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Minimal change disease (MCD) is a term used to describe the pathologic findings in a group of patients who present with heavy proteinuria, typically leading to nephrotic syndrome. On renal biopsy the findings include apparently normal glomeruli on light microscopy, negative immunofluorescence, and diffuse podocyte foot process effacement on electron microscopy. While occasionally MCD may be secondary to another condition such as lymphoma, in the majority of cases MCD is one of the idiopathic renal diseases. Because MCD is most likely to be the diagnosis in children presenting with the nephrotic syndrome, the majority of children do not undergo a kidney biopsy, but receive empiric treatment without one. Seventy percent of children with MCD present before age 5 years, and 20–30% of adolescents who present with nephrotic syndrome have MCD. Nevertheless, MCD is the third commonest finding in adults with nephrotic syndrome, after membranous nephropathy and focal, segmental glomerulosclerosis. The typical patient with MCD responds to therapy but experiences recurrent relapses.

  • Heavy proteinuria, typically leading to nephrotic syndrome.
  • Renal biopsy with minimal changes on light microscopy, negative immunofluorescent microscopy, and podocyte foot process effacement on electron microscopy (Figure 24–1).
  • Usually there is no known etiology, although secondary MCD may be associated with neoplastic disease, toxic or allergic reactions to drugs, infections, autoimmune disorders, or other miscellaneous disorders.

Figure 24–1.

A: Light microscopy (PAS stain) shows a completely normal looking glomerulus. B: Electron microscopy is normal except for the characteristic foot process effacement. (Photomicrographs courtesy of Arthur Cohen, MD.)

MCD is the most common cause of nephrotic syndrome in children and the third most common cause of nephrotic syndrome in adults. In children the incidence of nephrotic syndrome is two to seven cases per 100,000 children and the prevalence is nearly 16 cases per 100,000. While most patients with MCD respond to therapy and have a good long-term prognosis, they are at risk for developing serious complications such as infection and thrombosis, and they are at risk for complications from therapy. The treatment of the MCD patient who is resistant to or dependent on corticosteroid therapy remains a challenge, despite the several therapeutic options available.

Since first postulated by Shaloub in the 1970s, the pathogenesis of MCD has been associated with the presence of a circulating factor capable of inducing proteinuria. Presumably, the circulating factor is secreted by lymphoid cells and functions as a vascular permeability factor or directly affects the function of the podocyte. The induction of remission by immunosuppressive medications further strengthens the argument that the circulating factor is secreted by immune cells whose function is inhibited by these agents. In addition, patients who develop end-stage renal disease from MCD or focal, segmental glomerulosclerosis (FSGS) are at risk for recurrent disease occurring rapidly after transplant. To date, the most promising ...

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