The effect of antilymphocyte induction therapy on renal allograft survival. A meta-analysis of individual patient-level data. Anti-Lymphocyte Antibody Induction Therapy Study Group

Abstract

Purpose: Randomized, controlled trials have not shown that the perioperative use of antilymphocyte antibodies (induction therapy) improves survival of cadaveric kidney allografts. This study combined individual patient-level data from published trials to examine the effect of induction therapy on allograft survival.

Data sources: Randomized, controlled trials identified from MEDLINE.

Study selection: Published trials that compared adult recipients of cadaveric renal allografts who did and did not receive antilymphocyte antibodies in the perioperative period were selected if individual patient-level data were available.

Data extraction and analysis: Individual patient-level data were collected for each of 628 study patients. Multivariable Cox proportional hazards regression was used to estimate the effect of induction therapy on allograft survival.

Results: The adjusted rate ratio for allograft failure with induction therapy compared with conventional therapy was 0.62 (95% CI, 0.43 to 0.90) (P = 0.012) over 2 years and 0.82 (CI, 0.62 to 1.09) (P = 0.17) over 5 years. The effect of induction therapy on allograft survival diminished over time; no benefit overall was seen after 2 years after transplantation (rate ratio, 1.13 [CI, 0.72 to 1.78]) (P > 0.2). Greater HLA-DR mismatch, delayed allograft function, diabetes mellitus in the recipient, African-American ethnicity of the recipient, and presensitization (panel-reactive antibody levels > or = 20%) were significantly associated with allograft failure at 5 years. Among high-risk patients, only those who were presensitized benefited from induction therapy at 2 years (rate ratio, 0.12 [CI, 0.03 to 0.44]) (P = 0.001). Results were similar at 5 years.

Conclusions: Using individual-level data, this study showed a benefit of induction therapy at 2 years, particularly among presensitized patients. Although the benefit of this therapy subsequently waned, presensitized patients continued to have benefit at 5 years.