Final Diagnosis -- Deterioration in renal function and viral load following treating a BK viruric patient with anti-rejection therapy
Deterioration in renal function and viral load following treating a BK viruric patient with anti-rejection therapy.
BKV nephropathy is an excessive immunosuppression complication in kidney transplant recipients that can lead to premature graft failure [2-4]. Serial urinary and plasma measurements of BKV load using real time PCR are now commonly used to monitor viral reactivation in kidney transplant patients, while a biopsy is necessary to make the diagnosis of BKV nephropathy. Reducing immunosuppression is the first approach for treating BKV infection , although drugs such as cidofovir, leflunomide, and fluoroquinolones may also be useful in special occasions.
It is not clear what therapeutic strategy should be applied when biopsies from viruric patients show tubulitis with no viral cytopathic effect, and a negative in-situ hybridization test for viral DNA, however, immunosuppression is frequently increased.
After treating this patient with anti-rejection treatment, serum Cr as well as viral load deteriorated despite the misleading improvement in renal biopsy. Immune cell function values (ICF) at the time of index biopsies was very low (30 ng ATP/ml) [much < previously described for pure renal acute rejection episodes (median 462 ng/ml ATP)]. Of note, we previously demonstrated that low immune cell function values were associated with patients with BKV reactivation especially viremia and to a lesser extent high load viruria . In this case, the observed interstitial inflammation and tubulitis seems be initiated or perpetuated by viral rather than allogeneic antigens.
- The spectrum of BKV induced pathology in the kidney might, therefore, be wider than is currently appreciated
- BKV may be able to induce renal allograft damage when present in the urine with no overt BKV nephropathy established by immunostain or in situ hybridization.
- Patients with BK viruria but no nephropathy may not respond to anti-rejection treatment
- In the absence of an organized study on such patients population, interpreting the biopsy findings in the context of quantitative urine and plasma BKV DNA values, together with the results of C4d stain and immune cell function might be of interest to guide the treatment options.
- Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999; 55(2):713-723.
- Ramos E, Drachenberg CB, Papadimitriou JC et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol. 2002; 13(8) : 2145-2151.
- Nickeleit V, Hirsch HH, Binet IF et al Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol. 1999; 10(5) : 1080-1089.
- Ahuja M, Cohen EP, Dayer AM et al. Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis. Transplantation. 2001;71(7) 896-899.
- Celik B, Shapiro R, Vats A et al. Polyomavirus allograft nephropathy: sequential assessment of histologic viral load, tubulitis, and graft function following changes in immunosuppression. Am J Transplant. 2003;3(11):1378-1382.
- I Batal, A Zeevi, A Heider, A Girnita, A Basu, H Tan, R Shapiro, P Randhawa. Measurements of Global Cell Mediated Immunity in Renal Transplant Patients with BK Virus Reactivation. Accepted AJCP
Contributed by Ibrahim Batal, M.D.