, P = 0.001), with higher suPAR level in SRNS patients that received the AA compared to those administered with CNIs at the 3rd and 6th months, but this difference was not statistically significant (P > 0.05). Conclusions: As a noninvasive tool, suPAR is a promising modality in monitoring SRNS therapy, and CNIs have a tendency to achieve faster remission than the AA.

POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).

Regulatory T-cell Changes in Patients with Steroid-Resistant Nephrotic Syndrome after Rituximab Therapy.

The aim of this study was to investigate the effect of rituximab (RTX) treatment on serum immunoglobulin (Ig) A, G, M levels, and B and CD4+CD25+FoxP3+ [T regulatory (Treg)] cell numbers in children who received RTX therapy with steroid-resistant nephrotic syndrome (SRNS). Twenty-three SRNS children who received RTX and 20 healthy children in the control group were included. In this cross-sectional cohort study, 23 children with SRNS levels were determined before and one month after RTX treatment by serum IgA, IgG, IgM, and percentages of CD4+CD25+ FoxP3+ cells and B CD19+ cells by flow cytometry (FASCalibur). RTX was administered at a total of four doses of 375 mg/m2/week. Before RTX treatment, percentages of Treg and IgG values were significantly lower in the SRNS group compared to the control group, respectively (P = 0.001). B-cells were significantly lower one month after RTX treatment than before RTX treatment, respectively (P = 0.001). One month after RTX treatment percentages of Tregs, it was found to be significantly higher than before treatment level (P = 0.001). Seventy percent (11/23) remission was achieved with RTX treatment. RTX treatment not only depletes the number of B-cells in SRNS patients but also causes an increase in the number of percentages of Treg cells.

Clinicopathological spectrum and treatment outcome of idiopathic steroid-resistant nephrotic syndrome in children at a tertiary care center

BackgroundIdiopathic steroid-resistant nephrotic syndrome (iSRNS) is a common problem in pediatric nephrology. About 10%–20% of children with nephrotic syndrome have iSRNS and almost 50 percent progress to end-stage renal disease. Very few studies have tried to study the histopathological spectrum, correlate clinical features, renal biopsy patterns and treatment outcome in children presenting with iSRNS in India. In this study, we compared the histopathologic distribution of different subtypes of glomerular morphologic patterns in iSRNS and the clinical and biochemical parameters at the time of diagnosis and outcome of patients after immunosuppressive therapy. MethodsIt is a retrospective cross-sectional study involving review of records of all children with iSRNS presenting to our pediatric nephrology OPD who underwent renal needle biopsy and followed-up for a period of atleast six months post biopsy. Histopathological subtypes were correlated with clinical features (viz. age of onset, gender, oliguria, microscopic hematuria, hypertension, serum creatinine at presentation, serum total protein, serum albumin, 24 h urine protein, persistent proteinuria after 12 weeks of calcineurin inhibitor therapy, and progress to end stage renal disease (ERSD), if any, outcome. ResultIt was found that minimal change disease (MCD) was overall the most common cause of iSRNS. These patients have a significantly greater incidence of remission with immunosuppression as compared with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy subgroup. ConclusionKidney biopsy is of prognostic value in children with iSRNS. The prognosis of children with SRNS owing to MCD is much better than with other nephropathy.

The genetics of steroid-resistant nephrotic syndrome in children.

The genetics of steroid-resistant nephrotic syndrome in children.

Steroid-resistant Nephrotic Syndrome in Children: A Mini-review on Genetic Mechanisms, Predictive Biomarkers and Pharmacotherapy Strategies.

Steroid-resistant nephrotic syndrome (SRNS) constitutes the second most frequent cause of chronic kidney disease in childhood. The etiology of SRNS remains largely unknown and no standardized treatment exists. Recent advances in genomics have helped to build understanding of the molecular mechanisms and pathogenesis of the disease. The genetic polymorphisms in genes encoding proteins which are involved in the pharmacokinetics and pharmacodynamics of glucocorticoids (GCs) partially account for the different responses between patients with nephrotic syndrome. More importantly, single-gene causation in podocytes-associated proteins was found in approximately 30% of SRNS patients. Some potential biomarkers have been tested for their abilities to discriminate against pediatric patients who are sensitive to GCs treatment and patients who are resistant to the same therapy. This article reviews the recent findings on genetic mechanisms, predictive biomarkers and current therapies for SRNS with the goal to improve the management of children with this syndrome.

Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome

BackgroundLimited and contradictory pharmacogenetic studies of NPHS2 gene R229Q polymorphism in nephrotic syndrome (NS) children of different ethnicities steered us to investigate the genotype frequency and associated risk of this polymorphism in Bangladeshi NS children. MethodsA prospective case-control study was conducted which comprised a total of 142 children having nephrotic syndrome (NS), divided into 2 groups: case group consisted of 40 children with steroid-resistant nephrotic syndrome (SRNS), and control group involved 102 children with steroid-sensitive nephrotic syndrome (SSNS). Both were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for R229Q polymorphism. ResultsThe results indicate the presence of R229Q polymorphism in 27.50% of SRNS and 12.75% of SSNS children. SRNS children possess 2.94-fold greater risk (p = 0.025) of carrying Arg/Gln genotype compared to SSNS children. Moreover, R229Q variant in SRNS children was observed as in a compound heterozygous form with p.Ala297Val located in exon 8. Age of onset (4–6 years) presents as a significant contributing factor (adjusted OR = 1.06; 95% CI = 1.023–1.094; p = 0.001) for SRNS susceptibility in Bangladeshi children. Contrarily, though the incidence of SRNS was higher in male children than female (80% vs 20%), gender remains to be a neutral factor (p = 0.257) in relation to SRNS susceptibility. ConclusionCompound heterozygosity of NPHS2 p.R229Q gene variant with p.Ala297Val may cause pathogenic SRNS in Bangladeshi children. Large scale studies are warranted to establish the genotype-phenotype correlation. It is recommended to screen for p.R229Q first and, if positive, for p.Ala297Val in Bangladeshi SRNS children.

Baseline characteristics and long-term outcomes of steroid-resistant nephrotic syndrome in children: impact of initial kidney histology.

Although many pediatric nephrologists consider focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) as separate clinical entities, whether the initial histology could affect clinical courses in children with steroid-resistant nephrotic syndrome (SRNS) suspected of having an immune-based etiology remains unknown, especially for long-term outcomes. We retrospectively reviewed long-term outcomes (> 3years; median follow-up, 9.1years) of 21 children with initial SRNS (FSGS, N = 9; MCD, N = 12) who achieved complete remission with immunosuppressive agents, including cyclosporine. At NS onset, incidence of acute kidney injury (67% vs. 8%, P < 0.05) and proportion of patients with non-selective proteinuria (56% vs. 0%, P < 0.01) were significantly higher in the FSGS group than the MCD group. Furthermore, median days until complete remission after treatment was significantly longer in the FSGS group than the MCD group (116days vs. 45days, P < 0.001). Although subsequent biopsy histology of the 12 patients in the MCD group was still identical in all MCD, three of nine patients in the FSGS group were reclassified from FSGS to MCD at second biopsy. At last visit, all patients maintained complete remission, and none developed chronic kidney disease. Initial presentation in the FSGS group was characterized by more severe clinical manifestations than the MCD group. If complete remission is achieved, FSGS and MCD in children with immune-mediated SRNS may constitute a single disease spectrum because the long-term outcomes are favorable, irrespective of initial histology.

Complications and renal biopsy profile in childhood steroid resistant nephrotic syndrome

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to study the complications and renal biopsy profile in childhood steroid resistant nephrotic syndrome.Methods: Retrospective observation study done in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Inclusion criteria was children aged 1-12 years diagnosed with steroid resistant nephrotic syndrome defined as absence of remission despite therapy with daily prednisolone at a dose of 2mg/kg/day for 4 weeks. Remission defined as urine albumin nil/trace in 3 consecutive early morning samples. Children less than 1 year of age, children with renal transplant and incomplete records were excluded. Period of study January 2013- December 2015. Informed consent was obtained and 75 cases who fulfilled the study criteria were included in this study. Variables assessed were incidence of hypertension (both at onset of disease and later during the course of disease), incidence of urinary tract infection and its microbiology, associated co-morbidities, complications of nephrotic syndrome and renal biopsy profile.Results: Incidence of hypertension at onset of disease was 13.3% and later during the course of the disease was 48%. Most common infection was UTI (28%) and the most common organism isolated in urine culture was E-coli. Incidence of other co-morbidities like asthma, atopy was 17.3%. No case had evidence of end stage renal disease. 60% of cases had undergone renal biopsy and minimal change disease was the most common biopsy finding.Conclusions: Hypertension and UTI remain important complications in nephrotic syndrome and hence all such children should be continued to be monitored for these complications. Minimal change disease (MCD) was the most common renal biopsy finding.

Clinicopathologic Features and the Association with Short-Term Outcome of Primary Membranous Nephropathy in Children: A Single-Center Study from Pakistan.

Membranous nephropathy (MN) is an uncommon cause of steroid-resistant nephrotic syndrome in children. Our study aimed to determine the clinicopathologic features of primary MN in children and their association with short-term outcome. This observational study was conducted from January 2009 to June 2017 at the Pediatric Nephrology Department. A total of 50 children were diagnosed with primary MN. Their clinical, laboratory, and histopathological findings on renal biopsy were recorded. The minimum follow-up was for six months. Clinicopathologic features were correlated with the outcome at the last follow-up. Data analysis was done using IBM SPSS Statistics for Windows software version 20.0. The mean age at onset was 10.92 ± 3.08 years (range: 4-17 years). The male-to-female ratio was 3:1. The serum albumin of ≤2.5 g/dL was seen in 40 patients (80%), hypertension was present in 38 (76%), and heavy proteinuria was seen in 32 children (70%). The mean estimated glomerular filtration rate (eGFR) at presentation was 178.71 ± 0.78 mL/min/1.73 m2. At the initial visit, nine children (18.4%) were in chronic kidney disease stage 2 and one (2%) in stage 4. Phospholipase A2 receptor antibody was present in five (15%) of 32 children tested. At the last follow-up (28 interquartile range: 25.5 months), 11 children (26%) were in complete remission and 25 (66%) had achieved partial remission. The mean eGFR had reduced to 145.84 ± 78.05 mL/min/1.73 m2. Patients with normal initial eGFR were more likely to go into remission (P = 0.001). The short-term outcome of childhood primary MN is relatively good in our setup. A multicenter collaborative study is required to determine prognostic factors and to standardize treatment in this uncommon nephropathy.

Interventions for idiopathic steroid-resistant nephrotic syndrome in children.

Interventions for idiopathic steroid-resistant nephrotic syndrome in children.

&lt;p&gt;Prevalence rates of histopathologic subtypes associated with steroid resistance in childhood nephrotic syndrome in Sub-Saharan Africa: a systematic review&lt;/p&gt;

IntroductionThe prevalence rates of the common histopathologic subtypes of childhood nephrotic syndrome associated with steroid resistance appear to be changing globally. In Sub Saharan Africa (SSA), the trend is similar over the past few decades.AimThis systematic review aims to determine the current prevalence rates of the histopathologic subtypes associated with childhood steroid-resistant nephrotic syndrome (SRNS) in SSA.MethodsA search of the PubMed, Google and African Journals Online databases was conducted from January to December 2018 using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow-chart to identify relevant articles which met the aim of the systematic review. A qualitative synthesis and descriptive analysis of the extracted data were then conducted. The mean values for the prevalence rates of the reported histopathologic subtypes were calculated. A meta-analysis was not done due to few numbers of studies reviewed. The review is registered with PROSPERO, number CRD42018111916.ResultsIn the West African sub-region, the currently reported histopathologic subtypes associated with childhood nephrotic syndrome are focal segmental glomerulosclerosis (FSGS), minimal-change nephropathy (MCN), membrano-proliferative glomerulonephritis (MPGN), membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MesPGN). The picture is the same in South Africa. More importantly, the predominant histopathologic lesions associated with steroid resistance are FSGS (West Africa) and MCN/FSGS (South Africa), with mean prevalence rates of 57.2% and 36.1% respectively.ConclusionThe prevalence of FSGS is currently high in childhood nephrotic syndrome in SSA. This histopathologic subtype remains the commonest lesion associated with SRNS in this part of the globe.

Prospects of genetic testing for steroid-resistant nephrotic syndrome in Nigerian children: a narrative review of challenges and opportunities.

The prevalence of childhood steroid-resistant nephrotic syndrome (SRNS) ranges from 35% to 92%. This steroid resistance among Nigerian children also reflects underlying renal histopathology, revealing a rare minimal-change disease and a varying burden of membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis (FSGS). FSGS tends to progress to end-stage kidney disease, which requires dialysis and/or renal transplantation. While knowledge of the molecular basis of NS is evolving, recent data support the role of mutant genes that otherwise maintain the structural and functional composition of the glomerular filtration barrier to account for many monogenic forms of FSGS. With the advent of next-generation sequencing, >39 genes are currently associated with SRNS, and the number is likely to increase in the near future. Monogenic FSGS is primarily resistant to steroids, and this foreknowledge obviates the need for steroids, other immunosuppressive therapy, and renal biopsy. Therefore, a multidisciplinary collaboration among cell biologists, molecular physiologists, geneticists, and clinicians holds prospects of fine-tuning the management of SRNS caused by known mutant genes. This article describes the genetics of NS/SRNS in childhood and also gives a narrative review of the challenges and opportunities for molecular testing among children with SRNS in Nigeria. For these children to benefit from genetic diagnosis, Nigeria must aspire to have and develop the manpower and infrastructure required for medical genetics and genomic medicine, leveraging on her existing experiences in genomic medicine. Concerted efforts can be put in place to increase the number of enrollees in Nigeria’s National Health Insurance Scheme (NHIS). The scope of the NHIS can be expanded to cater for the expensive bill of genetic testing within or outside the structure of the National Renal Care Policy proposed by Nigerian nephrologists.

NPHS1基因突变致儿童激素耐药型肾病综合征1例报道

NPHS1基因突变致儿童激素耐药型肾病综合征1例报道

Rituximab therapy for refractory steroid-resistant nephrotic syndrome in children.

Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.

NPHS2 V260E Is a Frequent Cause of Steroid-Resistant Nephrotic Syndrome in Black South African Children

IntroductionIn South Africa (SA), steroid-resistant nephrotic syndrome (SRNS) is more frequent in black than in Indian children.MethodsSeeking a genetic basis for this disparity, we enrolled 33 Indian and 31 black children with steroid-sensitive nephrotic syndrome (SSNS) and SRNS from KwaZulu-Natal, SA; SRNS children underwent kidney biopsy. We sequenced NPHS2 and genotyped APOL1 in 15 SSNS and 64 SRNS unrelated patients and 104 controls and replicated results in 18 black patients with steroid-resistant focal segmental glomerulosclerosis (SR-FSGS). Known FSGS genes (n = 21) were sequenced in a subset of patients.ResultsHomozygosity for NPHS2 V260E was found in 8 of 30 black children with SRNS (27%); all 260E/E carriers had SR-FSGS. Combining SR-FSGS patients from the 2 groups, 14 of 42 (33%) were homozygous for V260E. One black control was heterozygous for V260E; no Indian patients or controls were carriers. Haplotype analysis indicated that homozygosity for V260E was not explained by cryptic consanguinity. Children with NPHS2 260E/E developed SRNS at earlier age than noncarriers (34 vs. 78 months, P = 0.01), and none achieved partial or complete remission (0% vs. 47%, P = 0.002). APOL1 variants did not associate with NS. Sequencing FSGS genes identified a CD2AP predicted pathogenic variant in the heterozygous state in 1 Indian case with SR-FSGS.ConclusionNPHS2 260E/E was present in one-third of black FSGS patients, was absent in black controls and Indian patients, and affected patients were unresponsive to therapy. Genotyping V260E in black children from South Africa with NS will identify a substantial group with SR-FSGS, potentially sparing these children biopsy and ineffective steroid treatment.

Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry.

Background: Steroid resistant nephrotic syndrome (SRNS) is a rare condition, accounting for 10–15% of all children with idiopathic nephrotic syndrome. SRNS can be caused by genetic abnormalities or immune system dysfunction. The prognosis of SRNS varies from permanent remission to progression to end-stage kidney disease, and post-transplant recurrence is common.Objectives: The PodoNet registry project aims to explore the demographics and phenotypes of immune-mediated and genetic forms of childhood SRNS, to assess genotype-phenotype correlations, to evaluate clinical management and long-term outcomes, and to search for novel genetic entities and diagnostic and prognostic biomarkers in SRNS.Methods: In 2009, an international registry for SRNS was established to collect retro- and prospective information on renal and extrarenal disease manifestations, histopathological and genetic findings and information on family history, pharmacotherapy responsiveness and long-term outcomes. To date, more than 2,000 patients have been enrolled at 72 pediatric nephrology centers, constituting the largest pediatric SRNS cohort assembled to date.Results: In the course of the project, traditional Sanger sequencing was replaced by NGS-based gene panel screening covering over 30 podocyte-related genes complemented by whole exome sequencing. These approaches allowed to establish genetic diagnoses in 24% of the patients screened, widened the spectrum of genetic disease entities presenting with SRNS phenotype (COL4A3-5, CLCN5), and contributed to the discovery of new disease causing genes (MYOE1, PTPRO). Forty two percent of patients responded to intensified immunosuppression with complete or partial remission of proteinuria, whereas 58% turned out multi-drug resistant. Medication responsiveness was highly predictive of a favorable long-term outcome, whereas the diagnosis of genetic disease was associated with a high risk to develop end-stage renal disease during childhood. Genetic SRNS forms were generally resistant to immunosuppressive treatment, justifying to avoid such pharmacotherapies altogether once a genetic diagnosis is established. Even symptomatic anti-proteinuric treatment with RAS antagonists seems to be challenging and of limited efficacy in genetic forms of SRNS. The risk of post-transplant disease recurrence was around 30% in non-genetic SRNS whereas it is negligible in genetic cases.Conclusion: In summary, the PodoNet Registry has collected detailed clinical and genetic information in a large SRNS cohort and continues to generate fundamental insights regarding demographic and etiological disease aspects, genotype-phenotype associations, the efficacy of therapeutic strategies, and long-term patient and renal outcomes including post-transplant disease recurrence.

Urinary Neutrophil Gelatinase- Associated Lipocalin in Children with Idiopathic Nephrotic Syndrome: A Biomarker to Differentiate Between Steroid Sensitive and Resistant Forms of Disease

Background: Objectives of the study were to find out the ability of urinary neutrophil gelatinase- associated lipocalin (NGAL) as a biomarker to differentiate between steroid resistant nephrotic syndrome (SRNS) and steroid sensitive nephrotic syndrome (SSNS), and also to observe variation in levels, if any, between focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in SRNS patients.Methods: The study included 63 patients of idiopathic nephrotic syndrome (19 SSNS in relapse, 19 SSNS in remission and 25 SRNS), aged 2.5-16 years, along with 17 controls. Urinary NGAL was measured by ELISA and the values were normalised with urinary creatinine.Results: Median urinary NGAL/creatinine level was significantly raised in SRNS as compared to SSNS relapse, SSNS remission and controls (p 18.3 ng/mg had sensitivity of 84%, specificity of 97.4% and area under the curve of 0.935 (p< 0.001, 95% confidence interval 0.871-0.998) to differentiate SRNS from SSNS patients. Median urinary NGAL/creatinine value was significantly raised in children with FSGS as compared to MCD (p=0.003) in SRNS patients. It had significant positive correlations with duration of illness (r=0.342, p=0.006), urine protein creatinine ratio (r=0.594, p< 0.001) and negative correlation with serum albumin (r=0.470, p<0.001).Conclusion: Urinary NGAL/creatinine level correlated with activity of the disease and it can distinguish not only SRNS from SSNS but also FSGS and MCD histopathological sub-types of SRNS in children.

Analysis of native kidney biopsy: Data from a single center from Bihar, India.

This is a retrospective study of all native kidney biopsies performed at our center between October 1, 2012 and March 31, 2015. Relevant clinical and laboratory variables were recorded. Biopsy samples were processed for light microscopy and immunofluorescence in all cases. Histological classification was adapted from the World Health Organization recommendations. The indications for kidney biopsy were nephrotic syndrome in adults in 190 cases, rapidly progressive renal failure in 43, unexplained renal failure in 25, and steroid-resistant nephrotic syndrome in children in 12. The mean age of the patients was 31.48 ± 13.46 years. Male-to-female ratio was 1.87:1. Mean serum creatinine (SCr) of the patients was 2.36 ± 2.07 mg/dL. Primary glomerulonephritis accounted for 88.89% of cases (240) while secondary glomerulonephritis accounted for 7.40% of total cases (20). Interstitial disease accounted for 1.5% and vascular disease for 2.2%. The most common lesion among primary glomerulonephritis was focal segmental glomerulosclerosis (FSGS) (31.11%) followed by diffuse proliferative glomerulonephritis (DPGN) (13.33%) and membranous glomerulonephritis (MGN) (12.59%). Among secondary glomerulonephritis, lupus nephritis was the most common (5.56%). In patients with SCr 1.4 mg/dL or less (n = 131), FSGS was the most common histology (17.26%) followed by MGN (23.66%) and minimal change disease (7.63%). Whereas, in patients with SCr more than 1.4 mg/dL (n = 139), DPGN was the most common diagnosis (23.74%) followed by FSGS (17.26%) and IgAN (12.23%). Fourteen patients (5.2%) had one or more episode of gross hematuria, three of whom required blood transfusion. The overall FSGS was the most common lesion seen. When we consider only patients with deranged renal function, DPGN was the most common histopathological lesion. The reason for disproportionate high incidence for DPGN is not clear and requires further research.

Efficacy and safety of cyclosporine versus tacrolimus in steroid and cyclophosphamide resistant nephrotic syndrome: A prospective study

Calcineurin inhibitors (CNIs) are the preferred drugs for treatment of childhood steroid-resistant nephrotic syndrome (SRNS) who are also resistant to cyclophosphamide (CYC). Although few studies have shown a benefit of one over the other, efficacy and safety of either CNIs (tacrolimus [TAC] or cyclosporine [CSA]) in this special population remained to be assessed in long-term studies. Forty-five children with SRNS who were also resistant to CYC (CYC-SRNS) from January 2006 to June 2011, were included in the study. Patients were treated with CNI either TAC or CSA based on 1:1 allocations and were prospectively observed. Patients who were nonresponsive to CNIs had been treated with mycophenolate mofetil. Outcomes were measured in terms of remission of NS, adverse effects of drugs, and progression of disease. After 6 months of treatment, 16/23 (69.5%) patients on CSA achieved remission and 18/22 (81.8%) on TAC achieved remission (P = 0.3). The side effects hypertrichosis, and gum hyperplasia were significantly less in TAC group as compared to CSA group (P < 0.001). The 1-, 2-, 3-, 4-, and 5-year estimated renal survival (doubling of serum creatinine as event) in CSA group was 96%, 91%, 85%, 54%, and 33% and in TAC group was 96%, 95%, 90%, 89%, and 79%, respectively (P = 0.02). Although TAC and CSA are equally efficacious, TAC has significantly less side effects. The long-term outcome of renal function was significantly better in patients who were treated with TAC as compared to CSA.