Treatment Of Minimal Change Disease Research Articles

Minimal change glomerular disease associated with solid neoplasms: a systematic review.

Paraneoplastic minimal change disease (MCD) has been associated with hematological malignancies, whereas solid malignancies are commonly associated with membranous glomerulonephritis. In this systematic review of the literature, we describe the clinical features, treatment and outcome of MCD associated with solid neoplasms. We performed a systematic review of the MEDLINE, COCHRANE, EMBASE and SCOPUS databases, including case reports of adult patients with biopsy-proven MCD and solid malignancy, without language or time restrictions. Sixty-seven papers were included, presenting 86 cases with a mean age of 57.8 ± 14.7years; 41.0% were women. Nephrotic syndrome was the initial presentation in 96.2% of patients; 67.2% had kidney function impairment, and 21.2% required kidney replacement therapy. The most frequent malignancies were malignant thymoma (34.9%), kidney (14.0%), lung (12.8%), and gastrointestinal tumors (12.8%). In 40.7% of cases, the neoplasm diagnosis preceded MCD by 33.8 ± 46.1months, while in 31.4%, it followed diagnosis ofMCD by 12.4 ± 22.6months. In 27.9%, the neoplasm and kidney disease were diagnosed simultaneously. Immunosuppressive therapy was started in 79.1% of cases and tumor-specific treatment in 83.7%. Remission of MCD was achieved in 80.2% of patients: 38.2% responded to immunosuppressive treatment alone and 29.6% to oncological treatment alone. The association between MCD and solid neoplasms is well-documented. Immunosuppressive therapy alone induced nephrotic syndrome remission in over one-third of cases; most others responded to tumor-specific treatment. Solid tumor screening should be considered in MCD independently of the steroid response, though more data on solid tumor-associated MCD prevalence are needed for a definitive statement. CRD42024521854.

Advances in primary glomerulonephritis.

Primary glomerulonephritis comprises several renal-limited diseases that can cause haematoproteinuria, chronic kidney disease, nephrosis and end stage kidney disease. The most common of these are IgA nephropathy (IgAN), primary membranous nephropathy (PMN), Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). Although rare, these diseases cause a significant burden to health care systems, given the high cost of treating End Stage Kidney Disease (ESKD) with dialysis or transplantation. Until recently, the pathogenesis of primary gloerulonephritis has remained obscure. However, recent advances in understanding of how these diseases evolve has led to the introduction of novel therapeutic agents. Trials are underway or have recently completed that have huge implications for the standard of care for the primary glomerulonephritidies, and should dramatically reduce the number of patients who progress onto end stage kidney disease. This article reviews the international Kidney Disease Improving Global Outcomes (KDIGO) guidelines for the treatment of IgAN, PMN, FSGS and MCD, as well as recent research on pathogenesis and treatment.

#710 Rare manifestation of minimal change disease associated with prostate cancer

Abstract Background and Aims Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome as part of the paraneoplastic syndrome occurs in 11% of cases and is most often associated with membranous glomerulopathy. The association of minimal change disease (MCD) and prostate cancer is extremely rare, where only one case has been described in the available literature. Method We present the case of a 77-year-old patient who was admitted to the Transplantation-Nephrology Department of the University Hospital Martin with 3rd degree acute kidney injury and anasarca with fully developed nephrotic syndrome. Results During hospitalization, there was a gradual elevation of renal parameters and oliguria with the need for hemodialysis treatment. However, as part of the oncological screening, the level of prostate specific antigen was elevated (10.69 ng/l) with subsequent biopsy confirmed adenocarcinoma of the prostate in stage IIB (pT1cN0M0). Renal biopsy was performed with the finding of MCD, in light microscopy without pathological findings, with fully vital, normocellular glomeruli, without interstitial fibrosis and tubular damage, immunofluorescence without significant findings, in the electron microscope, pedicel podocyte fusions were present. Despite the generally valid recommendations for the treatment of prostate cancer of the given stage and age of the patient (follow-up), antiandrogen therapy was started in cooperation with the urologist along with the treatment of MCD with corticosteroids at a dose of 1 mg/kg. The patient experienced a significant improvement in renal parameters with the onset of diuresis without the need for dialysis treatment. Conclusion In the reported case, we describe a rare form of MCD associated with prostate cancer and a rare manifestation in the form of renal failure and the need for dialysis treatment with subsequent complete restitution of renal functions after KS treatment and antiandrogen treatment of the underlying oncological disease.

#657 Obinutuzumab is effective for the treatment of frequently-relapsing/steroid-dependent minimal change disease in adults

Abstract Background and Aims Higher relapse rates and steroid dependency are challenges in the treatment of minimal change disease (MCD). The aim of this study was to evaluate the efficacy and safety of obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, in adults with frequently relapsing (FR) or steroid-dependent (SD) minimal change disease (MCD). Method Patients with FR/SD MCD receiving obinutuzumab at our center between September 2022 and February 2023 were enrolled. Complete remission was defined as the reduction of proteinuria to 0.3g/d. The time to remission, the relapse rate, and adverse events were evaluated. Results Six patients with FR/SD MCD were included in the present study. The median age of the patients was 30.44 years (range 18.80-72.09 years) and 3 of them were male. Prior to treatment with obinutuzumab, five patients remained in nephrotic syndrome and one patient was in partial remission after previous treatment. One or two doses of 1g obinutuzumab were given. All six patients achieved a complete remission. Five patients with nephrotic syndrome achieved complete recovery within a range of 14 to 57 days. The patient, who initially achieved partial remission, reached complete remission within 27 days after receiving the first obinutuzumab dose. The average follow-up duration was 12.53 ± 1.97 months, during which there was no observed relapse. Furthermore, None of the patients experienced infusion-related adverse effects, serious infectious complications or neutropenia following treatment with obinutuzumab. Conclusion Obinutuzumab is an effective and safe treatment option for adult patients with FR/SD minimal change disease. Further randomized trials are needed to confirm these findings.

#2659 Clinical characteristics of patients with minimal change disease (MCD) that evolved to focal sclerosing glomerulosclerosis (FSGS)

Abstract Background and Aims Minimal change disease (MCD) and focal sclerosing glomerulosclerosis (FSGS) are both podocytopathies and are possibly diseases that lie on a similar spectrum with FSGS being the severe form. We aim to describe the clinical and laboratory parameters along with treatment and outcomes of MCD that were found to be FSGS on repeated biopsy. Method All patients who had undergone renal biopsy in Hospital Serdang and had documented diagnosis of FSGS from January 2007 until December 2022 were identified. Data was collected and analysed using SPSS version 17. Results were expressed in mean ± standard deviation (SD) unless stated otherwise. Results Total minimal change disease were 70 patients. A total of 14 were identified as FSGS on repeated biopsy. At time of biopsy, all patients presented as relapse in nephrotic syndrome (NS). Mean age of diagnosis was 18 years for MCD while mean age of FSGS diagnosis was 23.8 years. 11 were males and two patients had positive family history of kidney disease while 10 had some form of haematuria. All patients were on steroids with 4 of them developing steroid resistance. 11 patients were on second line agents either due to steroid resistance or toxicity. Majority of patients were on azathioprine followed by cyclosporine and mycophenolate mofetil. Mean follow up was 5.7 years. Those with MCD had higher platelet (mean 462) and total cholesterol (mean 14.2) values at diagnosis of FSGS. Mean relapse after diagnosis of FSGS was 2.2 episodes. (Patients remain in remission for 31 months before relapsing) As of December 2022, 9(65%) patients had normal kidney function, 2 end stage renal disease on dialysis while 3 CKD V had passed away due to acute coronary syndrome. Conclusion Minimal change disease is part of a spectrum podocytopathies along with FSGS. Those with frequent relapses in MCD, older children with nephrotic syndrome and those with presence of haematuria may be warranted for a repeated biopsy to rule out evolution to FSGS.

Relapse treatment with low-dose steroids in steroid-sensitive minimal change disease.

The treatment of minimal change disease (MCD) consists of a high dose of steroids for several months, implying significant drug toxicity. Nevertheless, relapses of steroid-sensitive MCD usually respond to lower doses of steroids. The objective of this study was to analyze whether a low dose of steroids (LDS) is effective for the treatment of MCD relapses. Since 2018, new relapses of steroid-sensitive adult patients with MCD in three Spanish centers have been treated with LDS. The cumulative dose of steroids, the time to remission, and the relapse-free time were compared between relapses treated with LDS and previous relapses of the same patients treated with a standard dose of steroids (SDS). A total of 51 relapses in 31 patients were treated with LDS and compared with 48 historical relapses of the same patients treated with SDS. The mean doses of prednisone adjusted by weight for the initial treatment were 0.45 mg/kg (0.40-0.51 mg/kg) in the relapses treated with LDS and 0.88 mg/kg (0.81-1.00 mg/kg) in those treated with SDS. The mean cumulative doses of prednisone in LDS- and SDS-treated relapses were 1,191 mg (801-1,890 mg) and 3,700 mg (2,755-5,800 mg), respectively. The duration of treatment was 63 days (42-117 days) in the LDS group and was 140 days (65-195 days) in the SDS group. All patients achieved complete remission within 1 month after steroid therapy in both groups. The times to remission of the LDS and SDS groups were 19.10 ± 12.80 and 18.93 ± 12.98 days, respectively (p = 0.95). Among the steroid-sensitive patients with MCD, relapse therapy with LDS (0.5 mg/kg) appears effective and allows minimization of the steroid cumulative dose.

State-of-the-art paradigm of corticosteroid therapy for immune-mediated inflammatory kidney diseases

Since 1950's corticosteroids (CS) have remained the cornerstone of immunosuppressive therapy for immune-mediated kidney diseases. However multiple adverse events, associated with the prolonged CS therapy, became the basis for the development of novel treatment approaches. Current evidence supports the implementation of the steroid-sparing regimens for the treatment of different types of glomerulonephritis. Randomised controlled trial PEXIVAS demonstrated the efficacy and safety of early steroid tapering, starting from the second week of therapy, in patients with ANCA-associated vasculitis with kidney involvement. Several trials showed the efficacy of oral prednisolone 0.3-0.5 mg/kg/daily as a part of multitarget therapy for severe proliferative lupus nephritis. A combination of calcineurin inhibitors and low-dose CS are effective for remission induction in membranous nephropathy, as well as the steroid-free rituximab regimen for the patients with moderate risk of disease progression. Medium dose CS showed promising effect in patients with IgA-nephropathy. Long-term high dose CS remain the standard-of-care for the treatment of minimal change disease and focal segmental glomerulosclerosis, however patients with steroid-dependent and relapsing disease tacrolimus and rituximab can help to achieve steroid-sparing effect. The role of CS pulse-therapy is currently debated, nevertheless it remains a compulsory treatment in several conditions. Thus, overall trend is directed towards the minimization of the maximal doses of CS and/or treatment duration. However, to implement this approach morphological verification of the diagnosis and personalized assessment of the potential risk and benefit are required.

Mechanisms and Clinical Research Progress of Rituximab in the Treatment of Adult Minimal Change Disease

Introduction: Minimal change disease (MCD) is a common subtype of primary nephrotic syndrome in adults. The pathogenesis of MCD is still not well understood, but some studies suggest that MCD is a T cell-mediated disease related to podocyte dysfunction. Previous research has also indicated the crucial role of B cells in the pathogenesis of MCD. Rituximab (RTX) is a recombinant chimeric mouse/human antibody targeting CD20 antigen. In recent years, RTX has been increasingly used in adult MCD patients. Methodology: We searched the PubMed database using the keywords “Minimal change disease”, “Nephrotic syndrome”, and “Rituximab” and obtained a total of 140 articles. We will now provide a literature review based on these 140 articles, according to our research topic. Discussion: This article provides an overview of the mechanisms and clinical research progress of RTX in the treatment of adult MCD. We have also discussed the current treatment methods for MCD, exploring the potential of using RTX as a first-line therapy for refractory adult MCD. Conclusion: MCD is a common pathological type of nephrotic syndrome, and the exact mechanisms are still not fully understood. Although RTX as a treatment of adult MCD has shown promising clinical results in patients with refractory adult MCD, the safety and efficacy of RTX still lack high-quality clinical evidence. Further research is needed to explore the pathogenesis of MCD and the RTX treatment for MCD.

Diagnosis and treatment of Minimal Change Disease in adults-2023

Minimal change disease is aglomerulopathy that clinically manifests as acute onset nephrotic syndrome. Adiagnosis is made by renal biopsy, implying the absence of glomerular lesions on light microscopy but detection of extensive podocyte foot process effacement on electron miscroscopy. Considering the typically excellent response to immunosuppressive measures (especially to glucocorticoids), an autoimmune pathogenesis is assumed. Although general prognosis is overall beneficial, steroid-dependent, steroid-resistant and frequently-relapsing disease courses may complicate the management of these patients and necessitate the use of alternative immunosuppressive treatment strategies. Here, the Austrian Society of Nephrology (ÖGN) provides aconsensus on how to best diagnose and manage adult patients with minimal change disease.

Tacrolimus treatment after short-term intravenous methylprednisolone in incipient minimal change disease for adults: A retrospective analysis

The present study aimed to investigate the efficacy and safety of tacrolimus for treating incipient minimal change disease in adults. The clinical data of 52 adult patients with minimal change disease of nephrotic syndrome diagnosed by renal biopsy in the First affiliated hospital of Zhengzhou University between August 2013 and August 2015 were retrospectively analyzed. According to the treatment plan, the patients were divided into a tacrolimus group and a glucocorticoid group. The efficacy and safety of tacrolimus in the treatment of minimal change disease in adult patients was analyzed and compared with that of glucocorticoids. The results revealed that the baseline characteristics of the two groups were similar (P>0.05). At 24 weeks, there was a significant difference in serum albumin between the two groups (P<0.01). The serum albumin levels of tacrolimus group was higher compared with the glucocorticoid group. In addition, the complete remission rates in the tacrolimus and glucocorticoid groups were 93.75 and 77.8%, respectively (P=0.095), and the mean complete remission time was 6.33±4.21 and 5.14±2.45 weeks, respectively (P=0.175). The relapse rate was 12.5 and 22.2% in the tacrolimus and glucocorticoid groups, respectively (P=0.368). During the follow-up, in tacrolimus group, the incidence of new onset diabetes or impaired glucose tolerance, osteoporosis, infection, abnormal liver function, Cushing's syndrome, acne and gastrointestinal symptoms were significantly less than those of glucocorticoids (P<0.05). In conclusion, tacrolimus treatment after short-time intravenous methylprednisolone is an effective treatment option with fewer adverse effects in adult onset minimal change disease.

MO237: Rituximab in Treatment of Minimal Change Disease and Primary Focal Segmental Glomerulosclerosis in Adults-Single Center Experience

Abstract BACKGROUND AND AIMS Rituximab (RTX) showed some efficacy in treatment of minimal change disease (MCD) and primary focal segmental glomerulosclerosis (pFSGS) [1]. The results of its off-label use and as steroid-sparing agent were especially promising in steroid-dependent, frequently relapsing or steroid-resistant forms of MCD and pFSGS in adults [2]. METHOD All patients treated with RTX in Department of Nephrology and Dialysis, University Hospital Dubrava, Zagreb, were retrospectively reviewed. Complete remission (CR), steroid-resistant nephrotic syndrome (SRNS), steroid-dependent nephrotic syndrome (SDNS), multidrug-resistant SRNS (MDR-SRNS) and calcineurin inhibitor (CNI)-resistant SRNS were defined according to KDIGO 2021 [3]. RESULTS Of 82 patients treated with RTX, 11 patients had biopsy proven MCD and pFSGS. Table 1 summarizes relevant demographic, clinical and treatment data. RTX was applied in five patients with SDNS, four patients with MDR-SRNS, one patient with CNI-resistant SRNS and one patient with active hepatitis C and newly onset MCD as a first line therapy. Median follow-up after initial diagnosis and RTX application was 122.9 (range 30–219) and 20 (range 3–117) months, respectively. All patients were initially treated with steroids, and RTX was the drug most commonly applied after treatment with CNI and cyclophosphamide (CYC). Median proteinuria at the time of RTX application was 10 g/day (range 2.5–16.7), 10 patients had preserved kidney function and only 1 patient with collapsing FSGS (case 11) had severe acute kidney injury. Mean cumulative dose of RTX for induction was 1700 mg and short course of steroids was used concomitantly in 10 cases (except case 5). CR was achieved in seven cases (six cases of MCD and one case of MDR-FSGS). Three of seven patients with CR to RTX experienced relapse of disease. Time to relapse was 6, 15 and 40 months in case 5, 3 and 11, respectively. Repeated RTX application led to CR in all three cases. CR persisted in five patients even after the steroids cessation. There were no serious adverse effects of RTX administration in our cohort. CONCLUSION RTX showed respectable efficacy in our cohort of adults with SDNS-MCD and in case of MDR collapsing FSGS. Although statistical comparison was not performed because of small number of patients, it seems that RTX is more effective in group of SDNS than MDR-SRNS. In our cohort, patients with relapse of RTX-sensitive disease responded to repeated application. Role of RTX in treatment of MCD and pFSGS should be evaluated in randomized clinical trials.

POS-480 MYCOPHENOLATE MOFETIL IN TREATMENT OF ADULT ONSET MINIMAL CHANGE DISEASE: OUTCOMES OF A TUNISIAN STUDY

Mycophenolate mofetil (MMF) is considered to be less effective than calcineurin inhibitors in the treatment of minimal change disease (MCD), but some studies have shown its comparable efficacy in patient not responding to corticosteroids with better tolerance than calcineurin inhibitors.The aim of this study is to describe the characteristics and outcomes of patients with MCD treated with MMF.

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease

BackgroundA dose of 0.5–1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD.MethodsWe conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics.ResultsNinety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H.ConclusionThe initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.

Spontaneous Bacterial Peritonitis in an Adult Patient with Minimal Change Disease

Patient: Male, 60-year-oldFinal Diagnosis: PeritonitisSymptoms: Abdominal pain • edema of lower extermitiesMedication: —Clinical Procedure: —Specialty: NephrologyObjective:Rare diseaseBackground:Pediatric patients with nephrotic syndrome have a high risk of developing spontaneous bacterial peritonitis (SBP). However, SBP in adults with nephrotic syndrome is very rare. We report a case of SBP induced by Escherichia coli in a 60-year-old male patient on immunosuppressive therapy for the treatment of minimal change disease (MCD).Case Report:The patient was hospitalized with abdominal pain and generalized edema that had lasted for 2 weeks. The patient first started treatment with high-dose oral prednisolone after being diagnosed with MCD 6 months ago. Complete remission of nephrotic syndrome was not achieved even after 5 months of treatment. Thus, the treatment was changed to combination therapy with cyclosporine and low-dose prednisolone. At the time of admission, leukocytosis, hypoalbuminemia, decreased serum immunoglobulin G (IgG), azotemia, and nephrotic-range proteinuria were observed. Ascitic fluid analysis showed a leukocyte count of 4960/μL (neutrophils 90%). On the suspicion of SBP associated with MCD, intravenous administration of empirical cefotaxime and supportive therapy were initiated; however, symptoms of peritonitis persisted. Extended-spectrum beta-lactamase-negative E. coli was found in ascites cultures. Laparoscopy-assisted peritoneal biopsy revealed no evidence of fungal infection; however, chronic inflammation without granuloma formation was noted. Afterward, cefotaxime was changed to piperacillin-tazobactam. After 4 weeks of antibacterial therapy, the peritonitis was cured and renal function was improved.Conclusions:Adult patients with steroid-resistant MCD accompanied by refractory ascites, severe hypoalbuminemia, and marked reduction in serum IgG are at a high risk of subsequent SBP and require careful monitoring.

Review of Glomerular Diseases: Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD)

Purpose: Idiopathic focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are chronic glomerulopathies which may compromise patients’ quality of life, and for which there is no cure. This literature review aimed to summarize our current understanding of the pathophysiology, clinical characteristics, and best available treatment for the two conditions in order to outline a consolidated treatment protocol and identify future research considerations.&#x0D; Methods: PubMed was systematically searched by a single reviewer in order to identify primary studies pertaining to the diagnosis, treatment and classification of FSGS and MCD. Additionally, a hand search of UpToDate was conducted to glean further information about the best available evidence as summarized for clinician use. Relevant information was extracted and synthesized.&#x0D; Results: Primary FSGS and MCD result from distinct pathogenic mechanisms, hypothesized to involve kidney injury via immune dysregulation. Patients require a kidney biopsy for diagnostic purposes. First-line treatment involves glucocorticoids (i.e. prednisone), although patients’ responsiveness may be inconsistent; second-line treatment is immunotherapy.&#x0D; Conclusion: This review summarized clinically-important information about FSGS and MCD, and emphasized the need for further research in the field of clinical nephrology. Large scale trials such as the Cure Glomerulonephropathy should be conducted to gather information about the affected population.

Respiratory Tract Infection: A Risk Factor for the Onset and Relapse of Adult-Onset Minimal Change Disease in Southern China.

Aims/Introduction Steroid resistance and frequent relapse are problems in the treatment of minimal change disease (MCD). However, epidemiological factors that influence steroid-resistant and relapse of MCD are rarely reported. This study evaluated potential factors that influence the onset and relapse of MCD and the epidemiological features of southern Chinese patients with adult-onset MCD. Patients and Methods Patients with adult-onset MCD were included from the Affiliated Hospital of Guangdong Medical University, which is located in the southernmost part of China's mainland, between 2015 and 2016. Potential influencing factors were investigated. Results Eighty-seven patients with incipient MCD were enrolled, and 85 of these patients were followed up; 71.8% (61/85) were steroid-sensitive and 28.2% (24/85) were steroid-resistant. In terms of seasonal distribution, the highest rate of incipient cases was in spring (39.1%, 34/87), which also showed a high rate of relapse cases (29.7%, 22/74). Among patients who were followed up for more than half a year and whose proteinuria completely resolved (69.4%, 59/85), 52.5% (31/59) were without relapse and 47.5% (28/59) were with relapse. Patients without relapse were older than those with relapse (P<0.05). Before disease onset, 20.7% (18/87) of patients with incipient MCD were diagnosed with infection, including 94.5% (17/18) with respiratory tract infection. Fourteen patients in complete remission posttreatment developed an infection before relapse, including 85.7% (12/14) with respiratory tract infection. Conclusion Steroid resistance and frequent relapse are current challenges for the treatment of adult-onset MCD in southern China, and respiratory tract infection may be a risk factor for onset and relapse. Additionally, younger patients with MCD tend to have more frequent relapse.

Rituximab as a front-line therapy for adult-onset minimal change disease with nephrotic syndrome.

Minimal change disease (MCD) accounts for 15% of adult nephrotic syndrome (NS) cases. Adult-MCD patients may have more severe clinical features than pediatric patients. In children, Rituximab (RTX) has been used since 2006 to treat frequently relapsing NS. In adults, data about the efficacy of RTX for MCD are limited. We report our experience on the use of RTX in adult biopsy-proven MCD. Our series includes 6 adult patients (2 males and 4 females), age 45–73 years, treated with RTX (4 weekly doses of 375 mg/m2). Proteinuria decreased from 11,2 (23–4.8) g/24 hours to 0.6 (0–2) g/24 hours after 6 months, and to 0.4 (0–1, 4) g/24 h in the 4 pts with the longer follow-up. Creatinine decreased from 1.95 (0.5–5) mg/dl to 0.88 (0.6–1.3) mg/l. Five patients achieved a complete renal remission, while in 1 pt proteinuria decreased by 75%. RTX successfully depleted CD19 lymphocytes in 100% of pts for at least 6 months. No clinically relevant adverse events have been observed. This case series shows a remarkable efficacy of RTX in treatment of MCD. RTX can be an attractive alternative both in recurrent forms and in induction-therapy of MCD. RTX may be preferentially used in patients at a high risk of development of the adverse effects of corticosteroids and should be considered as an alternative option in patients with recurrent NS. Additional data are needed to inform clinical practice on how best to use RTX in this patient population, so that definitive randomized trials can be planned.

MiR-499 Ameliorates Podocyte Injury by Targeting Calcineurin in Minimal Change Disease

Background: Podocyte injury is a hallmark of minimal change disease (MCD). Calcineurin inhibitors have been widely used in the current treatment of MCD, and miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD and test whether miR-499 delivery can improve MCD. Methods: An MCD mouse model was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using lentiviruses. Biochemical indicators including serum albumin, triglyceride, cholesterol, and 24-h urine protein were determined. Targets of miR-499 were confirmed using reporter gene activity assays. The ultrastructure of podocytes was analyzed using transmission electron microscopy. Results: MiR-499 significantly improved MCD-related symptoms and signs. Foot-process effacement was caused by PAN and partially reversed by miR-499. We identified that both CnAα and CnAβ were targets of miR-499, and were overexpressed in the presence of PAN. However, miR-499 reduced the expression of CnAα and CnAβ, leading to a decreased activity of calcineurin signaling in mouse podocytes in vitro and in vivo. In addition, miR-499 recovered PAN-induced reduction of cell viability. Conclusions: MiR-499 ameliorated podocyte injury by targeting CnAα and CnAβ in a PAN-induced MCD mouse model. Delivery of miR-499 can be a novel strategy for MCD treatment.

Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.

BackgroundVariability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis.MethodsParticipating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy.ResultsWe studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients.ConclusionsWe found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

Tricuspid valve chordae tendineae as protective filter to prevent massive pulmonary embolism.

Although several cases of thrombus-in-transit associated with pro-thrombotic conditions have been reported (1-3), a transit thrombus located in the right ventricular (RV) cavity is extremely rare (4,5). Here, we report a case of nephrotic syndrome (NS) with a RV thrombus-in-transit that threatened to cause a fatal pulmonary embolism (PE).