Steroid-dependent Nephrotic Syndrome Research Articles

Spectrum of Infections in Children with Primary Nephrotic Syndrome: Cross Sectional Study:

Background and Aim: Steroids are the mainstay of initial treatment in children with Idiopathic Nephrotic Syndrome (INS). The role of diuretics in children with NS is less clear in comparison to adults. In cases with severe or refractory edema, furosemide is often combined with albumin infusion (0.5 to 1 g/kg) to provide symptomatic relief. Methods: This study was a retrospective chart review of 17 patients with a diagnosis of Steroid Dependent Nephrotic Syndrome (SDNS) admitted for relapse of NS with severe edema who were resistant to diuretic therapy alone. The patients were treated as per unit protocol with an infusion of 100 ml intravenous albumin 20% over 4 hours and 2 doses (one in the morning at 10 AM and the other in the evening at 6 PM) of furosemide 1mg/kg for 3 days. Response to therapy and adverse events were evaluated. Results: The mean age of the study population was 10.58±1.5 years. All of the patients had severe edema and none of them had responded to intravenous diuretics alone. After co-administration of intravenous albumin infusion and furosemide, the mean weight loss per day per patient was 0.87±0.16 kg. Conclusion: A significant improvement was noted in all of the patients following co-administration of albumin and furosemide without any adverse events.

Intravenous Albumin and Diuretic in Nephrotic Syndrome with Severe Edema: Our Experience and Literature Review :

Background and Aim: Steroids are the mainstay of initial treatment in children with Idiopathic Nephrotic Syndrome (INS). The role of diuretics in children with NS is less clear in comparison to adults. In cases with severe or refractory edema, furosemide is often combined with albumin infusion (0.5 to 1 g/kg) to provide symptomatic relief. Methods: This study was a retrospective chart review of 17 patients with a diagnosis of Steroid Dependent Nephrotic Syndrome (SDNS) admitted for relapse of NS with severe edema who were resistant to diuretic therapy alone. The patients were treated as per unit protocol with an infusion of 100 ml intravenous albumin 20% over 4 hours and 2 doses (one in the morning at 10 AM and the other in the evening at 6 PM) of furosemide 1mg/kg for 3 days. Response to therapy and adverse events were evaluated. Results: The mean age of the study population was 10.58±1.5 years. All of the patients had severe edema and none of them had responded to intravenous diuretics alone. After co-administration of intravenous albumin infusion and furosemide, the mean weight loss per day per patient was 0.87±0.16 kg. Conclusion: A significant improvement was noted in all of the patients following co-administration of albumin and furosemide without any adverse events.

Multiple opportunistic infection-associated hemophagocytic lymphohistiocytosis in nephrotic syndrome: A case report

Multiple opportunistic coinfections during corticosteroid therapy for the nephrotic syndrome are uncommon. Infection-associated hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal multisystem disorder, manifesting as a state of hypercytokinemia in response to an infectious trigger. We describe a 4½-year-old boy with steroid-dependent nephrotic syndrome receiving high-dose steroids, who developed respiratory failure due to pulmonary tuberculosis, Cytomegalovirus, and Pneumocystis jirovecii coinfections; HLH complicated the course. Aggressive management of the underlying infections with antitubercular, antiviral, and antifungal therapy, prompt recognition of HLH, and immunomodulation with intravenous (IV) immunoglobulin and IV methylprednisolone enabled convalescence. This report emphasizes the serious risks of immunosuppression and the need for strict vigilance for rare opportunistic infections with multiple pathogens in patients receiving oral steroids for nephrotic syndrome. Clinical distinctions between severe sepsis and HLH may be ambiguous; a high level of suspicion is required for timely recognition and management.

Safety and efficacy of mycophenolate mofetil as first-line immunosuppressive therapy in children with steroid-dependent nephrotic syndrome

Introduction. More than half of children with idiopathic nephrotic syndrome have relapsed or become steroid-dependent after the disease’s onset. So far they, require long-term therapy with glucocorticosteroids and/or other immunosuppressive treatment to maintain remission. Despite the widespread use of immunosuppressive agents, there is no consensus for appropriate first-line therapy. Materials and methods. A retrospective study included children presenting with steroid-dependent nephrotic syndrome who received treatment with mycophenolate mofetil in the Nephrology department between 2003 and 2018 at the National Medical Research Center for Children’s Health (Moscow). Results. In total, withdrawal of corticosteroids was recorded in 24 (85.7%) patients, while the median remission period was 23 [12; 30] months, after glucocorticosteroids cessation - 19 [10; 24.5] months, the cumulative dose of steroids was reduced from 189 [125.9; 240] to 45.5 [19.5; 68.2] mg/kg per year and relapses rate per year from 1.9 [1.35; 2.35] to 0 during a year. Among children who did not overcome steroid dependence, the treatment failed in 3 patients, and in 1 child, the steroid dosage has been reduced to the lower dose. Conclusion. Mycophenolate mofetil has a favorable efficacy due to the significant reduction of the cumulative dose of steroids and maintenance of long-term remission of nephrotic syndrome after glucocorticosteroid cessation and may be recommended as the first-line therapy in children with steroid-dependent nephrotic syndrome.

A case report on usage of rituximab on complicated steroid-dependent nephrotic syndrome

Nephrotic syndrome (NS) is one of the common yet challenging childhood disease. Treating NS with immunosuppressants like corticosteroids is typically effective. However, there are significant evidences which displayed resistance patterns to the former drugs. Here in this case, a male patient came to the nephrology department with the history of steroid dependant nephrotic syndrome with complaint of its infrequent relapse. The condition was complicated since, the patient was on multiple steroids even after which there were recurrent episodes of syndrome. Considering the status, Mycophenolate mofetil was added as a supportive treatment for the management of the disease along with steroids, still the outcome was unremarkable. Hence, rituximab was ordered (four cycles). The outcome this time was appreciable, rituximab administration produced a positive result. No events were recorded during the treatment duration. 

Efficacy of tacrolimus in steroid dependent and steroid resistant childhood nephrotic syndrome - A retrospective study

Introduction: Nephrotic syndrome is a common renal disease in children. Majority of the children usually responds to steroids without any long term effects on kidney function.  However about 10-20% of children are usually steroid dependent or steroid resistant and require multiple additional immunosuppressive medications such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil and Rituximab. All these drugs are associated with specific adverse effects and lack of response to the drug can result in slow decline in renal function and development of end stage renal disease. Material and Methods:A retrospective study was done to determine the efficacy of tacrolimus in steroid dependent and steroid resistant nephrotic syndrome (SDNS and SRNS). 40 children with SDNS and SRNS were included in the study. All patients were observed for complete remission, partial remission, decline in renal function and adverse effects of the drug. Results:Study included 40 patients of SDNS (n=19) and SRNS (n=21) with 18 boys and 22 girls with mesangioproliferative glomerulonephritis (MPGN) in 1. Complete remission was achieved in 14 children in SDNS group and 11 children in SRNS group. 3 children in SDNS group and 4 children in SRNS group did not achieve any remission despite treatment for 6 to 12 months. Adverse effects of the drugs included infections, tremors and hyperglycemia and were similar in both the groups.mean duration of follow up of 24 months. Renal biopsy of patients showed minimal change disease (MCD) in 23, focal segmental glomerulosclerosis (FSGS) in 13, IgM nephropathy in 3 and Conclusion: Tacrolimus is efficacious in inducing and maintaining remission in children with steroid dependent and steroid resistant nephrotic syndrome with minimal adverse effects. Keywords: Steroid resistant nephrotic syndrome, Calcineurin inhibitor, cyclosporine, tacrolimus, minimal change disease.

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

BackgroundApproximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant.MethodsThis is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed.DiscussionThe study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols.Trial registrationThis trial was prospectively registered to the Clinicaltrial.gov (NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Trials Registry of India (CTRI/2019/04/018517 dated 09/04/2019).

Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis.

BackgroundThe efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), are still inconclusive.MethodsWe performed a systematic review and meta-analysis registered in  PROSPERO (CRD42019148102) by pooling data of cohort studies or case series on adult patients with difficult-to-treat NS. Steroid-resistant NS was excluded. The primary outcomes were the complete remission (CR) rate and the relapse rate. Partial remission (PR) rate, no response (NR) rate and adverse events were the secondary outcomes. A random-effects model was performed for all the outcomes. ResultsWe included 21 studies involving 382 adult MCD/FSGS subjects with a median follow-up duration from 12 to 43 months. RTX treatment induced a pooled 84.2% CR rate [95% confidence interval (CI): 67.7–96.3%], while MCD patients had a high 91.6% CR rate and FSGS patients a moderate 43% CR rate. However, 27.4% (95% CI 20.7–34.5%) of the patients relapsed during the follow-up. The pooled PR and NR rates were 5.8% (95% CI 1.2–12.5%) and 5.2% (95% CI 0.0–15.0%), respectively. RTX was associated with trivial adverse events and good tolerance.ConclusionsIn summary, by pooling results of current pilot studies, RTX may be an effective and relatively safe alternative for most adult FR or SD MCD/FSGS to displace calcineurin inhibitors or prednisone in the hierarchy of treatment. More clinical trials comparing RTX with other immunosuppressants and concerning the long-term adverse events are needed.

Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome

AimAim of the study was to determine if carotid intima media thickness in children with idiopathic nephrotic syndrome is greater than in healthy subjects, and to assess whether carotid intima media thickness in children with nephrotic syndrome is associated with clinical (including disease duration, cumulative dose of steroids, number of relapses) and biochemical parameters. MethodsA cross-sectional study included 40 patients with nephrotic syndrome (mean age 11.7±4.7 years). Steroid dependent nephrotic syndrome was established in 32 patients (80%), while 8 (20%) had steroid resistant nephrotic syndrome. Control group consisted of 20 age and gender matched healthy children. Blood pressure based on 24-h ambulatory blood pressure monitoring (ABPM), carotid intima media thickness, fasting glucose, insulin, HbA1c, lipid concentrations were measured in all children. ResultsA significant difference was detected in carotid intima media thickness values (P=0.036). Children with nephrotic syndrome had significantly greater carotid intima media thickness compared with healthy children (0.42±0.06 and 0.38±0.03mm). Carotid intima-media thickness was positively associated with duration of nephrotic syndrome (r=0.45; P=0.004), body mass index (r=0.48; P=0.002), daytime systolic blood pressure (r=0.46; P=0.003) and night-time systolic blood pressure (r=0.52; P=0.001). Multiple linear regression showed that duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness in children with nephrotic syndrome (R2=0.244; β=0.327; P=0.037). ConclusionThe findings of the present study suggest subclinical vascular damage in patients with nephrotic syndrome. Duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness.

Is Cyclosporine Ototoxic?

Cyclosporine was discovered in 1970, it was isolated from the fungus Tolypocladium inflatum in Switzerland (1). Soon after, an immunosuppressive property was suggested, and by 1978, it was used for the first time in human kidney transplantation to treat organ rejection post-transplant (2). It is now used as a treatment for solid organ, as well as bone marrow transplantation. Its immunomodulatory capacity has extended its use to other immune-mediated diseases such as severe forms of rheumatoid arthritis and psoriasis, steroid-dependent, frequently relapsing or steroid-resistant nephrotic syndrome, graft vs. host disease, refractory posterior uveitis/Behcet disease and amyotrophic lateral sclerosis (2, 3).

Retrospective single-arm cohort study of steroid-dependent minimal change nephrotic syndrome treated with very low-dose rituximab.

Conclusions regarding the best rituximab (RTX) dose to maintain remission and reduce immunosuppressant dependence in adult patients with steroid-dependent minimal change nephrotic syndrome (MCNS) are inconsistent. We report the first low-dose (< 375 mg/m2 BSA) RTX therapy, administered once every 6 months. In this retrospective single-arm cohort study, we investigated the safety and efficacy of low-dose RTX therapy to reduce and ultimately stop prednisolone (PSL) and cyclosporine (CyA) treatment. 13 patients (8 men and 5 women; aged 16 - 65 years; 8-year median treatment history; 12 patients concurrently taking CyA) with steroid-dependent MCNS were chosen to maintain remission following low-dose RTX (200 mg/body) administration. The median period of subject observation following the first RTX dosing was 34 months (cumulative RTX dose: 400 - 1,400 mg). RTX significantly reduced PSL and CyA doses during the final observation in each subject (median dose: PSL 15→0 mg/day, p = 0.0002; CyA 80→0 mg/day, p = 0.0005). All patients maintained complete remission after discontinuing both drugs for a median complete remission (CR) maintenance period of 25 months. One patient showed relapse following the first RTX dose, but a temporary increase in PSL and CyA dose restored the remission. No serious RTX-related adverse effects were observed. Even with MCNS remission, peripheral CD19-positive cell count was not depleted in 90.5% of all cases. Low-dose RTX therapy appears to be effective in maintaining remission and reducing immunosuppressant doses in patients with steroid-dependent MCNS, which might involve a B-cell-independent mechanism.

Efficacy and safety of rituximab for childhood refractory nephrotic syndrome: A meta-analysis of randomized controlled trials

BackgroundIdiopathic nephrotic syndrome is the most common glomerular disease in children, but there are still some difficulties in treating childhood steroid-dependent or steroid-resistant nephrotic syndrome (SDNS/SRNS). Rituximab (RTX) might be an effective and safe choice. MethodsStudies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to April 2020. Only randomized controlled trials (RCT) were included. ResultsOf 1383 screened articles, 6 RCTs with 334 participants were included. RTX was better than the control group at improving relapse-free rate in the short term [RR (risk ratio) (95% CI (confidence interval)), 1.84(1.41, 2.39)]. As for long-term, RTX did not show significant improvement [RR (95% CI), 4.43(.57, 34.67)]; but in subgroup analysis, RTX was still better than conventional drugs and tacrolimus [RR (95% CI), 9.91(1.95, 50.52) and 1.42(1.15, 1.75), respectively]. And there was a difference between the two groups of prednisolone dose after treatment [MD (mean difference) (95% CI), −.22(−.36, −.09) mg/kg/d)]. However, RTX did not significantly improve serum albumin and creatinine [MD (95% CI), 3.46(−1.40, 8.32)g/L and −3.66(−11.79, 4.48)μmol/L, respectively]. No significant differences between the RTX and the control group were found in total adverse events (AEs) or serious AEs. ConclusionChildhood SDNS/SRNS patients appear to benefit from RTX in relapse-free rate and dose of prednisolone use. Also, RTX did not significantly increase the incidence of AEs. But RTX did not show improvements in biological indicators, more studies are required to explain the effect of RTX.

Development and Validation of a Highly Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique to Determine Levamisole in Plasma and Saliva.

Levamisole is used as a steroid-sparing drug for the treatment of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome in children. As part of a large multicentre randomized controlled trial with levamisole, pharmacokinetic and pharmacodynamic parameters of levamisole in children with idiopathic nephrotic syndrome were investigated, as well as the feasibility of using saliva as an alternative and patient-friendly matrix for determining levamisole concentrations. In this study, the authors presented the development and validation of a highly sensitive method for determining levamisole in plasma and saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In 100 μL samples, proteins were precipitated with 750 μL acetonitrile/methanol 420:80 (v/v) with levamisole-D5 as an internal standard. Calibration standards were prepared over a range of 0.1 ng/mL-50 ng/mL. To determine ultrafiltration efficiency, the ultrafiltrate was obtained by centrifuging blank plasma samples over the filter. Both filtered and nonfiltered samples were analyzed. For plasma, accuracy and within-run and between-run imprecision were between 95.0% and 100% and <14.5%, respectively, and for saliva, between 100.9% and 107.5%, and <13.3%. No significant matrix effects were observed. Samples were stable at benchtop for 24 hours and -80°C, for at least 14 months (stability experiments ongoing). The ultrafiltration efficiency of unbound concentrations in plasma was lower than 85% (58.9%) but stable, and, therefore, the observed concentration should be corrected. Based on observations, the developed measure can determine levamisole concentrations in participant saliva samples.

Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial

IntroductionGuidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to...

Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.

Rituximab in children with steroid sensitive nephrotic syndrome: in quest of the optimal regimen.

Rituximab has emerged as an effective and important therapy in children with complicated frequently relapsing and steroid-dependent nephrotic syndrome to induce long-term disease remission and avoid steroid toxicities. The optimal rituximab regimen is not totally well defined, and there are many varying practices worldwide. We will in this review describe how patient factors, rituximab dose, and use of maintenance immunosuppression affect treatment outcomes. Specifically, low-dose rituximab without concomitant immunosuppression is associated with shorter relapse-free duration while other regimens have comparable outcomes. Patients with more severe disease generally have worse response to rituximab. Although rituximab appears to be generally safe, there are growing concerns of chronic hypogammaglobulinemia and impaired immunity especially in young children. Reliable prognostications and biomarkers for guiding subsequent treatments to avoid excessive treatments are yet to be identified. In this review, we will outline the, as we see it, best approach of rituximab in childhood steroid sensitive nephrotic syndrome at the present state of knowledge.

Unfavorable impact of anti-rituximab antibodies on clinical outcomes in children with complicated steroid-dependent nephrotic syndrome.

Anti-rituximab antibodies (ARA) are associated not only with adverse events, such as infusion reactions (IR) and serum sickness, but also with rituximab efficacy. However, the clinical relevance of ARA in children with steroid-dependent nephrotic syndrome (SDNS) remains unknown. We retrospectively reviewed clinical outcomes of 13 children with complicated SDNS receiving repeated single-dose rituximab treatments at 375 mg/m2 to assess whether ARA formation could impact toxicity and efficacy of additional rituximab. Pre-rituximab 22 samples collected from patients who developed IR during the second or subsequent rituximab doses were measured by electrochemiluminescence analysis. ARA were identified in 5 of 13 patients (9 of 22 samples). Median time to recovery of CD19+ B cells to > 1% of total lymphocytes and median relapse-free time after rituximab treatment were significantly shorter in the 9 ARA-positive samples than the 13 ARA-negative samples (41 vs. 100 days, p < 0.01 and 119 vs. 308 days, p < 0.05, respectively). Kaplan-Meier analysis showed that time to CD19+ B cell recovery after rituximab was significantly shorter in ARA-positive samples than in ARA-negative samples (p < 0.005). Severe IR developed in two ARA-positive patients and serum sickness in one ARA-positive patient. The incidence of ARA formation was high in the pre-rituximab samples of patients with complicated SDNS who developed IR during the second or subsequent rituximab doses, suggesting that ARA formation might have an unfavorable impact on the toxicity and efficacy of additional rituximab doses in these patients.

P0238LONG-TERM OUTCOME OF CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME

Abstract Background and Aims Little is known about the long-term outcome of childhood idiopathic nephrotic syndrome (INS), in particular long-term complications, rate of relapses, frequency of prolonged steroid (S) and immunosuppressive treatment (IS). The choice of immunosuppressive drug remains discussed. Our aim was to study the long-term outcome in adulthood of patients with INS diagnosed during childhood. Method In this monocentric retrospective study, we included all adult patients (&amp;gt;18 years) admitted in our nephrology department between 2013 and 2019 with INS diagnosed during childhood. Patients who reached ESRD during childhood were excluded. Data regarding the outcome in adulthood were obtained through clinical database and medical charts. Results Eighty-two patients (M/F = 2/1) were included. Sixty-height patients had steroid-sensitive nephrotic syndrome (SSNS), including 52 with steroid-dependant nephrotic syndrome (SDNS). The other 14 patients had steroid-resistant nephrotic syndrome (SRNS). The median age at diagnosis was 3.9 years (1.2-16.5). The median number of relapses during childhood was 12 (0-52), 0.9/patient/year. 89% of patients received IS therapy in addition to S during childhood: median number of successive therapeutic lines was 3 (0-10) per child. Median follow-up during adulthood was 4.6 (0.1-25) years. 67% of patients experienced at least one relapse during adulthood, with a median number of relapses of 0.53 (0-3.7)/patient/year. Risk of relapse during adulthood was significantly associated with the total number of relapses during childhood (p=0.015) and with the number of relapses per year during childhood (p=0.007). 45% of patients received IS in addition to S during adulthood, mainly mycophenolate mofetil (23/82), calcineurin inhibitors (21/82) and rituximab (12/82). High blood pressure was observed in 22% of patients. At last follow-up, median eGFR was 90 (64-117) mL/min/1.73m in SSNS patients, 86 (57-126) mL/min/1.73m in SDNS patients and 70 (23-113) mL/min/1.73m in SRNS patients. Only 4/82 patients presented with eGFR lower than 60 mL/min/1.73m. Among them, 3 had SRNS. Only 1 thrombo-embolic event and 3 severe infections were reported. Bone densitometry was performed in 26 adult patients and osteopenia was found in 19 of them (73%). Conclusion The incidence of relapses in adulthood was relatively high in our study. However bias related to inclusion criteria could play a role. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent but major complications were rarely reported.

P1800RITUXIMAB ENHANCES THE EXPRESSION OF INTERLEUKIN-6 VIA TOLL-LIKE RECEPTOR 3 SIGNALING IN HUMAN PODOCYTE

Abstract Background and Aims The etiology of idiopathic nephrotic syndrome (INS) in children remains unclear, but it is well known that viral infections often cause relapses of INS. Since toll-like receptor 3 (TLR3), a ligand of viral dsRNA exists in podocytes, dysregulation of TLR3 signaling in podocytes may be involved in the pathogenesis of INS. Recently, rituximab (RTX) a specific antibody to human CD20, has been successfully used to treat children with intractable nephrotic syndrome (frequent relapse nephrotic syndrome, FRNS, and steroid dependent nephrotic syndrome, SDNS). It has been reported that depletion of B cell is main mechanism of RTX treatment. However, some patients experienced recurrence before peripheral blood B cell recovery, whereas selected patients have sustained remission even after peripheral blood B cell recovery. Considering that dramatic effects of RTX in the treatment of INS, it is speculated that some B cell-independent mechanisms of RTX exist. In this context, some recent studies have reported a direct effect of RTX on podocyte, targeting sphingomyelinase phosphodiesterase acid-like 3b (SMPDL3b), but detailed mechanisms remain to be determined. In this study, we examined whether RTX influences TLR3 signaling in cultured human podocyte. Method Immortalized human podocytes in culture were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA. RTX were added before or after the treatment of poly IC. Then, expression of interleukin (IL)-6 were measured using real time RT-PCR and ELISA. Direct binding of RTX to podocyte were confirmed by immunofluorescence. Results Poly IC induced the expression of IL-6 in cultured human podocyte in a concentration and time-dependent manner. IL-6 expression induced by poly IC were enhanced in both mRNA and protein level by pretreatment of RTX. RTX itself were apparently stained on podocyte by immunofluorescence. Conclusion RTX binds directly to cultured human podocyte and enhances the IL-6 expression induced by poly IC. Since IL-6 from podocyte was reported to be engaged in regulating glomerular inflammation by cross-talk with endothelial cells, exploring the role of enhanced IL-6 from podocyte by RTX, at least in a part, suggests a direct mechanism of RTX in treating intractable nephrotic syndrome in children.

SARS-CoV-2 infection in Spanish children with chronic kidney pathologies

BackgroundThere is little information about Coronavirus Disease 2019 (COVID-19) in children with underlying chronic renal pathologies.Cases reportFrom March until April 15, 2020, 16 children with chronic renal pathologies were diagnosed with COVID-19 in Spain. Of these, 6 had end-stage kidney disease (ESKD) (3 transplant recipients and 3 on chronic hemodialysis). The severity of symptoms was mild in all the patients, with little radiological involvement. Three patients were asymptomatic. Fever and upper respiratory symptoms were the most frequent findings. Basal glomerular filtration worsened in 3 patients; however, recovery was rapidly achieved with rehydration and drug dose adjustment. In 2 patients diagnosed with steroid-dependent nephrotic syndrome, COVID-19 provoked a disease relapse. None required oxygen therapy, and 7 could be managed as outpatients.ConclusionsCOVID-19 disease appears to have a similar clinical course in children with underlying chronic renal pathologies, even in immunosuppressed cases, as in healthy children of the same age; however, special attention must be paid to fluid management and drug dose adjustment.