Deceased donor transplantation in the elderly--are we creating false hope?

BACKGROUND: Increasing numbers of older patients are developing established renal failure and considering kidney transplant as a renal replacement therapy (RRT) option. The probability of older patients actually receiving a deceased donor kidney transplant is unclear, preventing informed choice about pursuing the option of transplantation. We sought to analyse our RRT population to determine the probability of receiving a deceased donor kidney transplant in patients commencing RRT categorized by age and for whom there was no suitable living kidney donor. METHODS: Patients commencing dialysis in our centre between 1992 and 2009 were identified. Time to listing on the deceased donor transplant waiting list and time to first deceased donor transplant were determined by Kaplan-Meier analysis for patients, categorized by age, with censoring at the date of first living donor kidney transplant, death or last dialysis. RESULTS: One-thousand-five-hundred-and-thirteen patients were categorized into groups by age in years [1: <35 (n = 134), 2: 35-49.9 (n = 207), 3: 50-64.9 (n = 415), 4: >65-74.9 (n = 438) and 5: ≥ 75 (n = 319)]. The probability of being listed for deceased donor transplant within 1 year of commencing RRT was 75, 54, 27, 4 and 0.8% in Groups 1-5, respectively. If listed, the probability of receiving a deceased donor transplant within 5 years of starting RRT was 81, 48, 26, 8 and 0% in Groups 1-5, respectively. In Groups 1-4, 93% (n = 63), 87% (n = 65), 76% (n = 45) and 100% (n = 7) of the patients, respectively, who received a deceased donor transplant were alive and off dialysis 1 year after transplant. The reason patients who were listed did not receive a transplant was usually death on the waiting list. CONCLUSIONS: The likelihood of being listed for transplant falls with increasing age at the time of starting RRT. Even for patients listed for transplant, the probability of older patients actually receiving a transplant is much lower than for younger patients, with only 8% of listed patients aged 65-74.9 years being transplanted within 5 years. This is partly the result of death on the waiting list but may also be related to organ allocation policies. Assessment for possible deceased donor transplantation involves a considerable investment in time and effort for the patient, as well as in health care resources, and a patient's decision whether to proceed with assessment should be informed by the kind of information we have produced. As there may be regional and national variations in practice, each centre should generate such data for use locally.

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - A high risk community-hospital interface.

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.

The impact of delayed graft function on the long-term outcome of renal transplantation.

Recent studies provide conflicting conclusions regarding the impact of delayed graft function (DGF) on the long-term outcome of renal transplantation. Some centres report DGF as an independent risk factor for reduced long-term graft and patient survival, while others report no impact on long-term outcome. Further scrutiny of data from these studies reveals differences in the definition of DGF, definition of long-term outcome, and statistical methods that may partly explain the variability. The commonest definition of DGF is the need for dialysis in the first week post-transplant, but this may be less informative than definitions that consider DGF as a continuous variable such as time to achieving creatinine clearance > 10ml/min. Acute rejection (AR) occurs more commonly in patients with DGF and variability in the impact of DGF may also relate to strategies to detect and treat AR during DGF. Centres with a vigilant strategy are likely to note a lower impact of DGF because the associated long-term adverse impact of AR is minimised. Furthermore, many centres reduce the dose of calcineurin inhibiting drugs and/or use polyclonal antibody therapy during DGF but the long-term impact of this strategy is unclear. Newer agents such as humanised anti-IL2 monoclonal antibodies and rapamycin may have a role, but controlled studies are required to define the optimal immunosuppressive regimen for patients with DGF. In the meantime, measures to minimise ischaemic damage to the transplant kidney and intensive surveillance for AR with weekly renal biopsy in patients with DGF are recommended.

The influence of pre-operative electrocardiographic abnormalities and cardiovascular risk factors on patient and graft survival following renal transplantation.

Premature cardiovascular disease (CVD) is the leading cause of mortality and of graft loss in renal transplant recipients. However, the pattern of cardiovascular risk factors (specifically modifiable risk factors) is not well established and may be different from the general population. In this study we investigated the importance of electrocardiographic abnormalities and conventional cardiovascular risk factors present at the time of first renal transplantation in a longitudinal follow-up study of 515 patients. Overall, 45.8% were cigarette smokers, 13.0% were diabetic, 75.1% had "hypertension", 12.2% had symptoms of angina pectoris and 9.1% had a past history of myocardial infarction or stroke. Two thirds of ECG tracings were abnormal. 58.7% of men and 37.5% of women had left ventricular hypertrophy (LVH). Overall, 28.2% had simple LVH, 20.5% had LVH with repolarisation changes ('strain'). 434 patients had complete data for multivariate analyses of patient and graft survival. A Cox multivariate analysis of patient survival (patients whose graft failed were censored in the analysis) identified: age (hazard ratio 1.03/year), diabetes (2.72), smoking (1.81) and family history of premature CVD (2.17) as independent risk factors for patient survival. An abnormal ECG was also independently associated with outcome, with the exception of isolated left ventricular hypertrophy. Left ventricular hypertrophy with strain, or ischaemic changes were associated with adverse outcome with a hazard ratio of 1.96 and 3.30 respectively. A similar analysis of the determinants of graft survival (patients who died with a functioning graft were censored in the analysis) identified: acute rejection (hazard ratio 2.38), cigarette smoking (1.48) and age (1.04/year) as independent predictors of graft failure. These data demonstrate a high prevalence of ECG abnormalities and CV risk factors in renal transplant recipients. Moreover, ECG abnormalities and "conventional" cardiovascular risk factors are associated with poor graft and patient outcome and represent potentially remediable risk factors for renal transplant recipients.

The advanced age deceased kidney donor: current outcomes and future opportunities.

BACKGROUND: Due to the aging general population, deceased donors > or =55 years will form an increasingly larger proportion of the deceased kidney donor pool. METHODS: Using data from the United States Renal Data System, we determined the change in graft survival between 1996 and 2000 among 32,557 recipients of donors aged <55 years and > or =55 years in univariate and multivariate survival analyses. We identified donor risk factors for graft loss that might influence the decision to accept or reject donors <55 and > or =55 years. The initial glomerular filtration rate established 6 months after transplantation (initial GFR), and the stability of GFR in the first post-transplant year (GFR at 12 months post-transplantation-GFR at six months post-transplantation) were compared between recipients of donors <55 and > or =55 years and the association of these factors with graft survival was determined. RESULTS: In 2000, one-year graft survival in donors > or =55 years was 86.7%. Between 1996 and 1999 the projected graft half life improved from 11.4 to 14.5 years for recipients of donors <55 years (P < 0.01); however, there was no improvement for recipients of donors > or =55 years (8.2 to 9.2 year, P= 0.46). Among donor factors studied, only cold ischemic time >24 hours identified recipients of donors > or =55 years at risk for graft loss. Compared to recipients of donors <55 years, recipients of donors > or =55 years established a lower initial GFR (42 vs. 56 mL/min/1.73 m(2), P < 0.0001), and had less stable GFR in the first post-transplant year (-1.5 vs. -0.6 mL/min/1.73 m(2), P <.0001). Recipients from donors > or =55 years with initial GFR > or =50 mL/min/1.73 m(2) and no drop GFR during the first post-transplant year had graft survival that was superior to that of donors <55 years with either initial GFR <50 mL/min/1.73 m(2) or a drop in GFR during the first post-transplant year. CONCLUSION: Donors > or =55 years are a valuable resource. Despite improvements in immunosuppression, rejection, and delayed graft function, the projected increase in long-term graft survival among recipients of donors <55 years was not shared among recipients of donors > or =55 years. Recipients of donors > or =55 years had lower initial GFR, and less stable GFR during the first post-transplant year. Limiting cold ischemic time to <24 hours may improve outcomes among recipients of donors > or =55 years. Future studies to maximize initial GFR and minimize early loss of GFR in recipients of donors > or =55 years may lead to improved outcomes from deceased donors > or =55 years.

Chronic kidney disease progression in native and transplant kidneys.

PURPOSE OF REVIEW: The present review addresses the recent literature demonstrating important differences in the rate of progression of kidney function decline between transplant recipients and patients with native kidney disease. It also highlights the need for prospective studies to determine the importance of nonimmune factors that are established risk factors for progression of native kidney disease in the transplant setting. RECENT FINDINGS: Transplant recipients establish modest levels of kidney function but have rates of kidney function decline that are slower than those in patients with native kidney disease. Continued improvements in long-term graft survival have not been achieved despite significant advances in immunosuppression. There is increasing observational evidence that nonimmune factors that play a causal role in progression of native kidney disease may also be important determinants of allograft decline. There are fundamental differences between transplant recipients and patients with native kidney disease that preclude extrapolation of evidence from native kidney disease to the transplant setting. SUMMARY: Transplant recipients are a unique group of chronic kidney disease patients. Prospective studies to determine the importance of nonimmune factors such as hypertension, proteinuria, dyslipidemia, diabetes, and anemia in the transplant setting are needed.