Screening for BK Viremia

The article by Knight et al. is an important contribution to the growing literature on polyoma infection in kidney transplant recipients (1). Despite the Kidney Disease: Improving Global Outcomes recommendations, the optimal methods of screening, ideal preemptive intervention (reduction or switch in immunosuppression), and most effective disease treatment remain a work in progress (2). Modeling studies suggest that screening might well be cost-effective and possibly cost-saving; however, a randomized trial has not been done (3). One of the important issues identified by their study is the relatively unfavorable experience for those with very high viral loads (>100,000 copies/mL) (1). These patients probably have well-established disease, can be biopsy negative given the patchy nature of the disease, and are difficult to treat. Screening is ideally intended to detect individuals at “risk of disease” or during an earlier stage of disease and intervene preemptively. Subjects with high viral loads may represent screening failures. The question is whether these failures are a result of a deficient screening strategy or are they the result of aggressive disease in a vulnerable graft. For screening to be effective, tests should be done on time, the test results should be available promptly, and the interventions should be initiated quickly. After reading this study, we reviewed our recent experience. Despite initiating a quality assurance program to ensure compliance with screening, the number of cases with peak viral loads more than 100,000 copies/mL actually increased from 3 of 136 screened subjects (from January 2004 to January 2008) to 5 of 125 screened subjects (from October 2010 to December 2012) (4). This lack of improvement is of concern. Further examination of these most recent five patients with high viral loads is interesting. All suffered delayed graft function and three were from donors after circulatory death (DCD). One of these suffered an episode of cytomegalovirus colitis and two experienced acute rejection (one after the episode of cytomegalovirus colitis) before the onset or viremia. In two patients, there was a delay in screening and immunosuppression reduction; however, one was only on tacrolimus and prednisone because of leukopenia. There have been no graft losses and only one patient has a serum creatinine that is marginally higher than baseline on follow-up. In four of the five patients, viral loads have fallen significantly and none were treated with cidofovir. Incidentally, our center did not procure DCD donors before 2008. Of the 261 patients screened at our center noted above, 21 patients had a peak viral load between 10,000 and 100,000 copies/mL. None have lost their transplant from polyoma infection or rejection. Although Knight et al. show that some of these subjects with modest viral loads have pathologic evidence of polyoma infection on biopsy, in our experience, they respond to a reduction in immunosuppression. Overall, our experience remains positive but not perfect. There are some important questions to ask of Knight et al.’s study. How many patients with viral loads more than 100,000 copies/mL had screening tests that were delayed or not acted on promptly? How many of these patients had significantly lower viral loads at initial detection? How many had poor kidney function from other causes before the onset of polyoma viremia? How many were DCD organ recipients or had delayed graft function or followed an episode of acute rejection or were simultaneous with acute rejection? The first questions represent failure to screen effectively and intervene, and the remaining questions point to a cohort potentially at risk for aggressive disease. Just as screening for colorectal cancer will not prevent all cancer deaths, screening for polyoma will miss some patients and may harm others (reduced immunosuppression and later rejection). Screened patients with high initial viral loads may well be construed as screening failures. Understanding whether this is from failure to screen as recommended or is cohort at risk that requires a more intense screening strategy or prompt definitive treatment requires further study. This increased risk cohort may benefit from prophylaxis. However, switching to sirolimus in patients with delayed graft function may not be wise (5). More than ever randomized trials in this area are needed. Meteb M. AlBugami Bryce A. Kiberd Department of Medicine Dalhousie University Halifax, Nova Scotia, Canada

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