Adult-onset Minimal Change Disease Research Articles

Activation of the inflammasome and pyroptosis cascade in podocytes of patients with minimal change disease.

In contrast to childhood minimal change disease (MCD), adult-onset MCD frequently recurs and requires prolonged immunosuppressive therapy. Accordingly, an investigation of the pathogenesis of adult MCD is required. MCD is usually accompanied by severe dyslipidaemia. Oxidized low-density lipoprotein (ox-LDL) is known to function in a damage-associated molecular pattern (DAMP) through CD36, triggering the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. However, the relationship between MCD pathogenesis and NLRP3 inflammasome/pyroptosis activation via CD36 is not fully understood. We conducted comprehensive histological and clinical evaluations by analysing renal biopsy (RBx) specimens and urine samples obtained from 26 patients with MCD. These samples were compared with control kidneys from 15 transplant donors and urine samples from 15 healthy volunteers. The number of podocytes was lower in the MCD group than in the control group. Urinary ox-LDL levels were higher in the MCD group than in the control group. Immunofluorescence staining revealed that NLRP3 and CD36 were upregulated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in patients with MCD. Steroid therapy performed before RBx appeared to maintain the podocyte number and reduce urinary ox-LDL and IL-18 levels. In MCD, the NLRP3 inflammasome and pyroptosis cascade seem to be activated via upregulation of CD36 in podocytes, associated with increased urinary ox-LDL. Elevated urinary IL-18 levels suggest that pyroptosis may occur in MCD. Further research is required to confirm the significance of the podocyte NLRP3 inflammasome/pyroptosis in MCD.

Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease: An Analysis From the Cure Glomerulonephropathy Network

Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response. Prospective, multicenter, observational study. CureGN participants with proven MCD on biopsy. Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period. Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure. Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission. The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P<0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P=0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P=0.002). CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy. Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response. Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab.

Rituximab and a Short Course of Corticosteroids for Initial Management of Adult-Onset Minimal Change Disease

Rituximab and a Short Course of Corticosteroids for Initial Management of Adult-Onset Minimal Change Disease

Demographic, clinical and laboratory characteristics of adult-onset minimal change disease in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

In our study, diagnostic and demographic characteristics of patients diagnosed with minimal change disease (MCD) by biopsy, clinical and laboratory findings in our country were investigated. Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented are cross-sectional and includes application data for the biopsy period. Of 3875 patients, 233 patients with MCD (median age 35.0years) were included in the study, which constitutes 6.0% of the total glomerulonephritis database. Renal biopsy was performed in 196 (84.1%) patients due to nephrotic syndrome. Median serum creatinine was 0.7 (0.6-1.0) mg/dl, mean eGFR was 104 ± 33ml/min/1.73 m2 and median proteinuria 6000mg/day. The number of patients under the age of 40years was 139 (59.7%) (Group A), and the number of patients aged 40years and over was 94 (40.3%) (Group B). Compared to Group A, global sclerotic glomeruli (24 vs. 43, p < 0.001) interstitial inflammation (15 vs. 34, p < 0.001), interstitial fibrosis (20 vs. 31, p = 0.001, vascular changes (10 vs. 25, p < 0.001) and tubular atrophy (18 vs. 30, p < 0.001) were found to be significantly higher in Group B. There was no difference in immunofluorescent staining properties between the two groups. Our data are generally compatible with the literature. Chronic histopathological changes were more common in patients aged 40years and older than younger patients. Studies investigating the effects of these different features on renal survival are needed.

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.

Interventions for minimal change disease in adults with nephrotic syndrome.

Interventions for minimal change disease in adults with nephrotic syndrome.

Clinical Characteristics and Outcomes of Adults with Nephrotic Syndrome Due to Minimal Change Disease.

Purpose: Minimal change disease (MCD) is considered a relatively benign glomerulopathy, as it rarely progresses to end-stage kidney disease. The aim of this study was to describe the characteristics and outcomes of adults with MCD and identify potential risk factors for relapse. Patients & Methods: We retrospectively studied a cohort of adults with biopsy-proven MCD in terms of clinical features and treatment outcomes. Baseline characteristics and outcomes were recorded and predictors of relapse were analyzed using logistic regression multivariate analysis. Results: 59 patients with adult-onset primary MCD with nephrotic syndrome were included. Mean serum creatinine at diagnosis was 0.8 mg/dL (±2.5) and estimated GFR (eGFR) was 87 mL/min/1.73 m2 (±29.5). Mean serum albumin was 2.5 g/dL (±0.8) and 24 h proteinuria 6.8 g (±3.7). Microscopic hematuria was detected in 35 (58.5%) patients. 42 patients received prednisone alone, six patients received prednisone plus cyclophosphamide, five patients received prednisone plus cyclosporine, one patient received prednisone plus rituximab and five patients did not receive immunosuppression at all since they achieved spontaneous remission. During a mean follow up time of 34.7(22.1) months, 46.1% of patients experienced at least one episode of relapse. The mean age of patients who did not experience a relapse was significantly higher than that of patients who relapsed while relapsers had a significantly longer duration of 24 h proteinuria prior to biopsy compared to non-relapsers. Overall, 10% of patients experienced acute kidney injury while the mean eGFR at the end was 82 mL/min/1.73 m2 (±29.1) and one patient ended up in chronic dialysis. Overall, the proportion of non-relapsers, who experienced acute kidney injury (17%) was significantly higher than the one recorded among relapsers (0%).Conclusion: In this series of patients, almost 46% of adult-onset nephrotic MCD patients experienced a relapse, although their renal progression was rare. Younger onset age was an independent risk factor for relapse in adult-onset MCD patients.

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.

IgM mesangial deposition as a risk factor for relapses of adult-onset minimal change disease

BackgroundImmunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive.MethodsIn this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups.ResultsAnalysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116–0.784, p = 0.010).ConclusionsOur findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.

Adult-onset minimal change disease: the significance of histological chronic changes for clinical presentation and outcome.

Data on pathologic features with prognostic utility in adults with minimal change disease (MCD) are limited. We assessed the relationship between histologic chronic changes and clinical presentation and outcomes. The consecutive records of 79 patients with MCD and minimum of 6months follow-up were retrospectively reviewed. Kidney survival was the primary endpoint (doubling serum creatinine or dialysis initiation). Secondary endpoints were time to remission and relapse. Total chronicity score was the sum of glomerulosclerosis (0-3), interstitial fibrosis (0-3), tubular atrophy (0-3), and arteriolosclerosis (0/1). The median renal chronicity score was 1; 77% had minimal (0-1), 18% mild (2-4), and 5% moderate (5-7) chronicity. Fifty percent had a null score; they were younger, had higher eGFR, similar proteinuria, better renal survival, and lower mortality. Mean kidney survival time was 5.7 (95% CI 5.2-6.2) years; 89% reached a form of remission at a median of 8weeks; 31% relapsed at a mean of 26months. Chronic changes severity predicted both relapses and kidney survival, each one-point increase in score raised with 27% the risk of relapse and with 31% the risk of dialysis initiation. Acute kidney injury (AKI) was present in 42% of the patients; they had more often mesangial proliferation, interstitial inflammation, tubular atrophy, arteriosclerosis, podocyte villous hypertrophy, and higher chronicity score. Standardized grading of chronicity was a predictor of kidney survival and disease relapse and was related to AKI. Older patients with severe nephrotic syndrome and with increased chronicity score could represent a high-risk category.

Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease.

BackgroundMinimal change disease (MCD) is a common form of nephrotic syndrome in adults. However, the molecular mechanism underlying the pathogenesis of MCD remains incompletely understood. In this study, we aimed to investigate the role of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset MCD patients.MethodsThe lymphocyte subsets, 34 cytokine levels of Th1/Th2/Th17, serum and urine concentrations of CD80, and expression of CD80 in glomeruli were analyzed in 28 cases (15 males and 13 females; average age: 34.1 years, age range: 18–56 years), including 10 patients with MCD in relapse, nine patients with MCD in remission and nine healthy controls.ResultsThere was no significant difference of CD3+CD4+ cells proportion among patients with MCD in relapse, MCD in remission and healthy controls (P = 0.802). The cytokine levels of GM-CSF and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) in patients with MCD in relapse increased 1.5 times higher than those in remission. An evident increase in the excretion of urinary CD80 was found in patients with relapsed MCD compared with those in remission (598.4 ± 115.8 vs 81.78 ± 7.04 ng/g creatinine, P < 0.001) and healthy controls (598.4 ± 115.8 vs 67.44 ± 8.94 ng/g creatinine, P < 0.001). CD80 expression was observed in podocyte of MCD patient in relapse by immunofluorescence technique.ConclusionsThe cytokines GM-CSF and TRANCE are increased and the urinary CD80 levels are elevated in adult-onset MCD patients in relapse, indicating a disorder of Th1/Th2/Th17 balance and that the elevated excretion of CD80 may underlie the pathogenesis and development of adult-onset MCD.

Increased number and activation of peripheral basophils in adult-onset minimal change disease.

Nowadays, the pathogenesis of minimal change disease (MCD) is still not well‐known, and the current understanding on MCD is mainly based on data derived from children, and very few adults. Here, we comprehensively analysed the correlation between the changes of peripheral basophils and the incidence rate and relapse of adult‐onset MCD. The results showed that in patients at the onset of MCD, the ratio and activation of basophils were all higher than those of healthy controls (all P < .05). In vitro test results showed that basophils from healthy controls can be activated by the serum taken from patients with MCD. Among 62 patients at the onset of MCD, with complete remission after treatment and 1 year of follow‐up, the relative and absolute basophil counts before treatment were higher in the long‐term remission group (n = 33) than that of the relapse group (n = 29). The basophil counts were significantly higher in the infrequent relapse group (n = 13) than that of the frequent relapse group (n = 16; P < .05). These findings suggested that basophil may play a pathogenic role in adult‐onset MCD, and the increased number and activation of peripheral basophils could predict recurrence in adult MCD.

Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Disease Activity in Adult-Onset Minimal Change Disease

Cell adhesion molecules have been documented to be elevated in numerous immune inflammatory diseases. Minimal change disease (MCD) is an immune disorder. This study aimed to evaluate whether levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) reflect disease activity in adult-onset MCD. A sandwich enzyme-linked immunosorbent assay was used to measure the soluble adhesion molecules in 40 patients with nephrotic-range proteinuria and biopsy-proven MCD, obtained at the time of diagnosis and during remission. Thirty-five age- and sex-matched healthy volunteers served as controls. Patients with MCD during the active stage showed significantly higher levels of sVCAM-1 and sE-selectin when compared to controls. Moreover, sVCAM-1 had significantly positive correlations with both urine protein and serum cholesterol, and was negatively associated with serum albumin. Multiple analyses showed that serum albumin was an independent predictor of sVCAM-1. The correlations between sE-selectin and other clinical parameters were not statistically significant. At follow-up, these markers systematically decreased as the disease went into remission, but the increase in sVCAM-1 persisted even in patients obtaining complete remission for 6 months. Patients with active MCD had increased levels of sVCAM-1 and sE-selectin. The correlation between sVCAM-1 and proteinuria, serum albumin and cholesterol and its decline during remission indicate that sVCAM-1 is associated with disease activity.

Tacrolimus as the first-line agent in adult-onset minimal change disease: A randomized controlled study

Steroids have been the cornerstone of first-line therapy in adult-onset minimal change disease (MCD). The period of exposure to high dose steroids may be longer in adult MCD patients and would result in higher rates of steroid-related side effects. Although tacrolimus (TAC) is known to be effective in steroid-dependent/resistant MCD as well as in nephrotic syndrome due to other causes, there are minimal data available for assessing the effectiveness of TAC as the first-line agent in adult MCD. This is a prospective, open-label, randomized controlled study conducted from April 2014 to March 2016. Patients were randomized into two groups A and B which received TAC for 12 months and oral steroids for six months, respectively. Primary outcomes were remission rates, drug resistance was measured at 6, 12,and 18 months in each group and secondary outcomes were relapse rates, sustained remission rates, dependency, and adverse effects were measured at 18 months in both groups. At six months, total response (TR, i.e., complete and partial remission) was achieved in 80% in the TAC group and 78.26% in the steroid group (P = 1.000). At 12 months, TR was 60% in the TAC group and 43.48% in the steroid group (P = 0.386). At 18 months, TR rate was 44% in the TAC group and 43.48% in the steroid group (P = 1.000). About 32% in the TAC group and 39.13% in steroid group had relapsed by 18 months. Serious adverse effects were similar in the two groups, but overall adverse effects were more in the steroid group. TAC as a primary agent is not inferior to steroids in inducing remission. TAC may be considered as an alternative agent to steroid in high-risk groups such as elderly patients, uncontrolled diabetes and young females as a primary agent in the management of adult MCD.

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.

CD80 and CTLA-4 as diagnostic and prognostic markers in adult-onset minimal change disease: a retrospective study.

BackgroundMinimal change disease (MCD) is a form of idiopathic nephrotic syndrome. Compared to children, adult-onset MCD patients are reported to have delayed responses to glucocorticoid treatment. Several studies of children have suggested detecting urinary CD80 levels to diagnose MCD. There are no effective diagnostic methods to distinguish steroid-sensitive MCD from steroid-resistant MCD unless treatments are used.MethodsIn a total of 55 patients with biopsy-proven MCD and 26 patients with biopsy-proven idiopathic membranous nephropathy, CD80 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in serum, urine and renal tissue were analyzed.ResultsSteroid-sensitive MCD patients in remission had lower urinary CD80 levels and higher CTLA-4 levels than patients in relapse (156.65 ± 24.62 vs 1066.40 ± 176.76 ng/g creatinine; p < 0.0001), (728.73 ± 89.93 vs 151.70 ± 27.01 ng/g creatinine; p < 0.0001). For MCD patients in relapse, mean urinary CD80 level was higher, and CTLA-4 level was lower for those who were steroid-sensitive than those who were steroid-resistant (1066.40 ± 176.76 vs. 203.78 ± 30.65 ng/g creatinine; p < 0.0001), but the mean urinary CTLA-4 level was lower (151.70 ± 27.01 vs. 457.83 ± 99.45 ng/g creatinine; p < 0.0001). CD80 expression in glomeruli was a sensitive marker to diagnose MCD. The absent or minimal expression of CTLA-4 in glomeruli could distinguish steroid-sensitive MCD from steroid-resistant MCD.ConclusionsGlucocorticoid treatment may result in complete remission for only MCD patients with strongly positive CD80 expression and negative CTLA-4 expression in glomeruli, or higher urinary CD80 level and lower CTLA-4 level.

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.

Tacrolimus improves proteinuria remission in adults with cyclosporine A-resistant or -dependent minimal change disease.

Cyclosporin A (CsA) is considered as an effective treatment option for steroid-resistant or-dependent patients with adult-onset minimal change disease (MCD). However, CsA resistance or dependence is also observed in these patients. Tacrolimus (TAC) is a calcineurin inhibitor that is potent in cytokine suppression. The authors aim to evaluate the efficacy and safety of TAC therapy in CsA-resistant and-dependent adult-onset MCD patients. Patients with adult-onset MCD were enrolled in our department from 2008 to 2012. All patients were demonstrated to be resistant to or dependent on CsA therapy. Prednisone (0.5mg/kg per day) combined with TAC (0.05-0.1mg/kg per day) were prescribed to these patients for at least 6months. The primary outcome was complete or partial remission of proteinuria. Secondary outcomes included time required for complete or partial remission, adverse events, number of relapses, and TAC dosages. A total of 11 MCD patients were enrolled in this observational study. The numbers of patients who presented with resistance to or dependence on CsA were 7 and 4, respectively. The total remission rate was 90.9% (10/11) with the complete remission rate 72.7% (8/11). Most remission patients achieved remission during the first 2months of TAC therapy. Patients who presented with dependence on CsA had achieved complete remission with TAC therapy, while outcomes for CsA-resistant patients were four complete remissions, two partial remissions and one resistance. The adverse events were observed in this study included infection, diarrhoea, and worsened hypertension. Five patients who had remission experienced relapse. Tacrolimus improves proteinuria remission in adults with CsA-resistant or -dependent MCD.

Predictors of Relapse in Adult-Onset Nephrotic Minimal Change Disease

Minimal change disease (MCD) is a well-known benign primary glomerulonephritis because of its distinct rare tendency to progress to end-stage renal disease. However, factors associated with relapse in adults are not well known. We aimed to identify predictors of relapse in adult-onset MCD patients.A retrospective cohort of 195 patients with adult-onset primary MCD with nephritic syndrome and disease onset between 1979 and 2013 was followed up for >12 months. The number of relapses was counted and predictors of relapse were analyzed.A total of 195 patients were included. Median age at diagnosis was 38 years (IQR, 23–53 years) and 113 (57.9%) were men. During 81 months (IQR, 44–153 months) of follow-up, 92% of patients achieved remission after initial treatment. However, only 60 (32.8%) did not experience a relapse and 11 patients failed to remit. Among the remaining 124 patients, 65 experienced a relapse once or twice and 59 experienced a relapse more than twice. Younger onset age, increased severity of nephrotic features such as lower serum albumin levels and higher cholesterol level were associated with relapse. Interestingly, the grade of mesangial proliferation was lower in patients who experienced a relapse. Initial combined treatment with corticosteroids (CS) and cyclophosphamide reduced the number of relapses. In addition, patients with shorter treatment duration tended to experience relapse more often. Multivariate analysis showed that younger onset age, combined mesangial proliferation, initial treatment regimen, and treatment duration were independent risk factors for relapse. Progression to end-stage renal disease was developed in only a patient.In conclusion, more than two-thirds of adult-onset nephrotic MCD patients experienced relapse, although their renal progression was rare. Younger onset age, CS without cyclophosphamide treatment, and shorter treatment duration were independent risk factors for relapse in adult-onset MCD patients.

Efficacy and safety of leflunomide in treatment of steroid-dependent and steroid-resistant adult onset minimal change disease

To observe the efficacy and safety of leflunomide combined with prednisone therapy (LEF therapy) in the treatment of patients with adult onset steroid-dependent and steroid-resistant minimal change disease (MCD). 16 MCD patients who had been treated with LEF therapy were retrospectively analyzed. 87.5% (14/16) of the patients were steroid-dependent and 12.5% (2/16) of the patients were steroid-resistant. The initial dose of LEF was 10 - 20 mg/day combined with prednisone 0.25 - 1.0 mg/kg/day, gradually tapering after 8 weeks. Clinical and laboratory data at baseline, 2nd, 4th, 8th, 12th, 24th, and 48th week were analyzed compared with initial course of prednisone monotherapy (PRED monotherapy) and cyclophosphamide combined with prednisone therapy (CTX therapy). All the 16 patients achieved different levels of remission in LEF therapy. 93.8% (15/16) of the patients, including the two steroid-resistant patients, achieved complete remission. During the treatment, 8 patients had adverse effects which could be well tolerated. Compared LEF therapy with PRED monotherapy (n = 16), the dose of prednisone to maintain remission was reduced (from median 22.5 mg/day to median 7.5 mg/day, p = 0.041); relapse rate during the follow-up decreased from 100% to 31.3% (p = 0.002); the median time before relapse increased from 20.3 weeks to 32.5 weeks. Compared LEF therapy with CTX therapy (n = 12), the dose of prednisone to maintain remission was reduced significantly (from median 22.5 mg/day to median 5.0 mg/day, p = 0.003); relapse rate during the follow-up decreased from 100% to 31.3% (p = 0.001); the median time before relapse increased from 11.7 weeks to 32.5 weeks. LEF therapy seems to be effective in steroid-resistant and steroiddependent MCD. This therapy may reduce the amount of prednisone to maintain remission and reduce the relapse rate compared with PRED monothrerapy and CTX therapy. LEF therapy was usually well tolerated.