Trends in the Incidence of End-Stage Kidney Disease in Type 1 and Type 2 Diabetes in Australia, 2010-2019.

RATIONALE & OBJECTIVE: Trends in end-stage kidney disease (ESKD) among people with diabetes may inform clinical management and public health strategies. We estimated trends in the incidence of ESKD among people with type 1 and type 2 diabetes in Australia from 2010-2019 and evaluated their associated factors. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 71,700 people with type 1 and 1,112,690 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS). We estimated the incidence of kidney replacement therapy (KRT) via linkage to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the incidence of KRT or death from ESKD by linking the NDSS to the ANZDATA and the National Death Index for Australia. PREDICTORS: Calendar time, sex, age, and duration of diabetes. OUTCOME: Incidence of KRT and KRT or death from ESKD. ANALYTICAL APPROACH: Incidence of ESKD, trends over time, and associations with factors related to these trends were modeled using Poisson regression stratified by diabetes type and sex. RESULTS: The median duration of diabetes increased from 15.3 to 16.8 years in type 1 diabetes, and from 7.6 to 10.2 years in type 2 diabetes between 2010 and 2019. The incidence of KRT and KRT or death from ESKD did not significantly change over this time interval among people with type 1 diabetes. Conversely, the age-adjusted incidence of KRT and KRT or death from ESKD increased among males with type 2 diabetes (annual percent changes [APCs]: 2.52% [95% CI, 1.54 to -3.52] and 1.27% [95% CI, 0.53 2.03], respectively), with no significant change among females (0.67% [95% CI, -0.68 to 2.04] and 0.07% [95% CI, -0.81 to 0.96], respectively). After further adjustment for duration of diabetes, the incidence of ESKD fell between 2010 and 2019, with APCs of-0.09% (95% CI, -1.06 to 0.89) and-2.63% (95% CI, -3.96 to-1.27) for KRT and-0.97% (95% CI, -1.71 to-0.23) and-2.75% (95% CI, -3.62 to-1.87) for KRT or death from ESKD among males and females, respectively. LIMITATIONS: NDSS only captures 80%-90% of people with diabetes; lack of clinical covariates limits understanding of trends. CONCLUSIONS: While the age-adjusted incidence of ESKD increased for males and was stable for females over the last decade, after adjusting for increases in duration of diabetes the risk of developing ESKD has decreased for both males and females. PLAIN-LANGUAGE SUMMARY: Previous studies showed an increase in new cases of kidney failure among people with type 2 diabetes, but more recent data have not been available. Here, we report trends in the rate of kidney failure for people with type 2 diabetes from 2010 to 2019 and showed that while more people with type 2 diabetes are developing kidney failure, accounting for the fact that they are also surviving longer (and therefore have a higher chance of kidney failure) the growth in this population is not caused by a higher risk of kidney failure. Nevertheless, more people are getting kidney failure than before, which will impact health care systems for years to come.

Retrospective case-control study exploring pretransplant predictors for loss of kidney transplant function or death among indigenous kidney transplant recipients.

BACKGROUND: The factors affecting the outcomes among Indigenous kidney transplant recipients is not fully understood. We conducted a retrospective case control study to identify risk factors beyond those explained by the ANZDATA registry. AIM: To identify the risk factors for loss of kidney transplant function or death among Indigenous kidney transplant recipients. METHODS: Cases were defined as all Indigenous Australian kidney transplant recipients from 1 January 2005 to 31 December 2015 from the major hospitals in the Northern Territory (NT) and South Australia (SA) who experienced graft loss (including patient death) up to 2-years post-transplant. Controls (matched 4:1) were defined as all indigenous kidney transplant recipients during the same period with functioning transplants at 2-years post-transplant operation. Matching was done on gender and diabetes status. Regression analysis adjusted for age was used for comparing cases and controls. RESULTS: There were 17 cases and 68 matched controls. Among cases, the odds ratio for more than one hospital admission episode (compared with ≤1 episode) in the 2-year pretransplant period was 6.2 (95% confidence interval, 1.2-32.5). However, there were no significant differences in the frequency of comorbidities at renal replacement therapy start, cardiovascular intervention pretransplant, pretransplant infection screening, age and gender of the donors, frequency of admission episodes where an infection was documented, the total length of inpatient stay or admission to intensive care unit during pretransplant hospital admission between cases and controls. CONCLUSION: Early graft loss was associated with a higher frequency of hospital admissions in the 2-years pretransplant period. In contrast, other measured factors in the pretransplant period did not predict these adverse outcomes.

Hip Arthroplasty Outcomes in the Presence of Kidney Failure: A National Data Linkage Study.

BACKGROUND: Patients who have kidney failure are at higher risk of requiring total hip arthroplasty (THA) and are at higher risk of complications. This study compared the rate of revision surgery and mortality following THA between patients who have kidney failure receiving long term dialysis or who had a kidney transplant and those who did not have kidney failure. METHODS: A data linkage study was performed using data from 2 national registries: a registry of dialysis and kidney transplant patients and a registry of THA procedures. Both registries had coverage of almost all procedures or treatments in Australia. Data from September 1999 to December 2016 were used. Mortality and revision surgery were compared between patients receiving dialysis, those who had a functioning kidney transplant, and patients who did not have kidney failure using Cox and Fine-Gray (competing risk) regression models. A total of 383,478 primary THA procedures were identified as people receiving dialysis (n = 490), who had a functioning kidney transplant (n = 459), or who did not have kidney failure (n = 382,529). RESULTS: There was no significant difference in the overall rate of revision surgery between the groups (dialysis versus no kidney failure HR = 1.20; 95% CI 0.76, 1.88, transplant versus no kidney failure (hazard ratio) HR = 1.01; 95% (confidence interval) CI 0.66, 1.53). The risk for death after surgery was significantly higher in the dialysis group compared to both the functioning transplant group (HR = 3.44; 95%CI 1.58, 7.5), and in those without kidney failure (HR = 4.13; 95%CI 3.25, 5.25). CONCLUSION: The rate of mortality after THA in patients on dialysis is higher than in patients who have a functioning transplant or those who do not have kidney failure, but there is no early excess mortality to suggest a difference in this metric due to the surgery.

Excess all-cause and cause-specific mortality for people with diabetes and end-stage kidney disease.

AIMS: Excess mortality is high in the setting of diabetes and end-stage kidney disease (ESKD), but the effects of ESKD beyond diabetes itself remains incompletely understood. We examined excess mortality in people with diabetes with versus without ESKD, and variation by age, sex and diabetes type. METHODS: This study included 63,599 people with type 1 (aged 20-69 years; 56% men) and 1,172,160 people with type 2 diabetes (aged 30+ years; 54% men), from the Australian National Diabetes Services Scheme. Initiation of renal replacement therapy and mortality outcomes were obtained via linkage to the Australia and New Zealand Dialysis and Transplant Registry and the National Death Index, respectively. Excess mortality was measured by calculating the mortality rate ratio (MRR) for people with versus without ESKD via indirect standardisation. RESULTS: A total of 9027 people developed ESKD during 8,601,522 person-years of follow-up. Among people with type 1 diabetes, the MRR was 34.9 (95%CI: 16.6-73.1) in men and 41.5 (20.8-83.1) in women aged 20-29 years and was 5.6 (4.5-7.0) and 7.4 (5.5-10.1) in men and women aged 60-69 years, respectively. In type 2 diabetes, MRRs were 16.6 (8.6-31.8) and 35.8 (17.0-75.2) at age 30-39 years and were 2.8 (2.6-3.1) and 3.6 (3.2-4.1) at age 80+ years in men and women, respectively. Excess cause-specific mortality was highest for peripheral artery disease, cardiac arrest, and infections, and lowest for cancer. CONCLUSIONS: Among people with diabetes, excess mortality in ESKD is much higher at younger ages and is higher for women compared with men.

Factors influencing fertility rates in Australian women receiving kidney replacement therapy: analysis of linked Australia and New Zealand Dialysis and Transplant Registry and perinatal data over 22 years.

BACKGROUND: Pregnancy in women receiving kidney replacement therapy (KRT) is uncommon, and trends and factors influencing fertility rates remain poorly defined. METHODS: The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) was linked to mandatory perinatal data sets (all births from 1991 to 2013, ≥20 weeks' gestation) in four Australian jurisdictions. Overall, age- and era-specific fertility rates were calculated based on general and KRT population denominators. RESULTS: From 2 948 084 births, 248 babies were born to 168 mothers receiving KRT (37 babies born to 31 dialysed mothers; 211 babies born to 137 transplanted mothers). Substantial agreement between ANZDATA and perinatal data sets was observed for birth events and outcomes. Transplanted women had higher fertility rates than dialysed women in all analyses, with 21.4 live births/1000 women/year [95% confidence interval (CI) 18.6-24.6] in transplanted women, 5.8 (95% CI 4.1-8.1) in dialysed women and 61.9 (95% CI 61.8-62.0) in the non-KRT cohort. Fertility rates for dialysed women rose in recent years. After adjusting for maternal age and treatment modality, Caucasian women had higher fertility rates, while women with pre-existing diabetes, or transplanted women with exposure to KRT for ≤3.0 years had lower rates. As expected, transplanted women with a pre-conception estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2 or transplant-to-pregnancy interval of <1.0 year had lower fertility rates. Geographical location, socioeconomic status and primary disease (glomerulonephritis versus other) did not affect fertility rates. CONCLUSIONS: Reporting of births to ANZDATA is sufficiently accurate to justify ongoing data collection. Rising fertility rates in dialysed women may indicate permissive attitudes towards pregnancy. Treatment modality, ethnicity, diabetes, pre-conception eGFR, transplant-to-pregnancy interval and duration of KRT exposure were associated with fertility rates. These factors should be considered when counselling women with kidney disease about parenthood.

Changes in excess mortality among adults with diabetes-related end-stage kidney disease: a comparison between the USA and Australia.

BACKGROUND: The number of people with diabetes-related end-stage kidney disease (ESKD-DM) has doubled in the last two decades. We examined changes in excess mortality for people with ESKD-DM in the USA and Australia. METHODS: In this retrospective cohort study, we included adults (ages 20-84 years) receiving renal replacement therapy (RRT) for ESKD-DM in the USA (n = 1 178 860 from the United States Renal Data System, 2002-17) and Australia (n = 10 381 from the Australia and New Zealand Dialysis and Transplant Registry, 2002-13). ESKD-DM was defined as those with diagnosed diabetes at time of RRT initiation and mortality status was captured from national death registries. Annual standardized mortality ratios (SMR) were stratified by treatment modality, and age, sex and race (USA only). Trends were assessed using join point regression and annual percent change (APC) was reported. RESULTS: Overall, in the dialysis population SMR decreased from 2006 to 2014 in the USA (from 12.0 to 10.1; APC -2.1) and from 2002 to 2013 in Australia (from 12.0 to 9.4; APC -3.4). In the transplant population, SMR decreased from 6.2 to 4.0 from 2002 to 2013 in the USA, and did not significantly change from 2002 to 2013 in Australia. By subgroup, excess mortality was higher in women (versus men), younger (versus older) adults, dialysis (versus transplant) patients, and in Asian or Pacific Islanders and American Indian or Alaskan Natives (AI/AN) (versus Whites and Blacks). SMRs declined similarly across all subgroups excluding AI/AN (USA) and transplant patients (Australia), where relative declines were smaller. CONCLUSIONS: Excess mortality for people with ESKD-DM treated with dialysis or transplant has decreased in the USA and Australia, but progress has stalled from ∼2013 in the USA. Nevertheless, mortality remains more than nine times higher in ESKD-DM versus the general population, with important variations by subgroups. Given the increasing burden of diabetes in the population, a focus on reducing excess mortality risk in the ESKD-DM population is needed.

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.

Home Versus Facility Dialysis and Mortality in Australia and New Zealand.

RATIONALE & OBJECTIVE: Mortality is an important outcome for all dialysis stakeholders. We examined associations between dialysis modality and mortality in the modern era. STUDY DESIGN: Observational study comparing dialysis inception cohorts 1998-2002, 2003-2007, 2008-2012, and 2013-2017. SETTING & PARTICIPANTS: Australia and New Zealand (ANZ) dialysis population. EXPOSURE: The primary exposure was dialysis modality: facility hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated PD (APD), or home HD. OUTCOME: The main outcome was death. ANALYTICAL METHODS: Cause-specific proportional hazards models with shared frailty and subdistribution proportional hazards (Fine and Gray) models, adjusting for available confounding covariates. RESULTS: In 52,097 patients, the overall death rate improved from ~15 deaths per 100 patient-years in 1998-2002 to ~11 in 2013-2017, with the largest cause-specific contribution from decreased infectious death. Relative to facility HD, mortality with CAPD and APD has improved over the years, with adjusted hazard ratios in 2013-2017 of 0.88 (95% CI, 0.78-0.99) and 0.91 (95% CI, 0.82-1.00), respectively. Increasingly, patients with lower clinical risk have been adopting APD, and to a lesser extent CAPD. Relative to facility HD, mortality with home HD was lower throughout the entire period of observation, despite increasing adoption by older patients and those with more comorbidities. All effects were generally insensitive to the modeling approach (initial vs time-varying modality, cause-specific versus subdistribution regression), different follow-up time intervals (5 year vs 7 year vs 10 year). There was no effect modification by diabetes, comorbidity, or sex. LIMITATIONS: Potential for residual confounding, limited generalizability. CONCLUSIONS: The survival of patients on PD in 2013-2017 appears greater than the survival for patients on facility HD in ANZ. Additional research is needed to assess whether changing clinical risk profiles over time, varied dialysis prescription, and morbidity from dialysis access contribute to these findings.

The IDEAL trial in Australia and New Zealand: clinical and economic impact.

BACKGROUND: The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry. METHODS: We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000-2010) and following (2010-2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice. RESULTS: From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19-0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [-0.01 mL/min/1.73 m2/year (95% CI -0.03-0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year. CONCLUSIONS: The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.

Serum phosphate and mortality in incident dialysis patients in Australia and New Zealand.

AIM: Hyperphosphataemia is associated with increased adverse outcomes, including mortality. Re-examining this association using up-to-date data reflecting current and real-world practices, across different global regions and in both haemodialysis and peritoneal dialysis patients, is important. METHODS: We describe the association between serum phosphate and all-cause and cardiovascular mortality in incident dialysis patients between 2008 and 2018 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Time-dependent Cox proportionate hazards models were used. Models were adjusted for available covariates and fitted for the overall cohort, and also each dialysis modality. RESULTS: 31 989 patients were followed over 97 122 person-years at risk (mean age at first dialysis 61 years, 38% female, 67% haemodialysis). We observed a U-shaped association between serum phosphate and all-cause mortality. In the fully adjusted model, categories of serum phosphate above and below 1.25-1.99 mmol/L were associated with progressively higher risk, reaching a hazard ratio of 2.13 (95% CI 1.93-2.36, p < .001) for serum phosphate ≥2.75 mmol/L, and 1.56 (95% CI 1.44-1.69, p < .001) for serum phosphate <1.00 mmol/L. Low and high levels of serum phosphate were also associated with increased risk of cardiovascular mortality, however the association with high serum phosphate was more pronounced ("J-shaped relationship"). The associations were consistent across sub-analyses of patients receiving haemodialysis and peritoneal dialysis treatment. CONCLUSION: In this large contemporary dialysis cohort, both high and low levels of serum phosphate were independently associated with increased risk of mortality. Future studies are required to determine whether treatment of abnormal serum phosphate levels improves mortality.

Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. METHODS: In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity. RESULTS: A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans. CONCLUSIONS: Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.

An update on chronic kidney disease in Aboriginal Australians.

We provide a brief update on some aspects of chronic kidney disease (CKD) in Indigenous Australians, with CKD referring to all stages of pre-terminal kidney disease, as well as to end-stage kidney failure (ESKF), whether or not a person receives renal replacement therapy (RRT). Recently recorded rates of ESKF and RRT were 6- and 8-fold those recoded for non-Indigenous Australians with age adjustment, while non-dialysis CKD hospitalizations and CKD-attributed deaths were 8-fold and 3-fold higher. The median age of Indigenous people who developed ESKF was ~ 30 years less than for non-Indigenous people, and 84% of them received RTT, while only half of non-Indigenous people with ESKF did so. However, the nationwide average Indigenous incidence rate of RRT appears to have stabilized. The 2012 Australian Health Survey showed elevated levels of CKD markers in Indigenous people at the community level. For all CKD parameters, rates among Indigenous people were strikingly correlated with increasing remoteness of residence and socioeconomic disadvantage, and there was a female predominance in remote areas. The burden of renal disease in Australian Indigenous people is seriously understated by Global Burden of Disease Mortality methodology, because it employs underlying cause of death only, and because deaths of people on RRT are frequently attributed to non-renal causes. These data give a much-expanded view of CKD in Aboriginal people. Methodologic approaches must be remedied for a full appreciation of the burden, costs, and outcomes of the disease, to direct appropriate policy development.

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.

Trends in Incidence of ESKD in People With Type 1 and Type 2 Diabetes in Australia, 2002-2013.

RATIONALE & OBJECTIVE: The number of people with diabetes and end-stage kidney disease (ESKD) is increasing worldwide, but it is unknown whether this indicates an increasing risk for ESKD in people with diabetes. We examined temporal trends in the incidence of ESKD within the Australian population with diabetes from 2002 to 2013. STUDY DESIGN: Follow-up study using a national health care services registry. SETTING & PARTICIPANTS: Registrants with type 1 or type 2 diabetes in Australia's National Diabetes Services Scheme (NDSS). PREDICTORS: Age, sex, indigenous status, diabetes type, and calendar year. OUTCOME: Incidence of ESKD (dialysis or kidney transplantation) or death ascertained using the Australian and New Zealand Dialysis and Transplant Registry and the Australian national death index. ANALYTICAL APPROACH: NDSS registrants were followed up from 2002 or date of registration until onset of ESKD, death, or December 31, 2013. The incidence of ESKD in type 1 diabetes was calculated only in those younger than 55 years. RESULTS: Among 1,375,877 registrants between 2002 and 2013, a total of 9,977 experienced incident ESKD, representing an overall incidence of ESKD in people with diabetes of 10.0 (95% CI, 9.8-10.2) per 10,000 person-years. Among those with type 1 diabetes, the age-standardized annual incidence was stable during the study period. Among those with type 2 diabetes, the incidence increased in nonindigenous people (annual percentage change, 2.2%; 95% CI, 0.4%-4.1%) with the greatest increases in those younger than 50 and those older than 80 years. No significant change over time was observed in indigenous people, although the adjusted incident rate ratio for indigenous versus nonindigenous was 4.03 (95% CI, 3.68-4.41). LIMITATIONS: Lack of covariates such as comorbid conditions, medication use, measures of quality of care, and baseline kidney function. CONCLUSIONS: The age-standardized annual incidence of ESKD increased in Australia from 2002 to 2013 for nonindigenous people with type 2 diabetes but was stable for people with type 1 diabetes. Efforts to prevent the development of ESKD, especially among indigenous Australians and those with early-onset type 2 diabetes, are warranted.

Changes in Body Mass Index and Rates of Death and Transplant in Hemodialysis Patients: A Latent Class Joint Modeling Approach.

BACKGROUND: The relationship between body mass index (BMI) and patient survival in end-stage kidney disease is not well understood and has been the subject of much debate over recent years. METHODS: This study used a latent class joint modeling approach to identify latent groups that underpinned associations between patterns of change in BMI during hemodialysis and two competing events: transplant and death without transplant. We included all adult patients who initiated chronic hemodialysis treatment in Australia or New Zealand between 2005 and 2014. RESULTS: There were 16,414 patients included in the analyses; 2,365 (14%) received a transplant, 5,639 (34%) died before transplant, and 8,410 (51%) were administratively censored. Our final model characterized patients based on five broad patterns of weight change (BMI trajectories): "late BMI decline" (about 2 years after commencing hemodialysis); "rapid BMI decline" (immediately after commencing hemodialysis); "stable and normal/overweight BMI"; "stable and morbidly obese BMI"; or "increasing BMI." Mortality rates were highest among classes with declining BMI, and the timing of weight loss coincided with the timing of increases in mortality. Within the two stable BMI classes, death rates were slightly lower among the morbidly obese. CONCLUSIONS: The findings from this descriptive analysis suggest a paradoxical association between obesity and better survival. However, they also suggest that the shape of the BMI trajectory is important, with stable BMI trajectories being beneficial. Future research should be aimed at understanding the causes of weight changes during dialysis, to determine whether there could be strategies to improve patient survival.

The Spectrum of Adverse Pregnancy Outcomes Based on Kidney Disease Diagnoses: A 20-Year Population Study.

BACKGROUND AND OBJECTIVES: Kidney disorders in pregnancy may be under-recognized and have variable impact on outcomes depending on diagnosis. Population-level data are limited, particularly for Australia, and comparison of impact of different kidney disorders on pregnancy has rarely been assessed. This study examined the prevalence and outcomes of varied kidney disorders using population-level perinatal data from a large cohort. METHODS: Women with singleton pregnancies > 20 weeks' gestation from the South Australian Pregnancy Outcomes Unit (1990-2012). Women with a kidney disorders diagnostic code were grouped into categories (immunological, cystic/genetic, urological, vesicoureteral reflux (VUR), pyelonephritis and "other"). Key pregnancy outcomes were assessed, with adjustment for demographic variables. RESULTS: Kidney disorders were reported in 1,392 (0.3%) of 407,580 births. These pregnancies had increased risk of pregnancy-induced hypertension (OR 2.16, 95% CI 1.82-2.56), induction of labor (RRR vs. spontaneous birth 2.10, 95% CI 1.87-2.36), all Caesarean section (OR 1.31, 95% CI 1.17-1.47) as well as Caesarean section without labor (RRR 1.82, 95% CI 1.57-2.10), preterm birth (< 37 weeks; 2.76, 95% CI 2.40-3.18), low birth weight (< 2,500 g) infants (OR 2.43, 95% CI 2.07-2.84), and neonatal intensive care admission (OR 2.64, 95% CI 2.12-3.29). Diagnostic subgroups demonstrated differing patterns of adverse outcomes, enabling the development of a matrix of risk. Women with immunological renal conditions and VUR had greatest risk overall, and only women with immunological diseases had increased risk of small-for-gestational age < 10th centile (OR 2.36, 95% CI 1.26-4.42). Women with nonchronic urological conditions and pyelonephritis had increased risk of preterm birth, but not other adverse events. VUR conferred particularly increased risk of Caesarean section and induced labor. CONCLUSIONS: In a cohort of > 1,300 women with varied kidney disorders, increased adverse obstetric and perinatal events were observed, and the nature and magnitude of risk differed according to diagnosis. In particular, vesicoureteric reflux is not a benign condition in pregnancy. Women with nonchronic conditions still had increased risk of preterm birth. We confirm that women with kidney disorders warrant vigilant and tailored prepregnancy care and clinical care in pregnancy.

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.

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.

Kidney transplant graft outcomes in 379 257 recipients on 3 continents.

Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow-up registry data from 1988-2014 for 379 257 recipients of first kidney-only transplants using Cox regression. Compared to the United States, 1-year adjusted graft failure risk was significantly higher in the United Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18-1.26, P < .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14-1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84-0.96, P = .001). In contrast, long-term adjusted graft failure risk (conditional on 1-year function) was significantly higher in the United States compared to Australia, New Zealand, and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001). Thus long-term kidney graft outcomes are approximately 25% worse in the United States than in 3 other countries with well-developed kidney transplant systems. Case mix differences and residual confounding from unmeasured factors were found to be unlikely explanations. These findings suggest that identification of potentially modifiable country-specific differences in care delivery and/or practice patterns should be sought.