Elderly Kidney Transplant Recipients Research Articles

Immunoreactivity of CD3+CD4+ in Stable Young, Middle Aged, and Elderly Kidney Transplant Recipients Receiving Maintenance Tacrolimus and Mycophenolic Acid Immunosuppression

Immunoreactivity of CD3+CD4+ in Stable Young, Middle Aged, and Elderly Kidney Transplant Recipients Receiving Maintenance Tacrolimus and Mycophenolic Acid Immunosuppression

Observational study of risk factors associated with clinical outcome among elderly kidney transplant recipients in Sweden – a decade of follow‐up

Kidney transplantation (Ktx) in elderly has become increasingly accepted worldwide despite their higher burden of comorbidities. We investigated important risk factors affecting long-term patient and graft survival. We included all (n = 747) Ktx patients >60 years from 2000 to 2012 in Sweden. Patients were age-stratified, 60-64, 65-69 and >70 years. Follow-up time was up to 10 years (median 7.9 years, 75% percentile >10 years). Primary outcome was 10-year patient survival in age-stratified groups. Secondary outcomes were 5-year patient and graft survival in age-stratified groups and the impact of risk factors including Charlson comorbidity index (CCI) on patient and graft survival. Mortality was higher in patients >70 years, after 10 years (HR 1.94; 95% CI 1.24-3.04; P = 0.004). Males had a higher 10-year risk of death (HR 1.39; CI 95% 1.04-1.86; P = 0.024). Five-year patient survival did not differ between age groups. In multivariate Cox analysis (n = 500), hazard ratio for 10-year mortality was 4.6 in patients with CCI ≥7 vs. <4 (95% CI 2.42-8.62; P = 0.0001). Higher CCI identified ESKD patients with 4.6 times higher risk of death after Ktx. We suggest that this index should be used as a part of the preoperative evaluation in elderly.

MP37-18 PHARMACOKINETICS OF IMMUNOSUPPRESSANTS AMONG YOUNG, MIDDLE, AND ELDERLY KIDNEY TRANSPLANT RECIPIENTS: ITS IMPACT FOR CLINICAL OUTCOMES

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery I (MP37)1 Sep 2021MP37-18 PHARMACOKINETICS OF IMMUNOSUPPRESSANTS AMONG YOUNG, MIDDLE, AND ELDERLY KIDNEY TRANSPLANT RECIPIENTS: ITS IMPACT FOR CLINICAL OUTCOMES Ryuichiro Sagehashi, Mitsuru Saito, Takuro Saito, Ryohei Yamamoto, Nobuhiro Fujiyama, Souki Kashima, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, Shintaro Narita, Shigeru Satoh, and Habuchi Tomonori Ryuichiro SagehashiRyuichiro Sagehashi More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takuro SaitoTakuro Saito More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Nobuhiro FujiyamaNobuhiro Fujiyama More articles by this author , Souki KashimaSouki Kashima More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Habuchi TomonoriHabuchi Tomonori More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002046.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We investigated that pharmacokinetics of immunosuppressants among young, middle, and elderly kidney transplant recipients and its impact for clinical outcomes. METHODS: A total of 179 pairs of recipients and donors who underwent living kidney transplantation in our institute between November 2009 and April 2019 were enrolled in this study. Recipients were divided into three groups according to age at transplantation: the young (<55 years, 98 patients), middle-aged (55–64 years, 54 patients), and elderly groups (≥65 years, 27 patients). All recipients received the combination therapy, consisting of tacrolimus (TAC), mycophenolate mofetil (MMF), prednisolone (PSL), and basiliximab. Moreover, from October 2013, everolimus (EVR) was added and TAC and MMF doses were reduced after 14 postoperative days. In immunologically high-risk patients, single dose of rituximab at 200 mg/body was administered and 1–4 sessions of antibody removal were performed before transplantation. Doses of immunosuppressants were not arranged according to age of recipients. RESULTS: The age of donor in the elderly group was significantly higher than the other groups (p<0.01, respectively); however, no significant difference in the donors’ renal function was observed among groups. Immunologically high-risk patients in the middle-aged and elderly groups were significantly higher than that in the young group (p=0.01, respectively). In the pharmacokinetic analysis, no significant differences in trough levels and AUC of TAC, MPA, and EVR, were observed among the groups. No infectious death was observed in this cohort, and incidences of hospitalization for infectious events did not differ among groups. In addition, incidences of rejection and de novo malignancies between the young and elderly groups were similar. No significant difference of the death censored graft survival was observed among groups. CONCLUSIONS: In the modern immunosuppressive protocol, the aging process itself may have little effect on the pharmacokinetics of immunosuppressants. It may be necessary to refrain from easy dose reduction of immunosuppressants in elderly kidney transplant recipients . Source of Funding: We have no financial relationships to disclose. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e653-e653 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryuichiro Sagehashi More articles by this author Mitsuru Saito More articles by this author Takuro Saito More articles by this author Ryohei Yamamoto More articles by this author Nobuhiro Fujiyama More articles by this author Souki Kashima More articles by this author Atsushi Koizumi More articles by this author Taketoshi Nara More articles by this author Kazuyuki Numakura More articles by this author Shintaro Narita More articles by this author Shigeru Satoh More articles by this author Habuchi Tomonori More articles by this author Expand All Advertisement Loading ...

Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients

BackgroundIn 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression.MethodsThis open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is ‘successful transplantation’, defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m2 in stratum A and ≥ 45 ml/min per 1.73 m2 in stratum B, after 2 years, respectively.ConclusionsThe OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients.Trial registrationClinicalTrials.gov: NCT03797196, registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019.

Donor type and 3-month hospital readmission following kidney transplantation: results from the Netherlands organ transplant registry

BackgroundHospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs.MethodsWe included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders.ResultsAmong 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly.ConclusionA lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.

Pharmacokinetic and Pharmacodynamic Considerations in Relation to Calcineurin Usage in Elderly Kidney Transplant Recipients.

This review summarizes how possible age-related changes in tacrolimus and cyclosporine pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future. Advancing biological age leads to physiological changes that can affect drug absorption, distribution, metabolism and excretion, as well as immune system responsiveness. Some studies have shown that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors, suggesting that doses may need to be lowered in elderly recipients. Only one study has examined how aging effects drug target enzyme activity and demonstrated that age does not correlate with the calcineurin inhibitor half-maximal inhibitory concentration. Several studies have shown elderly kidney transplant recipients have increased risk of both morbidity and mortality, compared to younger adults due to increased susceptibility to immunosuppressant side effects, particularly cardiovascular disease, infection and malignancy. Current immunosuppressant dosing and monitoring protocols often make no adjustments for age. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established. Blood draw by micro-sampling may be useful for drug monitoring in this cohort in the future, as blood collection is minimally invasive and less painful than venepuncture. Micro-sampling could also make further pharmacokinetic, pharmacodynamics and outcome studies in the elderly more feasible.

Induction Immunosuppressive Therapy for Kidney Transplant in Elderly Recipients: A Single-Center Experience.

The number of elderly kidney transplant recipients is increasing, and age-tailored induction immunosuppression regimens are needed. We compared safety and efficacy of basiliximab versus thymoglobulin at various dosages. Of 590 kidney transplants at our center from 2012 to 2019, 119 (20.1%) were for recipients over 65 years of age; 118 patients received deceased donor kidneys, and 1 received a related living donor kidney. We retrospectively reviewed medical records for demographics, baseline characteristics, donor characteristics, induction regimens, infectious complications, graft function, and patient survival. Patients were subdivided into the following 4 induction immunosuppression groups: basiliximab (n = 15, 12.6%), 3 mg/kg thymoglobulin (n = 8, 6.7%), 4.5 mg/kg thymoglobulin (n = 67, 56.3%), and 6 mg/kg thymoglobulin (n = 29, 24.4%). All patients received pulse doses of methylprednisolone followed by a prednisone taper. Other maintenance immunosuppression agents included tacrolimus and mycophenolic acid. Recipients in the basiliximab and 3 mg/kg thymoglobulin groups were older (median age ⟩70 years; P ⟨ .001). The 4.5 and 6 mg/kg thymoglobulin groups had higher proportions of African American patients and patients with calculated panel reactive antibody over 20%. There were significantly fewer infectious complications in the basiliximab and 3 mg/kg thymoglobulin groups. Despite differences in biopsy-proven acute rejection rates, estimated glomerular filtration rate and graft and patient survival rates at 1 year were similar across groups. All patients with biopsy-proven acute rejection were African American patients. Kidney transplant in patients ≥65 years is safe and feasible. Changes in this unique population's immune system warrant age-tailored regimens. We found that patients at low immunologic risk would benefit from basiliximab orthymoglobulin at 3 mg/kg. Regardless of calculated panel reactive antibodies, African American patients should be considered as high immunologic risk group forrejection, and higher thymoglobulin dosing should be considered.

Factors Influencing Long-Term Patient and Allograft Outcomes in Elderly Kidney Transplant Recipients

IntroductionIndividuals aged ≥65 years are increasingly prevalent on the waitlist for kidney transplantation, yet evidence on recipient and donor factors that define optimal outcomes in elderly patients after kidney transplantation is scarce.MethodsWe used multivariable Cox regression modeling to determine the factors associated with all-cause death, death with a functioning graft, and overall and death-censored graft survival, using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry.ResultsA total of 802 kidney transplant recipients aged ≥65 years underwent their first transplantation between June 2006 and December 2016. Median age at transplantation was 68 years (interquartile range = 66−69 years). The 1-year and 5-year overall patient and graft survivals (95% confidence interval [CI]) were 95.1 (93.5−96.7) and 79.0 (75.1−82.9), and 92.9 (91.1−94.7) and 75.4 (71.3−79.5), respectively. Factors associated with higher risks of all-cause death included prevalent coronary artery disease (adjusted hazard ratio [95% confidence interval] = 1.47 [1.03–2.11]), cerebrovascular disease (1.99 [1.26–3.16]), increasing graft ischemic time (1.06 per hour [1.03–1.09]), donor age (1.02 per year [1.01–1.03]), delayed graft function (1.64 [1.13−2.39]), and peritoneal dialysis pretransplantation (1.71 [1.17–2.51]).ConclusionPrevalent vascular disease and peritoneal dialysis as a pretransplantation dialysis modality are risk factors associated with poorer outcomes in transplant recipients aged ≥65 years. Careful selection and evaluation of potential candidates may improve graft and patient outcomes in older patients.

Clinical outcomes in elderly kidney transplant recipients: emphasis on choice of induction immunosuppressive therapy

Clinical outcomes in elderly kidney transplant recipients: emphasis on choice of induction immunosuppressive therapy

Mortality from cancer is not increased in elderly kidney transplant recipients compared to the general population: a competing risk analysis.

The impact of cancer on death of elderly kidney transplant recipients has been extensively investigated, but with conflicting results. Unlike their younger counterparts, in elderly kidney transplant recipients cardiovascular and infectious disease may outweigh cancer in causing the patient's death. Using competing risk analysis on a large retrospective cohort of kidney transplant recipients, we estimated the cause-specific cumulative incidence and hazard of death in different age categories and calculated standardized mortality ratios (SMRs) to compare mortality rates with the general population. Six thousand seven hundred eighty-nine kidney transplant recipients were followed-up for a median of 9years. Ten years after transplantation, in transplant recipients aged 20-39, 40-59, and 60+, the cumulative incidence of cancer-related death was 0.6 (95% confidence interval [CI]: 0.3-1.0), 2.9 (2.3-3.6) and 5.3% (3.5-7.5), whereas the SMR was 9.1 (5.5-15.0), 2.0 (1.6-2.5), and 0.8 (0.6-1.0), respectively. At variance with young recipients, the hazard and the cumulative incidence of cardiovascular-related death in elderly recipients was well above that of cancer-related death. Relative to the general population, cancer-related death is increased in young but not in elderly kidney transplant recipients because of the more marked increased incidence of competing cause of death in the latter category.

Logistic Regression Model in a Machine Learning Application to Predict Elderly Kidney Transplant Recipients with Worse Renal Function One Year after Kidney Transplant: Elderly KTbot.

Background Renal replacement therapy (RRT) is a public health problem worldwide. Kidney transplantation (KT) is the best treatment for elderly patients' longevity and quality of life. Objectives The primary endpoint was to compare elderly versus younger KT recipients by analyzing the risk covariables involved in worsening renal function, proteinuria, graft loss, and death one year after KT. The secondary endpoint was to create a robot based on logistic regression capable of predicting the likelihood that elderly recipients will develop worse renal function one year after KT. Method Unicentric retrospective analysis of a cohort was performed with individuals aged ≥60 and <60 years old. We analysed medical records of KT recipients from January to December 2017, with a follow-up time of one year after KT. We used multivariable logistic regression to estimate odds ratios for elderly vs younger recipients, controlled for demographic, clinical, laboratory, data pre- and post-KT, and death. Results 18 elderly and 100 younger KT recipients were included. Pretransplant immune variables were similar between two groups. No significant differences (P > 0.05) between groups were observed after KT on laboratory data means and for the prevalences of diabetes mellitus, hypertension, acute rejection, cytomegalovirus, polyomavirus, and urinary infections. One year after KT, the creatinine clearance was higher (P = 0.006) in youngers (70.9 ± 25.2 mL/min/1.73 m2) versus elderlies (53.3 ± 21.1 mL/min/1.73 m2). There was no difference in death outcome comparison. Multivariable analysis among covariables predisposing chronic kidney disease epidemiology collaboration (CKD-EPI) equation <60 mL/min/1.73 m2 presented a statistical significance for age ≥60 years (P = 0.01) and reduction in serum haemoglobin (P = 0.03). The model presented goodness-fit in the evaluation of artificial intelligence metrics (precision: 90%; sensitivity: 71%; and F1 score: 0.79). Conclusion Renal function in elderly KT recipients was lower than in younger KT recipients. However, patients aged ≥60 years maintained enough renal function to remain off dialysis. Moreover, a learning machine application built a robot (Elderly KTbot) to predict in the elderly populations the likelihood of worse renal function one year after KT.

COVID-19 in elderly kidney transplant recipients.

The SARS‐Cov‐2 infection disease (COVID‐19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID‐19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti‐retroviral and tocilizumab. Short‐term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D‐dimer, C‐reactive protein, and IL‐6 at their first tests. COVID‐19 is frequent among the elderly KT population and associates a very early and high mortality rate.

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti-thymocyte globulin vs basiliximab.

Elderly transplant recipients experience lower rates of acute rejection with higher rates of infectious complications compared to their younger counterparts. While less intensive immunosuppression may be preferable, there are no recommendations for depleting versus non-depleting induction strategies. We sought to compare infectious complications between anti-thymocyte globulin (ATG) and basiliximab (IL2RA) induction in elderly kidney transplant recipients (KTRs). We reviewed 146 KTRs ≥65years receiving ATG or IL2RA induction. Per institution protocol, ATG was administered to patients with the following characteristics, irrespective of age: African American (AA), PRA ≥20%, and/or re-transplantation. Infectious complications (bacterial, viral, and invasive fungal) at 1year were compared. There were significantly more AA, deceased donors, and sensitized KTRs in the ATG group, reflecting criteria for induction agent. ATG KTRs experienced higher rates of overall infectious complications (77% vs 56%, P=.01), driven by increased bacterial (54% vs 39%, P=.08) and viral infections (51% vs 35%, P=.05). Urinary tract infections (UTIs) and CMV in particular occurred at high rates among ATG patients (46% and 32%, respectively). In multivariate analysis, the only independent risk factor associated with increased risk for infection was induction with ATG (adjusted HR 1.71 [95% CI 1.04-2.83], P=.04). Overall rates of immunologic outcomes were low. Elderly KTRs receiving ATG are at an increased risk for infectious complications, largely attributed to high rates of UTIs and CMV. Additional strategies aimed at mitigating these complications in elderly patients requiring ATG may be beneficial.

Induction Therapy in Elderly Kidney Transplant Recipients With Low Immunological Risk.

In nonimmunized patients, similar rejection rates are observed for patients who have undergone thymoglobulin (antithymocyte globulins [ATG]) or basiliximab (BSX) therapy. While ATG may improve delayed graft function, it may also be associated with higher infection rates and malignancy risk. We compared survival and clinical outcomes in elderly recipients with low immunological risk according to their induction therapy. We conducted a multicentric study on nonimmunized patients ≥65 years of age receiving a first kidney transplant between 2010 and 2017. The principal outcome was patient and graft survival. Secondary outcomes were cumulative probabilities of infection, first acute rejection episode, malignancy, de novo donor specific antibody, posttransplant diabetes (PTD), cardiac complications, estimated glomerular filtration rate, and occurrence of delayed graft function. Cox, logistic, or linear statistical models were used depending on the outcome studied, and models were weighted on the propensity scores. Two hundred and four patients were included in the BSX group and 179 in the ATG group with the average age of 71.0 and 70.5 years, respectively. Patient and graft survival at 3 years posttransplantation were 74% (95% CI, 65%-84%) and 68% (95% CI, 60%-78%) in ATG and BSX group, respectively, without significant difference. Occurrence of PTD was significatively higher in BSX group (23% versus 15%, P = 0.04) due to higher trough levels of Tacrolimus on month 3 (9.48 versus 7.30 ng/mL, P = 0.023). There was no difference in other evaluated outcomes. In elderly recipients, ATG does not lead to poorer outcomes compared with BSX and could permit lower trough levels of Tacrolimus, thus reducing occurrence of PTD.

Comparison of Alemtuzumab Versus Basiliximab Induction Therapy in Elderly Kidney Transplant Recipients: A Single-Center Experience

Background: The optimal choice of induction immunosuppression for elderly kidney transplant recipients remains unclear. Although alemtuzumab has been associated with escalating risk of death and graft loss in this population, this risk has not been adequately explored. The purpose of this study was to compare the safety and efficacy of alemtuzumab with basiliximab induction in this population. Methods: This is a retrospective matched cohort study of kidney transplant recipients aged ≥65 years. Patients who received alemtuzumab induction were matched (1:2) to a basiliximab control. The primary outcome was allograft survival. The incidence of acute rejection, infection, and all-cause mortality was measured. Results: Fifty-one and 102 patients were included in the alemtuzumab and basiliximab groups, respectively. Baseline demographics were similar between groups, except for more living donor transplant recipients in the alemtuzumab group (26/51 [51%] vs 31/102 [30.4%], P = .02). Acute cellular rejection occurred more frequently within the first year in the basiliximab group (P = .02). There was no difference in rates of infection within the first year. Graft and patient survival rates were similar over the follow-up period. Patients receiving basiliximab had a higher glomerular filtration rate at 2 years posttransplant (59 mL/min/1.73 m2 vs 49 mL/min/1.73 m2, P = .03). Conclusions: Alemtuzumab induction is associated with similar outcomes to basiliximab in elderly kidney transplant recipients.

Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population.

There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26±2y), healthy elderly (HEld) (n=15, 79±7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36±7y) and ESRD elderly (EnEld) (n=31, 65±3y) prior to Ktx regarding their naïve, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4+ memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required. (ClinicalTrials.gov number: NTC01631058).

Combination Therapy with BCAA Intake and Physical Therapy Improved Leg Strength in Japanese Elderly Kidney Transplant Recipients Diagnosed as Sarcopenia

Combination Therapy with BCAA Intake and Physical Therapy Improved Leg Strength in Japanese Elderly Kidney Transplant Recipients Diagnosed as Sarcopenia

Holistic Long-Term Care Over Elderly Kidney Transplant Recipients

Kidney transplantation is an optimal method of renal replacement therapy in patients with phase V chronic kidney disease. Elderly patients (older than 60 years) with a kidney transplant create a significant and constantly growing pool of patients with this type of organ transplantation. In this group of patients, long-term care should be particularly stringent and vigilant. Apart from typical conditions associated with chronic kidney disease and possible post-transplant complications as well as side effects of immunosuppressive treatment, the patient also experiences changes and limitations associated with the progress of age and diseases typical for old age, characterized by a higher risk of infection, and changed pharmacokinetics/pharmacodynamics. Undoubtedly, patients should remain under the medical care of qualified transplantologists, but constant cooperation with a general practitioner and geriatrician would be of added value. Study results show that although most of the elderly kidney recipients have constant contact with their general practitioners, and almost half of them use private care, contribution of the geriatrician to the transplant care system is unsatisfactory, and elderly kidney recipients would expect more extensive outpatient care.

Estimated glomerular filtration rate in stable older kidney transplant recipients-are present algorithms valid? A national cross-sectional cohort study

Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine-based equations in stable elderly KTR. A national cross-sectional study was performed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different creatinine-based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equation. All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMRCR , and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMRCR , and MDRD in recipients 60-69 years old had nonsignificant bias. The CKD-EPI had significant bias in both groups. If one should choose a single equation for follow-up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMRCR equations are probably the best alternatives.

Sirolimus Associated with Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial.

There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimus-mycophenolate (23 patients). Cytomegalovirus infection rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.