BK virus‐associated transplant nephropathy: Need for increased awareness in children

Since the first report of BK virus (BKV) in the urine of a renal transplant recipient in 1971, BK virus-associated renal allograft nephropathy (BKVAN) has been emerging as an important cause of renal allograft dysfunction over the last decade (1, 2). However, most studies on BKVAN have been reported from adult patients and there is a paucity of literature on pediatric renal transplant recipients. Last year Ginevri et al. published their retrospective experience on pediatric transplant recipients from Italy (3). In this issue Haysom et al. and Herman et al. report prospective studies of polyomavirus on pediatric renal transplant recipients from Australia and Belgium respectively (4, 5). BKVAN can present in many different ways and can affect both children and adult renal transplant recipients. Haysom et al. studied 18 pediatric (mostly adolescent) renal transplant patients prospectively for development of BK viruria and viremia. They have shown that the prevalence of BK viruria (33%) and seropositivity (56%) in older children (median age 15 years), with renal transplants in Australia is similar to that reported by Ginevri et al. from Italy and comparable with the rates reported in adults in some series (2, 3). Only one of the 18 patients developed viremia and none developed full-blown BKVAN. Similar results are also reported by Herman et al. who showed that, of the 46 generally younger pediatric renal transplant patients (mean age 9 yr), nine (20%) developed viruria and five (11%) had concomitant viremia. They did not study the serological status of the patients. Two of the five patients with viremia developed biopsy proven BKVAN, giving an incidence of about 4% in their series. The prevalence of BKVAN in adults appears to be progressively increasing and may affect 5–7% of kidney transplant recipients (6–9). This rise in BKVAN over the last few years has been attributed to a number of factors, including: an increased awareness, more frequent use of biopsies, improved methods for diagnosis and introduction of new and more potent immunosuppressive drugs. The magnitude of this problem in children is only beginning to emerge and is probably similar to adults. Both Haysom et al. and Herman et al. studies, thus, provide ground work for future prospective studies that should be undertaken to identify the scope of this vexing disease in pediatric renal transplant recipients. Generally BKVAN is diagnosed on a kidney biopsy in asymptomatic patients presenting with a rise in serum creatinine level (10–12). In most adults BKVAN is presumed to result from reactivation of virus latent in the renal tubules. However, a different scenario may be operative in children especially if they are very young (<5–7 yr of age). They may have a primary infection with BKV, as alluded to by Haysom et al. and also reported by our group (12). A viral prodrome consisting of low-grade fever, myalgias and mild gastro-enteritis was seen in one of our pediatric BKVAN patients prior to onset of allograft dysfunction and may be an inconstant feature of primary BKV infection in children (12). In addition to asymptomatic presentation, BKVAN has been diagnosed in patients who have presented with features that were variably diagnosed including: acute rejection, echogenic mass, interstitial nephritis, and ureteric stenosis (1, 7, 12, 13). The key to establishing the diagnosis of BKVAN remains the recognition of BKV inclusions in tubular and glomerular epithelial cells in renal allograft biopsy specimens (10). The diagnosis can be confirmed by immunohistochemistry using antibodies to the simian virus 40 T antigen or in situ hybridization or by electron microscopy (2). Viral inclusions in BKVAN are often Dr Vats is a consultant for ViraCor Laboratories. Pediatr Transplantation 2004: 8: 421–425