Risk for BK viremia and nephropathy after desensitization.

Barbosa and colleagues report their experience analyzing polyoma (BK) viremia in kidney allograft recipients after human leukocyte antigen (HLA) desensitization with intravenous immunoglobulin (IVIG) and rituximab (1). Compared to a nondesensitized group (n=284), the desensitized group (n=187) had double the incidence of BK viremia (10% vs. 20%, respectively; PG0.001) but equivalent incidence of BK nephropathy (1% vs. 2% respectively; P=0.28). Importantly, long-term patient and graft survivals were equivalent (despite more rejection in the HLA-desensitized cohort). The period of analysis was contemporary (2007 onward) and incorporated a comprehensive BK viremia surveillance strategy to detect polyoma virus replication. In a multivariate analysis, only desensitization was identified as an independent risk factor for development of BK viremia. We have previously demonstrated that patients who are desensitized just before surgery (plasma exchange with low dose IVIGTrituximab/splenectomy) have higher rates of BK nephropathy compared to compatible kidney allograft recipients (2). In this retrospective analysis of a prospectively maintained cohort, ABO-incompatible (n=62) and HLA-incompatible (transplantation across preformed donor-reactive antibodies, n=221) kidney allograft recipients had BK nephropathy rates of 17.7% and 5.9%, respectively (compared to 3.0% in compatible kidney allograft cohort). However, using a logistic regression model, only ABO-incompatible kidney transplantation and age were found to be independent predictors for BK nephropathy and not HLA incompatibility. Comparing the results from these two publications, a number of issues are worthy of further discussion. In our analysis, we did not observe any difference in rates of rituximab, splenectomy, T-cell depletion therapy, or number of pre-plasmapheresisorpost-plasmapheresis sessions among HLA-incompatible recipients who did or did not develop BK nephropathy. Although BK nephropathy rates were slightly higher in the HLAincompatible versus compatible kidney allograft cohort, it appeared unlikely that desensitization alone is a significant factor and likely reflects higher overall maintenance immunosuppression. This is supported by our observation of higher BK nephropathy rates in the ABOincompatible versus HLA-incompatible cohort, despite less posttransplant plasmapheresis and T-cell depletion induction in blood group-incompatible patients. The two studies differ with respect to method of desensitization (high-dose IVIG/rituximab at Cedars Sinai, plasmapheresis/low dose IVIG at Johns Hopkins), which limits likefor-like comparison between the two cohorts. Despite this, given the differing analyses derived from these two studies, more studies should be performed to determine the role of desensitization in the development of BK viremia and nephropathy in the context of antibodyincompatible kidney allograft recipients. It would be interesting if Barbosa and colleagues could perform a comparative analysis of HLA-desensitized kidney allograft recipients who did versus did not develop BK viremia to ascertain potential risk factors within the HLA-desensitized group. For example, we identified a higher proportion of black HLA-incompatible kidney allograft recipients who developed BK nephropathy compared to those who did not (percentage of blacks in the BK nephropathy vs. non-BK nephropathy groups, 31% vs. 18%, respectively; P=0.01). It would be interesting to ascertain whether this observation was replicated in the data from Barbosa and colleagues. Although Barbosa and colleagues did not identify any significant difference in BK nephropathy rates, lack of protocol biopsies limits the detection of BK nephropathy in a high-risk cohort within the first year after transplantation. In our cohort, 13 (of 221) HLA-incompatible kidney allograft recipients developed BK nephropathy, and five of those cases were diagnosed by protocol biopsy. Only one case of BK nephropathy was identified (by indication biopsy) beyond the first year after transplantation. It is therefore likely that some patients with BK viremia had undetected BK nephropathy in the cohort from Barbosa and colleagues due to the absence of protocol biopsies (3). Therefore, the lack of difference in BK nephropathy rates between the desensitized and nondesensitized cohorts must be interpreted with caution. Regardless of these caveats, both these publications highlight that HLAincompatible kidney allograft recipients are at higher risk for BK virus than compatible kidney allograft recipients and require heightened surveillance. Both groups demonstrate the success of BK surveillance to prevent loss of allograft function. Surveillance protocols should consist of structured BK viremia screening and low threshold for indication biopsy. We would argue that protocol biopsies are important to detect subclinical BK nephropathy in a high-risk cohort because risk for allograft loss is greater with BK nephropathy compared to BK viremia alone. Screening for BK viremia alone will reduce, but not eliminate, risk for BK nephropathy (4) and in the context of HLA-incompatible kidney transplantation, the stakes are high. Early identification will facilitate tapering of immunosuppression (5), but in the context of a desensitized cohort of immunologically difficult kidney allograft recipients, this should be done after careful assessment of risks versus benefits. CORRESPONDENCE