BK & JC Polyoma Viruses Cause Kidney Transplant Rejection

Active BK polymoma virus infection has been conclusively linked to kidney transplant rejection. Cytomegalovirus, Epstein-Barr virus, and other viruses are also known to be involved.

Human polyoma virus infection of renal allografts: histopathological diagnosis, clinical significance, and literature review. O Pappa, AJ Demetris, RB Raikow, PS Randhawa. Mod Pathol 1996 Feb;9(2):105-109.

Human polyoma virus-associated interstitial nephritis in the allograft kidney. PS Randhawa, S Finkelstein, V Scantlebury, R Shapiro, C Vivas, M Jordan, MM Picken, AJ Demetris. Transplantation 1999 Jan 15;67(1):103-109.

Post-transplantation polyomavirus infections. S Boubenider, C Hiesse, S Marchand, A Hafi, F Kriaa, B Charpentier. J Nephrol 1999 Jan-Feb;12(1):24-29.

Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. I Binet, V Nickeleit, HH Hirsch, O Prince, P Dalquen, F Gudat, MJ Mihatsch, G Thiel. Transplantation 1999 Mar 27;67(6):918-922.

Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. V Nickeleit, HH Hirsch, IF Binet, F Gudat, O Prince, P Dalquen, G Thiel, MJ Mihatsch. J Am Soc Nephrol 1999 May;10(5):1080-1089.

Human polyoma virus in renal allograft biopsies: morphological findings and correlation with urine cytology. CR Drachenberg, CO Beskow, CB Cangro, PM Bourquin, A Simsir, J Fink, MR Weir, DK Klassen, ST Bartlett, JC Papadimitriou. Hum Pathol 1999 Aug;30(8):970-977.

Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant patients. DN Howell, SR Smith, DW Butterly, PS Klassen, HR Kligman, JL Burchette, SE Miller. Transplantation 1999 Nov 15;68(9):1279-1288.

BK virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. V Nickeleit, HH Hirsch, M Zeiler, F Gudat, O Prince, G Thiel, MJ Mihatsch. Nephrol Dial Transplant 2000 Mar;15(3):324-332.

Pathophysiology of chronic allograft rejection. AJ Demetris, RJ Duquesnoy, JJ Fung, et al. Medscape Transplantation 2000 Mar 29.

Testing for polyomavirus type BK DNA in plasma to identify renal allograft recipients with viral nephropathy. V Nickeleit, T Klimkait, IF Binet, P Dalquen, V Del Zenero, G Thiel, MJ Mihatsch, HH Hirsch. N Engl J Med 2000 May 4;342(18):1309-1315.

Nephropathy due to polyomavirus type BK. PS Randhawa, AJ Demetris. New Engl J Med 2000 May 4;342(18):1361-1363. Editorial.

Human polyomavirus BKV and renal disease. KV Shah. Nephrol Dial Transplant 2000;15(6):754-755. Review article.

New perspectives: Late complications after transplantation. D Snydman. Medscape News re XVIII International Congress of the Transplantation Society, 2000 Aug 27. "It has long been known that infections have various effects on the kidney allograft. Infection affects the kidney in 5 distinct ways. Direct effect -- parenchymal infection (ie, polyomavirus); Indirect effect -- systemic response to infection such as immune complex formation or thrombotic microngiopathy (eg, hepatitis C virus [HCV] infection); Potentiation of rejection (ie, cytomegalovirus [CMV] infection); infiltration of kidney with neoplastic cells (ie, Epstein-Barr virus [EBV] infection); Toxic or allergic response to antimicrobial agents." A CME credit article.

BK virus nephropathy. ISMETT (Mediterranean Transplant Institute) and University of Pittsburgh Medical Center. Medscape ID Journal Club 2000;17(11).

Ask the experts on ... Kidney transplant recipient with polyoma virus? P Randhawa. Medscape 2000 Dec 5. "Polyoma virus is believed to be a complication of increased immunosuppression. Therefore, it is logical that treatment consist of reduction in the dose of immunosuppressive drugs...."

Ask the experts on ... Polyomavirus infection after renal transplantation? P Randhawa. Medscape 2001 Feb 13. "Experience with 2 other commonly latent viruses, cytomegalovirus (CMV) and Epstein-Barr virus, suggests that reinfection is not universal after graft loss and may have more to do with excessive immunosuppression than with continued latency of the virus." Also the antiviral cidofovir could be tried.

Steroid-resistant kidney transplant rejection: diagnosis and treatment. HA Bock. J Am Soc Nephrol 2001 Feb;12 Suppl 17:S48-S52. Review.

Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis. M Ahuja, EP Cohen, AM Dayer, B Kampalath, CC Chang, BA Bresnahan, S Hariharan. Transplantation 2001 Apr 15;71(7):896-899. "Irreversible graft failure is more prevalent with polyoma virus infection."

JC VIRUS INFECTION IN ALLOGRAFT KIDNEYS: Analysis by Polymerase Chain Reaction and Immunohistochemistry. P Randhawa, F Baksh, N Aoki, D Tschirhart, aS Finkelstein. Transplantation 2001 May 15;71(9):1300-1303. "JCV DNA was found in 7 (36.8%) of 19 allograft kidney biopsy specimens with viral nephropathy and 0 (0%) of 19 native or allograft biopsy specimens without viral nephropathy."

Other Viruses and Transplant Rejection

The clinical significance of cytomegaloviral inclusions in the allograft kidney. R Kashrap, R Shapiro, M Jordan, PS Randhawa. Transplantation 1999 Jan 15;67(1):98-103.

The relationship between cytomegalovirus and chronic allograft dysfunction. RK Avery. Medscape Transplantation Clinical Management 2000 Vol 7. CME.

The expansion of CD4+CD28- T cells in patients with chronic kidney graft rejection. A Pawlik, M Florczak, M Masiuk, G Dutkiewicz, B Machalinski, J Rozanski, L Domanski, B Gawronska-Szklarz. Transplant Proc 2003 Dec;35(8):2902-2904. 20 healthy individuals, 20 patients after renal transplantation with stable graft function, and 20 with chronic graft rejection. In patients with stable graft function, the median frequency of CD4+CD28- T cells was 3.1% and was significantly higher in comparison to the control group (1.4%) (P <.01).The highest subset CD4+CD28- cells was detected in patients with chronic graft rejection (10.65%). The amount of CD4+CD28- cells was significantly higher in this group in comparison to patients with stable graft function (P <.01)."

Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection. EM van Leeuwen, EB Remmerswaal, MT Vossen, AT Rowshani, PM Wertheim-van Dillen, RA van Lier, IJ ten Berge. J Immunol 2004 Aug 1;173(3):1834-1841. "In this study, we show that in primary CMV infections, CD4(+)CD28(-) T cells emerge just after cessation of the viral load, indicating that infection with CMV triggers the formation of CD4(+)CD28(-) T cells. In line with this, we found these cells only in CMV-infected persons [emphasis added]. CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin. Importantly, CD4(+)CD28(-) cells were to a large extent CMV-specific because proliferation was only induced by CMV-Ag, but not by recall Ags such as purified protein derivative or tetanus toxoid. CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative. Thus, CD4(+)CD28(-) T cells emerge as a consequence of CMV infection."

Anti-smoking hate propaganda to deny transplants to smokers

Nevertheless, the anti-smoking criminals Bertram L. Kasiske and Dagmar Klinger, at the Hennepin County Medical Center in Minneapolis, Minnesota, have perpetrated a fraudulent study purporting to show that smoking negatively affects graft survival, and advocating that smokers should be denied kidney transplants on this grounds. Their study is a fraud because it is based on the anti-smokers' favorite deceit, namely multivariate analysis.

There is no such thing as determining "independent effects of smoking on outcomes" by statistical means. In fact, the paper by Phillips and Smith demonstrates that analyses such as these are merely devices for generating bogus "risk factors" as a result of confounding by infection.

The study by Kasiske and Klinger failed to even mention BKV as a cause of kidney transplant rejection. Furthermore, they jammed together kidney disease of every possible etiology, with differing outcomes, most of which have prevalence which varies by social class (which cannot be adjusted out), and in which infections are known or suspected causes. And, by examining outcomes besides kidney rejection, such as heart disease, they exploited every other kind of confounding by infection as well.

Their pretense that their motive is "to maximize the overall benefit" from transplants is transparently specious. Because they propose to deny transplants on the basis of group generalities instead of according to the prognosis of individual cases, they would actually reduce the overall benefit instead.

Morally, their proposal is as utterly putrid as anything devised in Nazi Germany, because what they really want is to harvest organs from smokers for use in non-smokers, while denying smokers this benefit.

• ATTENTION MALPRACTICE LAWYERS: If these criminals have failed to attempt to identify and properly treat BKV-caused transplant rejection in their patients, then they should be sued for medical malpractice. Their victims should not cower and let these worthless quacks put them on the defensive! This applies to their non-smoking victims as well.

Cigarette smoking in renal transplant recipients. B Kasiske, D Klinger. J Am Soc Nephrol 2000;11(4):753-759.

Hemorrhagic cystitis in transplant patients

Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. AY Leung, CK Suen, AK Lie, RH Liang, KY Yuen, YL Kwong. Blood 2001 Sep 15;98(6):1971-1978. "BK viruria was quantitatively related to the occurrence of HC after BMT" in 50 patients.

Cardiovascular disease and kidney transplant patients

Cytomegalovirus replication and "herpesvirus burden" as risk factor of cardiovascular events in the first year after renal transplantation. E Gomez, A Laures, JM Baltar, S Melon, B Diez, M de Ona. Transplant Proc 2005 Nov;37(9):3760-3763. "Among 121 renal transplant recipients, 13 presented cardiovascular events, all associated with CMV replication (P = .004).... All patients with these events were seropositive for CMV, HSV, VZV, and EBV, as opposed to 64.8% without them (P = .009)."

Reactivation of infection

Age-Related Urinary Excretion of BK Polyomavirus by Non-immunocompromised Individuals. S Zhong, HY Zheng, M Suzuki,Q Chen, H Ikegaya, N Aoki, S Usuku, N Kobayashi, S Nukuzuma, Y Yasuda, N Kuniyoshi, Y Yogo, T Kitamura. J Clin Microbiol 2007 Jan;45(1):193-198. In 9 age groups of 50 healthy volunteers or non-immunocompromised patients, "The rate of BK viruria was relatively low in subjects aged <30 years old, but gradually increased with age in subjects >/=30 years old. However, BK viruria was less frequent than JC viruria in adults. The detected BKV isolates were classified into subtypes and detection rates for individual subtypes were compared among age groups; this analysis showed that viruria of subtypes I (the most prevalent subtype) and IV (the second most prevalent subtype) occurred more frequently in older subjects."

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cast 12-30-06