definition ,types , inclusion & exclusion criteria , risk factors , ethical issues of marginal kidney donor

1. MARGINAL
KIDNEY DONOR
DR.LEELA KRISHNA

2. INTRODUCTION
– Renal transplant is the treatment of choice for a medically
eligible patient with end stage renal disease
– The number of renal tranplants has increased rapidly over the
last two decades
– Large gap b/w the number of patients awaiting for a transplant
and receiving a transplant - increasing the demand for renal
allografts
– Expanded criteria donor (ECD ) – limit the mortality and
morbidity , increase the number of deceased donor kidney

3. CONTD…
– Performing renal transplant with a perfectly healthy kidney to all
patients with ESRD is ideal scenario
– But growing awaiting , shortage of kidneys – makes it neccesary to
make some compromises , use so called marginal or border line
donors can increase donor pool by almost 20 to 25 %

4. DEFINITION
– Expanded criteria donors /marginal donors are not clearly defined
– Simply means usage of suboptimal quality cadaveric renal grafts ,
non heart beating donors (NHBD) and living donors with some
acceptable medical risks

5. OUTCOMES
– With increase in demand for allografts , many centres world wise used
marginal kidneys with informed consent
– Although short & long term outcomes with such grafts were inferior to
normal criteria kidneys ,
– Had significant survival advantage over the waitlisted dialysis patients
– Poor long term outcome may be the consequence of an imbalance b/w
number of viable nephrons suppliedand metabolic demand of the recipient
– Gap becomes wider when marginal donors are transplanted after prolonged
ischemia

6. CONTD…
– High rate of delayed graft function, more acute rejection episodes and
decreased long term graft function
FACTORS - 1)prolonged cold ischemia time
2)increased immunogenicity
3)impaired ability to repair tissue
4)impaired function with decreased nephron mass

7. OPTIMISED ALLOCATION
– Proposed by bryce kiberd for retreiving kidneys
– Visible scarred kidneys should be discarded
– Performing biopsy in some deceased donor kidneys ( age > 55 & older
, donor creatinine clearence ( < 60 – 70 ml/min , )
– Discarding advanced arteriolar sclerosis or interstitial fibrosis
– Allocating these grafts to older >59 yrs ,diabetic ,avoid the sensitized,
minimize cold ischemic time and avoid large weight or age
mismatches
– Older donor kidney in older patients ( lee et `al 1999, kasiske et al
2002 , smits et al 2002 , voiulescu et al 2002 )

8. TYPES OF MARGINAL DONOR
– Complex living donor
– Non heart beating donor ( NHBD )
– Deceased or cadaveric donor

9. INCLUSION CRITERIA
– Elderly donors
– GFR – 60 to 70 ml/min
– Mild hypertension
– Donor with stone disease
– Donors with renal cysts
– Donors with BMI >30
– Others – tuberculosis,DM, proteinuria, hematuria, malignancy,
family h/o of ESRD, cmv infections

10. EXCLUSION CRITERIA
– RELATIVE CONTRAINDICATIONS
Age <18 yrs but able to give informed
consent
Age > 70 impaired intellectual but able to
give informed consent
Females of child bearing age
Smoking
Dvt/ PE
Renal tract abnormalities
– ABSOLUTE CONTRAINDICATIONS
Inability to give consent
Hypertensive end organ disease
Pregnancy
Impaired glucose intolerance
Systemic disease effecting kidneys
Renal disease ,
Iv drug abuse,
Major Respiratory /cardiac diasease

11. COMPLEX LIVING DONORS
– The term complex living donors used by Resse
– referred to all Suboptimal donors where decision making is a
problem due to lack of sound medical data or consesus
guidelines
– Categorized complex living donors based on certain risk factors

12. RISK FACTORS ASSOCIATED WITH
COMPLEX LIVING DONOR
1) Evidence of current renal disease - hematuria, proteinuria,
nephrolithiasis
2) Direct risk of ckd - hypertension, elderly
3) Reduced nephron mass , age > 65 yrs
4) Genetic risk factors - h/o of ESRD in lst relative
5) Cardiovascular risk factor – smoking,hypertension,hypelipedemia
6) Risk factor for ckd – diabetes in first degree relative , impaired fasting
glucose
7) Other – black race, sickle trait

13. ELDERLY LIVING DONORS
– Normal GFR changes with age and decreases over time
– Decrease is approximately 1ml/minper1.73 m2 per year after age
40
– A GFR > 80 ml/min is generally considered as accepted value,
some consider > 60 ml/min
– GFR corrected to age rather than age itself determines
acceptability for donation

14. Contd…
– Matas and colleageus identified donor age greater than 55 yrs to
be a significant factor for late graft loss
– Inferior outcomes of an older kidney might be a function of an
anatomical and physiological changes that occur during aging
– Rates of short term morbidity & mortality do not seem to be
higher for elderly donors

15. HYPERTENSIVE LIVING DONORS
– BP monitoring – ABPM ( ambulatory blood pressure
monitoring ) – more sensitive
– > 140 /90 mmhg – are generally not acceptable as donors
– Low risk group - > 50 yrs of age , GFR > 80 ml/min , urinary
albulmin excretion < 30 mg/day , easily controlled
hypertension - may be accepatable as donors ( AMSTERDAM
consensus conferrence , delmonico et al 2005 )

16. DIABETIC DONORS
– Generally excluded – increased risk of post operative
complications - diabetic nephropathy and renal failure
– DN occurs in familial clusters and heredity - determine
susceptibility
– h/o of diabetes , fbs . >126 mg/dl on atleast two occasions ( 2hr
glucose + ogtt > 200 mg/dl ) – should not donate

17. NEPHROLTHIASIS
– It is reasonable to accept donors only those patients with out stones at the time of
evaluation + 24 hr urine collection of calcium ,urate and oxalate ( normal values )
– Stones caused by inherited disorders, inflammatory bowel disease, systemic disease
are at high risk of recurrence – should not be considered for donation
– An asymptomatic potential donor with no h/o of calciuria /colic is found to have single
stone on evaluation may be suitable for evaluation if
A) No metabolic abnormality , urinary infection exists , if muitiple stones or
nephrocalcinosis are not evident on ct
B) Current stone is < 1.5 cm in size, removable during transplant

18. Contd…
– AST ( american society of transplantation ) guidelines that a
kidney stone former may donate kidney if
A) Only one stone has ever formed ,stones have been multiple , but
none have formed > 10 yrs and none seen in radiograph
B) Donor screening for metabolic abnormalities ,life time follow up
for periodic risk assesement ,medical treatment and hydration

19. OBESE DONORS
– BMI > 30 kg/m2 - obese – high risk for proteinuria,FSGS, kidney
function - increased rates of DM, HTN,metabolic syndrome
– BMI > 35 kg/m2 - discouraged for donation ( delmonico et al ,2005 )
– < 35 kg/m2 – with out comorbidity is accepatable for donation and
encouraged to lose weight prior to kidney donation
– DYSLIPEDEMIA - faster rates of progression + ckd,
– Isolated dyslipedemia is not a contraindication for donation

20. HISTORY OF MALIGNANCY
– Risk of clinical and subclinical malignancy increases with age ,especially over
50 yrs
– Currently malignancy is a contraindication for organ donation ,except for low
grade non melanoma skin cancer
– Prior history of malignancy is accepatable of prior treatment of malignancy
A) Does not decrease renal reserve or place the donor at increased risk of ESRD
B) Does not increase the operative risk of nephrectomy
C) Has cured cancer , and is not potentially transmissible ( ca.colon dukes A>
5YRSago), non melanoma skin cancer or carcinoma in situ of cervix

21. CONTD…
– Informed consent should be obtained with both donor and
recepient that transmission of malignant disease cannot be
completely excluded

22. TRANSMISSIBLE
INFECTIONS
– HIV – contraindication for donation
– CMV , EBV - measured , delay in transplant till pcr becomes negative
most of adults are positive - risk of post transplantation
lymphoprolifertive disorder ( PTLD ) is concern in cmv ,ebv negative
individuals receiving positive donors
– Risk is not as high to prohibit renal transplantation
– HCV – positive donor can be considered if donor pcr is negative
– HBV – current status is not accepted
– PULMONARY TB – genitourinary tract should be examined prior
– SYPHILIS – FTA absorption test , positive treat accordingly

23. ETHICAL ISSUES
– Very complex in accepting marginal criteria donors
– Marginal donors may themselves add up the pool of chronic kidney
disease in long term
– Consent by both donor and recepient should be taken regarding
delayed graft function, expected decrease in graft survival ,expected
decrease in waiting time, expected increase in survival
– Cost factors
– Need for hemodialysis , further hospital readmissions due to poor or late
onset graft function
– Oppurtunistic infections

24. MARGINAL CADAVERIC KIDNEY
DONOR
– Can be defined as all donors older than 60 yrs , donors > 50 yrs with
any of the following criteria
– 1) hypertension 2) cerebrovascular cause of brain death 3) pre
retrieval serum creatinine > 1.5 mg/dl ,with degree of
glomerulosclerosis >15 % and prolonged ischemia
– High risk of graft failure > standard criteria donors
– Substantial reduction in morbidity ,improved life expectancy

25. NON – HEART –BEATING DONORS
( NHBD )
– Kidneys transplanted from non heart beating donors regarded as marginal or
extended criteria grafts due to associated period of warm ischemia
– NHBD is a donor who has suffered an irreversible brain injury ( stroke
/trauma ) but does not fulfil the criteria of brain death
– Patient is pronounced dead only after sustained cardiac asystole , which
results in prolonged warm ischemia and damage to procured organs
– Rate of significantly higher rate of delayed graft function is noted compared
to heart beating donors

26. CONTD….
– Many transplant centers are reluctant to use kidneys from NHBDs
due to
relatively higher incidence of primary non function ( PBF)
– Issues like uncertainity regarding diagnosis of death on the basis
of cessation of cardiac activity , and family consent

27. ROLE OF KIDNEY BIOPSY
– Outcomes of ECD kidney transplantation are improved when a pre implantation
biopsy of donor kidney is evaluated using scoring system introduced by kapinsiki
and colleagues
– Donor renal pathology – 0 to 3 ( none to severe disease )
– Glomerulosclerosis,interstitial fibrosis ,tubular atrophy and vascular disease
– Donor vessel score of 3/3 is associated with 100 % incidence of delayed graft
function and significant worse renal function at one year

28. PATIENT MANAGEMENT –
IMMUOSUPRESSIVE PROTOCOLS
– Optical management is a challenge in ECD kidney tranplannt receipents
– Increased rates of acute rejections and delayed graft function
– Management is based on potential nephron protecting strategies ,
including cold ischemia time minimization ,pulsatile perfusion
preservation
– immunosupression focused on nephrotoxicity minimization , adeqaute
infection prophylaxis
– Calcineurin inhibitors , responsible for postponing chronic allograft
dysfunction ,better long term graft survival
– Nephrotoxicity is more in older patients

29. CONTD..
– Various strategies of cni withdrawal , minimization as well as
avoidance were utilized by
– Antibody induction , MMF ,steroids
– MMF monotherapy or MMF plus steroids
– Antibody induction ,sirolimus, MMF ,steroids
– Conversion from a calcineurin inhibitor based regimen to sirolimus
based regimen

30. TAKE HOME MESSAGE
– Use of marginal donors for kidney transplantation increases the
numbers of donors kidney available results in shorter waiting times
– Limits morbidity and mortalitilty associated with long term dialysis
therapy
– management protocols for ecd kidney tranplantation should be
based on nephron protecting strategies like minimising cold ischemia
time ,tailored immunosupression with early CNI minimization or
delayed moderate dose , CNI addition after induction ,adequate
infection prophylaxis