Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients

Abstract

Background: Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking.

Methods: We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival.

Results: Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.

Conclusion: rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.

Keywords: BK viral infection; HIV - human immunodeficiency virus; immunosuppressant; kidney transplanation; thymoglobulin.

Figure 1

Complications of anti-thymocyte globulin induction in HIV-infected kidney transplant recipients (n=27). (A) Kaplan-Meier estimates of de novo malignancies and (B) infections requiring hospitalization after kidney transplantation. (C) Details of infections requiring hospitalization (B) in 27 HIV-infected kidney transplant recipients managed with. Other infections included cholecystitis (n=2), bacteremia (n=2), implantable cardioverter-defibrillator infection (n=1), Candida glabrata fungemia (n=1), pulmonary tuberculosis (n=1), Pneumocystis jirovecii pneumonia (n=1), Rhinovirus (n=1), Cytomegalovirus colitis (n=1), liver abscess (n=1) and Shiga toxin-producing E coli (n=1). (D) CD4 cell counts (cells/mm³) after kidney transplantation. Boxplots show the 10^th, 25^th, 50^th, 75^th, and 90^th percentiles. UTIs, urinary tract infections; PNA, pneumonia; CDI, Clostridium difficile infection; SSTIs, skin and soft tissue infections; PDAP, peritoneal dialysis-associated peritonitis.

Figure 2

Patient and allograft outcomes of HIV-infected kidney transplant recipients managed with anti-thymocyte globulin induction (n=27). (A) Kaplan-Meier estimates of allograft survival, (B) patient survival, (C) and acute rejection. (D) Estimated glomerular filtration rates (GFR) using the 4-parameter Modification of Diet in Renal Disease (MDRD) formula. Boxplots show the 10^th, 25^th, 50^th, 75^th, and 90^th percentiles. DDRT, deceased donor renal transplant.