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Fever, Infection, and Rejection After Kidney Transplant Failure

Woodside, Kenneth J.1; Schirm, Zachary W.1; Noon, Kelly A.1; Huml, Anne M.2; Padiyar, Aparna2; Sanchez, Edmund Q.1; Sarabu, Nagaraju2; Hricik, Donald E.2; Schulak, James A.1; Augustine, Joshua J.2,3

doi: 10.1097/01.TP.0000437558.75574.9c
Clinical and Translational Research

Background Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection.

Methods One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure. Patients were stratified by the presence of full immunosuppression versus minimal (low-dose prednisone) or no immunosuppression, before hospital admission. Subsequent rates of documented infection and nephrectomy, as well as patient survival, were ascertained.

Results Hospitalization with fever within 6 months of allograft failure was common, occurring in 44% of patients overall. However, among febrile hospitalized patients who had been weaned off of immunosuppression before admission, only 38% had documented infection. In contrast, 88% of patients maintained on immunosuppression had documented infection (P<0.001). In both groups, dialysis catheter–related infections were the most common infection source. Allograft nephrectomy was performed in 81% of hospitalized patients with no infection, compared to 30% of patients with documented infection (P<0.001). Mortality risk was significantly higher in patients with concurrent pancreas transplants or who were hospitalized with documented infection.

Conclusions Maintenance immunosuppression after kidney allograft failure was associated with a greater incidence of infection, while weaning of immunosuppression commonly resulted in symptomatic rejection with fever mimicking infection on presentation. Management of the failed allograft should include planning to avoid both infection and sensitizing events.

1 Division of Transplant Surgery, Department of Surgery, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio.

2 Division of Nephrology, Department of Internal Medicine, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio.

3 Address correspondence to: Joshua J. Augustine, M.D., Division of Nephrology, Department of Internal Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, LKS 5048, Cleveland, OH 44106.

This research was supported in part by a grant from the Leonard Rosenberg Foundation.

The authors declare no conflicts of interest.

E-mail: joshua.augustine@uhhospitals.org

K.J.W. participated in making the research design, in writing the article, in performing the research, and in analyzing the data. Z.W.S. participated in performing the research. K.N. participated in performing the research. A.M.H. participated in writing the article. A.P. participated in writing the article. E.Q.S. participated in writing the article. N.S. participated in writing the article. D.E.H. participated in writing the article. J.A.S. participated in writing the article. J.J.A. participated in making the research design, in writing the article, in performing the research, and in analyzing the data.

Received 7 June 2013. Revision requested 18 June 2013.

Accepted 27 September 2013.

Accepted November 20, 2013

© 2014 by Lippincott Williams & Wilkins