More on MYH9 and "HTN-Associated ESRD"

What's the most common cause of ESRD in the U.S. after diabetes? The classic answer here is "hypertension", though this answer is a controversial one, as there are many who believe that hypertension alone is not sufficient to cause the degree of renal disease seen in ESRD. Certainly, there are many, many individuals with elevated blood pressures who never go on to develop CKD, suggesting that hypertension alone cannot explain everything.

A potential alternative explanation for individuals with "hypertension-induced ESRD" comes from polymorphisms in the MYH9 gene, according to a Kidney International article by Freedman et al. Polymorphisms in MYH9, which I have written about in another post, have recently been shown to be associated with an increased risk of FSGS and HIVAN in African-American patients. In the paper mentioned above, the authors tested for several known polymorphisms of the MYH9 gene in nearly 700 African-American dialysis patients given the diagnosis of "hypertension-associated ESRD." Interestingly, they found a strong association between ESRD and certain SNPs--with impressive odds ratios (OR) of up to 3.4.

The MYH9 gene product, myosin-IIA, is expressed in podocytes and is known to play a role in organization of the cytoskeleton. Thus, it is postulated that partial loss-of-function provided by various polymorphisms could cause subtle abnormalities in podocyte foot process and slit diaphragm organization. These findings furthermore imply that perhaps the entity we call "hypertension-associated ESRD" is in fact a defect in podocytes similar to FSGS. It will be interesting to see how this story plays out and whether or not immunosuppressive therapies we find useful in the management of FSGS might also be useful for treatment of hypertension-associated ESRD. It's obviously too early to suggest that this be attempted, but these studies provide a new framework with which to think about a substantial subset of ESRD patients.