Elderly Kidney Transplant Recipients Research Articles

Optimizing outcomes in elderly kidney transplant recipients

New data suggest that the survival of elderly kidney transplant recipients is better than that of the general elderly population. These findings draw attention to the growing category of elderly patients with end-stage renal disease who require an enhanced depiction of their risk profile for renal transplantation.

Recipient‐related predictors of kidney transplantation outcomes in the elderly

It is not clear whether in old people with end-stage renal disease kidney transplantation is superior to dialysis therapy. We compared mortality rates between kidney transplant recipients (KTRs) and the general population across different age categories. We also examined patient and allograft survival in 15667 elderly KTRs (65-<90yr old, 36% female) within three age subgroups (65-<70, 70-<75, and ≥75yr). The rise in the relative risk of death in older age groups was substantially less in KTRs than in the general population, that is, 1.8 and 2.0 vs. 21.4 and 76.6 in those aged 65-<75 and ≥75yr, respectively, compared with 15- to <65-yr-old people (reference group). In 65- to <70-yr-old KTRs, obesity (BMI>30kg/m(2) ) was associated with 19% higher risk of graft failure (HR: 1.19 [1.07-1.33], p=0.002). Diabetes was a predictor of worse patient survival in all age groups but poorer allograft outcome in the youngest age group (65-<70yr old) only. None of the examined risk factors affected allograft outcome in the oldest group (≥75yr old) although there was a 49% lower trend of graft failure in very old Hispanic recipients (HR: 0.51 [0.26-1.01], p=0.05). Kidney transplantation may attenuate the age-associated increase in mortality, and its superior survival gain is most prominent in the oldest recipients (≥75yr old). The potential protective effect of kidney transplantation on longevity in the elderly deserves further investigation.

Evaluating Safety and Efficacy of Rabbit Antithymocyte Globulin Induction in Elderly Kidney Transplant Recipients

The optimal immunosuppression regimen for elderly kidney transplant recipients is poorly defined. We sought to evaluate the short-term efficacy and safety of thymoglobulin in geriatric recipients of deceased-donor kidneys. A single-center, retrospective analysis was undertaken between elderly (≥ 65 years) (n=137) and nonelderly (n=276) kidney transplant recipients who received rabbit antithymocyte globulin induction and calcineurin inhibitor, mycophenolic acid, and prednisone maintenance. The mean age was 70 versus 52 years. Fewer elderly patients had an earlier transplant or panel reactive antibodies > 20%, but had more machine perfused, older, and extended criteria donor kidneys. Elderly patients received lower rabbit antithymocyte globulin (5.4 vs 5.6 mg/kg; P = .04) and initial mycophenolic acid doses (1620 vs 1774 mg; P = .002), and experienced less delayed graft function (31.1% vs 50.0%; P < .001). Death-censored graft survival and graft function at 3 years and biopsy-proven acute rejection at 1 year were comparable; however, there was lower 3-year patient survival in elderly patients. Donor age was the only factor associated with reduced patient survival. Rates of malignancy, infection, or thrombocytopenia were similar; however, leukopenia occurred less frequently in elderly patients (11.7% vs 19.9%; P = .038). Elderly kidney transplant recipients receiving rabbit antithymocyte globulin did not experience different short-term graft survival, graft function or rates of infection, malignancy or hematologic adverse reactions than did nonelderly patients; they experienced fewer episodes of delayed graft function, but had lower 3-year patient survival.

Quantification of the Early Risk of Death in Elderly Kidney Transplant Recipients

To inform decision making regarding transplantation in patients ≥ 65 years, we quantified the early posttransplant risk of death by determining the time to equal risk and equal survival between transplant recipients and wait-listed dialysis patients in the United States between 1995 and 2007 (total n = 25468). Survival was determined using separate multivariate nonproportional hazards analyses in low-, intermediate- and high-risk cardiovascular risk patients. Compared to wait-listed patients with similar cardiovascular risk, standard criteria (SCD) and expanded criteria (ECD) recipients had a higher risk of death in the perioperative and early-posttransplant period. In contrast, low and intermediate risk living donor (LD) recipients had an immediate survival advantage compared to similar risk wait-listed patients. In all risk groups, transplantation was associated with a long-term survival advantage compared to dialysis, but there were marked differences in time to equal risk of death, and time to equal survival by donor type. For example, survival in high-risk recipients of an LD, SCD and ECD transplant became equal to that in similar risk wait-listed patients 130, 368 and 521 days after transplantation. Early posttransplant mortality risk is eliminated in low- and intermediate-risk patients, and markedly reduced in high-risk patients with LD transplantation.

Delayed Graft Function Is Associated with an Increased Risk of Early Death Post-Transplant in Elderly Kidney Transplant Recipients

The proportion of elderly kidney transplant recipients worldwide continues to grow over time. Even in patients aged over 70, transplantation confers a long-term survival benefit compared to dialysis. However, there remains a higher risk of death in the first 125 days post-transplant in these patients. Therefore, understanding risk factors for death early post-transplant is important in the elderly. In most regions, elderly patients are more likely to receive a deceased donor transplant kidney from older donors, which may confer a DGF. We sought to examine the impact of DGF on early post-transplant survival in elderly transplant recipients. Methods: Using data from the USRDS, we utilized Cox PH models to examine the association of DGF with death within the first 6 months post-transplant in deceased donor kidney transplant recipients aged 18-39 (n=17,366), 40-49 (n=18,047), 50-59 (n=21,333), 60-69 (n=15,333), and 70+ years (n=4308) during 1997-2007. Results: The incidence of DGF was similar in all age groups, ranging from 20-23%. The table outlines the hazards for death in the first 6 months post-transplant in those with DGF compared to those without DGF in each age group, unadjusted and adjusted for donor, recipient, and transplant factors. In each model, DGF was associated with a higher hazard of death within the first 6 months in recipients aged 70 and older, whereas this was not seen in other age groups.Table: [Hazard for Death (including death after graft loss]Conclusions: DGF is associated with a higher risk of death in the early post-transplant period in elderly recipients. These results highlight the need to tailor allocation of organs and peri-operative management in the elderly to minimize the risk DGF and its associated impact on early death post-transplant.

Delayed Graft Function Is Associated with an Increased Risk of Early Death Post-Transplant in Elderly Kidney Transplant Recipients

Delayed Graft Function Is Associated with an Increased Risk of Early Death Post-Transplant in Elderly Kidney Transplant Recipients

Examining Survival Gain of the Elderly Kidney Transplant Recipients Compared to General Population in the US

Examining Survival Gain of the Elderly Kidney Transplant Recipients Compared to General Population in the US

Poor Outcomes in Elderly Kidney Transplant Recipients Receiving Alemtuzumab Induction

Introduction: Alemtuzumab and rabbit antithymocyte globulin (rATG) are being used with increasing frequency as induction agents in kidney transplantation. Using the US Renal Data Base System, we analyzed the safety profile of these agents in the elderly. Methods: In a cohort of patients transplanted from January 2000 to July 2009 and followed through 2009, we assessed the effect of induction on allograft loss and death among elderly recipients. Recipients were censored at dates of allograft loss, death or the end of study. Independent associations between induction agents and allograft loss or death were examined using multivariate analysis with forward stepwise Cox regression. Results: Among 130,402 patients with first transplants, 14,907 were age 65 years or older. 4,466 (30%), 3,049 (20.5%), 1,501 (10.1%), and 999 (6.7%) were induced with thymoglobulin, basiliximab, daclizumab, and alemtuzumab, respectively. After adjusting for baseline differences, induction with alemtuzumab was associated with an increased risk of graft loss and death, with an adjusted hazard ratio (AHR) of 1.26 (95% CI 1.08–1.48). Risk was also present at other age cutoffs [age >60 (AHR 1.16; 95% CI 1.03–1.31; p = 0.014), age >70 (AHR 1.43; 95% CI 1.13–1.81; p = 0.003) and age >75 (AHR 1.68; 95% CI 1.07–2.63; p = 0.024)]. Conclusions: In the elderly, alemtuzumab is associated with an escalating risk of death and graft loss in recipients of kidney transplantations.

Age, exclusion criteria, and generalizability of randomized trials enrolling kidney transplant recipients.

The proportion of elderly (≥65 years) kidney transplant recipients (KTRs) doubled in the United States from 1999 to 2008. Given higher mortality, more medication side effects, and less rejection among elderly KTRs, optimal care of these patients may require tailored decisions about transplant therapeutics. It is unknown whether participants in transplant clinical trials-which generate the best evidence for patient care-are representative of the aging population of KTRs. Using PubMed, we identified randomized trials involving KTRs from 1999 to 2008 and determined age-exclusion criteria and the mean age of participants. The mean age of these trial participants was compared with the mean age of the overall population of incident KTRs in the United States. The 87,222 participants in 573 trials were significantly younger than the US KTR population (P<0.05). This age discrepancy worsened over the study period (during the years 2006 to 2008, the mean age was 45 years for trial participants versus 50 years for US KTRs, P<0.05). Thirty percent of trials had an exclusion criterion based on older age, and 16% excluded recipients aged 65 years or older. In multivariable regression, immunosuppression trials (P<0.01) and trials in higher impact journals (P=0.03) were more likely to exclude the elderly, but there was no significant difference in exclusion of elderly patients based on a trial's geographic location. Trial participants are younger than KTRs in the United States and many trials exclude older patients. Transplant investigators should make strong efforts to recruit patients across the total age spectrum.

Risk variables associated with the outcome of kidney recipients &gt;70 years of age in the new millennium

New and more potent immunosuppressive protocols have markedly reduced the occurrence of rejections following organ transplantation. Accordingly, survival of elderly kidney transplant recipients has been substantially improved in the new millennium. The present study was performed to identify variables associated with the outcome of kidney transplant recipients >70 years of age in the modern era. A single center retrospective study was performed, evaluating clinical and survival data from all patients >70 years of age receiving their first kidney transplant between 2000 and 2005. Survival data were analyzed using Cox proportional hazard models and the Kaplan-Meier method. During the time period, 160 recipients >70 years of age received their first transplant. The following factors were negatively associated with patient survival: age at transplantation; hazard ratio (HR) 1.09 per year, 95% confidence interval (CI) (1.01-1.18), time on dialysis before transplantation; HR 1.29 per year 95% CI (1.06-1.59) and presence of diabetes at transplantation; HR 1.78 95% CI (1.00-3.16). Thirty-five patients (22%) experienced an acute rejection episode during the first 90 days post-transplant. Acute rejection episodes did not influence on patient or graft survival. Patients with post-transplant pathological oral glucose tolerance test (OGTT) at 10 weeks after transplantation had significantly inferior survival compared to patients with normal OGTT. In a population of kidney transplant recipients >70 years of age with relatively low incidence of acute rejection episodes, age, time on dialysis before transplantation, concomitant diabetes mellitus and development of a pathological OGTT 10 weeks after transplantation were associated with inferior patient survival.

The impact of reduced immunosuppression on graft outcomes in elderly renal transplant recipients

Optimal immunosuppression (IS) for elderly kidney transplant recipients is unknown. We conducted a retrospective cohort study of recipients aged 60 yr or older to examine the impact of reduced IS on graft outcomes. Group 1 patients (n = 101) were initiated on mycophenolate mofetil 2 g/d and tacrolimus, target level 10-12 ng/mL; Group 2 patients (n = 88) with 1 g/d and 8-10 ng/mL, respectively. Dose adjustments were made as required. The groups were comparable except for diabetes, end-stage renal disease duration, and induction. Mycophenolate mofetil dose was reduced in 62% and 38% of the patients, respectively (p < 0.01). Patients were followed for 23.8 +/- 14.2 and 21.3 +/- 11.8 months post-transplant (p = 0.2). Twenty-seven cases in Group 1 (26.7%) and eight in Group 2 (9.1%) lost their grafts (p = 0.01); 19 (18.8%) and 7 (8.0%) cases in each group because of death, respectively (p = 0.09). Sixteen patients in Group 1 (15.8%) and 18 in Group 2 (20.5%) experienced acute rejection (p = 0.36). Patients in Group 2 had a lower risk of graft loss compared with those in Group 1 [adjusted hazard ratio (HR): 0.27, p = 0.006, 95% CI: 0.11-0.69]. There were no significant differences between the groups regarding graft function, BK virus nephropathy, and CMV infection. Our results suggest that reduction in overall IS in this group was associated with improved graft and patient survival.

Calcineurin Inhibitor-Free Immunosuppressive Strategy in Elderly Recipients of Renal Allografts From Deceased Donors: 1-Year Results From a Prospective Single Center Trial

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.

Clinical Outcomes in Elderly Kidney Transplant Recipients are Related to Acute Rejection Episodes Rather Than Pretransplant Comorbidity

Deciding whether an elderly patient with end-stage renal disease is a candidate for kidney transplantation can be difficult. We aimed to evaluate pre- and early posttransplant risk factors that could predict outcome in elderly kidney recipients. Data from all elderly (>or= 70 years, n=354), senior (60-69 years, n=577), and control (45-54 years, n=563) patients receiving their first kidney transplant at our center from 1990 to 2005 were retrieved. Patient and graft survival were analyzed in a Cox model addressing the common risk factors including Charlson comorbidity index (CCI), pretransplant dialysis time, and early acute rejection episodes. Acute rejection in the first 90 days, Hazard ratio (HR) 1.74 (1.34-2.25); time on dialysis, HR 1.02 (1.01-1.03) per month; and donor age more than 60 years, HR 1.52 (1.14-2.01) predicted mortality in the elderly. CCI score did not predict mortality in the elderly, HR 1.05 (0.98-1.12); but did so both in senior, HR 1.17 (1.08-1.27) and control recipients, HR 1.33 (1.19-1.48). Delayed graft function, HR 3.69 (2.01-6.79); donor age more than 60 years, HR 2.42 (1.30-4.49); and presence of human leukocyte antigen antibodies, HR 3.96 (1.38-11.37) were independent predictors for death-censored graft loss in the elderly. Adequate immunosuppression with low frequency of rejection episodes improves the outcome for elderly kidney recipients as does a reduction of time on dialysis. CCI score at transplantation does not seem helpful in the selection of elderly patients for kidney transplantation but plays a significant role in patients under 70 years of age.

Reduced Elimination of Cyclosporine A in Elderly (&gt;65 Years) Kidney Transplant Recipients

Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients. Twenty-five renal transplant recipients on CsA treatment were included in the study. CsA doses were adjusted by C2 monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n=11, mean 73 years) and younger: 18 to 64 years (n=14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABCB1 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABCB1 expression were performed in all patients. Elderly patients achieved target C2 levels with lower CsA doses than the younger patients (4.3+/-0.8 vs. 6.1+/-2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7+/-5.1 vs. 30.5+/-11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABCB1 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics. The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.

Long-term results of a calcineurin inhibitor-free immunosuppression based on Thymoglobulin(R) and mycophenolate mofetil in elderly kidney transplant recipients

Long-term results of a calcineurin inhibitor-free immunosuppression based on Thymoglobulin(R) and mycophenolate mofetil in elderly kidney transplant recipients

Prospective Age-Matching in Elderly Kidney Transplant Recipients—A 5-Year Analysis of the Eurotransplant Senior Program

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Modifiable Factors Predicting Patient Survival in Elderly Kidney Transplant Recipients

No AccessJournal of UrologyAdult urology1 Feb 2006Modifiable Factors Predicting Patient Survival in Elderly Kidney Transplant Recipients H. Cardinal, M.J. Hébert, E. Rahme, I. Houde, D. Baran, M. Masse, A. Boucher, J. Le Lorier, and Elderly Recipients Transplant Group H. CardinalH. Cardinal More articles by this author , M.J. HébertM.J. Hébert More articles by this author , E. RahmeE. Rahme More articles by this author , I. HoudeI. Houde More articles by this author , D. BaranD. Baran More articles by this author , M. MasseM. Masse More articles by this author , A. BoucherA. Boucher More articles by this author , J. Le LorierJ. Le Lorier More articles by this author , and Elderly Recipients Transplant Group More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)00364-2AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Modifiable Factors Predicting Patient Survival in Elderly Kidney Transplant Recipients." The Journal of Urology, 175(2), p. 649 Nephrology and Pharmacoepidemiology Departments, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Division of Clinical Epidemiology, Nephrology Department, McGill University Health Center, McGill University and Nephrology Department, Hopital Maisonneuve-Rosemont, Montréal and Nephrology Departments, Centre Hospitalier de l’Université Sherbrooke, Université Sherbrooke, Sherbrooke and Centre Hospitalier de l’Université Laval, Université Laval, Quebec, Quebec, Canada© 2006 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 2February 2006Page: 649 Advertisement Copyright & Permissions© 2006 by American Urological AssociationMetricsAuthor Information H. Cardinal More articles by this author M.J. Hébert More articles by this author E. Rahme More articles by this author I. Houde More articles by this author D. Baran More articles by this author M. Masse More articles by this author A. Boucher More articles by this author J. Le Lorier More articles by this author Elderly Recipients Transplant Group More articles by this author Expand All Advertisement PDF DownloadLoading ...

Modifiable factors predicting patient survival in elderly kidney transplant recipients

Elderly transplant candidates represent an increasingly important group on the waiting list for kidney transplantation. Yet the factors that determine posttransplantation outcomes in this population remain poorly defined. We performed a population-based retrospective cohort study involving all patients aged 60 years or older who received a first cadaveric kidney transplantation between 1985 and 2000 in the province of Quebec. The main outcomes were patient survival, overall graft survival, and treatment failure (patient death or graft loss within the first posttransplant year). Survival analyses were performed using a Cox proportional hazard model. Logistic regression identified factors predicting treatment failure. On multivariate analysis, the modifiable factors associated with patient survival were active smoking at transplantation [hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.22-3.60)], body mass index (BMI) (HR 1.34 for a 5-point increase, 95% CI 1.05-1.67), and time on dialysis before transplantation (HR 1.10 for a 1-year increase, 95% CI 1.02-1.18). The only modifiable factor associated with graft survival was active smoking at transplantation (HR 2.04, 95% CI 1.24-3.30). Treatment failure was associated with time on dialysis before transplantation (odds ratio for dialysis >/=2 years 3.28, 95% CI 1.34-7.9). Our results show that active smoking, obesity, and time on dialysis before transplantation are modifiable risk factors associated with an increased risk of mortality after transplantation in elderly recipients. They represent potential targets for interventions aimed at improving patient and graft survival in elderly patients.