What are the histologic findings of acute interstitial nephritis secondary to valganciclovir?
Fernando Giron, MD
Recently, I attended a symposium on cytomegalovirus (CMV) disease. Attending this conference were some of the world's experts in CMV disease. Having never seen interstitial nephritis caused by antiviral drug therapy, I asked if anyone else had experience with valganciclovir-related interstitial nephritis. There seemed to be a consensus, that other differentials be entertained. Patients who are taking valganciclovir are by definition highly immunosuppressed; either they are in the immediate posttransplant period or are being treated for CMV disease. Such patients are at risk for reactivation of polyoma virus of the BK type (BKV), and this pathogen is now blamed for increasing numbers of kidney allograft losses. BKV was first described in a kidney transplant patient in 1971. Since then we have learned much about this virus. It is a DNA virus that shares 70% homology with simian virus 40. As many as 80% of adults have been infected, most during childhood. It is estimated that 5% of renal transplant recipients have clinically significant BKV disease, and that 35% of these patients will lose their allograft. Figures 1-4 show the characteristic tubulo-interstitial lymphocytic infiltration on kidney biopsy that is not infrequently confused with rejection. Intranuclear inclusions are seen at high magnification and the diagnosis is established with the characteristic appearance on electron microscopy. Of note, the treatment is the judicious reduction of immunosuppression. Drugs such as cidofovir have shown in vitro activity, but have not been proven to be efficacious clinically. The key is to suspect this infection in any patient not responding to antirejection therapy or in the patient with significant interstitial nephritis on renal allograft biopsy.
Tubulointerstitial nephritis with a predominantly lymphocytic infiltrate with focally enlarged tubular epithelial cells. (Light microscopy, original magnification x 100.)
Tubular epithelial cells with large smudge nuclei and basophilic chromatin. (Light microscopy, original magnification x 300.)
Renal tubule epithelial cell with a distinct intranuclear inclusion. (Electron micrograph, original magnification x 4500.)
Inclusion consists of crystalline arrays of nonenveloped, round, electron-dense particles, measuring 45 nm in diameter on average, assembled into small, loose, crystalline lattices. (Electron micrograph, original magnification x 30,000.)