https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2005.00742.x

Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction.

Molecular studies suggest that the simian polyomavirus SV40 is present in the human population, possibly introduced in contaminated polio vaccine. However, no recent seroepidemiological data exist in England on SV40 or on the two human polyomaviruses, BKV and JCV. A comparative age seroprevalence study was undertaken on 2,435 residual sera from 1991 by haemagglutination inhibition (HI) for BKV and JCV, and virus neutralisation for SV40. The overall rates of seropositivity for BKV and JCV were 81% and 35%, respectively, and each was significantly related to age (P < 0.001). BKV seroprevalence reached 91% at 5-9 years of age, but JCV seroprevalence reached only 50% by age 60-69 years. There was a highly significant association between BKV antibody titre and age (P < 0.001), titres decreasing linearly at a rate of 8.7% per 10 years (95% CI = 7.4-10% drop). Significantly more males than females had antibody to JCV (P = 0.013). In individuals under 40 years of age there was a significant negative association between the presence of antibody to BKV and JCV (P < 0.001). By contrast, the antibody prevalence to SV40 remained at 1.3-5% throughout all age groups and titres were low. There was a significant positive association between the presence of antibody to SV40 and antibody to both BKV (P < 0.001) and JCV (P = 0.009), and also to the geometric mean titre (GMT) of BKV antibody (P = 0.011). The results indicate that BKV and JCV are transmitted by different routes. There is no serological evidence that SV40 entered the human population during the past 80 years, and the possibility of cross-reaction with BKV or JCV antibody must be considered.

Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40

Background. Asymptomatic polyoma virus infection documented by urine cytology or serology is well known, but the clinical course of biopsy-proven interstitial nephritis is not well defined. Methods. Twenty-two cases were identified by histology, immunostaining, in situ hybridization, electron microscopy, or polymerase chain reaction. Results. The clinical features mimicked acute rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy (n=2), or drug toxicity (n=1). Histology showed homogenous intranuclear inclusions. In situ hybridization showed BK virus (BKV) to be the predominant species, but polymerase chain reaction documented JC virus co-infection in one of five cases so tested. Electron microscopy in seven cases showed 20-51-nm virions. The two cases diagnosed at nephrectomy received no therapy. Initial antirejection therapy in 12 cases led to clearance of the virus in 1/12 (8%), partial therapeutic response in 3/12 (25%), and graft loss in 8/12 (67%) cases. The last recorded creatinine in patients with functional grafts ranged from 1.9 to 7.0 (median: 4.5) mg/dl, 0.4-45 (median: 4.0) months after initial diagnosis. The remaining eight cases treated by reduction of immunosuppression at the outset have been free of graft loss for 0.2-10.0 (median: 4.8) months since diagnosis, and clearance of virus has been documented in three of six (50%) cases. The serum creatinine in these patients is 1.7-6.0 (median: 2.4) mg/dl, 0.2-10 (median: 4.8) months after diagnosis. Follow-up biopsies performed 1-23.5 months after diagnosis show chronic allograft nephropathy. Conclusions. Polyoma virus tubulo-interstitial nephritis-associated graft dysfunction usually calls for judicious decrease in immunosuppression and monitoring for acute rejection. Development of methods to serially quantify the viral load in individual patients could potentially improve clinical outcome.

Human polyoma virus-associated interstitial nephritis in the allograft kidney

. Polyomavirus (PV) exceptionally causes a morphologically manifest renal allograft infection. Five such cases were encountered in this study, and were followed between 40 and 330 d during persistent PV renal allograft infection. Transplant (Tx) control groups without PV graft infection were analyzed for comparison. Tissue and urine samples were evaluated by light microscopy, immunohistochemistry, electron microscopy, and PCR. The initial diagnosis of PV infection with the BK strain was made in biopsies 9 ± 2 mo (mean ± SD) post-Tx after prior rejection episodes and rescue therapy with tacrolimus. All subsequent biopsies showed persistent PV infection. Intranuclear viral inclusion bodies in epithelial cells along the entire nephron and the transitional cell layer were histologic hallmarks of infection. Affected tubular cells were enlarged and often necrotic. In two patients, small glomerular crescents were found. In 54% of biopsies, infection was associated with pronounced inflammation, which had features of cellular rejection. All patients were excreting PV-infected cells in the urine. PV infection was associated with 40% graft loss (2 of 5) and a serum creatinine of 484 ± 326 μmol/L (mean ± SD; 11 mo post-Tx). Tx control groups showed PV-infected cells in the urine in 5%. Control subjects had fewer rejection episodes ( P P = 0.01). It is concluded that a manifest renal allograft infection with PV (BK strain) can persist in heavily immunosuppressed patients with recurrent rejection episodes. PV mainly affects tubular cells and causes necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis. Urine cytology can serve as an adjunct diagnostic tool.

Polyomavirus Infection of Renal Allograft Recipients From Latent Infection to Manifest Disease

Background Reactivation of polyomavirus type BK (BK virus) is increasingly recognized as a cause of severe renal-allograft dysfunction Currently, patients at risk for nephropathy due to infection with the BK virus are identified by the presence of cells containing viral inclusion bodies (“decoy cells”) in the urine or by biopsy of allograft tissue Methods In a retrospective analysis, we performed polymerase-chain-reaction assays for BK virus DNA in plasma samples from 9 renal-allograft recipients with BK virus nephropathy; 41 renal-allograft recipients who did not have signs of nephropathy, 16 of whom had decoy cells in the urine; and as immunocompromised controls, 17 patients who had human immunodeficiency virus type 1 (HIV-1) infection (stage C3 according to the classification of the Centers for Disease Control and Prevention) and who had not undergone transplantation Results In all nine patients with BK virus nephropathy, BK virus DNA was detected in the plasma at the time of the initial histologic 

Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy.

Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.

https://jcp.bmj.com/content/jclinpath/31/4/338.full.pdf

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Routine cytological screening of Papanicolaou-stained smears of the urinary sediment from 57 renal allografts in 51 patients has resulted in the detection of seven cases of Human Polyoma Virus (HPV) BK infection--14% of the total number. Infection was confirmed by virus isolation and electron microscopy (EM). The cytological, histological and ultra-structural data are described and related to the clinical progress of the patient. Four out of the seven cases are discussed in more detail as histological material was available; in three of these, there was evidence of stenosis of the transplant ureter with virus infected cells in the ureteric epithelium and in one case also in the renal tubules. Administration of high dose steroids may provoke active infection with HPV in ureteric epithelium damaged by ischaemia and inflammation. The similarity between the clinical features of an HPV infection and a rejection episode make it imperative to confirm the diagnosis quickly and accurately. Cytological examination of the urinary deposit by light microscopy is a simple, inexpensive procedure which provides positive diagnosis of the typical virus inclusions within an hour of receiving the urine specimen in the laboratory. This can be confirmed by removing single cells from the original cytological slide preparation and processing them for EM using a technique described by Coleman et al [1].

J M Poulding

Papers

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Human polyoma virus (HPV)--a significant pathogen in renal transplantation.