Minimal Change Disease

Abstract

Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

Shortening the Duration of Corticosteroid Exposure in Minimal Change Disease: Can We Treat Adults Like Children?

“…Reporter bias may account for this lack of difference, however, as adverse events were prospectively surveyed among the short-term treated patients and extracted from registry records in the historical, conventionally treated cohort patients. For example, whereas most studies in the literature report a rate of infection between 5 and 15% in adults with MCD on corticosteroids [1][2][3], only 6 of the 140 (4.3%) adult MCD patients in the longterm steroid group had such complications. Despite no statistically significant adverse event differences between the short-and long-term steroid groups, some clear trends have emerged including a lower incidence of infectious-related hospitalization, peptic ulcer disease, and femoral head osteonecrosis.…”

“…Patients frequently experience adverse effects of corticosteroid therapy, and a high rate of relapse further plagues the clinical course of MCD across all age spectrums, often necessitating repeat exposure to steroids and/or other, potentially toxic immunosuppressive agents [2]. Therefore, since the initial recognition that corticosteroids led to a remission of "nil disease," nephrologists have consistently sought the answer to a relatively straightforward question for MCD: What is the least amount of corticosteroids my patient needs to achieve a remission and not relapse immediately?The answer to that question has been worked out for the pediatric MCD population over a span of more than 5 decades, and the current standard of care is a regimen of daily corticosteroids (e.g., prednisone 60 mg/m 2 ) for 4 weeks followed by an additional 4-8 weeks of alternate day corticosteroids (e.g., prednisone 40 mg/m 2 ) [3]. A number of clinical trials and a meta-analysis of these trials have found no additional benefit for children with MCD in extending corticosteroid exposure past the 2-or 3-month mark [4][5][6][7].…”

Glucocorticoids in the Treatment of Glomerular Diseases

“…Nevertheless, frequent relapsers and steroid-dependent patients may develop signs of glucocorticoid toxicity and will require different therapies. Glucocorticoid-sparing strategies include a course of 2-3 months of cyclophosphamide, levamisole, mycophenolate (18), cyclosporine (19), or rituximab (20).…”

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

“…Minimal change disease (MCD), also called lipid nephrosis, is a common type of primary glomerular diseases and one of the most common reasons for nephrotic syndrome [1]. MCD accounts for 70–90% of nephrotic syndrome in children and approximately 15% in adults [1, 2].…”

“…MCD accounts for 70–90% of nephrotic syndrome in children and approximately 15% in adults [1, 2]. MCD is mainly characterized by proteinuria due to the damage of podocytes [3].…”