Improving Long-term Outcomes in Kidney Transplantation: Interventions Before Transplant

By Dr. Abhinav Humar

In the United States, roughly about 25000 Kidney transplants are done on yearly basis. At UPMC, the standard protocol followed is to induce transplant patients on thymoglobuline and then taper them off steroids quickly in the post-transplant period. The standard immunosuppression in the post-transplant period includes the use of steroids, tacrolimus and mycophenolate. The patients are monitored carefully with standard blood tests and DSA is conducted at regular intervals throughout the transplant. Protocol biopsy will be done in patients at 3 months and at 12 months post-transplant to guide in immunosuppression. Patient survival and graft survival both are important and are closely interlinked; death with function is an important cause of graft loss and patient survival is significantly negatively impacted if there is graft failure or even graft dysfunction.

Kidney for Life initiative

The objective of this initiative is to ensure that a single kidney survives the life span of the recipient and it prevents the need for retransplantation. 

There was a study published in NEJM by Hariharan et al, who studied long-term survival after kidney transplantation in the >18 years age group over a period of the year 1996-2019 and examined 6 different groups in 4-year cohort to look at the outcomes. Data shows an increase in the number of transplants, that too in deceased donor kidney transplants compared to live donor kidney transplants. Demographic data shows that median age, mean dialysis duration, the percentage of individuals with diabetes, donation after cardiac death and delayed graft function have increased with each subsequent time frame. Mention patient and graft survival rates from the same study (exact rates are around 98% and 96% respectively).

About 15% of liver donor kidney transplants in the USA are in the form of paired exchange, which has a lot of potential. In the most recent outcomes in 2012-2015 compared to 1996-99, there is almost a 10% increment in both patient and graft survival. There is a steady decrease in the attrition rate of death and early graft loss in 1 to 5 years in the last 5 years.  

The important interventions before transplant include early referral, pre-emptive transplant and health optimization. Outcomes are better if transplantation is done before the patients are subjected to any significant period of dialysis. When considering a deceased donor, judicious use of high KDPIs, HIV and Hep C positive donors, virtual cross match and machine preservation may impact the transplant. Living donor transplants are better in terms of long-term outcomes; better matching includes the use of eplet matching.

‘Kidney for Life initiative’ is started by National Kidney Registry, USA which coordinates the paired exchange program. The main objective behind this initiative is better donor-recipient matches with: 

• Reduced risk of de novo antibodies
• Lower risk of rejection
• Less risk of graft failure
• Opportunity for safely reducing immunosuppression
• Fewer side effects from immunosuppressive medication

Living Donor Paired Exchange (LDPE)

The incidence of living donor-paired exchange has increased from 0% to 14.1%. Live donor paired exchange (LDPE) is superior to desensitisation. LDPE can expand to other types of situations such as size and age matching from the donor to the recipients, risk factors such as CMV and eplet/immunological matching for the patients. Low eplet mismatch correlates better with all immunological endpoints including T cell-mediated rejection (TCMR), DSA, and ABMR.