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.

Multimodality Tachycardia-Induced Stress Testing Predicts a Low-Risk Group for Early Cardiovascular Mortality After Renal Transplantation.

BACKGROUND: Cardiovascular events remain a major cause of death in kidney transplant recipients. The optimal noninvasive workup to prevent peritransplant cardiac mortality remains contentious. METHODS: We conducted a retrospective analysis to assess the renal transplantation cardiovascular assessment protocol within a single-center population over a 5-year period. Asymptomatic patients aged less than 45 years with no history of cigarette smoking, without diabetes mellitus, and dialysis-dependent for less than 24 months did not undergo cardiac testing before listing. All other asymptomatic patients underwent a noninvasive, tachycardia-induced stress test, where a target heart rate of 85% predicted for age and gender was required. The primary endpoints were rates of acute myocardial infarction (AMI) and cardiovascular death at 30 days after renal transplantation. RESULTS: Between 2015 and 2019, 380 recipients underwent cardiac evaluation: 79 (20.8%) were deemed low cardiovascular risk and placed on the renal transplant waitlist without further assessment; 270 (71.1%) underwent a tachycardia-induced stress test; and 31 (8.1%) were deemed high risk and proceeded directly to invasive coronary angiography (ICA). In the 5-year follow-up, 3 patients (0.8%) experienced an AMI 30 days after renal transplantation, all of which occurred in the high-risk "direct to ICA" cohort. No events were documented in the low-risk cohort or in patients who had a negative tachycardia-induced stress test. There were no cardiovascular deaths within 30 days after transplantation. CONCLUSION: A negative tachycardia-induced cardiac stress test, achieving 85% of predicted heart rate, was associated with a 0% AMI rate and no cardiovascular deaths at 30 days after renal transplantation.

Center-Effect of Incident Hemodialysis Vascular Access Use: Analysis of a Bi-national Registry.

Background: Commencing hemodialysis (HD) with an arteriovenous access is associated with superior patient outcomes compared with a catheter, but the majority of patients in Australia and New Zealand initiate HD with a central venous catheter. This study examined patient and center factors associated with arteriovenous fistula/graft access use at HD commencement. Methods: We included all adult patients starting chronic HD in Australia and New Zealand between 2004 and 2015. Access type at HD initiation was analyzed using logistic regression. Patient-level factors included sex, age, race, body mass index (BMI), smoking status, primary kidney disease, late nephrologist referral, comorbidities, and prior RRT. Center-level factors included size; transplant capability; home HD proportion; incident peritoneal dialysis (average number of patients commencing RRT with peritoneal dialysis per year); mean weekly HD hours; average blood flow; and achievement of phosphate, hemoglobin, and weekly Kt/V targets. The study included 27,123 patients from 61 centers. Results: Arteriovenous access use at HD commencement varied four-fold from 15% to 62% (median 39%) across centers. Incident arteriovenous access use was more likely in patients aged 51-72 years, males, and patients with a BMI of >25 kg/m2 and polycystic kidney disease; but use was less likely in patients with a BMI of <18.5 kg/m2, late nephrologist referral, diabetes mellitus, cardiovascular disease, chronic lung disease, and prior RRT. Starting HD with an arteriovenous access was less likely in centers with the highest proportion of home HD, and no center factor was associated with higher arteriovenous access use. Adjustment for center-level characteristics resulted in a 25% reduction in observed intercenter variability of arteriovenous access use at HD initiation compared with the model adjusted for only patient-level characteristics. Conclusions: This study identified several patient and center factors associated with incident HD access use, yet these factors did not fully explain the substantial variability in arteriovenous access use across centers.

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.

Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage.

BACKGROUND: Living kidney donors are a highly selected healthy population expected to have high survival postdonation, but mortality studies are limited. Our study aimed to compare mortality in living kidney donors with the general population in Australia and New Zealand, hypothesizing that donor survival would exceed average survival. METHODS: All living kidney donors in Australia, 2004-2013, and New Zealand, 2004-2012, from the Australian and New Zealand Living Kidney Donor Registry were included. We ascertained primary cause of death from data linkage with national death registers. Standardized mortality ratios and relative survival were estimated, matching on age, sex, calendar year, and country. RESULTS: Among 3253 living kidney donors, there were 32 deaths over 20 331 person-years, with median follow-up 6.2 years [interquartile range: 3.9-8.4]. Only 25 donors had diabetes-fasting blood sugar level predonation, of which 3 had impaired glucose tolerance. At discharge, the median creatinine was 108 µmol/L and estimated glomerular filtration rate was 58 mL/min/1.72 m2. Four deaths occurred in the first year: 2 from immediate complications of donation, and 2 from unrelated accidental causes. The leading cause of death was cancer (n = 16). The crude mortality rate was 157 (95% confidence interval [CI], 111-222)/100 000 person-y, and the standardized mortality ratio was 0.33 (95% CI, 0.24-0.47). The 5-year cumulative relative survival was 1.019 (95% CI, 1.014-1.021), confirming that the survival probability in living kidney donors was 2% higher relative to the general population. CONCLUSIONS: As expected, mortality in living kidney donors was substantially lower than the general population and is reassuring for potential donor counseling. The Living Donor Registry only captured a third of the deaths, highlighting the benefit of data linkage to national death registries in the long-term follow-up of living kidney donors.

Impending challenges of the burden of end-stage kidney disease in Australia.

Sex and age-specific incidence rates of patients with treated end-stage kidney disease (ESKD) in Australia are comparable to those in European countries, but substantially lower compared with those in the United States, Canada and many Asian countries. The incidence rates of treated ESKD in Australia increase with advancing age; however, the incidence of ESKD is likely to be underestimated because a proportion of patients with ESKD (about 50%) remain untreated. Late referral to nephrologists has reduced over the past decade, temporally associated with improved ESKD recognition. However, late referral still occurs in one in five Australians with ESKD. One in two Australians with ESKD has diabetes, with up to 35% of cases directly attributed to diabetes. Mortality rates for patients with ESKD remain substantially higher compared with the age-matched general population, although there has been a significant improvement in survival over time. Cardiovascular disease and cancer are the two most common causes of death in patients with ESKD.

Development and implementation of an enhanced recovery after surgery protocol for renal transplantation.

BACKGROUND: Successful implementation of enhanced recovery after surgery (ERAS) in kidney transplantation requires multidisciplinary consultation, education and attention to protocol. This study discusses the process implementation pathway of the ERAS protocol and its outcome. METHODS: A standardized ERAS protocol was designed for the renal transplant recipient and implemented in July 2017. Data collected prospectively of recipients transplanted from July 2017 to December 2018 were compared to prospectively collected data of recipients who were transplanted prior to ERAS implementation from January 2016 to July 2017 from our renal database. The parameters of interest included length of stay, incidence of delayed graft function and readmission rate. RESULTS: There was no difference in the demographics and the incidence of delayed graft function across both groups, although subgroup analysis suggested a significantly lower incidence of delayed graft function with kidneys donated after circulatory death in the cohort that were managed by the ERAS protocol. The median length of stay for patients on the ERAS protocol was 5 days (range 3-16 days). This was 2 days shorter than the median length of stay for patients not on the ERAS protocol (7 days; range 5-14, P < 0.001). This statistically significant difference in length of stay was consistent across all donor subgroups (living donor, donor after cardiac death and donation after brainstem death). Seventy-nine percent of the patients on the ERAS protocol were discharged on post-operative day 4. CONCLUSION: An ERAS protocol for renal transplant patients is feasible. Our data show that successful implementation of ERAS in kidney transplantation is possible and results in significant cost savings due to shorter length of stay.

Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis.

BACKGROUND: Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients. METHODS: To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics. RESULTS: AR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results. CONCLUSIONS: AR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.

Risk factors for and outcomes of delayed graft function in live donor kidney transplantation - a retrospective study.

Delayed graft function (DGF) in deceased donor kidney transplantation is associated with worse outcomes. DGF has been less well studied in live donor transplantation. We aimed to examine the risk factors for DGF, and associations between DGF and short- and long-term outcomes in live donor kidney transplant recipients. Using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included live donor kidney transplants performed in Australia and New Zealand over 2004-2015 and excluded pediatric recipients (n = 440), pathological donors (n = 97), grafts that failed in the first week (as a proxy for primary non function; n = 38), and grafts with missing DGF data (n = 46). We used multivariable logistic regression to identify the risk factors for DGF and the association between DGF and rejection at 6 months; Cox proportional hazards models to examine the relationship between DGF and patient and graft survival; and linear regression to examine the association between DGF and eGFR at 1 year. DGF occurred in 77 (2.3%) of 3358 transplants. Risk factors for DGF included right-sided kidney [odds ratio (OR) 2.00 (95% CI 1.18, 3.40)], donor BMI [OR 1.06 per kg/m2 (95% CI 1.01, 1.12)]; increasing time on dialysis and total ischemic time [OR 1.09 per hour (1.00, 1.17)]. DGF was associated with increased risk of rejection at 6 months [OR 2.37 (95% CI 1.41, 3.97)], worse patient survival [HR 2.14 (95% CI 1.21, 3.80)] and graft survival [HR 1.98 (95% CI 1.27, 3.10)], and worse renal function at 1 year [Coefficient -9.57 (95% CI -13.5, -5.64)]. DGF is uncommon after live donor kidney transplantation, but associated with significantly worse outcomes. The only modifiable risk factors identified were kidney side and total ischemic time.

Quantifying lead time bias when estimating patient survival in preemptive living kidney donor transplantation.

Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998-2017. Patients were transplanted preemptively (n = 1435) or after receiving up to 6 months of dialysis (n = 712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left-truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min per 1.73 m2 in the non-pre-emptive, and 9.6 mL/min per 1.73 m2 in the preemptive group. In the matched cohort (n = 1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non-pre-emptive 1.12 (95% confidence interval [CI] 0.79-1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4 mL/min per 1.73 m2 /year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.

Access to waitlisting for deceased donor kidney transplantation in Australia.

AIM: A detailed analysis of waitlisting for deceased donor kidney transplantation in Australia has not previously been reported. We aimed to determine if patient characteristics associated with waitlisting identify areas of potential inequality in access to transplantation in Australia. METHODS: A competing risk time-to-event model was used to determine predictors of waitlisting for all adult incident renal replacement therapy patients in Australia between 2006 and 2015. Secondary analysis was performed to determine predictors of overall access to transplantation (using a combined outcome of waitlisting and living donor transplantation). RESULTS: The cohort consisted of 21 231 patients with a median age of 63 years. Overall, 4361 (20.5%) were waitlisted and 1239 (5.8%) received a living donor transplant without being previously waitlisted. Primary analysis revealed that medical comorbidities, older age, smoking status and body mass index were all significant predictors of waitlisting and that and there was variation in waitlisting practice across states Despite adjustment for the above factors, demographic characteristics, including Indigenous ethnicity (subdistribution hazard ratios (SHR) 0.46 (95% confidence interval (CI) 0.38-0.55)), female gender (SHR 0.85 (95% CI 0.80, 0.91)) and residence in a regional area (SHR 0.88 (95% CI 0.81-0.95)) were also associated with a lower likelihood of waitlisting. Secondary analysis showed younger age and higher socio-economic advantage were additional predictors of overall access to transplantation, driven by higher rates of living donor transplantation. CONCLUSION: Demographic as well as clinical characteristics are associated with reduced likelihood of waitlisting for kidney transplantation in Australia. Further analysis and auditing should be considered to determine if this reflects other unmeasured factors or highlights a need to address inequality.

Challenges of kidney paired donation transplants involving multiple donor and recipient surgeons across Australia.

BACKGROUND: The Australian kidney paired donation program adopted the principles of within-chain simultaneous live donor surgery and of organ transport, with the requirement of keeping cold ischemia time (CIT) to <12 h. Whether these principles could be adhered to and what impact on transplant outcome they might have is unknown. METHODS: We evaluated the logistic challenges and outcomes of the first 100 kidney transplants performed in the Australian kidney paired donation program. RESULTS: Within 4 years, 17 donor surgeons at 12 centres were involved in 37 chain exchange surgeries. Sixteen kidneys were transplanted at the same hospital and 84 required transport to the recipient hospital. Mean (±SD) within chain anaesthetic induction time variability was 8 ± 18 min and mean individual surgeon operating time was 115 ± 44 min. In two cases, delays during donor surgery resulted in increased CIT by 1 h because of deferred transport. CIT was 2.6 ± 0.6 h for non-shipped and 6.8 ± 2.8 h for shipped kidneys, four kidneys had CIT of 12-14 h. Immediate allograft function was observed in 85% of recipients, with no difference between shipped and non-shipped kidneys. There were only two cases of delayed graft function requiring temporary dialysis; both had CIT <7 h. There was no difference in serum creatinine at 1 month between non-shipped and shipped kidneys (105 ± 26 versus 112 ± 50 µmol/L) and allograft survival at 1 year was 97%. CONCLUSION: The study provided a favourable audit of kidney transplant activity, despite challenges of simultaneous surgery, organ transport coordination and prolonged CIT. The decision to ship donor kidneys rather than the donor was demonstrated to be feasible and safe.

EARLY PERITONITIS AND ITS OUTCOME IN INCIDENT PERITONEAL DIALYSIS PATIENTS.

BACKGROUND: Early-onset peritonitis is a serious complication of peritoneal dialysis (PD) and is associated with heightened risks of technique failure and death. The risk factors for early peritonitis and its outcomes are unknown. METHODS: This registry study examined all incident Australian PD patients between 2003 and 2014. The primary outcome was early peritonitis, defined as onset within 12 months of starting therapy. Secondary outcomes were medical cure, relapse/recurrence, catheter removal, peritonitis-associated technique failure, and peritonitis-associated death. RESULTS: Of 9,845 patients, 2,615 experienced 3,827 early-peritonitis episodes (0.50 episodes per patient-year). Early peritonitis was more common in patients who were male, obese, had a history of cigarette smoking or cerebrovascular disease, used continuous ambulatory PD, and had received prior renal replacement therapy for > 90 days. Remoteness was a risk modifier for the association between race and early peritonitis; remote Aboriginal, Torres Strait Islander, Maori and Pacific Islander patients had the highest risk. Obese patients were more likely to achieve medical cure. Older patients were less likely to achieve cure and more likely to experience peritonitis-associated death. CONCLUSIONS: In summary, several factors predicted early peritonitis in incident PD patients. Modified approaches to patient selection, training techniques, and prevention strategies should be considered in high-risk individuals.

Recurrent glomerulonephritis after kidney transplantation: risk factors and allograft outcomes.

Recurrent glomerulonephritis after kidney transplantation is a feared complication because it is unpredictable and may have a negative impact on graft outcomes. To better understand this we collected data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry accumulated over 30 years. The incidence, risk factors, and outcomes of recurrent glomerulonephritis in transplant recipients were determined using adjusted Cox proportional hazard and competing risk modeling. A total of 6,597 recipients with biopsy-proven glomerulonephritis as the primary cause of end-stage kidney disease were followed for 51,871 person-years (median duration 7.7 years). The four most common types of glomerulonephritis were IgA nephropathy in 2501 patients, focal segmental glomerulosclerosis (FSGS) in 1403, membranous in 376, and membranoproliferative (MPGN) nephropathy in 357 patients. Among these four types, recurrence was reported in 479 of 4637 patients, and of these, 212 lost their allograft due to recurrence. Older age at transplantation (adjusted hazard ratio [per year increase] 0.96 [95% confidence interval 0.95 - 0.97]) was associated with a lower risk of recurrence. Significantly, the five-year graft survival was 30% for recipients with recurrent MPGN and 57-59% for recipients with FSGS, IgA, and membranous nephropathy. Transplant recipients with recurrent disease were twice as likely to lose their allografts compared to those without recurrence (adjusted hazard ratio 2.04 [1.81-2.31]). Thus, recurrent glomerulonephritis remains a significant cause of graft loss in transplant recipients.

The influence of chronic kidney disease and age on revascularization rates and outcomes in acute myocardial infarction - a cohort study.

BACKGROUND: There is a paucity of data on the complex interaction between chronic kidney disease, age and its impact on management and outcomes in acute myocardial infarction. METHODS: A state based claims dataset that collects data on all hospitalizations (representing 32.3% of the Australian population) was used to identify all patients admitted with a principal diagnosis of acute myocardial infarction (ICD10 codes: I21.0-I21.4) over a four-year period. Patients were linked to the state death registry and followed until death or end of follow-up (31 December 2009). Chronic kidney disease was defined as the presence of any of 65 ICD10 diagnostic codes for chronic kidney disease. The primary outcomes were receipt of revascularization, length of hospital stay and mortality adjusted for age, comorbidities and prior revascularization at presentation. RESULTS: Of the 40,472 patients with acute myocardial infarction, chronic kidney disease was present in 4814 patients (11.9%). Median follow-up was 2.8 years (range 0-5.5 years). In the multivariable model, there was a marked interaction between chronic kidney disease and age ( p<0.001). Chronic kidney disease was a powerful marker of lower revascularization rates (median age group of 70-79 years: odds ratio 0.68; 95% confidence interval 0.59-0.78; p<0.001), especially in those over the age of 50 years. The impact of chronic kidney disease on length of stay (median age group of 70-79 years vs. referent age group 18-39 years: incidence rate ratio 1.41; 95% confidence interval 1.32-1.51; p<0.001) and long-term mortality (median age group of 70-79 years: hazard ratio 2.19; 95% confidence interval 2.01-2.39; p<0.001) was mitigated with increasing age. CONCLUSION: Chronic kidney disease is an important deterrent for the receipt of revascularization in older patients, but age is the primary determinant of length of stay and mortality.

Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Emerging evidence from recently published observational studies and an individual patient data meta-analysis shows that mammalian target of rapamycin inhibitor use in kidney transplantation is associated with increased mortality. Therefore, all-cause mortality and allograft loss were compared between use and nonuse of mammalian target of rapamycin inhibitors in patients from Australia and New Zealand, where mammalian target of rapamycin inhibitor use has been greater because of heightened skin cancer risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our longitudinal cohort study included 9353 adult patients who underwent 9558 kidney transplants between January 1, 1996 and December 31, 2012 and had allograft survival ≥1 year. Risk factors for all-cause death and all-cause and death-censored allograft loss were analyzed by multivariable Cox regression using mammalian target of rapamycin inhibitor as a time-varying covariate. Additional analyses evaluated mammalian target of rapamycin inhibitor use at fixed time points of baseline and 1 year. RESULTS: Patients using mammalian target of rapamycin inhibitors were more likely to be white and have a history of pretransplant cancer. Over a median follow-up of 7 years, 1416 (15%) patients died, and 2268 (24%) allografts were lost. There was a higher risk of all-cause mortality with time-varying mammalian target of rapamycin inhibitor use (hazard ratio, 1.47; 95% confidence interval, 1.23 to 1.76) as well as in the fixed time model analyses comparing mammalian target of rapamycin inhibitor use at baseline (hazard ratio, 1.54; 95% confidence interval, 1.22 to 1.93) and 1 year (hazard ratio, 1.63; 95% confidence interval, 1.32 to 2.01). Time-varying mammalian target of rapamycin inhibitor use was associated with higher risk of death because of malignancy (hazard ratio, 1.37; 95% confidence interval, 1.09 to 1.71). There were no statistically significant differences in the risk of all-cause (hazard ratio, 0.98; 95% confidence interval, 0.85 to 1.12) and death-censored (hazard ratio, 0.85; 95% confidence interval, 0.69 to 1.03) allograft loss between the mammalian target of rapamycin inhibitor use and nonuse groups in the time-varying model as well as the fixed time models. CONCLUSIONS: Mammalian target of rapamycin inhibitor use was associated with a higher risk of all-cause mortality but not allograft loss.

Risk-Factor Profile of Living Kidney Donors: The Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry 2004-2012.

BACKGROUND: Recent literature suggests that living kidney donation may be associated with an excess risk of end-stage kidney disease and death. Efforts to maximize access to transplantation may result in acceptance of donors who do not fit within current guidelines, potentially placing them at risk of adverse long-term outcomes. METHODS: We studied the risk profile of Australian and New Zealand living kidney donors using data from the Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry over 2004 to 2012. We compared their predonation profile against national guidelines for donor acceptance. RESULTS: The analysis included 2,932 donors (mean age 48.8 ± 11.2 years, range 18-81), 58% female and 87% Caucasian. Forty (1%) had measured glomerular filtration rate less than 80 mL/min; 32 (1%) had proteinuria >300 mg/day; 589 (20%) were hypertensive; 495 (18%) obese; 9 (0.3%) were diabetic while a further 55 (2%) had impaired glucose tolerance; and 218 (7%) were current smokers. Overall 767 donors (26%) had at least one relative contraindication to donation and 268 (9%) had at least one absolute contraindication according to national guidelines. CONCLUSIONS: Divergence of current clinical practice from national guidelines has occurred. In the context of recent evidence demonstrating elevated long-term donor risk, rigorous follow-up and reporting of outcomes are now mandated to ensure safety and document any change in risk associated with such a divergence.

A scoring system to screen elderly potential kidney transplant recipients: a simple tool for a complex task.

Despite the rapid growth in the number of dialysis patients ⩾65, relatively few of these patients are receiving transplants. Dusseux et al. present a simple scoring system that helps to identify a group of such patients with a higher survival rate on dialysis. They suggest that such a screening tool might help to identify older patients for more comprehensive transplant assessment.