Young Kidney Research Articles

Elevated Septal Native T1 Time in CMR Imaging Suggesting Myocardial Fibrosis in Young Kidney Transplant Recipients.

Patients after kidney transplantation (KTx) in childhood show a high prevalence of cardiac complications, but the underlying mechanism is still poorly understood. In adults, myocardial fibrosis detected in cardiac magnetic resonance (CMR) imaging is already an established risk factor. Data for children after KTx are not available. This study aimed to explore cardiac function and structure with focus on myocardial fibrosis and associated risk factors in KTx recipients. 46 KTx recipients (mean age 16.0 ± 3.5 years) and 46 age- and sex-matched healthy controls were examined with non-contrast CMR imaging. Native T1 time (nT1), a marker for myocardial fibrosis, was measured at the interventricular septum. Other parameters comprised left ventricular mass index (LVMI), ejection fraction (LVEF), and global longitudinal strain (GLS). Multivariable linear regression analyses were used to explore associations with nT1. Mean nT1 was significantly higher in KTx recipients than in controls (1198.1±48.8ms vs. 1154.4±23.4ms, p<0.0001). Twenty-one (46%) had a nT1 above above the upper limit of the normal range (mean + 2SD of controls). KTx recipients showed higher LVMI z-scores (0.1±1.1 vs. -0.3±0.7, p=0.026), higher LVEF (67.3±3.8% vs. 65.3±3.6%, p=0.012), and lower GLS (-19.0±2.1% vs. -20.3±2.7%, p=0.010). Higher systolic blood pressure (SBP; ß=1.284, p=0.001), LVMI (ß=1.542, p<0.001), and LVEF (ß=3.535, p=0.026) were associated with longer nT1 only in KTx recipients, but not in controls. Only two KTx recipients exhibited left ventricular hypertrophy, however, a total of 18 displayed elevated nT1 with LVMI z-score within the normal range. Our data suggest the presence of cardiac remodeling with myocardial fibrosis in a significant proportion of young KTx recipients. Non-contrast CMR imaging has the potential to visualize early structural cardiac changes and could become an important diagnostic adjunct in the follow-up of KTx recipients. Longitudinal studies are needed to further evaluate the importance of nT1 in early identification of those at high risk for sudden cardiac death allowing to integrate preventive strategies.

Graft Loss in Pediatric and Young Adult Kidney Transplantation in New Zealand: Who Is at Greatest Risk and When?

Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post-KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA). A retrospective cohort analysis of all first kidney transplant recipients between birth-24 years of age, from 2000 to 2019 in New Zealand. Participant identification and data were obtained via the Australia and New Zealand Dialysis and Transplantation registry. Primary outcome was graft survival stratified by service type. Cox proportional hazard modeling assessed independent risk factors of graft loss. Two hundred forty-four children and AYA with a median follow-up of 7.3 years were included. Graft survival stratified by service provision group was not different. The incidence rate of graft loss was 37, 34, and 45 per 1000 persons per year for PO, PTA, and AO respectively. Crude age-specific graft failure rates were highest for 22-24-year-olds with inferior outcomes starting from age 16, peaking at 24 years. Older adolescence and young adulthood reflect a high-risk period for KT loss. Transfer to adult services was not associated with worse graft survival compared to those experiencing either AO or PO alone. Improved models of care are needed to improve graft survival in this vulnerable population within New Zealand.

347.7: Illness perceptions, medication beliefs and immunosuppression adherence in young adult kidney transplant recipients: A single-centre cohort study and comparative analysis.

347.7: Illness perceptions, medication beliefs and immunosuppression adherence in young adult kidney transplant recipients: A single-centre cohort study and comparative analysis.

365.10: Assessing readiness for transition among adolescent and young adult kidney transplant recipients.

365.10: Assessing readiness for transition among adolescent and young adult kidney transplant recipients.

Non-Maleficence toward Young Kidney Donors: A Call for Stronger Ethical Standards and Associated Factors in Multidisciplinary Nephrology Teams.

The rising frequency of live kidney donations is accompanied by growing ethical concerns as to donor autonomy, the comprehensiveness of disclosure, and donors' understanding of long-term consequences. To explore donors' satisfaction with the ethical competence of multi-professional nephrology teams regarding disclosure of donation consequences to live kidney donors. A cross-sectional study was performed among Israeli live kidney donors who had donated a kidney in two hospitals that belonged to the Ministry of Health's Transplantation Center one year after the donation, from December 2018 to December 2020. Data collection was conducted online and through face-to-face interviews with the donors in their native language (Hebrew or Arabic). Overall, 91 live kidney donors aged 18-49 years were enrolled. Of those, 65.9% were males, and 54.9% were academic donors. Among the live kidney donors, 59.3% reported that the motivation behind the donation was a first-degree family member vs. 35.2% altruistic and 5.5% commercial. Only 13.2% reported that the provided disclosure adequately explained the possible consequences of living with a single kidney. Approximately 20% of the participants reported that the disclosure included information regarding their risk of developing ESRD, hypertension, and proteinuria. The donors reported a low mean of the index score that indicates a low follow-up by the physician after the donation (mean = 1.16, SD = 0.37). The mean GFR level was significantly lower in the post-donation period one year following a kidney donation (117.8 mL/min/1.73 m2) compared with the pre-donation period (84.0 mL/min/1.73 m2), p < 0.001. Our findings display that donors' satisfaction with the ethical competence of multi-professional nephrology teams regarding the disclosure of donation consequences to live kidney donors is low. This study indicates that donors are at an increased risk of worsening kidney functions (creatinine and GFR), and BMI. Our findings underscore the imperative to advise donors that their condition may worsen over time and can result in complications; thus, they should be monitored during short and long-term follow-up periods. This study was not registered.

Older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T cells.

Older recipient age is associated with a significant decreased risk for rejection after kidney transplantation which is incompletely understood. In a longitudinal study, circulating alloreactive T cells were assessed of young (≤45 years) and older (≥55 years) stable kidney transplant recipients. Alloreactive T-cells were identified by CD137-expression and phenotype, cytokine producing and proliferative capacity, were evaluated using multiparameter flowcytometry. The results show that before transplantation frequencies of alloreactive CD4+ and CD8+ T-cells in older KT-recipients are significantly higher and shifted towards an effector memory-phenotype. However, the frequency of polyfunctional (≥2 pro-inflammatory cytokines) CD4+ T-cells was significantly lower and less IL2 was produced. The frequency of polyfunctional alloreactive CD4+ T-cells and proliferation of alloreactive T-cells donor-specifically declined after transplantation reaching a nadir at 12 months after transplantation, irrespective of age. A striking difference was observed for the proliferative response of alloreactive CD8+ T-cells. This was not only lower in older compared to younger recipients but could also not be restored by exogenous IL2 or IL15 in the majority of older recipients while the response to polyclonal stimulation was unaffected. In conclusion, older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T-cells.

Unraveling complexity: morbidity factors in elderly kidney transplant recipients.

The rising prevalence of end-stage renal failure in the elderly has led to an increased number of kidney transplantations in older individuals. While age does not solely determine transplant eligibility, frailty in elderly recipients significantly impacts post-transplant outcomes, particularly within the first year. The RETRAITE (REnal TRAnsplantIon ouTcome in Elderly recipients) study, a single-center retrospective cohort study at Grenoble Alpes University Hospital (France), examined kidney transplant recipients aged 70years and above transplanted between 2015 and 2020. The composite primary endpoint was defined as either of any hospital stay exceeding 40days, death and/or return to dialysis within the first post-transplant year. The study explored risk factors for recipient and graft survival, rejection, hospitalizations over 40days, and severe infections during the initial post-transplant year. Over six years, 149 patients aged 70years or older received transplants. Eleven patients died, and seven returned to dialysis within the first year, corresponding to a 1-year graft survival rate of 87.9%. At 1year, 49 patients (33%) met the composite endpoint. There was a significant association between the composite endpoint and curative anticoagulation [odds ratio (OR) 5.20; P<.001], peripheral arteriopathy (OR 3.14; P<.001) and delayed graft function (OR8.24; P<.001). This cohort then was merged with a cohort of 150 younger kidney transplanted patients and we confirmed these results. Time on dialysis, prolonged cold ischemia and donor age contributed to higher morbidity and mortality. Conversely, preemptive and living donor transplants were associated with lower morbidity and mortality. In this cohort aged over 70years, age alone did not statistically correlate with increased morbidity and mortality. Variables related to grafts and donors, especially curative anticoagulation, were linked to poorer outcomes, emphasizing the favorable impact of preemptive and living donor transplants on morbidity and mortality in elderly patients.

The EKFC equation outperforms the CKD-EPI and CKiD equations for GFR estimation in adolescent and young adult kidney transplant patients.

This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.

#614 Identifying distinct patient phenotypes in patients with chronic kidney disease

Abstract Background and Aims Patients with chronic kidney disease (CKD) are heterogeneous in terms of age, causes of CKD, and comorbidities. Although individual risk factors greatly influence patients’ risk of clinical outcomes, this heterogeneity is rarely used to guide clinical decision-making. In this study we aimed to derive phenotypes in patients with CKD based on characteristics commonly available in routine clinical practice and evaluated whether these phenotypes were associated with clinical outcomes. Method Patients from the Utrecht Patient Oriented Database (UPOD) who were 18 years or older with CKD (defined as an eGFR &amp;lt;60 ml/min/1.73 m2 or an UACR &amp;gt; 3 mg/mmol present for &amp;gt;3 months) and visited one of the cardiovascular outpatient clinics of the University Medical Center Utrecht between 2012 and 2019 were included. Patient phenotypes were derived with latent class analyses based on age, sex, CKD stage, cause of kidney disease, and (cardiovascular) comorbidities. The incidence rate/100 person years (IR/100PY) for all-cause mortality and kidney failure (defined as initiation of kidney replacement therapy or a sustained eGFR &amp;lt;15) and 95% confidence interval (95% CI) was calculated for each phenotype. Results Overall 9005 patients were included (mean age 65 ± 14 years, 42% women, mean estimated glomerular filtration rate (eGFR) 49 ± 17 ml/min/1.73 m2). The median follow-up was 3.8 years [interquartile range 1.8–6.4]. Latent class analysis identified 7 phenotypes with the following characteristics: phenotype 1 were young patients with primary kidney disease (10%); phenotype 2 were patients with diabetes and a preserved eGFR (9%); phenotype 3 were patients with low comorbidity and inflammation (28%); phenotype 4 were older patients with a history of cardiovascular disease (27%); phenotype 5 were older patients with a history of cardiovascular disease and severe CKD (16%); phenotype 6 were younger patients with a kidney transplant and low comorbidity (6%); and phenotype 7 were older patients with a kidney transplant and cardiovascular disease (6%). The risk of all-cause mortality and kidney failure differed significantly between the identified phenotypes. The phenotypes of younger kidney transplant recipients, younger patients with primary kidney disease, and diabetes with preserved eGFR had the lowest risk for all-cause mortality (for all, IR/100 PY &amp;lt;5) (Fig. 1). The phenotypes with an intermediate incidence rate for all-cause mortality were the low comorbidity and inflammation phenotype (IR/100PY 7.4, 95% CI 6.9–8.0), the phenotype of older patients with cardiovascular disease (IR/100PY 7.2, 95% CI 6.7–7.8), and the phenotype of older patients with a kidney transplant and cardiovascular disease (IR/100PY 6.5, 95% CI 5.5–7.6). The phenotypes with highest incidence rate for all-cause mortality was the phenotype of older patients with cardiovascular disease and severe CKD (IR/100PY 12.5, 95% CI11.5–13.4). The phenotypes with the lowest risk for kidney failure were the diabetes phenotype, the low comorbidity and inflammation phenotype, and the phenotype of older patients with cardiovascular disease (all IR/100 PY &amp;lt;1). The phenotype of older patients with cardiovascular disease and severe CKD also had the highest risk to develop kidney failure (IR/100PY 5.8, 95% CI 5.1–6.6), followed by the phenotype of patients with primary kidney disease (IR/100PY 4.4, 95% CI 3.7 −5.5). Conclusion We identified 7 different phenotypes of patients with CKD including 2 phenotypes of patients with a kidney transplant with different clinical characteristics and prognosis. The differences in risk of all-cause mortality and kidney failure warrants a different monitoring and follow-up across the different phenotypes within the setting of CKD. Future studies should invest In evaluating the implementation of our identified phenotypes in routine clinical practice or clinical trial design with respect to differences in treatments.

Young urologists and kidney transplantation training: A survey designed by the French Transplantation Committee of the French Association of Urology (CTAFU) and the French Association of Urologists in training (AFUF)

ObjectiveIn France, kidney transplantations (KT) are mainly performed by urologist. Young urologists and residents are involved in this activity mostly performed in emergency. How do they feel about KT training? Is KT an attractive part of the urologist activity? MethodsThis survey has been designed in the form of a questionnaire by the French Committee of Kidney Transplantation (CTAFU) and the French Association of Urologists in training (AFUF). It has been sent by e-mail to all the AFUF members. Interest in KT and performance of the training were evaluated. ResultsIn total, 126 members filed the form. Among the residents, 51.5% feel secure to perform KT at the end of their residency. KT is considered as an interesting surgery for 92.1% of the participants: 76.5% are willing to get involved in KT during their residency/fellowship. Among the participants, 44% are willing to continue a long-term involvement. Among the residents, 65.9% consider their practical training insufficient: 56.8% have been supervised for a KT performance during their residency and 86% declare a lack of practical training and had a patient-based learning. Among the residents, 92.1% declare an insufficient theorical training. Among the residents, 33.3% say the schedules of transplantation limit their interest in KT. Among the participants, 34.4% receive a transplant bonus in addition to the usual on-call salary. ConclusionYoung urologists wish to continue their involvement in KT activity, but improved theoretical and practical training are essential. In addition, the conditions under which this activity is performed and remunerated are a matter of concern. Level of evidence3

High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats.

We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes' expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly.

Old for young kidney transplantation: a responsible option for our patients to reduce waiting time?

PurposeThe Eurotransplant Senior program allocating grafts from donors ≥ 65 years to recipients aged ≥ 65 years has proven good results within the last 20 years. However, “old” grafts are also allocated to younger recipients < 65 years, and this outcome of “old for young” kidney transplantations (KT) still lacks detailed investigations.MethodsAll “old for young” KT performed at four tertiary referral centers were retrospectively compared including a recent follow-up, stratifying for “old for young” (donor ≥ 65 years to recipient < 65 years) vs. “very old for young” KT (donor ≥ 70 years to recipient < 65 years).ResultsOverall, 99 patients were included with 56 (56.6%) “old for young” and 43 (43.4%) “very old for young” KT. The median waiting time did not differ (60.7 vs. 45.8 months, respectively) at comparable living donation rates (57.1% vs. 44.2%) as well as intra- and postoperative results. At a median follow-up of 44 months (range 1; 133), the 3-year graft survival of 91% vs. 87% did not significantly vary. In subgroup analyses assessing living donation or donation after brain death (DBD) KT only, the graft survival was significantly longer for “old for young” KT within the living donation subgroup. In multivariate Cox regression analyses, the presence of panel-reactive antibodies was the only significant impact factor on graft survival (HR 8.32, p = 0.001).ConclusionThis analysis clearly demonstrates the effectiveness of the "old for young" approach, enabling favorable perioperative results as well as comparable data of graft- and overall survival, while reducing waiting time for eligible patients.

The combinatorial effect of age and biological sex on alloimmunity and transplantation outcome.

Both age and biological sex affect transplantation outcomes. We have recently shown in a large volume clinical analysis utilizing the SRTR data that graft survival is inferior in young female kidney transplant recipients. In this multi-factorial analysis, older female recipients presented with a trend towards improved transplant outcomes compared to both young female recipients and male recipients of any age. Those data supported by reports of those of others suggest that sex and age impact alloimmune responses both, individually and synergistically. Biological sex and hormone levels change throughout a lifetime with recognized effects on longevity in addition to an impact on the development and course of several disease preconditions. Detailed mechanisms of those sex and age-specific aspects have thus far been studied outside of transplantation. Effects on alloimmunity are largely unknown. Moreover, the combinatorial impact that both, biological sex and age have on transplant outcomes is not understood. Here, we summarize available data that analyze how age in combination with biological sex may shape alloimmune responses and affect transplant outcomes.

Psychosocial Health Among Young Adults With Kidney Failure: A Longitudinal Follow-up of the SPEAK (Surveying Patients Experiencing Young Adult Kidney Failure) Study

Rationale & ObjectiveThere have been no longitudinal studies examining the evolution of psychosocial health of young adults with kidney failure as they age. We aimed to address this in the SPEAK-2 [Surveying Patients Experiencing young Adult Kidney failure-2] study. Study Design5-year follow-up longitudinal survey of the original SPEAK cohort. Setting& Participants: 16- to 30-year-olds in the UK receiving KRT between 2015-2017 who participated in the SPEAK study. ExposuresKidney failure, and KRT modality. OutcomesPsychosocial health and lifestyle behaviours. Analytical ApproachWithin-cohort changes in psychosocial health were analysed using the paired t-test, Wilcoxon signed-rank test and McNemar’s test. We compared responses to the age-matched population, and examined the impact of changes in KRT modality on psychological health, using linear regression for continuous outcome variables and logistic, ordered logistic and multinomial logistic regression for binary, ordered categorical and unordered categorical variables respectively. ResultsWe obtained 158 survey responses; 129 had previously responded to SPEAK. Of these, 90% had a kidney transplant. Compared to the general population, respondents were less likely to be married or have children and were more likely to be living with their parents. They had nearly 15 times greater odds of being unable to work due to health (OR, 14.41; 95% CI, 8.0-26.01; P<0.001). Respondents had poorer quality of life and mental wellbeing, and were more likely to report psychological problems (OR 5.37; 95% CI 3.45-8.35; P<0.001). A negative association between remaining on or moving to dialysis and psychosocial health was observed, although this was attenuated when controlling for the psychosocial state in SPEAK. LimitationsLow response rate resulting in imprecise and potentially biased estimates, and impact of Covid-19 pandemic while survey was active on psychosocial health. ConclusionsYoung adults with kidney failure have persistent poorer psychosocial health compared to their healthy peers as they age. Our findings also suggest a potential causal relationship between KRT modality and psychosocial health.

Implementing a Structured Transition from Pediatric to Adult Care Can Impact Clinical Outcomes in Young Adult Kidney Transplant Recipients

Implementing a Structured Transition from Pediatric to Adult Care Can Impact Clinical Outcomes in Young Adult Kidney Transplant Recipients

Induced Senescent Cells Recruit Leukocytes and Permit Their Own Clearance from Healthy Young Kidneys

Induced Senescent Cells Recruit Leukocytes and Permit Their Own Clearance from Healthy Young Kidneys

Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy

IgA nephropathy (IgAN) is associated with a risk for posttransplant recurrence. Data are limited regarding graft loss attributable to recurrence of IgAN among pediatric and young adult kidney transplant (KT) recipients. This was a retrospective cohort study of patients aged 0 to 25 years from the Scientific Registry of Transplant Recipients who received a primary KT for IgAN. Patients with history of KT attributable to renal dysplasia were comparators. Outcomes included the incidence of graft loss attributable to IgAN recurrence, association with donor type, and posttransplant corticosteroid use. In total, 5475 transplant recipients were included, with 1915 patients with IgAN and 3560 patients with renal dysplasia. In a multivariable Cox proportional hazards model, IgAN was associated with higher risk of graft loss (adjusted hazard ratio [aHR], 1.35; 95% CI, 1.21-1.50; P < .001) compared with dysplasia. Graft loss was attributed to recurrent disease in 5.4% of patients with IgAN. In a multivariable competing risks analysis, patients with IgAN receiving a parental living-donor kidney were more likely to report graft loss from recurrent disease compared with patients with a nonparental living donor (aHR, 0.52; 95% CI, 0.31-0.91; P = .02). Posttransplant prednisone use was not associated with improved graft survival (P = .2). These data challenge existing paradigms in posttransplant management of patients with IgAN.

#2617 CHANGES IN PSYCHOSOCIAL HEALTH IN YOUNG ADULTS WITH KIDNEY FAILURE: A 5-YEAR FOLLOW-UP OF THE SPEAK STUDY

Abstract Background and Aims Young adulthood is a sensitive developmental period, and the psychosocial impact of kidney failure in this group is implicated in the observed high risk for transplant loss and death. In the Surveying People Experiencing young Adult Kidney failure (SPEAK) study we described differences in life-course outcomes, worse mental wellbeing and twice the likelihood of psychological disturbance among UK young adults with kidney failure (transplant or dialysis) compared to the general population. There have been no longitudinal studies investigating the natural history of these outcomes as young adults mature and get older. We undertook SPEAK-2 as a five-year follow-up study to address this. Method In this prospective observational study, respondents to SPEAK were invited to complete a revised online survey. PPI guided components of the original survey to amend. We analysed how psychosocial health had changed among respondents between studies using the paired t-test, Wilcoxon signed-rank test and McNemar's test for continues parametric and non-parametric data, and binary data respectively. We compared responses to age-matched respondents of the Health Survey for England 2012 using regression. Responses were weighted to increase generalisability. Results We had 158 survey responses. The analysis of psychological health change over time is presented in Table 1. A greater proportion of participants had evidence of psychological morbidity (45% versus 24% in the original SPEAK study; p&amp;lt;0.001). They had inferior mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale [WEMWBS] β, -1.76; 95% CI, -3.27 to -0.25; P = .02). No differences were identified in domains including quality of life (EQ5D). Key outcomes of the comparison to the age-matched general population are presented in Table 2. Respondents were less likely to be married or have children and were more likely to be living with their parents. They were almost 15 times more likely to report being unable to work due to health. Respondents had poorer quality of life and poorer mental wellbeing compared to the general population. They also five times greater odds of having psychological problems or mental ill health. Conclusion We report the first longitudinal study of the psychosocial health of a cohort of young adults with kidney failure as they age and mature. Over five years, we observed worse psychosocial health in terms of mental wellbeing and psychological morbidity. Respondents also lagged behind their peers in terms of life-course and psychosocial outcomes. Dedicated long-term follow-up is needed to clarify the extent and duration to which kidney failure in young adulthood impacts life participation and psychosocial health in the long term. Regardless, the degree of psychosocial ill health we have described warrants urgent increased support for this group.

#6679 ANALYSIS OF MACROPHAGE POPULATIONS IN THE KIDNEY WITH RENAL TUBULAR CELL-SPECIFIC SENESCENCE INDUCTION

Abstract Background and Aims Ageing is a risk factor for multiple diseases, including kidney disease. To improve quality of life, pharmaceutical treatments are given to ageing patients, often with side-effects and cross-reactions. Research is needed into the effects and mechanisms of ageing in order to identify new druggable targets to improve quality of life. Cells can become senescent with age and are seen at sites of tissue injury. Senescent cells (SCs) undergo irreversible cell-cycle arrest, but remain metabolically active, producing a range of signalling molecules called the senescence associated secretory phenotype (SASP, made up of pro-inflammatory/fibrotic elements). Senescent cells within the kidney post-acute kidney injury (AKI) may be involved in ongoing damage, leading in some cases to chronic kidney disease (CKD), possibly due to interactions with macrophages. We hypothesise that the recruitment of monocytes/macrophages by senescent cells is due to the signalling components present in their SASP. Method Pax8 is renal tubule marker. We use Pax8-creERT2;mdm2 fl/fl mice to study kidney-specific senescence induction in absence of age/injury. Upon administration of tamoxifen, the mdm2 alleles are floxxed out by cre recombinase, allowing p53 to stabilise and activate the p21CIP1 cell-cycle inhibitor, inducing senescence in Pax8+ kidney-specific cells. The use of an endogenous tdTomato reporter allows visualisation of cells undergoing successful recombination upon the administration of tamoxifen (TAM). Results As expected, cell-cycle inhibitor/SC marker, Cdkn1a was upregulated by qPCR in TAM-treated young murine whole kidneys 10-fold compared to controls (p = 0.0173) (Figure 1). Ccl2 (monocyte chemoattractant) was up-regulated 20-fold in young (p = 0.0405) TAM-treated TG mice vs controls (Figure 1). In agreement with an increase of Ccl2 transcripts, there was a significant increase of renal macrophages as quantified by flow cytometry of kidney digests (p = 0.0141) in TAM treated young TG mice. Immunofluorescence staining of transgenic mice revealed an increase of Iba1 positive macrophages, correlated with staining of tdTomato tubules, suggesting that increase in macrophage numbers was in response to senescence induction (Figure 2). Iba1-p21 co-stains show a increases in p21 positive cells in TAM-treated transgenic mice, evidently a result of construct activation and appear in proximity to the macrophages (Figure 2). Conclusion Apparent increases in macrophages due to the presence of senescent cells may indicate one of the mechanisms by which AKI progresses to CKD, particularly if inflammatory macrophage phenotypes are present and persist. Macrophage and monocyte populations fluctuate with age and the use of this model allows analysis of macrophage recruitment/polarisation due to senescent cell burden in the absence of age/injury and possible confounding factors, in young mice.

A review of elderly transplantation regarding complications, outcomes, and survival

BackgroundRenal transplant adds survival benefits to end-stage renal disease patients over dialysis, and a similar concept applies to elderly patients. Some of the challenges of transplanting old patients may involve age-related cancers and comorbid conditions such as cardiovascular disease. Studies had shown that advanced age is associated with better outcomes compared to dialysis despite receiving poorer quality organs. AimThis extended literature review aims to identify the common complications, outcomes, and survival benefits of kidney transplantation in the elderly population. MethodsAn extended literature review was done to identify studies that compared elderly transplant recipients with the younger kidney transplant recipient population. The study population included elderly kidney recipients aged sixty and above and younger kidney recipients below the age of sixty. This literature review aims to discuss complications facing elderly kidney recipients and compare transplant outcomes to younger kidney recipients. PubMed, Midline, and google scholar databases were searched and papers meeting the pre-set inclusion criteria were identified. ResultsA total of 212 papers were identified. After screening the results, 12 papers met the inclusion criteria and were included for review. 10/12 papers included patients' age cutoff point, one paper had cut-off age between 60 and 80 years, while the last paper recruited patients with ages above 70. Most of the studies mentioned young group age as below 60, 2/12 papers divided the young group into further subgroups of age. Two studies used paired donor organs for both young and elderly groups to eliminate donor bias. While other studies used living, deceased, or both living and deceased donors for both elderly and young groups. One study matched donor type and gender in both groups. The studies looked at patient and graft survival and complications. Elderly transplant patients suffered more hospitalization, infections, cardiovascular complications, malignancy, and surgical complications. Post-transplant diabetes was higher in the young recipient group in one study. ConclusionIn the case of elderly renal transplant recipients, the cut-off point for age to perform renal transplant is not clear but studies showed better survival and cost-effectiveness in elderly patients compared to patients on the waiting list even in older patient cohorts