Differential risks for adverse outcomes 3 years after kidney transplantation based on initial immunosuppression regimen: a national study

Transpl Int. 2016 Nov;29(11):1226-1236. doi: 10.1111/tri.12850. Epub 2016 Sep 28.

Abstract

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus-based ISx was associated with significantly higher three-year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine-based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid-free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.

Keywords: Medicare; cancer; immunosuppression; infections; kidney transplant; registries.

MeSH terms

  • Adolescent
  • Adult
  • Cyclosporine / therapeutic use
  • Diabetes Mellitus / diagnosis
  • Female
  • Humans
  • Immunosuppression
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycophenolic Acid / therapeutic use
  • Pneumonia / diagnosis
  • Renal Insufficiency / surgery
  • Risk
  • Sepsis / diagnosis
  • Sirolimus / therapeutic use
  • Tacrolimus / therapeutic use
  • United States
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus