Recent approaches to the pathogenesis of minimal-change nephrotic syndrome

Grimbert, Philippe; Audard, Vincent; Rémy, Philippe; Lang, Philippe; Sahali, Djillali

doi:10.1093/ndt/18.2.245

Cited by 86 publications

(67 citation statements)

References 24 publications

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“…Although the precise MCD pathogenesis remains unknown, immunologic perturbations, especially in T cells (26), and subsequent injury to glomerular podocytes (27), including reduced expression of nephrin (28)(29)(30), lead to massive proteinuria in MCD. In addition to its immunomodulatory effect, corticosteroid directly affects the gene expression of podocytes (31).…”

Section: Discussionmentioning

confidence: 99%

“…However, the lower relapse rate in the mPSL+PSL group during the several years of the observational period is hardly explained by the higher initial dose of corticosteroid in the mPSL+PSL group. One potential hypothesis for the long-term suppression of relapse by initial use of mPSL may be epigenetic modification (26). Because corticosteroid induces epigenetic changes (32,33) and because DNA methylation in PBMCs is modified in MCD patients (34), altering between remission and relapse (35), the higher initial dose of corticosteroid administered in the mPSL+PSL group may possibly induce long-term epigenetic changes, leading to a long-term suppression of relapse compared with the PSL group.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Methylprednisolone Plus Prednisolone with Prednisolone Alone as Initial Treatment in Adult-Onset Minimal Change Disease

Shinzawa¹,

Yamamoto²,

Nagasawa³

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Previous studies suggested that intravenous methylprednisolone possibly accelerates remission of proteinuria in adult-onset minimal change disease; its impact on relapse of proteinuria is unknown.Design, setting, participants, & measurements This multicenter retrospective cohort study included 125 adultonset minimal change disease patients diagnosed by kidney biopsy between 2000 and 2009 and treated initially with corticosteroid in five nephrology centers in Japan participating in the Study of Outcomes and Practice Patterns of Minimal Change Disease. Times to first remission and first relapse of proteinuria after initiating the first immunosuppressive therapy were compared between 65 patients with initial use of intravenous methylprednisolone followed by prednisolone and 60 patients with initial use of prednisolone alone using multivariate Cox proportional hazards models. After calculating the probability of receiving methylprednisolone and prednisolone using a logistic regression model (propensity score), the results were ascertained using propensity score-matched and -stratified models.Results During the median 3.6 years of observation (interquartile range=2.0-6.9), all 65 patients in the methylprednisolone and prednisolone group achieved remission within 11 (8-20) days of the corticosteroid initiation, whereas in the prednisolone group, 58 of 60 patients (96.7%) achieved remission within 19 (12-37) days (P,0.001). After achieving first remission, 32 (49.2%) patients in the methylprednisolone and prednisolone group and 43 (74.1%) patients in the prednisolone group developed at least one relapse. Multivariate Cox proportional hazards models revealed that methylprednisolone and prednisolone use was significantly associated with early remission (multivariate-adjusted hazard ratio, 1.56; 95% confidence interval, 1.06 to 2.30) and lower incidence of relapse (0.50; 95% confidence interval, 0.29 to 0.85) compared with prednisolone use alone. These results were ascertained in propensity score-based models. No significant difference was observed in incidence of adverse events, including infection, aseptic osteonecrosis, cataract, diabetes, and gastrointestinal bleeding.Conclusions Initial use of methylprednisolone was associated with earlier remission and lower incidence of relapse in adult-onset minimal change disease patients. Efficacy of methylprednisolone should be evaluated in randomized controlled trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of Methylprednisolone Plus Prednisolone with Prednisolone Alone as Initial Treatment in Adult-Onset Minimal Change Disease

Shinzawa¹,

Yamamoto²,

Nagasawa³

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Many studies have proposed a role for the immune system (2,4 -6), and this hypothesis is supported by a favorable response to anti-inflammatory drugs (2), a relation between relapses and viral infections or allergic reactions (5), the recurrence of the disease in transplanted patients (1) and an association with immunologic disorders (2).…”

mentioning

confidence: 99%

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

et al. 2008

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ABSTRACT:The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor ␤ 1 (TGF-␤ 1 ), monocyte chemoattractant protein-1 (MCP-1/ CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n ϭ 8), or steroid-resistant (SR, n ϭ 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-␤ 1 levels in SR patients were approximately 2.8-fold higher than control values (p Ͻ 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria Ͼ100 mg/m 2 /24 h) when compared with patients in remission (p Ͻ 0.05), and levels had a positive correlation with individual proteinuria values (p Ͻ 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-␤ 1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-␤ 1 could be related to worse response to corticosteroids. (Pediatr Res 64: 637-642, 2008)

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“…Prolonged remissions following measles, which downregulates CMI also endorses this hypothesis. T-cell abnormalities has been variably reported in minimal change disease (MCD) 14,15,16,17 . Increased free radical generations and decreased anti oxidantdefenses may play crucial role in the pathogenesis of nephrotic syndrome.…”

Section: Pathogenesismentioning

confidence: 99%