If you remember one thing about minimal change disease (MCD) from your preclinical courses, it’s probably that MCD is most commonly found in children. In fact, 70-90% of children with nephrotic syndrome are found to have MCD! In adults, this number is only around 10-15%. In this post, we’ll review the diagnosis of MCD with the help Dr. Peyman Dinarvand, a chief pathology resident at St. Louis University. After diagnosing, we’ll explore the pathophysiology and treatment of this disease.
Diagnosing a child with MCD does not require a kidney biopsy. Since the disease is so common in children with nephrotic syndrome, we can treat them empirically and make the diagnosis if they improve. In adults, however, definitive diagnosis is made with a kidney biopsy.
Upon initial inspection with light microscopy, the glomeruli appear normal. Here, we see that Dr. Dinarvand’s patient had no mesangial expansion, no sclerosis, and no atrophy.
The arrows in the PAS and silver stains highlight normal glomerular basement membranes:
The arrow in this trichrome stain marks healthy collagen without fibrosis:
However, with an electron microscope we can see the flattened epithelial foot processes indicated by the red arrows.
This is a classic example of what we expect to find in MCD: a patient with nephrotic syndrome with seemingly normal glomerular structure on histopathologic slides is found to have effacement of foot processes on electron microscopy.
MCD has traditionally been categorized as an immune-mediated disease. A potential hypothesis is that lymphocytes inappropriately release cytokines that acts as a vascular “permability factor,” ultimately leading to podocyte dysfunction. New research, however, suggests that the disease may be the result of intrinsic defects in the podocyte cytoskeleton. This failure of the cytoskeleton leads to a change in podocyte architecture resulting in increased permeability.
The treatment for MCD in children is simple: high-dose steroids. Treatment for adults is much more complicated and a nephrology consult is certainly warranted. If possible, limit the patient’s exposure to medications and environmental allergens that have been associated with MCD. Treatment-resistant MCD in adults will often look like focal segmental glomerulosclerosis on repeat biopsy. Future research will hopefully elucidate why certain patients respond well to treatment while others do not.
Dr. Jennifer Kaplan, MD, @kingdomplantayy
Dr. Peyman Dinarvand, MD