Living Donation in the Family Ethical and Medical Problems Dr Umberto Maggiore

Transcription

1 Living Donation in the Family Ethical and Medical Problems Dr Umberto Maggiore SS Trapianti Rene-Pancreas UO Nefrologia (Dir Prof C Buzio) Az. Ospedaliero-Universitaria di Parma Parma, ITALY

2 CATEGORIES OF DONATION BY LIVING PERSONS 1. DIRECTED DONATION TO A LOVED ONE 2. NONDIRECTED DONATION 3. DIRECTED DONATION TO A STRANGER Truog N Engl J Med 2005;353:5

3 ETHICAL ISSUES IN DONATION IN THE FAMILY 1. PRESSURE TO DONATE WITHIN THE FAMILY 2. WILLING TO DONATE REGARDLESS OF THE RISKS Spital Ethics of Organ Transplantation 2001;7:89

4 PRESSURE TO DONATE WITHIN THE FAMILY 1. EXTERNAL: ONE PERSON TRIES TO CONVINCE ANOTHER TO DONATE (eg spouse) 2. INTERNAL: FEELING OF OBLIGATION AND GUILT (eg sibling) Gordon Am J Transplant 2012, May 17

5 EXTERNAL PRESSURE UNUSUAL MORE AGAINST DONATION THAN IN FAVOUR OF DONATION Smith Am J Kidney Dis 1986;8:223

6 Spital Ethics of Organ Transplantation 2001;7:89 Gordon Am J Transplant 2012, May 17 INTERNAL PRESSURE FEAR OF FAMILY OSTRACISM FEAR OF LIFELONG GUILT SOCIOCULTURAL AND FINANCIAL DIFFERENCES o Europe o Asia o Developing Countries EXTENT: LIVER vs KIDNEY DONORS

7 Live Organ Donor Consensus Group JAMA 2000;284:2919 Steel Am J Transplant 2012, May 1 INTERNAL PRESSURE: SAFEGUARDS TRAINED MENTAL HEALTH PROFESSIONAL ie, clinical social worker, psychologist, psychiatrist, or psychiatric nurse experienced in transplantation INDEPENDENT DONOR ADVOCATE (TEAM) o not a transplant team member: conflict of interest o transplant center might engage a mental health professional who is not a member of the recipient care team

8 PLAUSIBLE MEDICAL EXCUSE FOR UNWILLING DONORS MEDICAL EXCUSE: BOW OUT GRACEFULLY NOT A FALSIFIED MEDICAL CONDITION o Undesired consequences of medical insurance o May still act as a donor in the future eg for their own children STANDARD OPTIONS o Borderline hypertension, glucose level o general contraindication Live Organ Donor Consensus Group JAMA 2000;284:2919

9 SOME DEGREE OF INTERNAL PRESSURE IS ACCEPTABLE INTERNAL PRESSURE: WRONG TO AUTOMATICALLY CONCLUDE DONATION IS NOT VOLUNTARY EXAMPLE: MOTHER TO CHILD DONATION o Emotional ties to their child o Sense of moral obligation COERCITIVE SITUATION (NOT COERCION) o Coercion requires that the decision is being forced by another person o Coercitive situation: feeling of obligation gives voice to mother autonomy Crouch Cambridge Quarterly Healthcare Ethics 1999;8:275 Spital In: Living Donor Organ Transplantation (Gruessner Benedetti) 2008; 51

10 ETHICAL ISSUES IN DONATION IN THE FAMILY 1. PRESSURE TO DONATE WITHIN THE FAMILY 2. WILLING TO DONATE REGARDLESS OF THE RISKS Spital Ethics of Organ Transplantation 2001;7:89

11 Fellner Am J Psychiat 1970;126:1245 Nuffield Council of Bioetics Human Tissue Ethical and Legal Issues 1995; 45 RAPID CONSENT FROM DEEP AFFECTION IS VALID DONORS MAY IMMEDIATELY VOLUNTEER UPON HEARING OF THE NEED, IN THE FACE OF LIMITED UNDERSTANDING OF RISKS: CONSENT MAY NOT BE FULLY INFORMED THE ETHICALLY SIGNIFICANT REQUIREMENT IS NOT THAT CONSENT BE COMPLETE, BUT THAT IT BE GENUINE : DONATION STILL REGARDED AS AUTONOMOUS CHOICE

12 DO DONORS HAVE A RIGHT TO DONATE AN ORGAN? NO: AUTONOMY OF THE RESPONSIBLE PHYSICIAN MUST ALSO BE RESPECTED THE PHYSICIAN DECIDES WHETHER HE IS MORALLY JUSTIFIED IN HELPING THE DONOR ACCOMPLISH IT IT MAY BE NOT ALWAYS REASONABLE FOR THE PHYSICIAN TO ACCEPT VOLUNTEERS WHO STRONGLY WISH TO DONATE DESPITE ADDED RISK Elliot J Med Ethics 1995;21:91

13 BALANCE BETWEEN RISK AND BENEFIT: DONOR S BENEFIT DONOR BENEFIT IS THE KEY TO JUSTIFIED LIVING ORGAN DONATION For physicians to recommend their patient as an acceptable organ donor they must first believe that the benefits for the potential donor are sufficient to offset the risk for the donor Spital Cambridge Quarterly Healthcare Ethics 2004;13:105

14 PSYCHOLOGICAL BENEFIT FOR THE DONOR CAN BE LARGE AND AT LEAST AS IMPORTANT AS PHYSICAL ONE o eg mothers who see their loved child returned to normal life o eg spouses having their cherished person available for sharing the joys of life UNJUSTIFIED REJECTION OF A SPOUSE/MOTHER MAY HAVE NEGATIVE CONSEQUENCES FORTHE DONORS THEMSELVES Gaston Am J Transplant 2010; 10:2574

15 ESTIMATES OF ANTICIPATED PSYCHOLOGICAL BENEFIT BEST EXPERTS ABOUT THE EXPECTED PSYCHOLOGICAL BENEFIT ARE THE DONORS THEMSELVES PHYSICIANS SHOULD INCORPORATE THE DONOR S VISION INTO THEIR DECISION MAKING PROCESS Kassirer New Engl J Med 1983;308:898

16 DONATION FROM MINORS AND NOT MENTALLY DEVELOPPED LACK OF DONOR BENEFIT IS THE STRONGEST POINT AGAINST DONATION TO SIBLINGS FROM MINORS AND FROM PEOPLE NOT MENTALLY DEVELOPED o may fail to understand the important role they played in the care of sibling o may not receive any psychological benefit as a result of their donation Crouch Cambridge Quarterly Healthcare Ethics 1999;8:275

17 DISCLOSURE OF INFORMATION THE PERSON WHO GIVES CONSENT TO BE A LIVE DONOR SHOULD BE COMPETENT, WILLING TO DONATE, MEDICALLY AND PSYCHOSOCIALLY SUITABLE, FULLY INFORMED OF THE RISKS AND BENEFIT AS A DONOR, AND FULLY INFORMED OF THE RISKS, BENEFIT, AND ALTERNATIVE TREATMENT AVAILABLE TO THE RECIPIENT Live Organ Donor Consensus Group JAMA 2000;284:2919

18 RISK ESTIMATES ESSENTIAL FOR DONOR ACCEPTANCE POLICY IF THE RISKS ARE TRULY UNKNOWN, OR ONLY A CURSORY ESTIMATE IS PROVIDED OVER A WIDE LOW TO HIGH RANGE, DECISION MAKING IS INDEFENSIBLE o donors faced with truly unknown risk cannot rationally decide o the transplant team cannot balance the risk and benefit of living donation Steiner Am J Transplant 2008;8:230

19 THE BURDEN OF FAMILY HISTORY OF ESRD A SIGNIFICANT PROPORTION (ie >20%) OF PATIENTS WITH ESRD WILL HAVE A FAMILY HISTORY (FH) OF RENAL DISEASE A NEGATIVE FAMILY HISTORY DOES NOT EXCLUDE PRIMARY RENAL GENETIC DISEASE ESRD, End-Stage Renal Disease BTS-RA UK Guidelines Transplantation 2012;93:666

20 FH OF ESRD IN LIVING RELATED KIDNEY TRANSPLANTATION: RISKS RISK FOR THE DONOR: MAY DEVELOP THE DISEASE AFTER DONATION FH, Family History ESRD, End-Stage Renal Disease Niaudet Nat Rev Nephrol 2010;6:736

21 YOUNG DONOR AGE: LONG-TERM LARGE RISK ESTIMATES THE YOUNGER THE DONOR, THE GREATER THE REMAINING BASELINE LIFETIME RISK FOR ESRD, AND THE LESS A NORMAL FOR NOW MEDICAL EVALUATION CAN FORESEE ESRD ESRD, End-Stage Renal Disease Steiner Am J Transplant 2010;10:737

22 YOUNG DONOR AGE: LONG-TERM LARGE RISK ESTIMATES EXAMPLE 25-year old donors have on average more than 50 years to live. Overt renal disease or medical findings that are risk factors for renal disease may well not be apparent 30 or 40 years before ESRD ensues: a normal for now medical evaluation in a young donor may provide little assurance of reduced baseline lifetime risk of ESRD Steiner Am J Transplant 2010;10:737

23 YOUNG DONOR AGE: LONG-TERM LARGE RISK ESTIMATES Lifetime Risk Risk left to be predicted for a 60-yr-old donor Risk left to be predicted for a 25-yr-old donor Steiner Am J Transplant 2010;10:737

24 YOUNG DONOR AGE & FH OF ESRD IN NON-MENDELIAN DISEASES FH, Family History ESRD, End-Stage Renal Disease Freedman Am J Nephrol 2005;25:529

25 FAMILIAL CLUSTERING OF IgA NEPHROPATHY at least 14% of IgAN pts in Brescia (Italy) Scolari Am J Kidney Dis 1999;33:857

26 YOUNG LIVING-RELATED DONOR CANDIDATES YOUNG DONOR CANDIDATES DESERVE THE SAME CONCEPTUAL (AND ETHICAL) APPROACH AS DONORS WITH AN ISOLATED MEDICAL ABORMALITY, DESPITE A NORMAL MEDICAL EVALUATION Steiner Am J Transplant 2010;10:737 BASELINE LIFETIME RISK MAY BE FURTHER INCREASED BY A FH OF RENAL DISEASE FH, Family History

27 PERSISTENT NON VISIBLE HEMATURIA IN RELATED DONORS Koushik Transplantation 2005;80:1425 kidney biopsy frequently reveals glomerular pathology which precludes donation, with the possible exception of thin basement membrane disease BTS-RA UK Guidelines Transplantation 2012;93:666

28 Niaudet Nat Rev Nephrol 2010; 6:736 BTS-RA UK Guidelines Transplantation 2012;93:666 MENDELIAN RENAL DISEASES IN LIVING RELATED KT: X-linked DISEASE Alport syndrome Fabry Disease Dent s Disease IS LIVING RELATED DONOR KT APPROPRIATE?, but heterozygous females, only if: >45yrs, no renal abnormality, no hearing deficiency if donor does not carry the mutation. Incrased risk in heterozygous females if donor does not have LMW proteinuria KT, Kidney Transplantation

29 MENDELIAN RENAL DISEASES IN LIVING RELATED KT: Aut Recessive DISEASE SRNS -Finnish Type (NPHS1) Aut Rec SRNS (NPHS2) Aut Rec SRNS (NPHS3) Pierson Syndrome Schiemke dystrophy Nephronophtisis Cystinosis ARPKD Alport syndrome Atypical HUS IS LIVING RELATED DONOR KT APPROPRIATE? except for carriers of Arg229Gln(q.R229Q) No* No SRNS, Steroid-Resistant Nephrotic Syndrome; HUS, Hemolytic-Uremic Syndrome; ARPKD, Autosomal Recessive PKD Niaudet Nat Rev Nephrol 2010; 6:736 *BTS-RA UK Guidelines Transplantation 2012;93:666

30 MENDELIAN RENAL DISEASES IN LIVING RELATED KT: Aut Dominant DISEASE ADPKD type 1 ADPKD type 2 Atypical HUS IS LIVING RELATED DONOR KT APPROPRIATE? UMOD associated nephropathy (normal FE ur ) Nail Patella Syndrome Tuberose sclerosis complex Von Hippel Lindau FSGS MYH9 var (e.g Epstein Dis.) : for unaffected relatives and/or for not carrying the mutation ARPKD, Autosomal Dominant PKD; HUS, Hemolytic-Uremic Syndrome; UMOD, UroMODulin No Niaudet Nat Rev Nephrol 2010; 6:736 *BTS-RA UK Guidelines Transplantation 2012;93:666

31 LIVING RELATED KIDNEY DONATION IN ADPKD Ultrasound, CT, or MRI Defer donation Imaging Defer donation 3 cysts (uni- or bilateral)? Genetic Linkage No 3 family members with ADPKD? No Recipient DNA sequencing Age<40 Age Age 60 Equivocal Imaging Study*** 2 cysts per kidney? 4 cysts per kidney? Defer donation No*** Proceed With Donation Genetic Testing Pathogenetic variant identified? Donors ADPKD mutation? No Defer donation No Defer donation Proceed With Donation Huang Transplantation 2009;87:133

32 LIVING RELATED DONATION IN ahus LIVING RELATED TRANSPLANTATION SHOULD BE AVOIDED IN ahus UNLESS ALL KNOWN MUTATIONS HAVE BEEN EXCLUDED IN THE DONOR ahus, Atypical Hemolytic-Uremic Syndrome BTS-RA UK Guidelines Transplantation 2012;93:666

33 GENETIC RENAL DISEASES CAUSED BY ALTERNATIVE COMPLEMENT PATHWAY DYSREGULATION C3 GLOMERULOPATHIES o Dense Deposit Disease (DDD) o MPGN Type I with isolated C3 deposition o Non-MPGN C3 Glomerulonephritis o Familial MPGN Type III o CFH-R5 Nephropathy MPGN, MembranoProliferative GlomeruloNephritis CFH, Complement Factor H Sethi Kidney Int 2012;81:434 Fakhouri Nat Rev Nephrol 2010;6:494

34 PROGRESSION FROM MPGN TO ahus MPGN ahus Fakhouri Nat Rev Nephrol 2010;6:494 Gnappi Pediatr Nephrol 2012; Jun 5 MPGN MPGN (1st KT) ahus (2nd KT) Lorcy Nephrol Dial Transplant 2011;26:3811 MPGN, MembranoProliferative GlomeruloNephritis ahus, Atypical Hemolytic-Uremic Syndrome KT, Kidney Transplant Manenti, Licht N Engl J Med 2012;367:86

35 RISK OF CLINICALLY RELEVANT RECURRENCE IN THE GRAFT disease recurrence (%) graft loss at 5-10 yrs (%) risk modifiers ahus MCP mutation risk, except LRD DDD Age onset; severity; LRD better # MPGN Type I & LRD worse: risk of recurrence?; C3 glomerulopathy 60 NA severity; recur. in a previous KT NPHS2 FSGS low if any low if any LRD better regardless etiology* FSGS Recur. in a previous KT: >75% risk IgA Nephropathy LRD worse: inconsistent evidence Prim hyperoxaluria High Risk High Risk KT only if Gly170Arg mutation LRD, Living-Related Donation; KT, Kidney Transplantation; graft loss at 5-10yrs refers to risk due to recurrence ahus, Atypical Hemolytic-Uremic Syndrome; DDD Dense Deposit Disease; MPGN, MembranoProliferative GlomeruloNephritis; FSGS, primary Focal Segmental GlomeruloSclerosis; NPHS2 pdocin gene mutation # Angelo Am J Kidney Dis 2011;57:291, Servais Kidney Int 2012, Mar 28 *Jungraithmayr J Am Soc Nephrol 2011;22:579