BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection

Abstract

BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology's dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.

Keywords: BK polyomavirus nephropathy; acute rejection; immunosuppressants; kidney transplant; tacrolimus.

Figure 1

The immune system of kidney transplant recipients is balanced between rejection and infection. Excessive immunosuppression may lead to infections, such as BK polyomavirus nephropathy (BKVN), nosocomial infections, latent infections, and community infections. Drug nephrotoxicity may also develop. On the opposite side, insufficient immunosuppression may result in allograft rejection. Both arms may cause significant kidney damage and renal allograft dysfunction.

Figure 2

Risk factors for BKPyV infection. Risk factors can be assorted into 3 categories: Transplant factors [39,56,62,63,64,65,67,68,70,71,72], donor factors [16,18,62,64,66,69], and recipient factors [16,18,56,64,69]. Understanding risk factors that affect before and after transplant can be helpful in immune balance. Abbreviations: HLA, human leukocyte antigen; BKPyV, BK polyomavirus; CMV, cytomegalovirus.

Figure 3

Conceptual illustration of evaluations, screening, diagnosis, and management for BKPyV infection. Abbreviations: KT, kidney transplant; BKPyV, BK polyomavirus; BKVN, BK polyomavirus nephropathy; IVIG, intravenous immunoglobulin; D/Dx, differential diagnosis.