Adult-onset Minimal Change Disease Patients Research Articles

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.

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.

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.

Age and prediction of remission and relapse of proteinuria and corticosteroid-related adverse events in adult-onset minimal-change disease: a retrospective cohort study

In adult-onset minimal-change disease (MCD) the predictors of remission and relapse of proteinuria and corticosteroid-related adverse events remain unknown. The multicenter retrospective cohort study, the STudy of Outcomes and Practice patterns of Minimal-Change Disease (STOP-MCD), included 142 adult-onset MCD patients in 5 nephrology centers in Japan. Primary outcomes were first remission of proteinuria defined by urinary protein (UP) <0.3g/day, UP/creatinine ratio (UPCR) <0.3, and/or negative/trace by dipstick test and first relapse of proteinuria defined by UP ≥1.0g/day, UPCR ≥1.0, and/or dipstick test ≥1+ followed by immunosuppressive therapy. Secondary outcomes were corticosteroid-related adverse events. During the median 3.6 (interquartile range, 2.0-6.9) years of the entire observational period, 136 (95.8%) and 79 (58.1%) patients developed at least 1 remission and 1 recurrence within a median of 15 (10-34) days and 0.90 (0.55-1.57) years, respectively. Compared with younger patients aged 15-29years at kidney biopsy, elderly patients aged ≥60years developed remission significantly later [hazard ratio 0.53 (95% confidence interval 0.32-0.88)], while older patients aged ≥45years were at a significantly lower risk of relapse [45-59years, 0.46 (0.22-0.96); 60-83years, 0.39 (0.21-0.74)]. However, older patients were significantly more vulnerable to severe infection, diabetes, and cataract as compared with younger patients. Younger patients had a higher risk of relapse while older patients had a lower risk of relapse but a higher risk of corticosteroid-related adverse events.

Glomerular glucocorticoid receptor expression is reduced in late responders to steroids in adult-onset minimal change disease

Compared to children, adult patients with minimal change disease (MCD) tend to have a slower response to steroids, but little is known about the factors influencing the steroid responsiveness in these patients. In this study, we investigated the difference in the expression of the glomerular glucocorticoid receptor (GCR) according to steroid responsiveness in 28 adult-onset MCD patients. Based on the response to steroid treatment, the patients were divided into early responders (ER, n=20) and late responders (LR, n=8) according to the response to steroids on the basis of 4 weeks of treatment. The clinical and laboratory findings, and the glomerular mRNA and protein expression of GCR and nephrin, assessed by real-time polymerase chain reaction and immunohistochemistry, respectively, were compared between the ER and LR groups. Ten microscopic haematuric patients in whom renal biopsy was performed and revealed no histological abnormalities were included for control (C). The mRNA expression of GCR was significantly lower in the LR than that in the ER group (P<0.01), whereas it was comparable between the C and ER groups. GCR protein expression was also decreased in the LR compared with the C and ER groups. In contrast, there was no significant difference in nephrin mRNA expression among the three groups. On the other hand, the GCR mRNA expression correlated inversely with the time to complete remission (r= -0.49, P<0.05), but not with the amount of proteinuria at presentation. In conclusion, the levels of glomerular GCR expression may be a useful predictor of steroid responsiveness in adult-onset MCD patients.