Long Term Survival after Kidney Transplantation

Publication Summary

Key Takeaways

  • Long-term survival after kidney transplantation has improved despite expanding donor and recipient acceptance criteria.
  • Continuing the trend to further improve graft survival requires a multi-faceted approach incorporating improved access to care pre- and post-transplant as well as innovative non-invasive biomarkers and better treatment of post-transplant rejection.
  • Accelerated uptake of telemedicine consequent to the COVID-19 pandemic has improved access to care.
  • Legislation to continue insurance coverage for long-term immunosuppression is anticipated to help essential adherence to immunosuppression.

Summary Statement

Long-term kidney transplant graft and patient survival has consistently improved with time. Much of the gain is attributed to superior understanding of pre-transplant immunological risk. Making further gains in graft and patient survival depends upon a holistic approach to reduce causes of graft loss and death.

Whilst rejection remains an important cause of graft loss, it is not the only determinant of patient survival. Efforts to improve graft survival could result in a reduction in the numbers of patients returning to dialysis and/or the transplant list; an increase the numbers of kidneys available to those on the transplant list; reduced waiting time; improved quality and length of life; and lower financial impact to patients and the health care system.

Summary

Long-term kidney transplant survival has improved form 42.3% for operations performed between 1996-1999 to 53.6% for operations performed in 2008-2011 (The most recent group for whom 10-year graft survival statistics are available). Similarly, patient survival in the two groups has risen from 60.5% to 66.9%.

The improvement in transplant and patient survival has occurred despite increases in donor and recipient characteristics, which are traditionally detrimental to graft survival [e.g. increasing recipient age, co-morbidity, duration on dialysis, re-transplants, increasing proportion of donation after circulatory death (DCD) kidneys, increasing donor age, increasing Kidney Donor profile Index (KDPI), and increasing anti-HLA antibody pre-sensitization].

Data on long-term graft and patient survival in the United States lags behind other registry data, i.e. Europe, Canada, Australia and New Zealand. A decline in survival starting three years after transplantation is thought to be due to, and is contemporaneous with, discontinuation of insurance coverage for long-term immunosuppressant drugs, which are key to graft survival.

The improvement in survival with time is attributed to a reduction in the observed rates of clinical acute rejection, better pre-transplant tissue typing practices, the use of paired-exchange programs, recognition of the importance of post-transplant viral infections and widespread prophylaxis against some (e.g. CMV) and improved medical management of the infectious, oncological, cardiovascular and metabolic complications of transplantation.

Causes of graft and patient loss are divided between first year and after the first year. In the first year after transplantation kidney transplant loss is caused by technical and vascular complications (41%), acute rejection (17%) and recurrent kidney disease (glomerulonephritis, 3%).

After the first year, chronic rejection accounts for 63% of graft loss and glomerulonephritis 6%. Death in the first year is equally split between cardiovascular disease and infection (31% each), though cancer contributes 7%. After the first year, cancer is the predominant case (29%), followed by cardiovascular disease (23%) and infection (12%).

The authors suggest that interventions designed to improve long-term survival can be broken down into five main categories:

  1. Donor Interventions
  2. Non-immunological recipient candidate interventions
  3. Pre-transplant immunological interventions
  4. Post-transplant interventions
  5. Socio-economic interventions

The main post-transplant interventions above and beyond the existing standard of care are:

  • improving personalization of immunosuppression drug levels
  • use of biomarkers for the diagnosis of (subclinical) acute rejection
  • improved therapies for acute rejection
  • improved access to transplantation
  • interventions to reduce nonadherence
  • and improved transition from adolescent to adult care.

 

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References
  1. Hariharan S, Israni AK, Danovitch G. Long-Term Survival after Kidney Transplantation. N Engl J Med. 2021 Aug 19;385(8):729-743. doi: 10.1056/NEJMra2014530. PMID: 34407344.