Cause of death for living kidney donors and people with kidney failure, in Australia and New Zealand (CELESTIAL)

@article{Rosales2022,

title = {Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013},

author = {Brenda M. Rosales and Nicole De La Mata and Claire M. Vajdic and Patrick J. Kelly and Kate Wyburn and Angela C. Webster},

doi = {10.1053/j.ajkd.2022.03.010},

issn = {0272-6386},

year  = {2022},

date = {2022-10-00},

urldate = {2022-10-00},

journal = {American Journal of Kidney Diseases},

volume = {80},

number = {4},

pages = {449--461},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Khou2022,

title = {Epidemiology of cardiovascular death in kidney failure: An Australian and New Zealand cohort study using data linkage},

author = {Victor Khou and Nicole L. De La Mata and Patrick J. Kelly and Philip Masson and Emma O'Lone and Rachael L. Morton and Angela C. Webster},

doi = {10.1111/nep.14020},

issn = {1440-1797},

year  = {2022},

date = {2022-05-00},

urldate = {2022-05-00},

journal = {Nephrology},

volume = {27},

number = {5},

pages = {430--440},

publisher = {Wiley},

abstract = {<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Cardiovascular mortality risk evolves over the lifespan of kidney failure (KF), as patients develop comorbid disease and transition between treatment modalities. Absolute cardiovascular death rates would help inform clinical practice and health‐care provision, but are not well understood across a continuum of dialysis and transplant states. We aimed to characterize cardiovascular death across the natural history of KF using a lifespan approach.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a population‐based cohort study of incident patients commencing kidney replacement therapy in Australia and New Zealand. Cardiovascular deaths were identified using data linkage to national death registers. We estimated the probability of death and kidney transplant using multi‐state models, and calculated rates of graft failure and cardiovascular death across demographic factors and comorbidities.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 60 823 incident patients followed over 381 874 person‐years, 25% (8492) of deaths were from cardiovascular disease. At 15 years from treatment initiation, patients had a 15.2% probability of cardiovascular death without being transplanted, but only 2.3% probability of cardiovascular death post‐transplant. Females had a 3% lower probability of cardiovascular death at 15 years (15.3% vs. 18.6%) but 4% higher probability of non‐cardiovascular death (54.5% vs. 50.8%). Within the first year of dialysis, cardiovascular mortality peaked in the second month and showed little improvement across treatment era.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Despite improvements over time, cardiovascular death remains common in KF, particularly among the dialysis population and in the first few months of treatment. Multi‐state models can provide absolute measures of cardiovascular mortality across both dialysis and transplant states.</jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeLaMata2021,

title = {Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study},

author = {Nicole L De La Mata and Brenda Rosales and Grace MacLeod and Patrick J Kelly and Philip Masson and Rachael L Morton and Kate Wyburn and Angela C Webster},

doi = {10.1136/bmj-2021-068247},

issn = {1756-1833},

year  = {2021},

date = {2021-11-16},

urldate = {2021-11-16},

journal = {BMJ},

publisher = {BMJ},

abstract = {<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate sex differences in mortality among people with kidney failure compared with the general population.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Population based cohort study using data linkage.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>Of 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Relative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Few differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Compared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients.</jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Khou2020,

title = {Cause of death for people with end-stage kidney disease withdrawing from treatment in Australia and New Zealand},

author = {Victor Khou and Nicole L De La Mata and Rachael L Morton and Patrick J Kelly and Angela C Webster},

doi = {10.1093/ndt/gfaa105},

issn = {1460-2385},

year  = {2021},

date = {2021-07-23},

urldate = {2021-07-23},

volume = {36},

number = {8},

pages = {1527--1537},

publisher = {Oxford University Press (OUP)},

abstract = {<jats:title>Abstract</jats:title>

               <jats:sec>

                  <jats:title>Background</jats:title>

                  <jats:p>Withdrawal from renal replacement therapy is common in patients with end-stage kidney disease (ESKD), but end-of-life service planning is challenging without population-specific data. We aimed to describe mortality after treatment withdrawal in Australian and New Zealand ESKD patients and evaluate death-certified causes of death.</jats:p>

               </jats:sec>

               <jats:sec>

                  <jats:title>Methods</jats:title>

                  <jats:p>We performed a retrospective cohort study on incident patients with ESKD in Australia, 1980–2013, and New Zealand, 1988–2012, from the Australian and New Zealand Dialysis and Transplant registry. We estimated mortality rates (by age, sex, calendar year and country) and summarized withdrawal-related deaths within 12 months of treatment modality change. Certified causes of death were ascertained from data linkage with the Australian National Death Index and New Zealand Mortality Collection database.</jats:p>

               </jats:sec>

               <jats:sec>

                  <jats:title>Results</jats:title>

                  <jats:p>Of 60 823 patients with ESKD, there were 8111 treatment withdrawal deaths and 26 207 other deaths over 381 874 person-years. Withdrawal-related mortality rates were higher in females and older age groups. Rates increased between 1995 and 2013, from 1142 (95% confidence interval 1064–1226) to 2706/100 000 person-years (95% confidence interval 2498–2932), with the greatest increase in 1995–2006. A third of withdrawal deaths occurred within 12 months of treatment modality change. The national death registers reported kidney failure as the underlying cause of death in 20% of withdrawal cases, with other causes including diabetes (21%) and hypertensive disease (7%). Kidney disease was not mentioned for 18% of withdrawal patients.</jats:p>

               </jats:sec>

               <jats:sec>

                  <jats:title>Conclusions</jats:title>

                  <jats:p>Treatment withdrawal represents 24% of ESKD deaths and has more than doubled in rate since 1988. Population data may supplement, but not replace, clinical data for end-of-life kidney-related service planning.</jats:p>

               </jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wyld2020,

title = {Cardiac Mortality in Kidney Transplant Patients: A Population-based Cohort Study 1988–2013 in Australia and New Zealand},

author = {Melanie L.R. Wyld and Nicole L. De La Mata and Philip Masson and Emma O’Lone and Patrick J. Kelly and Angela C. Webster},

doi = {10.1097/tp.0000000000003224},

issn = {0041-1337},

year  = {2021},

date = {2021-00-00},

urldate = {2021-00-00},

volume = {105},

number = {2},

pages = {413--422},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {<jats:sec>

            <jats:title>Background.</jats:title>

            <jats:p>Transplant recipients experience excess cardiac mortality. We compared circulatory death rates in Australian and New Zealand kidney transplant recipients to the general population and identified risk factors for circulatory death in kidney transplant recipients.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Methods.</jats:title>

            <jats:p>The primary cause of death for kidney transplant recipients aged ≥18 was established through ICD-10-AM codes using data linkage between the Australia and New Zealand dialysis and transplant registry and national death registers. We estimated standardized mortality ratios (SMRs) and developed a Fine–Gray competing risks model to determine risk factors for cardiac mortality.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Results.</jats:title>

            <jats:p>Of 5089 deaths in 16 329 kidney transplant recipients (158 325 person-years), 918 (18%) were cardiac. An increased risk of circulatory death was associated with older age (<jats:italic toggle="yes">P</jats:italic> < 0.001), male sex (<jats:italic toggle="yes">P</jats:italic> < 0.001), longer dialysis duration (<jats:italic toggle="yes">P</jats:italic> = 0.004), earlier era of transplantation (<jats:italic toggle="yes">P</jats:italic> < 0.001), ever graft failure (<jats:italic toggle="yes">P</jats:italic> < 0.001), known coronary artery disease (<jats:italic toggle="yes">P</jats:italic> = 0.002), and kidney failure from diabetes or hypertension (<jats:italic toggle="yes">P</jats:italic> < 0.001). The cardiac SMR was 5.4 [95% confidence interval (CI): 5.0-5.8], falling from 8.0 (95% CI: 4.9-13.1) in 1988 to 5.3 (95% CI: 4.0-7.0) in 2013 (<jats:italic toggle="yes">P</jats:italic> < 0.001). Females, particularly young ones, had significantly higher relative cardiac mortality than men. In recipients aged 40 years, the cardiac SMR was 26.5 (95% CI: 15.0-46.6) in females and 7.5 (95% CI: 5.0-11.1) for males.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Conclusions.</jats:title>

            <jats:p>Cardiac risks remain elevated in kidney transplant recipients and may be under-recognized, and prevention and treatment interventions less accessed, less effective or even harmful in female recipients.</jats:p>

          </jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rosales2019,

title = {Cancer mortality in kidney transplant recipients: An Australian and New Zealand population‐based cohort study, 1980–2013},

author = {Brenda M. Rosales and Nicole De La Mata and Claire M. Vajdic and Patrick J. Kelly and Kate Wyburn and Angela C. Webster},

doi = {10.1002/ijc.32585},

issn = {1097-0215},

year  = {2020},

date = {2020-05-15},

urldate = {2020-05-15},

journal = {Intl Journal of Cancer},

volume = {146},

number = {10},

pages = {2703--2711},

publisher = {Wiley},

abstract = {<jats:p>Cancer burden is increasing in kidney transplant recipients, but differences in mortality compared to the general population remain unclear. We sought to compare cancer mortality in paediatric and adult kidney transplant recipients with the general population and describe any differences, by site, age and sex, country and over time. We included kidney transplant recipients from the Australian and New Zealand Dialysis and Transplantation Registry, 1980–2013. Date of death and underlying cause of death were ascertained by data‐linkage and classified using ICD10AM codes. Indirect standardisation was used to estimate standardised mortality ratios (SMR). There were 5,284 deaths in 17,628 kidney transplant recipients over 175,084 person‐years of observation, including 1,061 (20%) cancer deaths. Relative cancer mortality was higher than the general population for all‐site (SMR 2.9, 95% CI 2.7–3.1) cancer and highest for nonmelanoma skin cancer (SMR 50.9, 95% CI 43.5–59.6) and lymphoma (SMR 42.2, 95% CI 35.3–50.5). Relative cancer mortality decreased with increasing age in men (<jats:italic>p</jats:italic> < 0.001) and women (<jats:italic>p</jats:italic> = 0.001) but never reached parity with the general population. Relative mortality did not change with age for skin and lip, or colorectal cancers (<jats:italic>p</jats:italic>‐value >0.1). Only relative colorectal cancer mortality increased over time (<jats:italic>p</jats:italic> = 0.002). Our study shows cancer mortality in kidney transplant recipients was higher than expected in the general population. The magnitude of excess mortality varied by cancer site, age and sex. Further evidence is needed to identify whether this variation is due to differences at diagnosis or access and effectiveness of cancer treatments in this population.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeLaMata2019,

title = {Excess Stroke Deaths in Kidney Transplant Recipients: A Retrospective Population-based Cohort Study Using Data Linkage},

author = {Nicole L. De La Mata and Patrick J. Kelly and Melanie Wyld and Philip Masson and Rustam Al-Shahi Salman and Angela C. Webster},

doi = {10.1097/tp.0000000000003091},

issn = {0041-1337},

year  = {2020},

date = {2020-00-00},

urldate = {2020-00-00},

volume = {104},

number = {10},

pages = {2129--2138},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {Kidney transplant recipients are thought to experience a high risk of stroke; however, little data exist. We aimed to compare the stroke deaths in kidney transplant recipients with the general population and identify risk factors for stroke death in kidney transplant recipients.

Cause of death was established using data linkage between the Australian and New Zealand Dialysis and Transplant Registry and national death registers: Australia, 1980–2013, and New Zealand, 1988–2012. We estimated standardized mortality ratios (SMR) and used competing risks models to identify risk factors. Subanalysis explored those with polycystic kidney disease.

Among 17 628 kidney transplant recipients, there were 158 stroke deaths and 5126 nonstroke deaths in 175 084 person-years. Those aged 30–49 years experienced more stroke deaths than expected, especially women (SMR in females: 19.7 [95% confidence interval, 12.9-30.3] and males: 9.1 [95% confidence interval, 5.6-14.6]). Higher risk of stroke death was associated with older age at transplant, ever graft failure, earlier era of transplant, preexisting cerebrovascular disease, and no previous malignancy. Polycystic kidney disease did not result in different SMR.

Kidney transplant recipients had excess stroke deaths, particularly at younger ages and women. Preexisting cerebrovascular disease was a potentially modifiable risk factor for stroke death, suggesting further studies of secondary stroke prevention for kidney transplant recipients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeLaMata2020b,

title = {Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage},

author = {Nicole L. De La Mata and Philip A. Clayton and Patrick J. Kelly and Stephen McDonald and Steven Chadban and Kevan R. Polkinghorne and Angela C. Webster},

doi = {10.1097/txd.0000000000000975},

issn = {2373-8731},

year  = {2020},

date = {2020-00-00},

urldate = {2020-00-00},

volume = {6},

number = {3},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {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.

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.

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 m<jats:sup>2</jats:sup>. 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.

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}