A delicate risk balance: BK nephropathy and kidney rejection

Dr. Didier Mandelbrot

Lurking in the bodies of about 90 percent of all adults is BK polyomavirus. Named for the initials of the kidney transplant patient (“B.K.”) from which the virus was isolated in 1971, BK polyomavirus is widespread and rarely causes disease. In most people, asymptomatic infection during childhood is followed by the virus becoming latent in the kidneys and urinary tract.

In kidney transplant recipients, however, the immunosuppression that is required to prevent rejection of the new kidney can cause the virus to reactivate and wreak havoc. Hallmarks of BK virus–associated nephropathy (BKN) include increased serum creatinine levels and inflammation of the kidney tubules. An estimated 2 to 8 percent of kidney transplant recipients develop BKN; about 50 percent of these will go on to lose their grafts. Unfortunately, there are no effective medications for either treatment or prevention of BKN. The standard of care is to reduce immunosuppression.

"This puts clinicians between a rock and a hard place: choose between reducing immunosuppression for BKN and risking rejection, or increasing immunosuppression for rejection and risking BKN," said Didier Mandelbrot, MD, professor (CHS), Nephrology and medical director of the UW Health kidney transplant program.

To pinpoint whether BKN or rejection poses greater risk for renal transplant recipients during the first 18 months post-transplant, Dr. Mandelbrot and first author Sandesh Parajuli, MD, assistant professor (CHS), Nephrology, analyzed 13 year's worth of data from the Wisconsin Allograft Recipient Database (WisARD). A total of 352 control patients were compared to 96 patients with BKN and 256 patients with rejection. The results were surprising, and countered conventional wisdom.

While rejection is feared, the researchers found that BKN actually hit transplant recipients harder. “In this large cohort with more than 13 years of data, we found that, in the initial period, BKN was more harmful than rejection, with significantly worse renal function at 6 months, 12 months, and 3 years,” wrote the authors. By five years post-transplant, 33 percent of BKN patients’ grafts had failed compared to 26 percent in the rejection group. While this difference did not reach statistical significance, kidney function up to three years after diagnosis was worse for BKN than rejection.

“Our findings have practical implications for transplant providers who may overemphasize the importance of rejection and underemphasize the importance of BKN, with resulting over-immunosuppression of patients with BKN,” wrote the authors.

The results suggest that further investigation, careful risk management, and clear communication are all needed. "Almost all patients have heard of rejection and often are terrified of the diagnosis because they do not adequately distinguish it from graft failure. The word ‘rejection’ is frightening,” said Dr. Mandelbrot.

“But as clinicians we need to be clear that not all rejection leads to allograft failure, and that aggressively increased immunosuppression - which is used to treat rejection - potentially increases the risk of patients developing BK nephropathy, which actually is at least as nephrotoxic to kidneys as rejection."

Additional authors of the study include Brad Astor, MD, MPH, associate professor, Brenda Muth, APNP, nurse practitioner, Maha Mohamed, MD, assistant professor (CHS), Neetika Garg, MD, assistant professor (CHS), and Arjang Djamali, MD, MS, professor and head, all of Nephrology; and Dixon Kaufman, MD, PhD, professor, Department of Surgery and chief, UW Health transplant division. The research was funded by the Virginia Lee Cook Foundation.

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Photo caption: Research led by Dr. Didier Mandelbrot analyzed data on kidney transplant recipients to understand the relative harm of two common renal transplant complications. Photo credit: Clint Thayer/Department of Medicine

Robyn Perrin, PhD