Effects of cytomegalovirus infection and prolonged cold ischemia on chronic rejection of rat renal allografts

Abstract Background Liver transplantation is considered to be the only curative treatment for patients with end stage liver disease. Postoperative infection remains to be one of the most common causes of morbidity and mortality throughout the past years. Cytomegalovirus (CMV) infection although considered to be a weak viral infection that usually passes asymptomatic in immunocompetent patients, however, it is considered one of the most common pathogens causing morbidities and mortality in liver transplant recipients. Multiple studies have been done to assess the risk factors for developing CMV infection. Objective Identification of risk factors predicting Cytomegalovirus infection in liver transplant recipients following transplantation. Methods This retrospective study was conducted on 194 patients and their donors who underwent living donor liver transplantation operation at Ain Shams centre for organ transplantation (ASCOT) at Ain Shams specialized hospital in the period between January 2010 and December 2016 with at least one year follow up period after operation for the recipient group. Results In our study, 194 patients undergoing liver transplantation at Ain shams centre for organ transplantation over seven years from January 2010 to December 2016 have been followed to assess risk factors affecting CMV infection development. Chronic rejection was found to be the most common factor associated with CMV infection followed by Cyclosporin (Neoral) as main postoperative immunosuppressant following liver transplantation. Other factors that were found to carry risk for CMV infection included younger age, advanced MELD score, positive CMV IgM status of the donors and recipients. Conclusion Differentiation of Cytomegalovirus disease from Cytomegalovirus infection isn’t always available as it requires tissue invasive techniques. Multiple risk factors have been attributed to cause Cytomegalovirus infection (viremia) . In our study, rejection (chronic rejection) was the factor that carries highest risk for Cytomegalovirus infection development followed by Cyclosporin .

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Anti-CD28 Monoclonal Antibody Therapy Prevents Chronic Rejection of Renal Allografts in Rats

Journal of the American Society of Nephrology ◽

10.1681/asn.v132519 ◽

2002 ◽

Vol 13 (2) ◽

pp. 519-527

Author(s):

Igor A. Laskowski ◽

Johann Pratschke ◽

Markus J. Wilhelm ◽

Victor M. Dong ◽

Francisca Beato ◽

...

Keyword(s):

Single Dose ◽

T Cell ◽

Chronic Rejection ◽

Interstitial Fibrosis ◽

Inflammatory Factors ◽

Renal Allografts ◽

Short Course ◽

Group 3 ◽

Group 2 ◽

Group 1

ABSTRACT. The effects of a signaling anti-CD28 mAb (JJ319), which interferes with the CD28-B7 T cell costimulation pathway thought to be involved in the development of chronic rejection of organ transplants, was investigated. Functional, morphologic, and molecular changes in rat renal allografts were examined up to 24 wk after placement. Control Lewis rats, recipients of F344 kidneys, received a single dose of a nonspecific mouse mAb intravenously on the day of transplantation (group 1). Group 2 animals were given anti-CD28 mAb in similar fashion. Group 3 animals were treated with a short course of cyclosporin A (CsA), and group 4 received both anti-CD 28 mAb and CsA. The majority (>95%) of animals in groups 2, 3, and 4 survived throughout the follow-up, compared with 28% in group 1 (P < 0.001). Group 2 and 4 recipients produced negligible proteinuria, whereas group 1 controls developed progressively increasing proteinuria after 4 wk and group 3 animals developed proteinuria by 24 wk. Allografts in groups 2 and 4 were morphologically unremarkable at 24 wk. Kidneys of group 1 animals rapidly developed changes of acute rejection, and those that survived long-term showed extensive glomerulosclerosis and interstitial fibrosis. Changes of early chronic rejection were noted in group 3 grafts. By reverse transcriptase–PCR, expression of representative inflammatory factors interferon-γ and interleukin-10 were significantly elevated at 24 wk only in the surviving group 1 animals. A single dose of a signaling anti-CD28 mAb administered at transplantation or in combination with a short course of CsA significantly prolonged recipient survival, normalized function, and preserved the morphology of renal allografts in an established model of chronic rejection. These data support an important role for T cell costimulation in the evolution of the chronic process.

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