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The Effect of Antilymphocyte Induction Therapy on Renal Allograft Survival: A Meta-Analysis of Individual Patient-Level Data

Lynda Anne Szczech, MD, MS; Jesse A. Berlin, ScD; and Harold I. Feldman, MD, MS
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For the Anti-Lymphocyte Antibody Induction Therapy Study Group* *For members of the Anti-Lymphocyte Antibody Induction Therapy Study Group, see Appendix. From the University of Pennsylvania, Philadelphia, Pennsylvania; and New York Medical College, Valhalla, New York. Grant Support: In part by National Institutes of Health Training Grant DK-07006, National Institutes of Health Center Grant DK-45191, and administrative and educational funds from the DCI Research and Education Development Fund. Dr. Szczech was supported in part as a Clinician Scientist in Nephrology by the American Kidney Fund. Dr. Feldman is an Established Investigator of the American Heart Association. Requests for Reprints: Harold I. Feldman, MD, MS, University of Pennsylvania Medical Center, Center for Clinical Epidemiology and Biostatistics, 720 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021. Current Author Addresses: Dr. Szczech: Westchester Medical Center, Division of Nephrology, New York Medical College, Valhalla, NY 10595.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;128(10):817-826. doi:10.7326/0003-4819-128-10-199805150-00004
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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. Multi-variable 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 > 0.02). Greater HLA-DR mismatch, delayed allograft function, diabetes mellitus in the recipient, African-American ethnicity of the recipient, and presensitization (panel-reactive antibody levels ≥ 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.


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Figure 1.
Overall unadjusted Kaplan-Meier survival curves.

The proportion of patients with surviving allografts is plotted against survival time in days over 5 years, stratified by treatment. IT = induction therapy.

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Figure 2.
Kaplan-Meier survival curves of allograft survival according to immunosuppressive regimen and presensitization (panel-reactive antibody [PRA] levels <20% or ≥ 20%). Top.Bottom.

At 2 years. At 5 years.

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