Long-term outcomes comparing belatacept- vs tacrolimus-based maintenance immunosuppression in kidney transplant recipients: A UNOS database analysis

Presenter: Adriana Montalvan, MD, Beth Israel Deaconess Medical Center, Boston, MA.

Long-Term Outcomes Comparing Belatacept- vs. Tacrolimus-Based Maintenance Immunosuppression in Kidney Transplant Recipients: A UNOS Database Analysis. Abstract TH-PO829. Presented Nov 2, 2023.

In a comparison of long-term outcomes in first kidney transplant recipients receiving either tacrolimus- or belatacept-based maintenance immunosuppression, the rates of death and death-censored graft failure were higher in the belatacept group, according to Adriana Montalvan, MD, Beth Israel Deaconess Medical Center, Boston, MA. Those discharged on belatacept, however, Montalvan said in a 2023 Kidney Week poster presentation, had a higher comorbid burden.

Calcineurin inhibitors have been the mainstay of maintenance immunosuppression in kidney transplant recipients. While these drugs have afforded improvements in acute rejection rates and short-term graft survival, long-term allograft survival has stagnated,1,2 with late graft losses often attributed to recipient death from comorbid conditions with a functioning kidney.3 Calcineurin inhibitors are associated with nephrotoxic risks, however, including hypertension, posttransplant diabetes, hyperlipidemia, neurotoxicity, and nephrotoxicity.4–7 Several immunosuppressants have been tried as nephron-sparing alternatives to maintenance calcineurin-inhibitors, but with limited success, Montalvan stated.

Belatacept, a costimulation blocker, was approved by the US Food and Drug Administration in 2011 with an indication for use in renal transplant recipients, based largely on comparisons with cyclosporine. More than 85% of renal transplant recipients, though, are discharged on a tacrolimus-based regimen.8

With fellow researchers, using the United Network of Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) file, Montalvan compared long-term outcomes in kidney transplant recipients receiving either tacrolimus or belatacept.

From the STAR file, investigators identified first kidney transplant patients receiving induction therapy and then either tacrolimus (N = 194,307) or belatacept (N = 5,152) between 2010 and 2022 as maintenance immunosuppression at discharge. Montalvan underscored that compared with patients discharged on tacrolimus, subjects discharged on belatacept were more likely to be older (53.5 vs 52.1 years), African American (35.2% vs 27.3%), and diabetic (36.6% vs 34.5%). Also, they had been longer on dialysis (974 vs 913 days), and received higher Kidney Donor Profile Index kidneys (36 vs 23) (P < .05).

The hazard ratios, 95% confidence intervals, and P values comparing tacrolimus vs belatacept recipients were as follows for the following outcomes among all patients:

  • Patient death 0.89 (0.82–0.97, P = .009)
  • Adjusted overall graft failure 0.97 (0.90–1.05, P = .457)
  • Death-censored graft failure 0.85 (0.78–0.94, P = .001)

Among patients receiving deceased donor kidneys:

  • Patient death 0.89 (0.82–0.97, P = .009)
  • Adjusted overall graft failure 0.97 (0.90–1.05, P = .457)
  • Death-censored graft failure 0.85 (0.78–0.94).

Among those receiving living donor organs:

  • Patient death 0.87 (0.74–1.03, P = .115)
  • Adjusted overall graft failure 0.97 (0.82–1.14, P = .683)
  • Death-censored graft failure 0.92 (0.75–1.12, P = .398).

Concluding, Montalvan commented on the higher risks of death-censored graft failure and patient death risk in patients discharged on belatacept as maintenance therapy. “It might be related to increased comorbidity, risk of early rejections despite the reduced nephrotoxic effects, and possibly increased viral and fungal infections associated with belatacept.” She observed that the retrospective nature and potential for selection bias are major limitations of database studies, and that therefore, randomized controlled trials comparing belatacept to tacrolimus are awaited.

References

  1. Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant 2011; 11(3):450–462. doi:10.1111/j.1600-6143.2010.03283.x
  2. Cohen JB, Eddinger KC, Forde KA, Abt PL, Sawinski D. Belatacept compared with tacrolimus for kidney transplantation: a propensity Score Matched Cohort Study. Transplantation 2017; 101(10):2582–2589. doi:10.1097/TP.0000000000001589
  3. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2012 Annual Data Report. Department of Health and Human Services, Health Resources and Service Administration; Rockville, MD: 2014.
  4. Ducloux D, Motte G, Kribs M, Abdelfatah AB, Bresson-Vautrin C, Rebibou JM, Chalopin JM. Hypertension in renal transplantation: donor and recipient risk factors. Clin Nephrol 2002; 57(6):409–413. doi:10.5414/cnp57409
  5. Vincenti F, Friman S, Scheuermann E, et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant 2007; 7(6):1506–1514. doi:10.1111/j.1600-6143.2007.01749.x
  6. Mathis AS, Davé N, Knipp GT, Friedman GS. Drug-related dyslipidemia after renal transplantation. Am J Health Syst Pharm 2004; 61(6):565–585. PMID:15061429
  7. Webster A, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev 2005;(4):CD003961.  doi:10.1002/14651858.CD003961.pub2
  8. Matas AJ, Smith JM, Skeans MA, et al. OPTN/SRTR 2013 annual data report: kidney. Am J Transplant 2015; 15(Suppl 2):1–34. doi:10.1111/ajt.13195

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