Persistent BK viremia does not increase intermediate-term graft loss but is associated with de novo donor-specific antibodies

Abstract

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney-pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40-393 days), and persistent BK viremia was defined as lasting ≥140 days. Kaplan-Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

Keywords: kidney transplantation; risk factors; transplant outcomes.

Figure 1.

Most patients transplanted at our center were included in the study. Creation of the patient cohort. Pancreas transplants alone, multi-organ transplants (except kidney-pancreas) and those with less than 90 day survival were excluded from the analysis.

Figure 2.

BK viremia precedes DSA class II. Histogram of time to detection of (A) BK viremia (median=137.7 days; IQR=95–238), (B) de novo class II DSA (median=356 days; IQR=175–485), and (C) de novo class I DSA (median=344 days; IQR=62–590) in patients with persistent BK viremia. Among patients with persistent viremia who developed de novo class II DSA, BK virus was detected before the DSA in 17.6% of them.

Figure 3.

Class II DSA was most common in patients with persistent BK viremia. Proportion of patients who developed a positive DSA (overall, class I, or class II) stratified by BK viral status. The proportion of patients with a positive class II DSA in the BK ever-positive group compared with the BK never-positive group was significantly greater (P=0.03) along with the proportion of patients in the persistent BK group compared with the BK never-positive group (P=0.001).

Figure 4.

BK viremia does not adversely affect patient or allograft survival. (A) Kaplan–Meier estimates of time to patient death stratified by BK viral status (BK positive versus BK never positive). (B) Kaplan–Meier estimates of time to all-cause allograft loss stratified by BK viral status (BK positive versus BK never positive).