an overview of the criteria for kidney donors and recipients

1. Kidney Transplantation Part 1: patient
selection and transplant outcome
Rubin Zhang, MD, FASN

2. A 50 YO AA male with CKD from HTN and
type 2 DM. His eGFR 18 cc/min. He is
asking you which treatment option may
provide best survival benefit.
1). PD
2). HD
3). Pre-emptive living donor kidney transplant
4). List for a deceased donor KT now

4. Ronald (age 23, left) donated a kidney to Richard (right) on
12/23/1954 in Peter Bent Brigham Hospital. Fingerprint and
Skin graft transplant were done for verification

5. Richard’s story
 Met his future wife, Clare, the recovery
room head nurse
 Married Clare, and had two daughters
 Died in March 14, 1963 (9 years after KT)

6. Ronald’s story
 Went to college, earned BS and MS in
Education
 Taught math for 37 years
 Died Dec 27, 2010 at age 79 (56 years
after KD)

8. Dr. Joseph Murray
 1990, Nobel Prize in Medicine
 “ We did not think we’d make history. We
did not even think of history. We thought
we were going to save a life”
 Died on 11/26/2012 at age 93

10. Patients With Certain Cancers Have a Better Chance of Surviving
5 Years After Diagnosis Than Patients Starting on Dialysis
1
Death rate of patients on dialysis at 5 years compared with patients with selected
solid tumor cancers (all stages)1,2,a
a Dialysis mortality data are taken from the USRDS 2014 Annual Data Report; cancer mortality data are from the American Cancer Society (ACS) Cancer Facts & Figures 2015.
1. USRDS. 2014 ADR chapters. http://www.usrds.org/2014/view/default.aspx. Accessed February 11, 2016. 2. ACS. Cancer
facts & figures 2015. http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf.
Accessed March 1, 2016.

11. Recipients of a Kidney Transplant Have a Longer Life Expectancy Than
Patients Who Remain on Dialysis
1
a Data are from the United States Renal Data System (USRDS) 2014 Annual Data Report; estimates are from 2012.
USRDS. 2014 ADR chapters. http://www.usrds.org/2014/view/default.aspx. Accessed February 11, 2016.
Expected remaining lifetime for recipients of a kidney transplant compared
with patients on dialysis (across sexes and various races)a
Based on estimates from 2012, recipients of a kidney transplant
had about 2.5 times more remaining years of life than patients on dialysis

12. Wolfe et al: NEJM 1999, 341:1725

13. Wolfe et al: NEJM 1999, 341:1725

14. Adjusted relative risk of death of first
CRT
Reference group: on waiting list, relative risk 1.0
Wolfe et al: NEJM 1999, 341:1725

15. Kidney Transplant as the preferred
treatment
 Survival benefit: detected in the first year
after transplant
 Better quality of life
 Restore fertility for young women
 Save Medicare money in the 2nd year: 1st
year of KT costs $100K, then 20K / year;
HD/PD costs 80K / year
 Save private payer’s money in the 1st
year.

16. Heterotopic kidney transplant
Renal artery
Transplanted
kidney
Renal vein
Ureter
Bladder

17. Transplant Work-up Steps
 When: ESRD or CKD with cCr < 20 ml/min
 How: send a referral to the transplant center
 Social worker calls patient and dialysis unit for patient’s information
and initial screening
 Patient and family member / care-giver come for transplant
education
 Financial approval for transplant work-up
 Clinic appointments with coordinator, MD, dietician, pharmacist and
psychologist
 Labs, images, screening, clearance per protocol
 Transplant selection meeting
 Living donor work-up

19. Absolute contraindications
 Active infections.
 Active malignancy.
 Active substance abuse.
 Reversible renal failure.
 Uncontrolled psychiatric disease.
 Documented active and ongoing treatment
nonadherence.
 A significantly shortened life expectancy.

20. Usual contraindications
 Progressive angina or known severe coronary heart disease that
are not amenable to angioplasty or bypass surgery
 History of AMI within the past 6 months
 Severe CHF, ejection fraction < 30 percent. Combined kidney-
heart transplants may be considered.
 COPD on home O2 or wheelchair-bound
 Irreversible pulmonary hypertension, mean PAP >40 and / or
PASP > 50
 Active or chronic active hepatitis
 Cirrhosis and/or portal hypertension. Combined liver-kidney
transplants may be considered.

22. Preoperative “Clearance”
 Cardiac contraindication: unstable angina,
decompensated CHF, unstable arrhythmia,
severe AS/MS
 Recent acute events: stroke, AMI, COPD
exacerbation, big surgery, GI bleeding, acute
hepatitis, etc
 Ongoing infections: dialysis access, diabetic
foot, cellulitis, osteomyolitis, etc
 Dialysis: fluid overload, uremia, K, etc.

23. Perioperative Medications
 Continue beta-blocker, clonidine, CCB, nitrates;
stop ACEI, ARB, minoxidil after transplant
 Continue ASA, statin; stop coumadin, plavix,
estrogen, phos-binders and sensipar
 Stop metformin and sulfonylureas; continue
long-acting insulin ½ dose; change to insulin drip
after surgery
 Type-1 diabetes: when NPO, give “baseline”
long-acting insulin Plus D5W

26. Wait-listed patients for KT

27. 2
a
Data are from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR). 2013 Annual
Data Report: Kidney.
Three-year outcomes are for adult patients waiting for a kidney transplant and first placed on the waiting list in 2010.
b
Includes patients who were still waiting, died, or were removed from the list.
Matas AJ et al. Am J Transplant. 2015;15(suppl 2):1-34 [supplementary material]. http://onlinelibrary.wiley.com/doi/10.1111/ajt.13195/suppinfo. Accessed
March 1, 2016.
63% of patients placed on the waiting list in 2010 did not receive a kidney
transplant within 3 yearsb
The median waiting time for a deceased donor kidney transplant was
4 years for adult patients active at listing in 2009

28. Observed & projected median wait times
Patients age 18 & older listed for a first-time kidney-only transplant in the given year.

29. Geographic disparity
Data source: www.optn.org, 2012

30. Strategies & terminologies
Traditional deceased donors: donation after brain
death, standard criteria donors (SCD) vs expanded
criteria donor (ECD, marginal donors)
Donation after circulatory death (DCD, non-heart-
beating donors); controlled vs. non-controlled
Kidney donor profile index (KDPI), replaces above
terminologies
Incompatible living donor kidney transplants: live donor
exchange, desensitization protocol

31. ECD’s Defined
Donor condition Age 50-59 Age=/> 60
CVA+HTN+Cr>1.5 X X
CVA+HTN X X
CVA+Cr>1.5 X X
HTN+Cr>1.5 X X
CVA X
HTN X
Cr>1.5 X
None above X

32. Survival at 10 Years Is Higher for Recipients of Living Donor Kidneys Than
for Patients Who Receive a Deceased Donor Kidney or Remain on Dialysis
3
Ask about whether a
living donor kidney
transplant could be an
option for you
Estimated 10-year
patient survival based on
data from 2002a
a Data are from the USRDS 2014 Annual Data Report; 10-year estimates are based on data from 2002.
USRDS. 2014 ADR charts. http://www.usrds.org/2014/view/default.aspx. Accessed February 11, 2016.

33. A Kidney Transplant From a Living Donor Results in Better Long-term
Outcomes Than a Transplant From a Deceased Donor or Dialysis
3
a
Data are from the USRDS 2014 Annual Data Report; 1-year data are from 2011, 5-year data are from 2007, and 10-year data
are from 2002.
USRDS. 2014 ADR chapters. http://www.usrds.org/2014/view/default.aspx. Accessed February 11, 2016.
Patient survival ratesa
Donor kidney survival ratesa
1-, 5-, and 10-year patient and graft survival rates

34. Major allocation Changes
Replace SCD/ECD with KDPI Incorporate A2/A2B to B
Add longevity matching:
Estimated Post-Transplant
Survival(EPTS)
Keep pediatric priority on KDPI
Increase priority for sensitized
candidates/cPRA sliding scale
Remove payback system
Include dialysis time Remove variances

35. The following 10 characteristics are used to calculate
the KDRI:
 Age
 Height
 Weight
 Ethnicity
 History of Hypertension
 History of Diabetes
 Cause of Death
 Serum Creatinine
 Hepatitis C Virus (HCV) Status
 Donation after Circulatory Death (DCD) Status
Kidney Donor Risk Index (KDRI)

36. The Kidney Donor Risk Index (KDRI):
It summarizes the risk of graft failure after kidney
transplant into a single number, it expresses the
relative risk of graft failure for a given donor
compared to the median kidney donor from last
year.
Values exceeding 1 have higher expected risk
than the median donor, and vice versa.

37. The Kidney Donor Profile Index
(KDPI): is a remapping of the KDRI
onto a cumulative percentage scale,
such that a donor with a KDPI of 80%
has higher expected risk of graft failure
than 80% of all kidney donors
recovered last year.

38. Estimated Kidney Graft Survival Rates
by Donor KDRI / KDPI
KDPI KDRI 1 Yr 3 Yrs 5 Yrs 8 Yrs
1% 0.55 94.0% 87.8% 80.5% 68.7%
5% 0.61 93.5% 86.7% 78.8% 66.2%
10% 0.65 93.1% 85.9% 77.6% 64.4%
20% 0.73 92.3% 84.4% 75.3% 61.1%
30% 0.81 91.5% 82.9% 73.0% 57.9%
40% 0.90 90.5% 81.1% 70.4% 54.4%
50% 1.00 89.5% 79.2% 67.6% 50.8%
60% 1.10 88.6% 77.4% 65.2% 47.6%
70% 1.23 87.3% 75.1% 61.9% 43.6%
80% 1.39 85.8% 72.4% 58.3% 39.2%
90% 1.62 83.7% 68.7% 53.3% 33.6%
95% 1.85 81.6% 65.2% 48.9% 28.9%
99% 2.30 77.7% 58.8% 41.1% 21.4%

40. Estimated Post-Transplant Survival (EPTS)
 Candidate age, time on dialysis, prior organ transplant,
diabetes status; 4 variables, more predictive than age alone
 Percentage scale, similar to KDPI, lower = better
 EPTS of 20 percent suggests that the patient would likely
survive longer than 80 percent of all other recipients.
Top 20% of candidates by EPTS (<20%) to receive top 20%
kidneys (KDPI<20%)
Longevity Matching for Recipients

41. Point changes: Sensitization
100

42. HLA typing and matching
 HLA, human leukocyte antigen, coded by the major
histocompatibility complex (MHC) genes
 Each parental chromosome 6 provides a haplotype
(a linked set of MHC genes) to offspring, mendelian
co-dominant inheritance
 HLA A, B, & DR were traditionally used for typing
and matching before transplant: 3 pairs, but 6
antigens
 HLA match importance: DR > B > A
 We also do HLA Bw, Cw, DP, and DQ

46. Table 1. Comparison of the Dominant Characteristics of Class I and Class II DSA
Class I DSA Class II DSA
HLA
antigens A, B, C DR, DQ, DP
epitopes location a- chain a- and ß- chains
expression all nucleated cells antigen-presenting cells
Preformed DSA
important very less
positive cross-match T cells B cells
transplant decision no transplant permissible
De Novo DSA
detection sooner later
IgG subclasses IgG1, IgG3 IgG2, IgG4
complement-binding strong weak / no
frequency fewer common, especially DQ
Antibody Mediated Rejection
phenotypes acute chronic, subclinical
presentation early later
graft dysfunction rapidly slowly
C4d deposit positive negative
treatment more responsive less responsive
graft loss early later
References: 6-10, 25-30.

47. Profile 1: A1, A3; B7, B8; DR4, DR12
Profile 2: A1, A24; B8, B13; DR4, DR15
 Living related
 Living unrelated, or one is a deceased
donor

48. Profile 1: A1, A3; B7, B8; DR4, DR12
Profile 2: A1, A24; B8, B13; DR4, DR15
 1A,1B,1DR match, or 1A,1B,1DR mismatch
 If 1 and 2 are living-related, then A1,B8,DR4
is the shared “haplotype”, or 1-haplotype
match
 If 1 and 2 are unrelated, then A1,B8,DR4 -
match is phenotypic, not genotypic, not
haplotypic

49. Profile 1: A2, A2; B8, B13; DR3, DR3
Profile 2: A2, A3; B8, B13; DR3, DR4
 1 as donor to 2 as recipient
 2 as donor to 1 as recipient

50. Profile 1: A2, - ; B8, B13; DR3, -
Profile 2: A2, A3; B8, B13; DR3, DR4
 1 as donor to 2
 2 as donor to 1

51. Profile 1: A2, - ; B8, B13; DR3, -
Profile 2: A2, A3; B8, B13; DR3, DR4
 Failure to identify 2nd
A and DR, usually due to
inheritance of same Ag from both parents
(homozygous)
 1 as donor to 2: 1A, 2B, 1DR match, Zero
mismatch, national sharing
 2 as donor to 1: 1A, 2B, 1DR match, 1A, 0B, 1DR
mismatch

52. National kidney sharing
 All (6) HLA antigen - matched kidneys
 Phenotypically matched
 Zero mismatch
 Deceased donor does not have any Ag
different from recipient, but recipient may
have Ag different from the donor

53. PRA
 The presence of antibodies in the recipient’s blood
against a panel of selected HLA antigens
representing donor population
 PRA defines sensitization, 0 to 100%
 Sensitization: blood transfusion, pregnancy,
previous transplants
 Higher PRA, more difficult to find a donor, longer
waiting time
 cPRA is calculated based on the patient listing of
“unacceptable” HLA antigens

54. Detection of HLA Antibodies

55. DSA
 DSA can be determined by HLA specific
antigen solid-phase binding assays
 Luminex, multiplexed particle-based Flow
 Mean fluorescence intensity (MFI) > 2000-
3000 for Class 1; > 5000-6000 for Class 2 as
clinically significant
 MFI of 4000 = positive Flow CM
 MFI of 9000 = positive CDC CM

58. T cell
Plasma cell
Donor APC
Endothelial cell
Class I HLA
T cell
h
B cell
Endothelial cell
Class II HLA
Direct stimulation
Pleotrophic effects
Growth factors
Leukocyte recruitment
Tissue injury
Endothelial proliferation
Fc receptor
NK cell
Macrophage
Neutrophil
Degranulation
Lytic enzymes
Tissue injury
Cell death
Complement-
binding DSA
C C C
1q 1r 1s
(C complex)
1
C ,C
4 2
C C
4b 2a
(C convertase)
3
C C C
4b 2a 3b
(C convertase)
5
C3
C3a
Anaphylatoxin
Inflammation
C5a
C3b
C
5
C
5b
C ,C ,C ,C
6 7 8 9
C5b-9
(Membrane attack complex)
Cell lysis
Complement-
nonbinding DSA

59. ADCC: antibody-dependent cellular cytotoxicity