Kidney Transplant Basics

survival of transplant v dialysis

-transplant > dialysis

-QOL transplant > dialysis

-cost transplant > dialysis

earlier transplant =

-better survival

waitlist eligibility in the US

-on dialysis or not on dialysis but GFR/eGFR </= 20 AND no contraindications to transplant

contradictions to transplant

-absolute (make transplant dangerous or futile): active malignancy, active infection, contraindication to surgery, non-kidney organ failure (and not listed for dual organ transplant) or other condition with very short life expectancy

-relative (subjective and contribute to disparities): active substance abuse, lack of insurance coverage, inadequate support, medical nonadherence, severe/uncontrolled psychiatric illness, condition that will markedly reduce allograft longevity

getting to transplant

disparities in referral/waitlisting

-racial minority

-lower SES

-lower educational attainment

-non-English speaking

-female

-obesity

-distance from transplant center

assigning waitlist priority

organ-recipient longevity matching

kidney allocation

-CPRA: calculated panel reactive antibodies

-KDPI: kidney donor profile index; estimated how long a given kidney may function once transplanted

-EPTS: estimated post transplant survival score; estimates how long a given candidate is likely to benefit from a kidney

kidney donor profile index

-medical match: age/height/weight/ethnicity, how the donor died, high bp/diabetes/hep C, donor’s creatinine

-time waiting

-distance between hospitals

KDPI and EPTS

-pediatric recipients <18 do not receive an EPTS score

-pediatric candidates have 1st offer <KDPI 35

donor source- living or deceased

what is a “mismatch”?

-ABO blood group antigens- “ABO compatible”

-HLA antigen mismatch: class I (HLA A, B- all nucleated cells), class II (HLA DR- APCs, B cells, endothelial cells, renal tubular epithelial cells)

pre-transplant antibodies to HLA molecules

CDC crossmatch

increasing live donor kidney transplants- paired kidney exchanges (“swaps”)

paired kidney exchanges- chains

current state of xenotransplant

-primarily done via FDA expanded access pathway, NOT via clinical trials- ethical concerns

kidney transplantation

special cases

-dual kidney transplant

-en-bloc kidney transplant

-retransplant

induction immunosuppression

-intense immunosuppression given in first week after transplant

-can be lymphodepleting or non-lymphodepleting agent (plus corticosteroids)

-goal: to reduce risk of acute rejection

choice of maintenance immunosuppression

maintenance immunosuppression

allograft function and surveillance

kidney transplant rejection

hazards of chronic immunosuppression

challenges to long-term success

why do transplants fail long-term?

the future

-better understanding and diagnosis of the rejection process- understand mechanisms leading to allograft injury/protection at the molecular level

-new/improved immunosuppressive agents- reduce alloantibody production

-improved organ donation rates

-xeno-transplantation

-tolerance induction

-tissue/organ culture- generate/repair

take home points