Author's Reply

Field: Medicine (Health Sciences)

We thank Kazory et al. (1) for their interest in our article (2). Concerning indications for stent placement, the decision to place stents during the study period was based on the surgeon, and we could not find information on specific indications for stent placement based on the operative notes. We agree with Kazory et al. that the possibility exists that these ureters were ischemic and required stenting. Review of follow-up information on these cases and controls did not have any documented ureteral complications. The diagnosis of nephropathy was based on allograft biopsy, and viruria was not monitored in all patients. We agree with Kazory el al. that monitoring of viruria after stent placement in prospective studies would provide useful information on reactivation of polyomavirus in this subset of patients. We report that ureteral stent placement was associated with an increased risk of polyomavirus-associated nephropathy. The next question that needs to be answered is whether this association is causal or not. We agree with Kazory et al. that polyomavirus-associated nephropathy was not diagnosed in the early posttransplant period when immunosuppression and ureteral irritation are highest but on an average of 14.6 months after transplant. This is likely because this was not a prospective study, viruria was routinely monitored, and diagnosis was only made after an increase in serum creatinine and subsequent allograft biopsy. Because of the observational nature of this study, it is possible that the observed association is caused by least in some part by confounding variables. Regression analysis was used to account for 2 known confounding variables, namely age and delayed graft function, but there are probably other unknown variables that influence this relationship. The results of this study should help investigators to develop prospective clinical trials to confirm this finding. The biological reactions to double-J stents in animal models include superficial epithelial destruction with erosions and ulcerations of the transitional epithelium and inflammatory reactive changes. The latter include mononuclear inflammatory infiltrate in the epithelium and lamina propria, edema of the lamina propria, mucous metaplasia, and transitional epithelial hyperplasia. These changes were noted after intubation of the animal ureters for 6 weeks. After these reactive urothelial changes, epithelial regeneration occurs. We postulate that regenerating and differentiating uroepithelial cells in a milieu of cytokines and other proinflammatory mediators may result in BK virus reactivation and replication by up-regulating transcription factors and cell surface receptors (3–5). In biopsy specimens, the virus has been shown to be abundant in the medulla and distal tubule cells. Viral particles are observed on apical tubular cell surfaces by electron microscopy suggesting that BK virus infects new cells via cell to cell spread. Thus, BK virus could follow an ascending route of infection from the transitional cells to the collecting ducts and tubules (6). Duvuru Geetha Department of Medicine John Hopkins University Baltimore, MD