Decline in native kidney function in liver transplant recipients is not associated with BK virus infection

Abstract

BK virus (BKV) infection is an established cause of allograft dysfunction in renal transplant recipients. The relationship between BKV infection and chronic kidney disease (CKD) post-orthotopic liver transplantation (OLT) is not well understood. This study aimed to determine the prevalence of BKV infection, its relationship to CKD and renal function loss over time in patients receiving OLT. Prevalence of BK viruria and viremia were studied in 41 post-OLT patients after a mean 6.5 Ϯ 4.7 years posttransplantation. Renal function was assessed using estimated glomerular filtration rate (eGFR) calculated from the yearly serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) formula. Polymerase chain reaction (PCR) was performed for detection of BKV DNA in urine and plasma. BK viruria was present in 24.2% of patients, but none of these OLT recipients had detectable BK viremia. Decoy cells in the urine were found in 9.7% patients, although none of these patients had BK viruria. CKD, defined as eGFR Ͻ60 mL/minute/1.73 m 2 , was found in 83% of OLT recipients. The yearly decline in eGFR was Ϫ6.9 Ϯ 17 and Ϫ9.2 Ϯ 18 mL/minute/year in BK viruria-positive and BK viruria-negative patients, respectively (P ϭ 0.39). There was no relationship between the presence or absence of BK viruria and either current eGFR, yearly decline in eGFR, number and type of immunosuppressive agents, or etiology of liver failure. In OLT recipients, BK viruria is not associated with BK viremia or native kidney dysfunction. It appears that the most probable pathway for the development of BKV nephropathy requires a second hit, such as kidney inflammation, kidney ischemia, or donor-recipient human leukocyte antigen mismatch.

The association between polyomavirus BK strains and BKV viruria in liver transplant recipients

“…Higher prevalence of BKV viruria in this study compared with that reported in other studies may be attributed to higher dosages of immunosuppressants used in the first three months after liver transplantation, leading to more intensive immunosuppression in our subjects. Despite high prevalence of BKV viruria in liver transplant recipients, the renal outcome seems unassociated with the presence of BKV viruria5825. Similarly, our data also demonstrated that eGFR was not significantly different in the high and low urinary BKV load groups except for the 2 nd and 3 rd months.…”

“…observed in a prospective study that persistent BKV viremia might be related to the impaired renal function in liver transplant recipients5. In contrast, other studies did not discover the association between BKV viremia and viruria with renal dysfunction in liver transplant patients678. The discrepancy in high association of BKV infection with renal allograft function in renal transplant recipients and no obviously causal relationship between BKV infection and renal function in liver transplant recipients may highlight the importance of the second hit such as ischemia or inflammation in the development of renal dysfunction in addition to BKV infection.…”

Polyomavirus-associated nephropathy

“…Clinical impact is relevant, as loss of the renal graft ranges from 30% up to > 80% of cases [12][13][14] ; in transplant centres where screening for polyomavirus replication in the urine and plasma is performed, the rate of graft loss is lower [15] . Several studies evidenced that BK viremia is only rarely observed in non-kidney solid organ transplant recipients and biopsy-confirmed cases of nephropathy have been described in few case reports [16][17][18][19][20][21][22] , despite the similar or even higher level of immunosuppression, thus supporting the role of organ determinants in the pathogenesis of PVAN.…”

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“…However, the fact that decoy cells also may emerge in other virus infections (John Cunningham virus, Simian virus 40, cytomegalovirus, adenovirus), 28 and that they may be discharged with urine in asymptomatic individuals and may be detected in urine in the presence of malignity, 29 renders its value questionable in diagnosing BK virus nephritis. This is supported by the fact that Salama and associates, 30 in their study comprising only liver transplant recipients, reported finding decoy cells in 9.7% of the patients without detecting viruria in any of them. Because BK virus may be discharged in urine in asymptomatic individuals even if nephritis is not clinically present, no matter which method is used for screening, the diagnostic value of viruria in urine is lower than that of BK viremia in diagnosing BK virus infection.…”