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.

Keywords: nephrotic syndrome; pathology; pediatric nephrology; podocyte; proteinuria; renal.

Figure 1.

Etiology of nephrotic syndrome according to age from 1 year onwards. (A) Minimal change disease. (B) Focal segmental glomerulosclerosis. (C) Membranous nephropathy. Data are approximated from Nachman et al. (1) and Cameron (2).

Figure 2.

Time-to-response to prednisone is much shorter in children than in adults with minimal change disease. Data are extrapolated from references Waldman et al. (12) and Vivarelli et al. (82) for children (A and B), from references (83) and Chen et al. (84) for adults (C and D).

Figure 3.

Pathogenesis of minimal change disease: hypotheses. In the presence of a normal glomerular basement membrane (shown at the center), with healthy podocyte foot processes (light blue), serum proteins, mainly albumin, remain within the glomerular capillary lumen. Mechanisms, that are as yet not fully elucidated but are partly intrinsic to the podocyte and partly due to the presence of soluble mediators released by a disregulated immune system (see top of the figure and text), modify this integrity. Therefore (red arrow), the actin cytoskeleton of the podocyte and the glomerular basement membrane are disrupted, and albumin and other serum proteins filter out of the bloodstream and into the urinary space. This leads to the intense proteinuria seen in nephrotic syndrome.