Calciphylaxis Episodes in the Australia and New Zealand Dialysis and Transplant Registry.

Introduction: Calciphylaxis is a rare disorder associated with significant morbidity and mortality. Data registries are an invaluable source of information for rare diseases. We reviewed cases of calciphylaxis recorded in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and evaluated associations and outcomes of this condition. Methods: Data was obtained on all cases of calciphylaxis reported between 2019 and 2022 in Australian and New Zealand patients on kidney replacement therapy (KRT). This cohort was compared to all patients in the registry who received KRT from 2019 to 2022 without an episode of calciphylaxis. Cox proportional hazards regression including a time-varying covariate for calciphylaxis episode was conducted for mortality with models restricted to patients on dialysis only. Results: From 2019 to 2022, 333 patients had calciphylaxis episodes reported. Overall incidence rate for patients on dialysis was 4.5 (4.1-5.1) episodes per 1000 patient-years on dialysis. Median age was 63 (interquartile range [IQR]: 55-73) years, 54% were female, 66% had diabetes, 59% were obese (body mass index [BMI] ≥ 30 kg/m2) and 77% were receiving hemodialysis (HD) treatment. Compared to patients without calciphylaxis (n = 46,526), patients with calciphylaxis were more likely to be older, female, and have diabetes, greater BMI, coronary artery, and peripheral vascular disease. The median time to calciphylaxis was 3.2 (IQR: 0.9-6.7) years after KRT commencement. Half of the patients with calciphylaxis died by 12 months from diagnosis. Adjusted hazard ratio (HR) of mortality for patients on dialysis with calciphylaxis <1 year and 1 to 4 years after an episode was 5.8 (4.9-6.9) and 1.5 (1.0-2.1), respectively compared to patients on dialysis without calciphylaxis. Conclusion: Calciphylaxis is a rare but life-threatening condition in people on KRT with the greatest mortality burden within 12 months of diagnosis.

Patient Perspectives of Center-Specific Reporting in Kidney Failure Care: An Australian Qualitative Study.

Introduction: Public reporting of quality of care indicators in healthcare is intended to inform consumer decision-making; however, people may be unaware that such information exists, or it may not capture their priorities. The aim of this study was to understand the views of people with kidney disease about public reporting of dialysis and transplant center outcomes. Methods: This qualitative study involved 27 patients with lived experience of kidney disease in Australia who participated in 11 online focus groups between August and December 2022. Transcripts were analyzed thematically. Results: Patients from all Australian states and territories participated, with 22 (81%) having a functioning kidney transplant and 22 (81%) having current or previous experience of dialysis. Five themes were identified as follows: (i) surrendering to the health system, (ii) the complexity of quality, (iii) benefits for patient care and experience, (iv) concerned about risks and unintended consequences, and (v) optimizing the impact of data. Conclusion: Patients desire choice among kidney services but perceive this as rarely possible in the Australian context. Health professionals are trusted to make decisions about appropriate centers. Public reporting of center outcomes may induce fear and a loss of balanced perspective; however, it was supported by all participants and represents an opportunity for self-advocacy and informed decision-making. Strategies to mitigate potential risks include availability of trusted clinicians and community members to aid in data interpretation, providing context about centers and patients, and framing statistics to promote positivity and hope.

Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study.

BACKGROUND: The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). METHODS: Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. RESULTS: A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. CONCLUSIONS: This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

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.

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

BACKGROUND: Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30 days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. RESULTS: Of 12 814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. CONCLUSIONS: Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.

Donors With a Prior History of Cancer: Factors of Non-Utilization of Kidneys for Transplantation.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68-3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58-3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

Trajectories of systolic blood pressure decline in kidney transplant donors prior to circulatory death and delayed graft function.

Background: Kidneys donated after circulatory death suffer a period of functional warm ischaemia before death, which may lead to early ischaemic injury. Effects of haemodynamic trajectories during the agonal phase on delayed graft function (DGF) is unknown. We aimed to predict the risk of DGF using patterns of trajectories of systolic blood pressure (SBP) declines in Maastricht category 3 kidney donors. Methods: We conducted a cohort study of all kidney transplant recipients in Australia who received kidneys from donation after circulatory death donors, divided into a derivation cohort (transplants between 9 April 2014 and 2 January 2018 [462 donors]) and a validation cohort (transplants between 6 January 2018 and 24 December 2019 [324 donors]). Patterns of SBP decline using latent class models were evaluated against the odds of DGF using a two-stage linear mixed effects model. Results: In the derivation cohort, 462 donors were included in the latent class analyses and 379 donors in the mixed effects model. Of the 696 eligible transplant recipients, 380 (54.6%) experienced DGF. Ten different trajectories, with distinct patterns of SBP decline were identified. Compared with recipients from donors with the slowest decline in SBP after withdrawal of cardiorespiratory support, the adjusted odds ratio (aOR) for DGF was 5.5 [95% confidence interval (CI) 1.38-28.0] for recipients from donors with a steeper decline and lowest SBP [mean 49.5 mmHg (standard deviation 12.5)] at the time of withdrawal. For every 1 mmHg/min reduction in the rate of decline of SBP, the respective aORs for DGF were 0.95 (95% CI 0.91-0.99) and 0.98 (95% CI 0.93-1.0) in the random forest and least absolute shrinkage and selection operator models. In the validation cohort, the respective aORs were 0.95 (95% CI 0.91-1.0) and 0.99 (95% CI 0.94-1.0). Conclusion: Trajectories of SBP decline and their determinants are predictive of DGF. These results support a trajectory-based assessment of haemodynamic changes in donors after circulatory death during the agonal phase for donor suitability and post-transplant outcomes.

Long-term Trends in Infection-Related Mortality in Adults Treated With Maintenance Dialysis.

RATIONALE & OBJECTIVE: Infection is 1 of the top 3 causes of death in patients receiving maintenance dialysis. We evaluated the trends over time and risk factors for infection-related deaths among people receiving dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We included all adults who began dialysis between 1980 and 2018 in Australia and New Zealand. EXPOSURE: Age, sex, dialysis modality, and dialysis era. OUTCOME: Infection-related death. ANALYTICAL APPROACH: Incidence was described and standardized mortality ratios (SMR) calculated for infection-related death. Fine-Gray subdistribution hazards models were fitted, with non-infection-related death and kidney transplantation treated as competing events. RESULTS: The study comprised 46,074 patients who received hemodialysis and 20,653 who were treated with peritoneal dialysis who were followed for 164,536 and 69,846 person-years, respectively. There were 38,463 deaths during the follow-up period, 12% of which were ascribed to infection. The overall rate of mortality from infection (per 10,000 person-years) was 185 and 232 for patients treated with hemodialysis and peritoneal dialysis, respectively. The rates were 184 and 219 for males and females, respectively; and 99, 181, 255, and 292 for patients aged 18-44, 45-64, 65-74, 75 years and over, respectively. The rates were 224 and 163 for those commencing dialysis in years 1980-2005 and 2006-2018, respectively. The overall SMR declined over time, from 37.1 (95% CI, 35.5-38.8) in years 1980-2005 to 19.3 (95% CI, 18.4-20.3) in years 2006-2018, consistent with the declining 5-year SMR trend (P<0.001). Infection-related mortality was associated with being female, older age, and Aboriginal and/or a Torres Strait Islander or Maori. LIMITATIONS: Mediation analyses defining the causal relationships between infection type and infection-related death could not be undertaken as disaggregating the data was not feasible. CONCLUSIONS: The excess risk of infection-related death in patients on dialysis has improved substantially over time but remains more than 20 times higher than in the general population.

Projecting the future: modelling Australian dialysis prevalence 2021-30.

Objectives To project the prevalence of people receiving dialysis in Australia for 2021-30 to inform service planning and health policy. Methods Estimates were based on data from 2011 to 2020 from the Australia & New Zealand Dialysis & Transplant (ANZDATA) Registry and the Australian Bureau of Statistics. We projected dialysis and functioning kidney transplant recipient populations for the years 2021-30. Discrete-time, non-homogenous Markov models were built on probabilities for transition between three mutually exclusive states (Dialysis, Functioning Transplant, Death), for five age groups. Two scenarios were employed - stable transplant rate vs a continued increase - to assess the impact of these scenarios on the projected prevalences. Results Models projected a 22.5-30.4% growth in the dialysis population from 14 554 in 2020 to 17 829 ('transplant growth') - 18 973 ('transplant stable') by 2030. An additional 4983-6484 kidney transplant recipients were also projected by 2030. Dialysis incidence per population increased and dialysis prevalence growth exceeded population ageing in 40-59 and 60-69 year age groups. The greatest dialysis prevalence growth was seen among those aged ≥70 years. Conclusion Modelling of the future prevalence of dialysis use highlights the increasing demand on services expected overall and especially by people aged ≥70 years. Appropriate funding and healthcare planning must meet this demand.

Pre-eclampsia after Kidney Transplantation: Rates and Association with Graft Survival and Function.

BACKGROUND: Transplanted women have high rates of pre-eclampsia. However, determinants of pre-eclampsia and association with graft survival and function remain uncertain. We aimed to determine rates of pre-eclampsia and its association with kidney transplant survival and function. METHODS: Retrospective cohort study analyzing post-kidney transplantation pregnancies (≥20 weeks gestation) from the Australia and New Zealand Dialysis and Transplant Registry (2000-2021). Graft survival was assessed in 3 models accounting for repeated pregnancies and episodes of pre-eclampsia. RESULTS: Pre-eclampsia status was captured in 357/390 pregnancies and occurred in 133 pregnancies (37%). The percentage of pregnancies reported to have pre-eclampsia rose from 27% in 2000-2004, to 48% from 2018-2021. Reported prior exposure to calcineurin inhibitors was high overall, and higher in women who had pre-eclampsia (97% vs 88%, p=0.005). Seventy-two (27%) graft failures were identified after a pregnancy, with median follow-up of 8.08 years. Although women with pre-eclampsia had higher median preconception serum creatinine concentration (1.24 ((IQR) 1.00-1.50) vs. 1.13 (0.99-1.36) mg/dL; p=0.02), in all survival models, pre-eclampsia was not associated with higher death-censored graft failure. In multivariable analysis of maternal factors (age, body mass index, primary kidney disease and transplant-pregnancy interval, preconception serum creatinine concentration, era of birth event and Tacrolimus or Cyclosporin exposure) only era and preconception serum creatinine concentration ≥1.24 mg/dL (odds ratio 2.48, 95% CI 1.19-5.18) was associated with higher pre-eclampsia risk. Both preconception eGFR <45 ml/min/1.73m 2 (adjusted HR 5.55, 95% CI 3.27-9.44, p<0.001) and preconception serum creatinine concentration ≥1.24 mg/dL (adjusted HR 3.06, 95% CI 1.77-5.27, p<0.001) were associated with a higher risk of graft failure even after adjusting for maternal characteristics. CONCLUSIONS: In this large and contemporaneous registry cohort, pre-eclampsia was not associated with worse graft survival or function. Preconception kidney function was the main determinant of graft survival.

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.

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.

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.

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.

Determinants of Perinatal Outcomes in Dialyzed and Transplanted Women in Australia.

Introduction: Drivers of adverse perinatal outcomes in pregnancies of women receiving chronic kidney replacement therapy (KRT) remain poorly understood. Methods: Births ≥ 20 weeks of gestation in Australian women receiving KRT were analyzed for perinatal outcomes stratified by maternal KRT exposure (dialysis or transplant, analyzed separately), by linking the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and perinatal data sets (1991-2013). Results: Of 2,948,084 babies (1,628,181 mothers), 248 were born to mothers receiving KRT (transplant, n = 211; dialysis, n = 37), with live birth rates ≥ 94%. The perinatal death rate was 162, 62, and 9 per 1000 births in the dialysis, transplant, and non-KRT cohorts, respectively. Babies exposed to KRT had increased odds of prematurity, small-for-gestational age (SGA), poor birth condition, resuscitation, intensive care admission, and longer hospitalization, with the dialysis cohort having worse outcomes. Preterm babies of dialyzed and transplanted mothers (compared with preterm babies with no KRT exposure) experienced 1.6- to 2.7-fold higher odds for all adverse outcomes, except birthweight < 2500 g, which was 11-fold higher for the dialysis cohort. In adjusted analyses, transplanted women with better allograft function (serum creatinine ≤ 120 µmol/l) still had >10-fold higher odds of preterm birth and low birthweight and 1.8- to 4.6-fold increased odds of other adverse outcomes. In transplanted women, mediation analysis revealed that pregnancy-induced hypertension contributed only a modest proportional effect (2.5%-11.2%) on adverse outcomes. Conclusion: Maternal dialysis and transplantation conferred excess perinatal morbidity, particularly for preterm babies, and even in women with good preconception allograft function. Pregnancy-induced hypertension is not the predominant determinant of perinatal morbidity. Preconception counseling of women with kidney disease should encompass discussion of perinatal complications.

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.

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.

Temporal changes and risk factors for death from early withdrawal within 12 months of dialysis initiation-a cohort study.

BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.