Search

Background: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown., Methods: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated., Results: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5., Conclusion: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Although evidence has confirmed that cyclosporine (CS) is efficacious against childhood-onset steroid-dependent and steroid-resistant nephrotic syndrome (SD/SRNS), some patients may continue to relapse during adulthood. However, predictive factors for adult active disease and kidney complications, such as chronic kidney disease (CKD) and hypertension, in this cohort remain unknown., Methods: We conducted a retrospective study on the long-term outcomes of 81 young adults with childhood-onset SD/SRNS treated with CS. The primary endpoint was the probability of active disease into adulthood. The secondary endpoint was the probability of developing kidney complications., Results: At the last follow-up (median age, 23.2 years; median disease duration, 15.8 years), 44 adult patients (54%) continued to have active disease, whereas 16 patients developed CKD or hypertension, respectively. The proportion of patients developing kidney complications was similar between the active disease and long-term remission groups. Young age at NS onset and history of relapse during the initial CS (median, 31 months) were independent predictive factors for active disease. Acute kidney injury at NS onset, focal segmental glomerulosclerosis, and irreversible CS nephrotoxicity were identified as risk factors for the development of CKD, whereas older age was identified as a risk factor for the development of CKD and hypertension., Conclusions: More than 50% of adult survivors treated with CS continued to have active disease, and each 20% developed CKD or hypertension. A long-term follow-up is necessary for patients with SD/SRNS to identify the development of kidney complications later in adulthood that can be attributed to prior disease and CS treatment in childhood, irrespective of disease activity. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Despite the fact that rituximab (RTX)-associated adverse events may be relatively frequent in younger patients, recent studies have reported RTX as a suitable first-line steroid-sparing agent for maintaining remission in children with steroid-dependent nephrotic syndrome (SDNS). However, the impact of age at RTX initiation on the long-term outcome remains unknown in this cohort., Methods: We retrospectively reviewed the clinical course of 61 patients with complicated SDNS who received a single dose of RTX (375 mg/m 2 ) followed by maintenance immunosuppressive agents (IS) from January 2008 to March 2021. In patients who achieved > 12 months of prednisolone-free remission, IS tapering within 6 months was tried to achieve. The primary endpoint was the probability of achieving long-term treatment-free remission at the last follow-up., Results: After RTX initiation, 52 patients (85.2%) relapsed after a median of 665 days, and 44 patients (72.1%) received additional RTX doses (total, 226 infusions). At the last follow-up (median observation period, 8.3 years; median age, 18.3 years), 16 patients (26.2%) achieved long-term remission. Multivariate analysis showed that older age at RTX initiation was the independent predictive factor for achieving long-term remission (odds ratio, 1.25; p < 0.05). The proportion of those who achieved long-term remission was significantly higher in patients aged ≥ 13.5 years than in those aged < 13.5 years at RTX initiation (52.6 vs 14.3%, p < 0.05). Persistent severe hypogammaglobulinemia did not develop in older children (≥ 13.5 years) at RTX initiation., Conclusion: For older children with complicated SDNS, RTX appeared to be a suitable disease-modifying therapy without persistent adverse events., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients., Methods: This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates., Results: The distribution of histologic variants according to the Columbia classification was 45% ( n =53) FSGS not otherwise specified, 21% ( n =25) cellular, 15% ( n =18) perihilar, 13% ( n =16) collapsing, and 6% ( n =7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P <0.001)., Conclusions: We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS., Competing Interests: R. Hamada reports research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., and Teijin Pharma Ltd.; and honoraria from Alexion Pharmaceuticals, Inc., Asahi Kasei Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. T. Horinouchi reports research funding from Otsuka Pharmaceutical Co., Ltd. K. Iijima reports consultancy for JCR Pharmaceuticals Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., and Zenyaku Kogyo Co., Ltd.; research funding from Air Water Medical, Inc., Astellas Pharma, Inc., Eisai Co., Ltd., JCR Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., and Zenyaku Kogyo Co., Ltd.; honoraria from Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Integrated Development Associates Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Shionogi & Co., Ltd., and Zenyaku Kogyo Co., Ltd.; a patent application on the development of antisense nucleotides for exon skipping therapy in Alport syndrome; and an advisory or leadership role for CJASN and Pediatric Nephrology (Editorial Board). S. Ito reports consultancy for Alexion Pharma, Takeda Pharmaceutical Company, Teijin Pharma, and Zenyaku Kogyo Co Ltd.; research funding from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., CSL Behring, Kyowa Hakko Kirin Co., Ltd., Maruho Pharma, Mitsubishi Tanabe Pharma, and Teijin Pharma Ltd.; honoraria from Alexion Pharma, Teijin Pharma Ltd., and Zenyaku Kogyo Co., Ltd.; an advisory or leadership role for Clinical Experimental Nephrology, JMA Journal, and the Korean Journal of Pediatrics; and participation in a speakers’ bureau for AbbVie LLC, Alexion Pharma, Asahi Kasei Pharma, Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring, Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Pfizer Japan, Inc., Sanofi Co., Ltd., Teijin Pharma Ltd., and Zenyaku Kogyo Co., Ltd. K. Kamei reports research funding from Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Public Foundation of Vaccination Research Center, Taiju Life Social Welfare Foundation, Terumo Foundation for Life Sciences and Arts, Ono Pharmaceutical Co; Otsuka Pharmaceutical Co., Ltd., Teijin Pharma Ltd; Shionogi Co., Ltd.; and honoraria from Baxter Ltd., Tanabe Mitsubishi Pharma, and Zenyaku Kogyo Co., Ltd. K. Matsuoka reports participating in a speakers’ bureau for Chugai Pharmaceutical Co., Ltd. K. Nozu reports research funding from Chugai Pharmaceutical Company, Dainippon Sumitomo Pharmaceutical Company, Kyowa Kirin Pharmaceutical Company, and Shionogi, Inc.; patents or royalties from Daiichi Sankyo Pharmaceutical Company; an advisory or leadership role for Kyowa Kirin Pharmaceutical Company and Toa Eiyo Ltd.; and receiving lecture fees from Chugai Pharmaceutical Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Ltd., Kyowa Kirin Pharmaceutical Company, Novartis Pharma Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far., Methods: We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS., Results: At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001)., Conclusions: UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant., (© 2022. Japanese Society of Nephrology.)

Mizoribine may be a safe and effective treatment for children with steroid-dependent nephrotic syndrome (SDNS). However, predictors of treatment response and long-term outcomes after mizoribine discontinuation remain unknown. We retrospectively reviewed the clinical course of 22 children aged ≤ 10 years (median age, 5.3 years) with SDNS who received high-dose mizoribine as the initial steroid-sparing agent (SSA). Mizoribine was administered at a single daily dose of 10 mg/kg (maximum, 300 mg/day) after breakfast. The dose was adjusted to maintain 2-h post-dose mizoribine levels of > 3 μg/mL and was tapered off after 12 months of steroid-free remission. Patients who regressed to SDNS were switched from mizoribine to other SSAs. The primary endpoint was probability of survival without regression to SDNS after mizoribine initiation. Ten patients were able to discontinue SDNS (response group), whereas twelve were switched from mizoribine to other SSAs (non-response group) during a median observation period of 6.0 years after mizoribine. The steroid-dependent dose prior to mizoribine was significantly lower in the response group than in the non-response group (p < 0.05). The Kaplan-Meier analysis revealed that the probability of regression-free survival was significant higher in patients with steroid-dependent dose of < 0.25 mg/kg/day than in those with steroid-dependent dose of ≥ 0.25 mg/kg/day (p < 0.05). During a median follow-up of 5.5 years after mizoribine discontinuation, all but one patient did not develop SDNS. High-dose mizoribine may be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes.

Background: 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., Methods: We retrospectively reviewed long-term outcomes (> 3 years; median follow-up, 9.1 years) of 21 children with initial SRNS (FSGS, N = 9; MCD, N = 12) who achieved complete remission with immunosuppressive agents, including cyclosporine., Results: 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 (116 days vs. 45 days, 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., Conclusions: 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.

Background: 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., Methods: We retrospectively reviewed clinical outcomes of 13 children with complicated SDNS receiving repeated single-dose rituximab treatments at 375 mg/m 2 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., Results: 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., Conclusions: 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.

Background: Although recent studies have shown that more than half of children with steroid-dependent nephrotic syndrome (SDNS) may continue to have active disease beyond childhood, the long-term outcome in this cohort treated with mycophenolate mofetil (MMF) after cyclosporine remains unknown, particularly in adulthood., Methods: We conducted a retrospective study of 44 adult patients (median age, 22.3 years) who received MMF for complicated SDNS (median age at MMF initiation, 13.3 years) at a single center. Complicated SDNS was defined as the case continuing to relapse after cyclosporine (CsA) treatment. When patients experienced relapses despite MMF initiation, they additionally received a rituximab infusion. The primary endpoint was the probability of achieving treatment-free remission for > 2 years., Results: Prior to MMF initiation, all patients received CsA for a median of 46 months and 19 received the 12-week cyclophosphamide. After switching from CsA to MMF, only four patients did not relapse during a median follow-up period of 9.6 years. At the last visit, only 15 of the 44 patients achieved treatment-free sustained remission. Multivariate analysis revealed that young age (< 6 years) at onset of nephrotic syndrome (odds ratio, 11.3) and the experience of steroid dependency during initial CsA treatment (odds ratio, 29.8) were the independent risk factors of active disease into adulthood after MMF initiation., Conclusions: Although none developed renal insufficiency and severe adverse effects of therapy, the introduction of MMF after CsA treatment may not be necessarily associated with improved long-term outcome of children with complicated SDNS.

Background: Although rituximab (RTX) may be effective treatment in children with nephrotic syndrome who are resistant to cyclosporine A and steroid (CsA-SRNS), long-term outcomes after B cell depleting therapy remain unclear., Case-Diagnosis/treatment: We retrospectively reviewed the clinical courses (median follow-up, 5.1 years) of six CsA-SRNS children (three boys; median age at RTX, 4.2 years) unresponsive to oral cyclosporine combined with ≥ 2 courses of intravenous methylprednisolone pulses, who received RTX within 6 months after disease onset (median 11 weeks). After initial RTX treatment (median two doses of 375 mg/m 2 ) followed by retreatment with intravenous methylprednisolone pulses and/or high-dose prednisolone, all patients achieved complete remission at a median of 158 days. Although 17 relapses occurred in five patients during follow-up, all but one patient became steroid sensitive. Severe neutropenia and hypogammaglobulinemia developed in two and four patients, respectively. However, no life-threatening infections were identified in the cohort. At last visit (median age, 11.3 years), all patients maintained complete remission without renal insufficiency., Conclusions: Although late-onset adverse events should be considered, particularly for young patients, early RTX treatment may have positive outcomes in children with CsA-SRNS in the long term.

Background: Mizoribine (MZR) therapy after cyclophosphamide (CPM) therapy may be an attractive option in patients with steroid-dependent nephrotic syndrome (SDNS) for the purpose of maintaining remission. This is because CPM is administered only once due to its severe side effects such as gonadal toxicity. However, the long-term prognosis after the treatment regimen remains unknown., Methods: We retrospectively analyzed the clinical course (median follow-up, 5.9 years) of 54 young children with SDNS (43 boys; age < 10 years) who had undergone 12-week CPM therapy. The patients were classified into two groups: group A, undergoing MZR therapy for > 12 months for maintaining remission after CPM therapy (N = 36), and group B, undergoing CPM monotherapy (N = 18)., Results: For 2 years after CPM therapy, 21 of the 36 group A patients were in sustained remission, whereas only 4 of the 18 group B patients had maintained remission (58% vs. 22%, p < 0.05). Furthermore, the rate of regression to SDNS after CPM was significantly lower in group A than in group B (6% vs. 39%, p < 0.05). At the last follow-up (mean age, 10.9 years), 27 of the 36 group A patients (75%) had not received any steroid-sparing agent after the treatment regimen., Conclusions: Single daily high-dose MZR therapy after CPM therapy may have positive outcomes in young children with SDNS in the long term.

Background: Nephrotic syndrome is a rare but severe feature of IgA nephropathy., Case Characteristics: Nine Japanese children with severe IgA nephropathy with nephrotic syndrome., Intervention: All received low-dose intravenous methylprednisolone (IVMP) within five weeks after the disease onset. Eight out of nine patients achieved resolution of proteinuria without severe adverse events., Message: Early low-dose intravenous methylprednisolone may be safe and effective for children with severe IgA nephropathy with nephrotic syndrome.

Background: In patients with complicated steroid-dependent nephrotic syndrome (SDNS), rituximab (RTX) followed by immunosuppressive agent (IS) can maintain remission without the use of prednisolone (PSL). However, available data on the predictive factors for relapse and the long-term outcome after this protocol are few., Methods: We retrospectively analyzed 43 SDNS patients who were followed-up for a long time (>2 years, mean 5.4 years) after a single dose of RTX (375 mg/m 2 ) from September 2007. After RTX, PSL was tapered off within 6 months; monotherapy with IS, such as cyclosporine or mycophenolate mofetil, was continued to prevent post-RTX relapse. For patients who achieved >12 months of PSL-free remission, IS was also tapered off., Results: Thirty-nine patients (91 %) could discontinue PSL without relapses at a median of 154 days after the initial RTX. The first relapse of NS occurred in 39 patients (91 %) at a median of 586 days; additional RTX doses were administered in 28 patients (65 %). Kaplan-Meier analysis showed that shorter CD19 cell depletion (<150 days) and younger age at RTX initiation (<12.5 years) were significantly associated with high risk for first relapse after RTX (log rank p < 0.05). In multivariate analysis, mycophenolate mofetil therapy as maintenance IS after RTX was the only predicted risk factor for first relapse (hazard ratio 2.75; p = 0.027). At the last follow-up, IS was still used in 33 patients (77 %); treatment-free remission (>12 months) was achieved in only five patients (12 %)., Conclusions: The introduction of RTX may not be necessarily associated with improved long-term outcome.

Background: A recent randomized control trial in children with steroid-resistant nephrotic syndrome revealed that two doses of rituximab did not reduce proteinuria., Case Characteristics: A 14-month-old boy developed refractory steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis., Observation: The patient achieved complete remission 11 months after disease onset following eight doses of rituximab combined with steroids and cyclosporine., Message: Long-lasting B cell depletion with repeated rituximab administrations may be required to achieve complete remission in patients with steroid-resistant nephrotic syndrome and massive proteinuria.

Background: Plastic bronchitis is a rare but life-threatening disorder and is usually associated with congenital heart disease or pulmonary disease., Case Characteristics: A 5-year-old boy with minimal change nephrotic syndrome who developed a relapse along with cough, fever and dyspnea., Observation: Chest X-ray showed atelectasis of right upper lobe of lung, and nasal swab was positive for influenza B virus. His respiratory condition worsened, and required ventilation; bronchoscopy revealed bronchial casts. This was followed by acute kidney injury which was successfully managed with hemodialysis., Message: Children with nephrotic syndrome on immunosuppressive agents can develop plastic bronchitis and acute kidney injury, following influenza virus infection.

Background: Recent randomized studies indicate that mycophenolate mofetil (MMF) is inferior to cyclosporine (CsA) in preventing relapses of nephrotic syndrome (NS). During the last decade, rituximab (RTX) has emerged as a rescue therapy in patients with complicated, frequently relapsing, or steroid-dependent NS., Case-Diagnosis/treatment: After introducing RTX in our single center, we analyzed 26 patients with steroid-dependent NS who had relapses while receiving long-term CsA and who were subsequently switched to MMF. MMF was adjusted to maintain a targeted predose mycophenolic acid (MPA) level of 2-5 μg/ml. Moreover, for patients who required MMF and high-dose prednisolone (PSL) to maintain remission, a single infusion of RTX (375 mg/m(2)) was added. The primary endpoint was the probability of achieving PSL-free remission for >1 year. At a mean follow-up of 28.8 ± 9.9 months, 11 of 26 patients (42 %) required RTX treatment, and 22 of those patients (85 %) achieved PSL-free sustained remission. The mean predose MPA levels for patients who achieved PSL-free sustained remission were significantly higher compared with those for patients who did not (3.1 μg/ml vs. 1.7 μg/ml, p < 0.05)., Conclusions: After RTX introduction, most patients were able to switch from CsA to MMF and achieve sustained PSL-free remission.

Unlabelled: The efficacy of rituximab (RTX) as the sole therapy for preventing relapses of nephrotic syndrome (NS) is transient in most patients; therefore, the optimal therapy required for maintaining a successful response to a biological agent remains a challenge. We conducted a prospective study to compare the efficacy of cyclosporine (CsA) with that of mycophenolate mofetil (MMF) as maintenance therapy after a single infusion of RTX. Of 29 patients with persistent steroid-dependent NS despite the use of CsA and/or MMF, 13 without chronic nephrotoxicity continued CsA therapy, maintaining a 2-h post-dose CsA level of 400-500 ng/ml (CsA group). The remaining 16 were treated with MMF, maintaining a pre-dose level of 2-5 μg/ml of mycophenolic acid (MMF group). The median duration of CsA and MMF treatment was 18 and 19 months, respectively. Despite the mean number of relapses before RTX treatment being significantly lower in the MMF group than in the CsA group (2.3/year vs. 4.6/year, p < 0.01), treatment failure occurred more frequently in the MMF group (7/16) than in the CsA group (2/13). The rate of sustained remission was also significantly higher in the CsA group than in the MMF group (p < 0.05)., Conclusion: In patients with severe steroid-dependent NS, CsA appears to be more effective than MMF for maintaining remission after a single infusion of RTX.