LIVE KIDNEY DONOR RISK PREDICTION ; NEW PARADIGM, NEW CALCULATORS PEDRAM AHMADPOOR MD

Transcription

1 LIVE KIDNEY DONOR RISK PREDICTION ; NEW PARADIGM, NEW CALCULATORS PEDRAM AHMADPOOR MD

2 Outline: PART 1 : Update on safety of nephrectomy for living donor candidate PART 2 : Latest guideline recommendation for using Software based risk calculation of ESRD risk with examples PART 3 How to measure kidney function in the potential donor?

3 RISKS FOR RECIPIENT CAN RENAL TRANSPLANTATION IMPROVE QUALITY AND/OR LONGEVITY OF LIFE OF RECIPIENT CAN THE RECIPIENT TOLERATE CARDIOVASCULAR STRESS OF ANESTHESIA AND OPERATION RISK OF TRANSMISSION OF INFECTIONS HIV HBV HCV HTLV-1 Strongyloides TB RISK OF OPPURTUNISTIC INFECTIONS : CMV,BK, PCJ, FUNGAL RISK OF TRANSMISSION OF CANCER RISK OF GRAFT LOSS AFTER TRANSPLANTATION donor derived ( age,sex, weight, living vs cadaveric vs nonheart beating, ECD, ischemic tim immunologic and nonimmunologic risks ( tx across DSA, FCXM positive tx, DGF, rejections, BK nonadherence, HT after tx, hyperlipidemia, obesity, PTDM )

4 RISKS FOR LIVING DONOR ESTIMATION OF PERIOPERATIVE PERIOD RISK FOR DONOR RISK OF ANESTHESIA, CV & Pulmonary status of donor OPERATION COMPLICATIONS infections, bleedings complication rate of 5 15%. MORTALITY ( 90 days for operation mortality 0,03% based on 80,000 donors) Risk factors for perioperative mortality: Men African American Hypertension no privae insurrance LONG TERM IMPACT OF NEPHRECTOMY FOR DONOR RISK OF RENAL FAILURE IN FUTURE HT ALBUMINURIA NEPHROLITHIASIS GOUT ETHICAL ISSUES PSCHYCOLOGICAL STABILITY & ABILITY ON DECISION MAKING FOR DONATION AND PSCHYCOLOGICAL IMPACTS IN THE FUTURE

5 OBSERVED in living donors EXPECTED national mortality rates 430 living donor nephrectomies in Stockholm from end of 1994

6 (204) Cause unknown in 17 MISSING DATA In conclusion, living kidney donation does not impact survival, kidney function, medical condition or psychological or social status over the very long-term.

7 869 citation At a mean ( matched for age, sex, and race

8 healthy nondonor cohort

9 They are not perfectly mactched

10 On the other hand

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12 Due to missing data for smoking (27.4%), systolic BP (6.3%), and BMI (17.3%), survival analyses were repeated after replacing missing data using multiple imputations

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14 IN NORWAY THERE IS JUST ONE CENTER THAT DO THE TRANSPLANTATION SO THERE IS UNIQUE IN TERMS OF LOW PERCENTAGE OF DATA LOSS IT IS SHOWN THAT IN UP TO 10 YEARS OF FOLLOW UP THERE IS NO DIFFERENCE IN MORTALITY BUT

15 Among these2269 donors, 1519 were first-degree relatives, 89 were other relatives, and 293 were unrelated. Can HR of ESRD be overestimated?

16 Based on newer better matched studies: Risk of all cause mortality,cardiovascular mortality and ESRD seems to be higher in living donors compared to matched population It needs to reconsider the factors associated with mortality and long term risk of ESRD in living donors

17 Among 8,325,115 participants in 7 cohorts,they have excluded those with absolute contraindications of kidney donation: - Estimated GFR of less than 45 ml per minute per 1.73 m2 of body-surface area (CKD EPI) - insulin-dependent diabetes mellitus - the use of four or more antihypertensive medications - a blood pressure of 160/90 mm Hg or more while the person was taking medication or 170/100 mm Hg or more while the person was not taking medication - a urinary albumin-to-creatinine ratio of 300 mg/gr cr or more - a history of coronary heart disease, stroke, congestive heart failure, or peripheral arterial disease - Popullation with no contraindication = 4,933,314-52,998 donors were included followed for a median of 4 to 16 years.

18 For a 40-year-old person with health characteristics that were similar to those of age-matched kidney donors, the 15-year projections of the risk of ESRD in the absence of donation varied according to race and sex; the risk was 0.24% among black men, 0.15% among black women, 0.06% among white men, 0.04% among white women. Risk projections were higher in the presence of a lower estimated GFR, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. In the model-based lifetime projections, the risk of ESRD was highest among persons in the youngest age group, particularly among young blacks. The 15-year observed risks after donation among kidney donors in the United States were 3.5 to 5.3 times as high as the projected risks in the absence of donation.

19 acceptable risk of ESRD 5 % (3.5 to 5.3 times)

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21 For a 40-year-old person with health characteristics that were similar to those of age-matched kidney donors, the 15-year projections of the risk of ESRD in the absence of donation varied according to race and sex; the risk was 0.24% among black men, 0.15% among black women, 0.06% among white men, 0.04% among white women. Risk projections were higher in the presence of a lower estimated GFR, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. In the model-based lifetime projections, the risk of ESRD was highest among persons in the youngest age group, particularly among young blacks. The 15-year observed risks after donation among kidney donors in the United States were 3.5 to 5.3 times as high as the projected risks in the absence of donation.

22 For example, if a transplant program sets the acceptable lifetime postdonation ESKD risk threshold at 5%, and assumes a donation attributable RR of 3.5 to 5.3 according to sex and race, then the acceptable predonation lifetime ESKD risk threshold would be approximately

23 if a transplant program decides a lifetime postdonation risk of kidney failure of up to 5% is acceptable, and if a candidate s projected risk is estimated to be above this threshold, the program should decline this candidate as a donor NO BECAUSE LIFETIME RISK IS HIGHER THAN 1.5

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25 OLDER AGE AT DONATION; LOWER RISK OF ESRD Higher risk particularly among young black persons

26 Do you accept her? You can expand your donor pool But still keeping low the risk of ESRD

27 LIVING DONATION MUCH BETTER GRAFT SURVIVAL

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29 severe, moderate, and normal/mild albuminuria (top to bottom, respectively) a KDIGO Controversies Conference report. Kidney Int. 2011;80:17-

30 Younger age,same albuminuria even with higher GFR

31 limitations US population data that can be different in other populations. Certain health characteristics of interest was not available, including heritable and environmental factors. Donor candidates with a family history of kidney disease (especially younger candidates with such history) would be expected to have a higher risk of ESKD than projected. The analysis does not include untreated low GFR as an outcome, a condition that is more common among older persons, nor did it assess the risk of other outcomes, such as hypertension or preeclampsia, that have been linked to kidney donation. The analysis did not estimate the age at which ESKD would be expected to develop in a donor candidate or the duration of ESKD before death. No data on single kidney GFR status

32 WRAP UP PART 1& 2 The risk of ESRD, CVD mortality and overall mortality is higher compared to matched but not donated population. Based on the recent studies you can better estimate risk of ESRD in your donors (UPDATED GUIDELINE) meanwhile you can increase your donor pool without imposing higher risk of ESRD. (although it has limitations.) Integrated decision making in the presence of different risk factors. Participation of donor in decision making more clealy

33 Outline: PART 1 : Update on safety of nephrectomy for living donor candidate PART 2 : Latest guideline recommendation for using Software based risk calculation of ESRD risk with examples PART 3 How to measure kidney function in the potential donor?

34 But How GFR must be measured?

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41 sotope diffusion mass spectrometry For e GFR measurement by CKD EPI, the enzymatic method is recommended

42 cr Initial test shall be CKD EPI cr 2009 or 2012 can be used as the initial test egfrcys If cr based techniques are biased Acceptable confirmatory test: mgfr egfrcr cys mclcr Repeated e GFRcr CKD EPI Repeat egfrcr can be acceptable if none of the other confirmatory tests are available

43 IT IS NECESSARY TO VERIFY GFR BY MORE COMPLICATED METHODS BEYOND e-gfr IN ALL CANDIDATES? Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation egfrcr high enough to ensure 95% probability that predonation mgfr was 90 ml/min per 1.73m2, suggesting that mgfr may not be necessary in a large proportion of donor candidates

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45 FOR PREDICTING PROBABILITY

46 No need for confirmatory test if post test probability is 95%

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49 The lifetime standardized renal reserve: the pre-donation mgfr value / the expected number of remaining years of life By Contraindicating donation if GFR of < 90 ml/ min / 1,73 you will lose 1/3 of donors And acceptance of elderly donors with GFR <90 ml/min/1,73 can be safe An absolute low GFR value in a donor candidate can be within the range of physiological normality and should not per se be interpreted as a contraindication to kidney donation.

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53 Trend of cadaveric versus living donation in Iran living cadaveric (2015) 2017 =2750 although number of living donation decreased but total Tx number increased

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56 Mean of age 30.4 ± 6 82% male

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59 Kidney Transplantation in France Kidney Transplantation Kidney Transplantation with living donor 2014

60 Deceased donors in France (in whom organs were retrieved) Mean Age Donor Number France 4 5 Mean Age Donor 6

61 Yearly number of living kidney donors in France since

62 Deceased donors older than 60y in France y y >80 y

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65 cr Initial test shall be CKD EPI If post test probability of having GFR <60 ml/min is > % cr concordance with m GFR no further testing is required mgfr or mclcr As confirmatory test: egfrcr cys can be acceptable if mgfr or mclcr are not available egfrcys was not used as the initial test Repeat egfrcr can be acceptable if none of the other confirmatory tests are available

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67 FOR PREDICTING PROBABILITY

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70 If post test probability be higher than 95 % it is reassuring Lower than that means you have to use confirmatory tests

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79 No need for confirmatory test if post test probability is 95%

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87 European cohort

88 KIND OF IRANIAN MODEL So let s take the left one

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90 Mrasures to decrease mortality of ESRD patients Increase our standard of care before and during dialysis all and all Decreasing waiting time for transplantatation encouraging transplantation increase graft survival = shorter waiting list

91 Measures to expand donor pool Increasing standard cadveric donations Accepting expanded criteria donors ( KDPI>85%) Establishing Non heart beating donation DAAC M3 M4 M2 M1 Increasing living related donations Widenening legal living donor donation ( tight friendship at least 2 years confirmed by official justice organisations) Kidney paired donation desensitisation protocols against HLA antibodies ABOI transplantation

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94 BP > 140/90 or antihypertensive drugs + AER>30 mg /d (TOD) exclude from donation

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97 Acceptable lifetime Post donation risk of kidney failure of 5%

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