Kidney Transplant in the Elderly! Robert Santella, M.D., F.A.C.P.
Incident Rate of ESRD by Age Age 75+ 65-74 From US Renal Data System, 2012
Should there be an age limit? Various guidelines: Canadian, UK, AST! Consistent theme is that chronologic age is less important than physiologic age and the nature and severity of coexisting conditions! Transplant candidates should have reasonable probability of surviving beyond current waiting times for transplantation! Elderly patients should be screened more aggressively! Note that the definition of elderly has shown an upward trend over time
Chronologic versus Physiologic Age
Proportion of Dialysis Patients Wait Listed Decreases With Age 250,000 200,000 Prevalent ESRD Wait Listed Patients 150,000 100,000 50,000 0 16% 21% 11% 3.4% 0.5% 18-39 40-59 60-69 70-79 >79 From US Renal Data System, 2012
15.8 13.2 0.59 a (0.53 0.65) 15.3 12.9 0.58 a (0.52 0.65) 17.8 15.0 0.67 b (0.53 0.86) 13.0 13.6 0.89 (ns) (0.64 1.22) Renal Transplantation in Patients Over 70 18.5 14.5 0.53 a (0.41 0.68) 15.0 12.8 0.56 a (0.45 0.68) 15.2 10.6 0.49 a (0.39 0.61) 15.3 12.5 0.52 a (0.42 0.65) 14.9 13.5 0.61 a (0.51 0.72) 16.4 13.6 0.58 a (0.50 0.68) Survival is lower in the transplant group for almost 2 years (time to equal survival),! but thereafter greater in the wait list group. FIGURE 2. Cumulative survival curves for elderly deceased donor transplant recipients and elderly wait-listed dialysis patients. Rao, et al. Transplantation April 27, 2007
Early Risk of Death in Elderly Kidney Transplant Recipients (patients over age 65) Living! Donor! SCD ECD Death Rate per 100 ptyrs in first year Days to Equal Survival Death Rate per 100 ptyrs in first year Days to Equal Survival Death Rate per 100 pt-yrs in first year Days to Equal Survival Low CV Risk 3 0 8 203 10 264 Medium CV Risk 3 0 9 285 14 304 High CV Risk 6 76 11 368 16 521 Survival is lower with lower quality donor and with greater CV risk Gill, et al. Am J Transplantation, 2013
Renal Transplantation in Patients Over 70 TABLE 3. Unadjusted graft survival among deceased donor and living donor kidney transplant recipients at 1, 2, and 3 years Transplant type Transplant recipients Graft survival, including death as an event (95% CI) N % 1 yr 2 yr 3 yr Deceased donor 2078 85.2 80.9 (79.1 82.7) 73.9 (71.8 75.9) 66.9 (64.6 69.2) Living donor 360 14.8 90.1 (86.6 93.4) 84.2 (80.2 88.5) 79.3 (74.6 84.4) Rao, et al. Transplantation April 27, 2007
Death Rates and Relative Mortality for Deceased Donor Kidney Transplant Recipients vs. Wait-Listed Patients 1990-2005 2007 Lippincott Williams & Wilkins Rao et al. TABLE 2. Unadjusted death rates and adjusted relative mortality risk for first deceased donor transplant recip versus wait-listed dialysis patients older than 70 years of age, 1990 2005 Group Deaths per 100 patient years at risk (unadjusted) Wait-listed patients Deceased donor transplant Overall mortality RR compared with wait-listed patients 95% All (age 70 yr) 15.8 13.2 0.59 a (0 Age 70 74 yr 15.3 12.9 0.58 a (0 Age 75 yr 17.8 15.0 0.67 b (0 Glomerulonephritis 13.0 13.6 0.89 (ns) (0 Diabetes 18.5 14.5 0.53 a (0 Hypertension 15.0 12.8 0.56 a (0 Other ESRD cause 15.2 10.6 0.49 a (0 Rao, Short et al. Transplantation wait OPO: 700 dapril 27, 2007 15.3 12.5 0.52 a (0 Medium wait OPO: 700 1350 d 14.9 13.5 0.61 a (0 Long wait OPO: 1350 d 16.4 13.6 0.58 a (0 a P 0.0001. b P 0.05.
Age is the Major Predictor of Graft Failure Faravardek, et, al. Transplantation 2013
Projected Life Expectancy After ESRD Onset: Effect of Time on Dialysis Schold, et al. Clin J Am Soc Neph 2006
Quality of Life in Older Kidney Transplant Recipients 100 80 KTx recipient 18-64 years National norm 100 80 KTx recipient 65 years National norm SF Score 60 40 SF Score 60 40 20 20 0 PF RP BP GH VT SF RE MH 0 PF RP BP GH VT SF RE MH PF=physical functioning, RP=limitation due to health, BP=body pain, GH=general health,! VT=vitality, SH=social functioning, RE=emotional role, MH=mental health!! Humar, et al. Experimental and Clinical Transplantation, 2003
Cost Effectiveness of Kidney Transplant in the Elderly In the general ESRD population kidney transplant is highly cost effective! In the elderly:! living donor transplantation is cost effective! deceased donor transplantation is economically attractive if < 2 year wait and variable with a 2-4 year wait! deceased donor kidney transplantation is not cost effective if wait time is extended 4 years
Outcomes of Transplants From Older Living Donors to Older Recipients: Recipient Outcomes Table 3. Transplant Outcomes by Donor Type OLD YLD ECD SCD P No. 1,133 5,873 4,551 12,197 DGF (%) 6.0 4.6 32.8 22.6 0.001 Primary nonfunction (%) 0.44 0.37 3.0 1.0 0.001 Acute rejection (%) At discharge 4.9 3.9 6.9 5.0 0.001 At 1 y 28.5 21.7 30.7 23.7 0.001 Mean SCr 1 y posttransplantation (mg/dl) 1.6 0.54 1.4 0.45 1.9 0.74 1.4 0.53 0.001 SCr 1.5 mg/dl at 1 y posttransplantation (%) 63.6 43.7 77.3 49.4 0.001 Mean egfr at 1 y posttransplantation (ml/min/1.73 m 2 ) 46.1 14.4 56.3 18.1 41.7 16.4 56.5 20.6 0.001 Note: Serum creatinine in mg/dl may be converted to DGF = delayed graft function! OLD = older living donor (>55 mean age = 61)! YLD = younger living donor (<55, mean age = 39)! ECD = expanded criteria donor! SCD = standard criteria donor mol/l by multiplying by 88.4; egfr in ml/min/1.73 m 2 may be Gill, et al. AJKD 2008
larly given their poor outcomes while on the Figure 2. Patient survival by donor type. Abb tions: OLD, older living donor; YLD, younger living transplant wait list.3 During the study period ECD, expanded criteria deceased donor; SCD, sta 1996 to 2005, a total of 30% of recipients older criteria deceased donor. Outcomes of Transplants From Older Living Donors than 60 years underwent living donor transplantation (17% from donors! 55Recipients: years). This Recipient donor transplantations to Older Outcomes in the elderly and a represents a growing trend of increased living creasing trend to use organs from OLDs. Here, we show that recipients ofgilltransp et al Graft Survival Patient Survival from OLDs (defined as donor age! 55 y had superior allograft and patient survival for reoperation or readmission to the hospipared with recipients of both SCD and ostoperative hypertension, and other unspecitransplants. Recipients of transplants from O omplications. Of 253 OLDs, 244 (96.4%) had lower rates of delayed graft function o reported acute complications. By comparimary nonfunction, and acute rejection comp of 1,331 YLDs, 1,294 (97.2%) had no rewith recipients of ECD transplants. Alth d acute complications. Of those with rerecipients of transplants from OLDs had gr d complications, there were no significant SCr levels at 1 year posttransplantation ences between OLDs and YLDs. pared with recipients of transplants from Y and SCDs, they had superior renal function DISCUSSION pared with recipients of ECD transplants. e long wait times for kidney transplants These results are in keeping with pre a significant impact on the elderly, particusingle-center and retrospective studies exa given their poor outcomes while on the Figure 2. Patient survival by donor type. Abbreviations: OLD, older living donor; YLD, younger living donor; plant wait list.3 During the study period ECD, expanded criteria deceased donor; SCD, standard to 2005, a total of 30% of recipients older criteria deceased donor. Gill, et al. AJKD 2008 60 years underwent living donor transplan(17% from donors! 55 years). This
Outcomes of Transplants From Older Living Donors to Older Recipients: Donor Outcomes Post donation estimated GFR Donors <60 Post donation estimated GFR Donors >60 539 donors, 1994-2006! Percent decline in GFR was not different between older and younger donors. Older donors had lower GFR pre-donation! No difference in donor survival Dols, et al. Am J Transplantation 2011
Older Kidney Donors Older donors have similar outcomes to younger donors: operative time, blood loss, length of stay, complications, change in GFR.! Older donors are less likely than younger donors to have enough time for risk factors, such as HTN, to lead to kidney disease.! OPTN (Organ Procurement & Transplantation Network) data show that most donors who develop renal failure and are placed on the recipient wait list are between 18-34 years and developed ESRD >15 years after donation.
Cumulative time on the wait-list (yr) 1 3 5 0.19 0.52 0.71 0.12 0.40 0.60 0.14 0.32 0.53 0.10 0.31 0.55 0.06 0.22 0.49 0.06 0.21 0.43 0.33 0.66 0.81 0.14 0.54 0.75 0.16 0.39 0.52 0.09 0.34 0.57 0.07 0.29 0.53 0.09 0.28 0.45 PRA, panel reactive antibody. Probability of Transplantation: Effect of Wait Time Table 6. Probability of death on the wait-list or removal from the wait-list by age and race Recipient Age (yr) 18 39 Race Cumulative time on the wait-list (yr) 1 3 5 40 49 50 59 $60 White Black Other White Black Other White Black Other White Black Other 0.03 0.13 0.26 0.01 0.06 0.17 0.02 0.07 0.18 0.04 0.16 0.29 0.01 0.08 0.19 0.02 0.08 0.19 0.06 0.20 0.36 0.02 0.11 0.24 0.04 0.13 0.26 0.07 0.27 0.47 0.03 0.14 0.31 0.03 0.15 0.36 Chang, et al. CJASN 2012
Half of Kidney Transplant Candidates Older than 60 Placed on the Waiting List Will Die before Receiving a deceased Donor Transplant Table 1. Proportion of older candidates who received a deceased-donor transplant and proportion of patient deaths at 5 yr after listing (1995 through 2007) a Patient Characteristic Level (%) 5-yr Probability of DDTx (%) b 5-yr Probability of Mortality (%) c Age 60 to 64 (50) 61 49 65 to 69 (34) Schold, et al. CJASN 2009 61 53 70 (17) 59 57 Primary diagnosis Diabetes (37) 54 58 Hypertension (20) 60 49 Other (43) 67 40 BMI 13 to 25 (29) 62 54 Registry data: 54,669 wait listed candidates over age 60, 1995-2007 Schold, et al. Clin J Am Soc Neph, 2009
Deceased vs. Living Donors in the Elderly
Benefit of Accepting High Infection Risk Donor Chow, et al, Am J Transplantation, 2013 Modeling of 65 yo, diabetic, 5 yrs to non-ird transplant Worst-case model: IV drug user donor (highest risk donor), assumes standard false neg rate with ELISA & 100% transmission and seroconversion from of infected donors
Risk of Immunosuppression in Elderly Kidney Recipients USRDS/UNOS Data Meier-Kriesche, et al. Transplantation 2000
Risk of Immunosuppression in Elderly Kidney Recipients Increased infection - opportunistic infectious death increased 8.7 times! Increased cancer! Decreased rejection rates, but possibly more difficult to treat rejection as chronic graft loss is higher in the elderly! Avoid lymphocyte depleting antibody induction (Campath, Thymoglobulin) which creates a dilemma in the highly HLA sensitized older recipient
Evaluation Issues in Elderly Transplant Candidates Conventional Factors - all increased in the elderly! Cardiac - CAD, CHF, Pulmonary HTN! Infection! Malignancy! Additional Issues Important in the Elderly! Cognitive Impairment! Functional Status! Frailty
Cognitive Impairment in Elderly Transplant Candidates Cognitive Impairment!! 10-30% of young and mid aged dialysis patients!! 30-55% of dialysis patients over 75 years!! Spousal support often lacking in the elderly
Decreased Functional Status is Associated with Death in Elderly Transplant Recipients UNOS data, >10,000 patients, SF-36 measurement data Reese, et al. Transplantation, 2013
Overconfidence
Frailty Definition - 3 or more! Unintentional weight loss (10 lbs. in 1 yr.)! Weakness (grip strength)! Slow walking speed (15 ft. in <6-7 sec)! Low physical activity! Self reported exhaustion
2010 Renal Physicians Association guideline on the appropriate initiation and withdrawal of dialysis (2,15) provides guidance in shared decision-making, advance care planning, prognosis evaluation, and palliative care and has been shown to be effective in improving nephrologists preparedness in EOL decision-making (16). death (2.24). Of those patients who tested positive for frailty, 27% had neither ADL disability nor comorbidity (two or more comorbidities). Additionally, those patients who were prefrail at baseline (46.6%) had an adjusted odds ratio of 2.63 of becoming frail in the next 3 4 years compared with those patients who had no frailty components (17). It must be emphasized that the operational definition of frailty varies widely according to the conceptual framework, and no gold standard exists (14,26). At what point does frailty become advanced or irreversible? Like the EOL concept (27,28), frailty can be viewed Mortality in Frail Elderly Dialysis Patients Consequences of Frailty for the Elderly Patient with Renal Disease The geriatric syndrome of frailty is a biologic wasting syndrome of older adults that spans multiple physiologic Table 1. Mean life expectancy by quartile following dialysis initiation according to age and renal phenotype Renal Phenotype Quartiles 25th Percentile (0 25; frail) 50th Percentile (25 75; vulnerable) 75th Percentile (75 100; healthy) Adapted from reference 33, with permission. Tamura, et al. Kidney Int, 2012 Life Expectancy by Age Group (yrs) 65 69 70 74 75 79 80 84 85 89 901 0.9 2.5 4.6 0.7 2.1 4.3 0.5 1.7 3.7 0.4 1.3 3.0 0.3 0.9 2.3 0.2 0.6 1.7
Frailty in Elderly Kidney Transplant Candidates Little specific data in kidney transplant population! Frailty is associated with:! Peri-operative complications! Length of stay and early readmission! Delayed graft function
Kidney Transplant In The Elderly: Summary Select elderly candidates likely to benefit from transplant with thoughtful individual review! Less focus on age and more attention to functional status! Predict wait time - no survival benefit beyond four years. Highly HLA sensitized elderly pose a problem! Half of all patients over 60 on the wait list will die before receiving a transplant! Best outcome = living donor! Elderly patients without living donors must consider older deceased donors and CDC high risk donors