Differences in excess mortality by recipient sex after heart transplant: An individual patient data meta-analysis.

BACKGROUND: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients. METHODS: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. RESULTS: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p = 0.05). CONCLUSIONS: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss.

Background: Diabetes mellitus (DM) is associated with a greater risk of mortality in kidney transplant patients, primarily driven by a greater risk of cardiovascular disease (CVD)-related mortality. However, the associations between diabetes status at time of first allograft loss and mortality on dialysis remain unknown. Methods: All patients with failed first kidney allografts transplanted in Australia and New Zealand between 2000 and 2020 were included. The associations between diabetes status at first allograft loss, all-cause and cause-specific mortality were examined using competing risk analyses, separating patients with diabetes into those with pre-transplant DM or post-transplant diabetes mellitus (PTDM). Results: Of 3782 patients with a median (IQR) follow-up duration of 2.7 (1.1-5.4) years, 539 (14%) and 390 (10%) patients had pre-transplant DM or developed PTDM, respectively. In the follow-up period, 1336 (35%) patients died, with 424 (32%), 264 (20%) and 199 (15%) deaths attributed to CVD, dialysis withdrawal and infection, respectively. Compared to patients without DM, the adjusted subdistribution HRs (95% CI) for pre-transplant DM and PTDM for all-cause mortality on dialysis were 1.47 (1.17-1.84) and 1.47 (1.23-1.76), respectively; for CVD-related mortality were 0.81 (0.51-1.29) and 1.02 (0.70-1.47), respectively; for infection-related mortality were 1.84 (1.02-3.35) and 2.70 (1.73-4.20), respectively; and for dialysis withdrawal-related mortality were 1.71 (1.05-2.77) and 1.51 (1.02-2.22), respectively. Conclusions: Patients with diabetes at the time of kidney allograft loss have a significant survival disadvantage, with the excess mortality risk attributed to infection and dialysis withdrawal.

A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant.

BACKGROUND: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. METHODS: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. RESULTS: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. CONCLUSIONS: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

Invasive Management and Outcomes in Acute Coronary Syndromes and Chronic Kidney Disease (ANZACS-QI 70).

AIMS: Guidelines recommend management with an invasive coronary angiogram in acute coronary syndromes (ACS), but most studies excluded patients with advanced chronic kidney disease (CKD). Our aims were to describe, in a comprehensive ACS cohort, the incidence of CKD, coronary angiography utilisation and outcomes, according to CKD stage. METHODS: National datasets were used to identify hospitalised ACS patients (2013 to 2018) in the Northern region of New Zealand. CKD stage was obtained from a linked laboratory dataset. Outcomes included all-cause and cause-specific mortality, and non-fatal myocardial infarction, heart failure and stroke. RESULTS: Thirty-eight percent (38%) of the 23,432 ACS patients had CKD stage 3 or higher: 2,403 (10%) had stages 4/5 CKD. Overall 61% received coronary angiography. Compared with normal renal function the adjusted rate of coronary angiography was lower in CKD stage 3b (RR 0.75, 95% confidence intervals [CIs] 0.69, 0.82) and stages 4/5 without dialysis (RR 0.41, 95% CIs 0.36, 0.46), but similar for those on dialysis (RR 0.89, 95% CIs 0.77, 1.02). All-cause mortality (mean follow-up 3.2 years) increased with CKD stage from 8% (normal kidney function) to 69% (stages 4/5 CKD without dialysis). Compared with coronary angiography, the adjusted all-cause and CVD mortality risks were higher in those without coronary angiography, except for those on dialysis, where these risks converged. CONCLUSIONS: Invasive management fell below an eGFR of 45 mL/min (≤ stage 3b), and nearly half of all deaths occurred in these patients. Clinical trials are needed to assess the role of invasive management in ACS and advanced CKD.

Kidney Donor Profile Index and allograft outcomes: interactive effects of estimated post-transplant survival score and ischaemic time.

Background: The Kidney Donor Profile Index (KDPI) is routinely reported by the donation agencies in Australia. We determined the association between KDPI and short-term allograft loss and assessed if this association was modified by the estimated post-transplant survival (EPTS) score and total ischaemic time. Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, the association between KDPI (in quartiles) and 3-year overall allograft loss was examined using adjusted Cox regression analysis. The interactive effects between KDPI, EPTS score and total ischaemic time on allograft loss were assessed. Results: Of 4006 deceased donor kidney transplant recipients transplanted between 2010 and 2015, 451 (11%) recipients experienced allograft loss within 3 years post-transplant. Compared with recipients of kidneys with a KDPI of 0-25%, recipients who received donor kidneys with a KDPI >75% experienced a 2-fold increased risk of 3-year allograft loss {adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.53-2.71]}. The adjusted HRs for kidneys with a KDPI of 26-50% and 51-75% were 1.27 (95% CI 0.94-1.71) and 1.31 (95% CI 0.96-1.77), respectively. There were significant interactions between KDPI and EPTS scores (P-value for interaction <.01) and total ischaemic time (P-value for interaction <.01) such that the associations between higher KDPI quartiles and 3-year allograft loss were strongest in recipients with the lowest EPTS scores and longest total ischaemic time. Conclusion: Recipients with higher post-transplant expected survival and transplants with longer total ischaemia who received donor allografts with higher KDPI scores experienced a greater risk of short-term allograft loss compared with those recipients with reduced post-transplant expected survival and with shorter total ischemia.

A multinational cohort study uncovered sex differences in excess mortality after kidney transplant.

Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02-1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females.

Sex Disparity in Cause-Specific and All-Cause Mortality Among Incident Dialysis Patients.

RATIONALE & OBJECTIVE: Early mortality rates of female patients receiving dialysis have been, at times, observed to be higher than rates among male patients. The differences in cause-specific mortality between male and female incident dialysis patients with kidney failure are not well understood and were the focus of this study. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Incident patients who had initiated dialysis in Australia and New Zealand in 1998-2018. EXPOSURE: Sex. OUTCOMES: Cause-specific and all-cause mortality while receiving dialysis, censored for kidney transplant. ANALYTICAL APPROACH: Adjusted cause-specific proportional hazards models, focusing on the first 5 years following initiation of dialysis. RESULTS: Among 53,414 patients (20,876 [39%] female) followed for a median period of 2.8 (IQR, 1.3-5.2) years, 27,137 (51%) died, with the predominant cause of death attributed to cardiovascular disease (18%), followed by dialysis withdrawal (16%). Compared with male patients, female patients were more likely to die in the first 5 years after dialysis initiation (adjusted hazard ratio [AHR], 1.08 [95% CI, 1.05-1.11]). Even though female patients experienced a lower risk of cardiovascular disease-related mortality (AHR, 0.93 [95% CI, 0.89-0.98]) than male patients, they experienced a greater risk of infection-related (AHR, 1.20 [95% CI, 1.10-1.32]) and dialysis withdrawal-related (AHR, 1.19 [95% CI, 1.13-1.26]) mortality. LIMITATIONS: Possibility of residual and unmeasured confounders. CONCLUSIONS: Compared with male patients, female patients had a higher risk of all-cause mortality in the first 5 years after dialysis initiation, a difference driven by higher rates of mortality from infections and dialysis withdrawals. These findings may inform the study of sex differences in mortality in other geographic settings.

Cigarette smoking and adverse health outcomes in patients treated with maintenance dialysis.

BACKGROUND: The association of smoking with new-onset cardiovascular disease, chronic lung disease, malignancy and mortality in dialysis is well-known. The smoking prevalence and its association with clinical outcome was assessed. METHODS: Multicentre cohort study using 'ANZDATA' Registry, 57 838 adults who commenced dialysis (>3 months) between 1990 and 2016 were included. Patients' demographics, initial dialysis modality, presence of comorbidities and smoking history are predictors. The primary outcome was all-cause mortality. Secondary outcomes were smoking prevalence, cause-specific mortality, non-skin cancers, cardiovascular and chronic lung diseases. RESULTS: Of the 57 838 patients, 56 512 (mean age of 58.9 ± 15.1 years, 40.1% female, 43% diabetic), had data on smoking history with 13.6% current, 40.7% former and 45.6% never smokers. Former and current smokers had 10% (HR 1.10; 95% CI: 1.08, 1.13) and 22%(HR 1.22; 95% CI: 1.18, 1.26) higher risk of all-cause mortality. They were 13% (HR 1.13; 95% CI: 1.09, 1.18) and 23% (HR 1.23; 95% CI: 1.17, 1.29) for CVD mortality. Smoking was associated with higher mortality from respiratory failure (HR 1.59; 95% CI: 1.13, 2.23, p = .073 and HR 1.33; 95% CI: 1.01, 1.74, p = .042) for current and former smokers. Current and former smokers had higher risk for non-skin cancer (HR 1.30; 95% CI: 1.19, 1.42 and HR 1.24; 95% CI: 1.17, 1.32). Smoking was associated with a higher rate of death from cancer (HR 1.26; 95% CI 1.19-1.33) and chronic lung disease (HR 1.48; 95% CI 1.15-1.92). Former and current smokers had a higher adjusted risk for de novo vascular disease (PVD, CVD), CAD (adjusted RR 1.1; 95% Cl: 1.09-1.12). CONCLUSIONS: In dialysis patients, smoking was associated with higher rates of all-cause mortality, cardiovascular mortality, respiratory failure, chronic lung disease and malignancy along with higher risks of non-skin cancers, de novo vascular disease and chronic lung disease.

Baseline Characteristics and Representativeness of Participants in the BEST-Fluids Trial: A Randomized Trial of Balanced Crystalloid Solution Versus Saline in Deceased Donor Kidney Transplantation.

Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. Methods: We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. Results: During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. Conclusions: BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.

The incidence of cancer recurrence and new cancer following commencement of dialysis.

Background: Patients with kidney failure have a higher cancer risk compared with the age-matched general population. However, the outcomes of incident dialysis patients with a prior cancer history are unknown. Methods: Using Australia and New Zealand Dialysis and Transplant Registry data (2000-2019), the outcomes and survival probabilities of incident dialysis patients with prior cancers and having experienced a cancer recurrence or having developed a new cancer after dialysis commencement were described. Results: Of 4912 patients with prior cancers before dialysis commencement, 323 (7%) and 343 (7%) patients experienced cancer recurrence or developed new cancers after dialysis initiation, respectively. The median time from dialysis commencement to cancer recurrence was 1.2 years [interquartile range (IQR) 0.5-2.8] and was 2.0 years (IQR 0.7-4.0) for new cancer occurrence. Of those with cancer recurrence, 80% presented with metastatic disease and one in two patients died from cancer, with a median time from cancer recurrence to death of 0.5 years (IQR 0.2-1.7). Of those who developed new cancer, urinary tract and respiratory cancers were the most frequent cancer types, with a median time from new cancer diagnosis to death of 1.3 years (IQR 0.4-3.1). The 3-year survival probabilities on dialysis following cancer recurrence and new cancer were 19% [95% confidence interval (CI) 15-24] and 41% (35-47), respectively. Conclusion: Among incident dialysis patients with a prior cancer history, 14% experienced cancer recurrence or developed a new cancer. Patients who experienced cancer recurrence or developed new cancer have poor outcomes, with ˂50% surviving beyond 3 years. These findings suggest the need to have a greater understanding of the characteristics, cancer screening, treatment responses and reasons for commencing dialysis in patients with kidney failure and prior cancer history, which may help in the shared clinical decision-making process when considering dialysis for these patients.

Interactions Between Donor Age and 12-Month Estimated Glomerular Filtration Rate on Allograft and Patient Outcomes After Kidney Transplantation.

Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (<30 ml/min/1.73 m2) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38-2.95] compared to eGFR of 30-60 ml/min/1.73 m2; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m2) was 0.67 [0.62-0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups (p < 0.01). Recipients with eGFR <30 ml/min/1.73 m2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m2, and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted.

Age-dependent Sex Differences in Graft Loss After Kidney Transplantation.

BACKGROUND: Sex differences in kidney graft loss rates were reported in the United States. Whether these differences are present in other countries is unknown. METHODS: We estimated the association between recipient sex and death-censored graft loss in patients of all ages recorded in the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study registries who received a first deceased donor kidney transplant (1988-2019). We used multivariable Cox regression models, accounting for the modifying effects of donor sex and recipient age, in each registry separately; results were combined using individual patient data meta-analysis. RESULTS: We analyzed 438 585 patients. Young female patients 13-24 y old had the highest crude graft loss rates (female donor: 5.66; male donor: 5.50 per 100 person-years). Among young recipients of male donors, females showed higher graft loss risks than males (0-12 y: adjusted hazard ratio [aHR] 1.42, (95% confidence interval [CI], 1.17-1.73); 13-24 y: 1.24 (1.17-1.32); 25-44 y: 1.09 (1.06-1.13)). When the donor was female, there were no significant differences by recipient sex among those of age <45 y; however, the aHR for females was 0.93 (0.89-0.98) in 45-59 y-old and 0.89 (0.86-0.93) in ≥ 60 y-old recipients. Findings were similar for all 3 registries in most age intervals; statistically significant heterogeneity was seen only among 13-24-y-old recipients of a female donor (I2 = 71.5%, P = 0.03). CONCLUSIONS: There is an association between recipient sex and kidney transplantation survival that is modified by recipient age and donor sex.

Early Graft Loss Following Transplantation From Expanded Criteria Donors.

BACKGROUND: Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index. METHODS: Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping. RESULTS: Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63). CONCLUSIONS: Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.

Socio-economic disparity, access to care and patient-relevant outcomes after kidney allograft failure.

Social disparity is a major impediment to optimal health outcomes after kidney transplantation. In this study, we aimed to define the association between socio-economic status (SES) disparities and patient-relevant outcomes after kidney allograft failure. Using data from the Australia and New Zealand Dialysis and Transplant registry, we included patients with failed first-kidney allografts in Australia between 2005 and 2017. The association between residential postcode-derived SES in quintiles (quintile 1-most disadvantaged areas, quintile 5-most advantaged areas) with uptake of home dialysis (peritoneal or home haemodialysis) within the first 12-months post-allograft failure, repeat transplantation and death on dialysis were examined using competing-risk analysis. Of 2175 patients who had experienced first allograft failure, 417(19%) and 505(23%) patients were of SES quintiles 1 and 5, respectively. Compared to patients of quintile 5, quintile 1 patients were less likely to receive repeat transplants (adjusted subdistributional hazard ratio [SHR] 0.70,95%CI 0.55-0.89) and were more likely to die on dialysis (1.37 [1.04-1.81]), but there was no association with the uptake of home dialysis (1.02 [0.77-1.35]). Low SES may have a negative effect on outcomes post-allograft failure and further research is required into how best to mitigate this. However, small-scale variation within SES cannot be accounted for in this study.

Death after Kidney Transplantation: An Analysis by Era and Time Post-Transplant.

BACKGROUND: Mortality risk after kidney transplantation can vary significantly during the post-transplant course. A contemporary assessment of trends in all-cause and cause-specific mortality at different periods post-transplant is required to better inform patients, clinicians, researchers, and policy makers. METHODS: We included all first kidney-only transplant recipients from 1980 through 2018 from the Australia and New Zealand Dialysis and Transplant Registry. We compared adjusted death rates per 5-year intervals, using a piecewise exponential survival model, stratified by time post-transplant or time post-graft failure. RESULTS: Of 23,210 recipients, 4765 died with a functioning graft. Risk of death declined over successive eras, at all periods post-transplant. Reductions in early deaths were most marked; however, recipients ≥10 years post-transplant were 20% less likely to die in the current era compared with preceding eras (2015-2018 versus 2005-2009, adjusted hazard ratio, 0.80; 95% confidence interval, 0.69 to 0.90). In 2015-2018, cardiovascular disease was the most common cause of death, particularly in months 0-3 post-transplant (1.18 per 100 patient-years). Cancer deaths were rare early post-transplant, but frequent at later time points (0.93 per 100 patient-years ≥10 years post-transplant). Among 3657 patients with first graft loss, 2472 died and were not retransplanted. Death was common in the first year after graft failure, and the cause was most commonly cardiovascular (50%). CONCLUSIONS: Reductions in death early and late post-transplant over the past 40 years represent a major achievement. Reductions in cause-specific mortality at all time points post-transplant are also apparent. However, relatively greater reductions in cardiovascular death have increased the prominence of late cancer deaths.

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature.

The mitochondrial DNA mutation mt.3243A>G is most commonly associated with maternally inherited diabetes and deafness (MIM 52,000), but it has protean phenotypes including renal disease due to focal segmental glomerulosclerosis. We describe monozygotic twins who both harboured this mutation and developed ESRD. Although otherwise genetically identical, the twins differed in their peripheral blood leucocyte levels of circulating mt.3243A>G heteroplasmy: 20 versus 10%, when assessed at 42 years of age. The twin with the higher heteroplasmy load developed end-stage kidney disease 15 years earlier than her sister. A review of the published literature supports a relationship between heteroplasmy level and the age at the development of the end stage of renal failure in patients with mt.3243A>G-related kidney disease.

KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.

Summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence. The strengths of recommendations are provided in the full report. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.