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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 kidney biopsy the findings include apparently normal glomeruli on light microscopy, negative immunofluorescence, and diffuse podocyte foot process effacement on electron microscopy (Figure 25–1). 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 most common finding in adults with nephrotic syndrome, after membranous nephropathy and focal, segmental glomerulosclerosis (FSGS). The typical patient with MCD responds to therapy but experiences recurrent relapses.

Figure 25–1.

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.)


  • 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 (see Figure 25–1).

  • 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.


MCD is the most common cause of nephrotic syndrome in children and the third most common cause of nephrotic syndrome in adults, affecting 10–15% of nephrotic adults. In children the incidence of nephrotic syndrome is 2–7 cases per 100,000 children and the prevalence is estimated at 16–100 cases per 100,000. In young children there is a male predominance of 2:1, but by adolescence the genders are equally affected. While most patients with MCD respond to therapy and have a good long-term prognosis, there are risks of developing serious complications such as infection and thrombosis, and the risks of 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 ...

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