Evaluation of the living kidney donor and risk of donor nephrectomy .pptx

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1. Evaluation of the living kidney donor and risk of donor nephrectomy Rabin Nepali DM, 1 st YEAR NEPHROLOGY

2. HISTORICAL PERSPECTIVE AND CURRENT STATUS 1954- In Boston, Peter Bent Brigham Hospital- first successful living donor kidney transplant. Surgical team led by Nobel Laureate Joseph Murray transplanted a kidney removed from Ronald Herrick into his identical twin brother Richard.

3. HISTORICAL PERSPECTIVE AND CURRENT STATUS The donor lived a further 56 years without sequelae . Prior to the advent of potent immunosuppressive regimes, transplantation of organs from living related donors offered the greatest opportunity for successful transplantation. Consensus among medical and ethical experts led to the legal acceptance of brainstem death criteria in late 1970s.

4. HISTORICAL PERSPECTIVE AND CURRENT STATUS Live donation re-emerged in the 1990s as an important source for kidney transplants. The ever-increasing waiting times for organs from deceased donors. The demonstration of a survival benefit associated with kidneys from living donors as compared to kidneys from deceased organ donors. The shift to minimally invasive procedures.

5. RATIONALE FOR LIVE KIDNEY DONATION Patients who receive living donor grafts have superior long-term survival, as well as shorter waiting times. Allows elective planning with optimization of the recipient’s health status. Pre-emptive transplantation- improved graft survival .

6. RATIONALE FOR LIVE KIDNEY DONATION Early graft function is significantly better for kidneys from living versus deceased donors. Deceased Living Primary non-function 2.7% 1.4% Delayed graft function 23.5% 3.4% Survival rates at 10 years 42.7% 59.6% OPTN/SRTR 2010 annual data report. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau; 2011.

7. THE EVALUATION PROCESS The core components of the evaluation process include: Education, counseling, and consent of the donor. (2) Psychosocial evaluation. (3) Medical evaluation. (4) Review of all results at a multidisciplinary meeting. February 2013, the Organ Procurement and Transplantation Network (OPTN)

8. Education, Counseling, and Consent of the Potential Donor Consent should first be given to undergo the evaluation process. Potential donors should be carefully educated about all aspects of the evaluation and must understand that they are free to withdraw from the process at any time. Supportive of the donor and defend the confidentiality of donor findings and donor decisions. February 2013, the Organ Procurement and Transplantation Network (OPTN)

9. Psychosocial Evaluation Should be carried out by a trained psychiatrist, psychologist, or social worker with a particular interest and expertise in transplantation. (1) Psychological assessment with identification of active mental health problems. (2) A social assessment including high-risk behaviors. (3) Assessment of the ability of the donor to consent ensuring that the donor’s decision is free of inducement or coercion. February 2013, the Organ Procurement and Transplantation Network (OPTN)

10. Medical Screening Process History and physical examination with specific focus on renal disease and family history of renal disease. Laboratory testing to evaluate renal function and determine immunological compatibility. Identification of transmissible infectious disease. Evaluation of renal anatomy. Completion of an age-appropriate health screening including cancer screening. February 2013, the Organ Procurement and Transplantation Network (OPTN)

11. History and Physical Examination Concentrate on symptoms and signs of renal disease, as well as personal and familial risk factors. Comorbidities, including hypertension, diabetes, cardiovascular or cerebrovascular disease, should be sought. Blood pressure – three separate measurements. Additional 24-hour blood pressure monitoring study as indicated.

12. Laboratory Testing Donor ABO typing. Complete blood count with platelet count and differential count. Fasting serum glucose and measurement of transaminases. Fasting lipid profile. Measurement of GFR by isotopic methods or a creatinine clearance calculated from a 24-hour urine collection. February 2013, the Organ Procurement and Transplantation Network (OPTN)

13. Laboratory Testing Measurement of urinary protein excretion. Coagulation studies to include the prothrombin time, and partial thromboplastin time. Urinalysis and urine culture (if clinically indicated). Chest X-ray. Electrocardiograph.

14. Laboratory Testing Patients with a history of kidney stones or nephrolithiasis (>3 mm) identified on imaging must have a 24-hour urine stone panel including calcium, oxalate, uric acid, citric acid, creatinine , and sodium. Tissue Crossmatch . Human leukocyte antigen (HLA) typing of the donor.

15. Identify Transmissible Infectious Disease Cytomegalovirus (CMV) antibody. Epstein-Barr virus (EBV) antibody. HIV antibody (anti-HIV) testing or HIV antigen/antibody (Ag/ Ab ) combination test as close as possible, but within 28 days prior to organ recovery.

16. Identify Transmissible Infectious Disease Hepatitis B surface antigen ( HBsAg ) testing as close as possible, but within 28 days prior to organ recovery. Hepatitis B core antibody (anti- HBc ) testing as close as possible, but within 28 days prior to organ recovery. Hepatitis C antibody (anti-HCV) testing as close as possible, but within 28 days prior to organ recovery. Syphilis testing.

17. Evaluation of Renal Anatomy Abdominal imaging using computed tomography angiography or magnetic resonance angiography.

18. Age-Appropriate Health Screening, Including Cancer Screening Prostate-specific antigen (Male >= 50). Gynecologic examination with Papanicolaou smear. Colonoscopy (Adults >= 50). Mammogram ( Female >= 40). Echocardiography and cardiac stress testing as indicated.

19. EXCLUSIONARY CRITERIA

20. Diabetes Individuals with a history of diabetes or fasting blood glucose >=􏰅126 mg/dl (7.0 mmol /L) on at least two occasions (or 2-hour glucose with OGTT >=􏰅200 mg/dl (11.1 mmol /L) should not donate. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

21. Renal function A GFR 􏰁<80 ml/minute or 2 SD below normal (based on age, gender, and BSA corrected to 1.73/m2) generally preclude donation. Kidneys from live donors with GFR <=􏰆80 ml/min are associated with relative risk of graft loss of 2.28 compared to those with greater pre nephrectomy GFR. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

22. Renal function Thiel and colleagues proposed that the conventional threshold of 80 mL/min needs to be revisited because it fails to adequately define donor acceptability; it is too low for young donors and too high for older ones. eGFR 40 = (40 mL/min/1.73 m2+ AD)/0.73, where AD is the age difference between 80 and the age at nephrectomy.

23. Renal function This formula is designed to help determine whether a potential donor will still have a GFR of at least 40 mL/min at age 80. For a 20-year-old potential donor, eGFR 40 = (40 + 60)/0.73 = 136 mL/min, and this should be the minimum eGFR to accept this 20-year-old donor. For a 60-year-old donor, on the other hand, this minimum would be 82 mL/min.

24. Renal function However, successful transplantation was noted from living donors with GFR as low as 65–70 ml/min, indicating a need for individualization and careful follow-up of donors with GFR of 􏰁<80 ml/min/1.73/m2. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

25. Urine Analysis for Protein A 24-hour urine protein of 􏰂>300 mg is a contraindication to donation. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

26. Urine Analysis for Blood Patients with persistent microscopic hematuria should not be considered for kidney donation unless urine cytology and a complete urologic work up are performed. If urological malignancy and stone disease are excluded, a kidney biopsy may be indicated to rule out glomerular pathology, such as IgA nephropathy. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

27. Hypertension Patients with a BP >􏰂140/90 by ABPM are generally not acceptable as donors. BP should preferably be measured by ABPM, particularly among older donors (􏰂>50 years) and/or those with high office BP readings. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

28. Hypertension If easily controlled hypertension and 􏰂>50 years of age, GFR> 􏰂80 ml/min, and urinary albumin excretion 􏰁<30 mg/ day ----> a low-risk group for development of kidney disease and may be acceptable as kidney donors. Donors with hypertension should be regularly followed by a physician. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

29. Hypertension 47 and 41% of centers excluded patients taking any antihypertensive medication or taking more than one medication, respectively. 2007 survey of kidney transplant centers in the United States

30. Obesity Patients with a BMI >􏰂35 kg/m2 should be discouraged from donating, especially when other comorbid conditions are present. Should be encouraged to lose weight prior to kidney donation and should be advised not to donate if they have other associated comorbid conditions. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

31. History of nephrolithiasis Patients with lithiasis should be screened for metabolic stone forming abnormalities. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

32. History of nephrolithiasis An asymptomatic potential donor with history of a single stone may be suitable for kidney donation if: No hypercalcuria , hyperuricemia , or metabolic acidosis. No cystinuria or hyperoxaluria . No urinary tract infection. Multiple stones or nephrocalcinosis are not evident on computed tomography (CT) scan. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

33. History of nephrolithiasis Asymptomatic potential donor with current single stone may be suitable if: The donor meets the criteria for single stone formers. Current stone is <􏰁1.5 cm in size or potentially removable during transplant. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

34. History of nephrolithiasis Stone formers who should not donate are those with: Nephrocalcinosis on X ray or bilateral stone disease Stone types that have high recurrence rates and are difficult to prevent, such as: A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

35. History of nephrolithiasis Cystine stones that have a high rate of recurrence and a need for urologic procedures in the donor. Struvite stones or infection stones that are difficult to eradicate and thus not feasible to transplant them into an immunosuppressed patient. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

36. History of nephrolithiasis Associated with inherited or other systemic disorders, such as primary or enteric hyperoxaluria , distal renal tubular acidosis because of the probability of a high rate of recurrence and the risk of renal insufficiency. Stones in the setting of inflammatory bowel disease with an increased risk of stones particularly after bowel resection, also increased risk of renal insufficiency. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

37. History of Donor Malignancy A prior history of the following malignancies usually excludes live kidney donation: Melanoma, testicular cancer, renal cell carcinoma, choriocarcinoma , hematological malignancy, bronchial cancer, breast cancer and monoclonal gammopathy . A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

38. History of Donor Malignancy A prior history of malignancy may only be acceptable for donation if: Prior treatment of the malignancy does not decrease renal reserve or place the donor at increased risk for ESRD. Prior treatment of malignancy does not increase the operative risk of nephrectomy. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

39. History of Donor Malignancy A prior history of malignancy usually excludes live kidney donation but may be acceptable if: The specific cancer is curable and the potential transmission of the cancer can reasonably be excluded. Examples include: colon cancer (Dukes A, 􏰂5 years ago), non- melanoma skin cancer, or carcinoma in situ of the cervix. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

40. Infectious Diseases HIV infection - An ELISA result positive for HIV-1 or HIV-2 should be confirmed by Western blot analysis. A positive test result excludes the donor. Hepatitis B - Positivity for hepatitis B surface antigen generally excludes the donor. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

41. Infectious Diseases Hepatitis C - HCV-positive donors should be excluded if the recipient is HCV negative. HCV-positive donors wishing to donate to HCV-positive recipients should undergo quantitative PCR testing. If the PCR finding is positive, the donor should be excluded. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

42. Infectious Diseases If the PCR finding is negative, the donor may still donate, since the kidney is not a known reservoir for HCV. Genotyping of HCV-positive donors and recipients should be done. Previously treated HCV-positive donors, especially those with favorable genotypes, can be considered as donors. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

43. Infectious Diseases CMV/EBV infection - Donors with positive result on immunoglobulin M and PCR testing for CMV cannot donate until their PCR test result is negative. It is preferable, if feasible, for a donor who is positive for both CMV and EBV to donate to a child who is positive, since posttransplantation lymphoproliferative disease is a major issue in seronegative children who receive organs from seropositive adults. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

44. Infectious Diseases TB - Active TB is a contraindication to donation. Donors with a history of TB may be considered, especially if they were treated and undergo extensive evaluation for genitourinary TB. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

45. Infectious Diseases Syphilis - Should be screened with RPR or VDRL. Positive test results should be confirmed by the fluorescent treponemal antibody absorption test. Donors with a positive result on the latter test should be treated before donation. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

46. Urinary tract infections The donor urine should be sterile prior to donation; asymptomatic bacteria should be treated per donation. Pyuria and hematuria at the proposed time of donation is a contraindication to donation. Unexplained hematuria or pyuria necessitates evaluation for adenovirus, tuberculosis, and cancer. Urinary tuberculosis or cancer are contraindications to donation. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

47. Determination of cardiovascular risk The clinical predictors of an increased perioperative cardiovascular risk (for non-cardiac surgery) by the American College of Cardiology/American Hospital Association standards fall into 3 categories: major, intermediate, minor. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

48. Determination of cardiovascular risk All major predictors : unstable coronary syndromes, decompensated heart failure, significant arrhythmias and severe valvular disease are contraindications to live kidney donation. Most of the intermediate predictors : mild angina, previous myocardial infarction, compensated or prior heart failure, diabetes mellitus are also contraindications to donation. Minor predictors : older age, abnormal ECG, rhythm other than sinus, low cardiac functional capacity, history of stroke or uncontrolled hypertension warrant individual consideration. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

49. Assessment of pulmonary issues A careful history and physical examination are the most important parts of assessing risk. Routine preoperative PFT is not warranted for potential live kidney donors unless there is an associated risk factor such as chronic lung disease. Increased risk of post operative pulmonary complication is associated with an FEV1 <70 % or FVC <70 % of predicted, or a ratio of FEV1/FVC <65 %. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

50. Smoking Cessation Smoking cessation at least 4 weeks prior to donation is advised, based on recommendations for patients undergoing elective surgical procedures. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

51. Alcohol Abstinence Cessation of alcohol abuse defined by DSM-3: 60g alcohol/day sustained 􏰅6 months should be avoided for a minimum of 4 weeks to decrease the known risk of post- operative morbidity. A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

52. EXCLUSIONARY CRITERIA Absolute contraindications ABO incompatibility. Proteinuria and/or hematuria Impaired renal function (defined as GFR <80 mL/min per 1.73 m2). Markedly abnormal urologic and renal vascular abnormalities.

53. EXCLUSIONARY CRITERIA Absolute contraindications Chronic active viral infection (HIV, Hepatitis B and C). Active malignancy. History of malignancy, arising from lung, breast, renal or urologic, gastrointestinal, or hematologic organs and melanoma.

54. EXCLUSIONARY CRITERIA Absolute contraindications Diabetes mellitus Nephrocalcinosis , bilateral kidney stones, or recurrent nephrolithiasis Poorly controlled psychosis Active substance abuse Pregnancy.

55. EXCLUSIONARY CRITERIA Some relative contraindications Active peptic ulcer disease History of nephrolithiasis Morbid obesity, most commonly defined as body mass index >35.

56. RISK OF DONOR NEPHRECTOMY IMMEDIATE RISK Atelectasis Pneumothorax Pneumonia Urinary tract infection Wound complication Deep vein thrombosis with or without pulmonary embolism Death, 3.1 per 10,000 donors .* * Segev DL, Muzaale AD, Caffo BS, et al. Perioperative mortality and long-term survival following live kidney donation. JAMA 2010; 303:959.

57. RISK OF DONOR NEPHRECTOMY LONG-TERM RISK Overall long-term survival after donor nephrectomy is the same as similar matched individuals who did not undergo surgery. Although 50% of the functioning renal mass is removed, compensatory hypertrophy returns the GFR to 70% of baseline at 10- 14 days and 75-85% of baseline at long-term follow-up.

58. RISK OF DONOR NEPHRECTOMY LONG-TERM RISK Change in Glomerular Filtration Rate with Age in Kidney Donors. Prevalence of Hypertension. Potential Acceleration of Kidney Disease in One Kidney.

59. QUALITY OF LIFE AFTER KIDNEY DONATION In general, living donors report a similar, or better, quality of life compared with the general population. Factors associated with decreased quality of life- poor donor or recipient physical outcome, a negative personal donor-recipient relationship, and financial hardship.

60. About 60% of the donors rated their physical health higher than the average for their age and gender peers in the U.S. general population. 62% of the donors rated their mental health higher than did their age and gender peers. Because individuals with serious physical or mental health problems are either discouraged from donating or disqualified once evaluated. QUALITY OF LIFE AFTER KIDNEY DONATION

61. Maternal and fetal outcomes No data to suggest it leads to significant hypertension, proteinuria, change in glomerular filtration rate, or abnormalities of the urinary sediment. To delay pregnancy until at least 2 months after nephrectomy to assess renal compensation prior to conception with evaluation including blood pressure, GFR, and assessment for microalbuminuria . A Report of the Amsterdam Forum On the Care of the Live Kidney Donor: Data and Medical Guidelines Transplantation 2005;79: S53–S66

62. Maternal and fetal outcomes 106 pregnancies post donation Vs 620 pregnancies prior to donation, and a random sample 21,511 pregnancies. Compared with pregnancy before donation, pregnancy after donation was associated with a significantly increased risk of preeclampsia (5.7 Vs 2.6%) and a non significant increase in stillbirth (2.8 Vs 1.1%). Reisaeter AV, Røislien J, Henriksen T, et al. Pregnancy and birth after kidney donation: the Norwegian experience. Am J Transplant 2009; 9:820.

63. Maternal and fetal outcomes However, there were no differences in adverse pregnancy outcomes between kidney donors and the general population. There is an increased risk for fetal loss, gestational diabetes, gestational hypertension, and preeclampsia with pregnancy after kidney donation, compared to pregnancy prior to kidney donation. ** **Ibrahim HN, Akkina SK, Leister E, et al. Pregnancy outcomes after kidney donation. Am J Transplant 2009; 9:825. ** 2102 kidney donors

64. Maternal and fetal outcomes The generally good outcomes should NOT exclude donors who have not completed child-bearing. However, we must be aware of the increased risks with pregnancy after kidney donation.

65. THANK YOU

66. Increased risk of diabetes Family history of diabetes. 2013 UpToDate