Abstract
Keywords: transplantation, AKI, BK polyomavirus, CMV, kidney transplantation, transaminitis
Case Description
A 62-year-old man with diabetic nephropathy was transplanted with a kidney from a deceased donor. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. No induction therapy was administered. Cytomegalovirus (CMV) serology was negative in both donor and recipient. He was discharged quickly with normal kidney function.
Nine months later, the patient reported loss of appetite and nausea. Laboratory tests revealed AKI (doubling of serum creatinine), hepatitis (threefold increase in serum alanine and aspartate aminotransferase levels), and the absence of de novo HLA antibody, leukocyturia, or proteinuria.
Urine cytology showed decoy cells with simian virus 40 (SV40) immunoassay. BK polyomavirus (BKPyV) quantitative plasma PCR viral load was high (10,128,020 IU/ml). Concomitantly, CMV quantitative plasma PCR revealed 2,173,546 IU/ml. An allograft biopsy showed an interstitial lymphoplasmacytic infiltrate with tubulitis (Figure 1A). Immunochemistery analysis confirmed BKPyV and CMV renal coinfection (Figure 1, B and C). Ganciclovir was started and mycophenolate mofetil was discontinued. Six weeks later, kidney function has stabilized; CMV and BKPyV viral loads have decreased considerably but have not yet normalized.
Figure 1.
Light microscopy and immunohistochemistry images. (A) Hematoxylin and eosin staining, magnification ×20: Renal allograft biopsy shows interstitial lymphoplasmacytic infiltrate with few neutrophils surrounding infected tubules. These are infiltrated by lymphocytes (black arrows), and infected tubular epithelial cells are characterized by a homogenous intranuclear inclusion of BKPyV (red arrows). (B) Immunohistochemistry, magnification ×15: This BKPyV infection was confirmed by SV40 immunohistochemistry which reveal by nuclear labeling the infected cells close to other healthy ones. (C) Immunohistochemistry, magnification ×33: Detection of a simultaneous infection by cytomegalovirus, proven by immunohistochemistry revealing rare nuclear positivity in glomerular cell.
Discussion
Coinfection with BKPyV and CMV in kidney transplant recipients is uncommon and poorly reported. Some data have suggested that plasma BKPyV positivity is strongly associated with CMV coinfection, suggesting that both viruses may be risk factors for each other.1 Only small retrospective case series have reported outcomes of patients infected with both viruses.2,3 Jehn et al.2 compared the outcomes of kidney transplant recipients presenting with concomitant BKPyV and CMV viremia (n=59), CMV viremia alone (n=182), and BKPyV viremia alone (n=102). They found a strong association between coinfection and occurrence of acute rejection. However, although patients with coinfection had lower graft function, there was no difference between groups regarding graft and patient survival. Kaul et al.3 also compared the outcomes of six patients with coinfection with those of 10 and four patients with CMV viremia alone or BKPyV viremia alone, respectively. Coinfection was not associated with the increased risk of acute rejection or patient survival or death-censored graft survival. Treatment of coinfection is not well-defined. However, reduction of immunosuppression4 should be applied as well as CMV treatment with (val)ganciclovir.5
Teaching Points
Coinfection with BKPyV and CMV in kidney transplant recipients is uncommon.
Outcomes of patients coinfected by both viruses are not well defined.
Management is based on recommendations for the treatment of each virus individually.
Acknowledgments
Informed consent was obtained from the patient.
Disclosures
All authors have nothing to disclose.
Funding
None.
Author Contributions
F. Lacave conceptualized the study; and A. Devresse and N. Kanaan provided supervision and were responsible for validation.
References
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