Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.

AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

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

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

The impact of antineutrophil cytoplasmic antibody-associated vasculitis on employment and work disability in an Australian population.

AIM: Although antineutrophil cytoplasmic antibody-associated vasculitis (AAV) most commonly affects older individuals, many patients develop the disease during their most productive working years. The aim of this study was to examine the effects of AAV on employment and work disability in a cohort of Australian patients of working age. METHODS: Patients attending a vasculitis clinic located in Melbourne, Australia, completed an employment questionnaire in addition to the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem. RESULTS: The average age of the 47 respondents was 47.8 ± 11.9 years (range 22-63 years), with a median disease duration of 60 months (range 10.2-318.5 months). There were 68.1% who were currently employed, but 20.6% of respondents employed at the time of diagnosis were no longer working and 10.6% had experienced a significant reduction in work hours since their diagnosis. There were 12.7% who were dependent on the disability support pension. The rate of work disability was 23.4%. Many participants considered themselves work impaired (41.9%), with 10.1% having missed work in the previous week. Furthermore, 44.7% of respondents reported that their financial stability had been negatively impacted by their vasculitis diagnosis. Fatigue was commonly reported. Work disabled patients were significantly more likely to be obese and less likely to have completed a tertiary education. Work disabled patients tended to be older, myeloperoxidase-antineutrophil cytoplasmic antibody positive, and have renal involvement and lung involvement. CONCLUSION: A proportion of people living with AAV in Australia experience a decline in employment and an increase in work disability when living with this condition.

The impact of an integrated diabetes and kidney service on patients, primary and specialist health professionals in Australia: A qualitative study.

BACKGROUND: To address guideline-practice gaps and improve management of patients with both diabetes and chronic kidney disease (CKD), we involved patients, health professionals and patient advocacy groups in the co-design and implementation of an integrated diabetes-kidney service. OBJECTIVE: In this study, we explored the experiences of patients and health-care providers, within this integrated diabetes and kidney service. METHODS: 5 focus groups and 2 semi-structured interviews were conducted amongst attending patients, referring primary health professionals, and attending specialist health professionals. Maximal variation sampling was used for both patients and referring primary health professionals to ensure an equal representation of males and females, and patients of different CKD stages. All discussions were audiotaped and transcribed verbatim, before being thematically analysed independently by 2 researchers. RESULTS: The mean age (SD) for specialist health professionals, primary care professionals and patients who participated was 45 (11), 44 (15) and 68 (5) years with men being 50%, 80% and 76% of the participants respectively. Key strengths of the diabetes and kidney service were noted to be better integration of care and a perception of improved health and management of health. Whilst some aspects of access such as time between referral and initial appointment and having fewer appointments improved, other aspects such as in-clinic waiting times and parking remained problematic. Specialist health professionals noted that health professional education could be improved. Patient self-management was also noted by to be an issue with some patients requesting more information and some health professionals expressing difficulty in empowering some patients. CONCLUSIONS: Health professionals and patients reported that a co-designed integrated diabetes kidney service improved integration of care and improved health and management of health. However, some aspects of the process of care, health professional education and patient self-management remained challenging.

Arteriovenous access practices in Australian and New Zealand dialysis units.

BACKGROUND: The creation and maintenance of dialysis vascular access is associated with significant morbidity. Structured management pathways can reduce this morbidity, yet practice patterns in Australia and New Zealand are not known. We aimed to describe the arteriovenous access practices in dialysis units in Australia and New Zealand. METHODS: An online survey comprising 51 questions was completed by representatives from dialysis units from both countries. In addition to descriptive analysis, responses were compared between units inside and outside of major cities. RESULTS: Of 64 contacted units, 48 (75%) responded (Australia 43, New Zealand 5), representing 38% of dialysis units in Australia and New Zealand. While 94% of units provided pre-dialysis education, only 60% reported a structured pre-dialysis pathway and 69% had a dedicated vascular access nurse. Most units routinely monitored fistula/graft function using flow rate measurement (73%) or recirculation studies (63%). A minority used routine ultrasound (35%). Thrombectomy, fistuloplasty and peritoneal dialysis catheter insertion were rarely performed by nephrologists (4%, 4% and 17% of units, respectively). Units outside of a major city were less likely to have access to a local vascular access surgeon (6/13 (46%) vs 35/35 (100%), P < 0.001). There were no other significant differences between units on the basis of location. CONCLUSION: Much variation exists in unit management of arteriovenous access. Structured pre-dialysis pathways and dedicated vascular access nurses may be underutilised in Australia and New Zealand. The use of regular access blood flow measurement and ultrasound is common in both countries despite a lack of data supporting its effectiveness. There is room for both practice improvement and a need for further evidence to ensure optimal arteriovenous access care.

Risk Indices in Deceased-donor Organ Allocation for Transplantation: Review From an Australian Perspective.

Over the last decade, organ donation and transplantation rates have increased in Australia and worldwide. Donor and recipient characteristics for most organ types have generally broadened, resulting in the need to consider more complex data in transplant decision-making. As a result of some of these pressures, the Australian software used for donor and recipient data management is currently being updated. Because of the in-built capacity for improved data management, organ allocation processes will have the opportunity to be significantly reviewed, in particular the possible use of risk indices (RIs) to guide organ allocation and transplantation decisions. We aimed to review RIs used in organ allocation policies worldwide and to compare their use to current Australian protocols. Significant donor, recipient, and transplant variables in the indices were summarized. We conclude that Australia has the opportunity to incorporate greater use of RIs in its allocation policies and in transplant decision-making processes. However, while RIs can assist with organ allocation and help guide prognosis, they often have significant limitations which need to be properly appreciated when deciding how to best use them to guide clinical decisions.

Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure.

Reliable estimates of the long-term outcomes of acute kidney injury (AKI) are needed to inform clinical practice and guide allocation of health care resources. This systematic review and meta-analysis aimed to quantify the association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD), and death. Systematic searches were performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies in hospitalized adults that used standardized definitions for AKI, included a non-exposed comparator, and followed patients for at least 1 year. Risk of bias was assessed by the Newcastle-Ottawa Scale. Random effects meta-analyses were performed to pool risk estimates; subgroup, sensitivity, and meta-regression analyses were used to investigate heterogeneity. Of 4973 citations, 82 studies (comprising 2,017,437 participants) were eligible for inclusion. Common sources of bias included incomplete reporting of outcome data, missing biochemical values, and inadequate adjustment for confounders. Individuals with AKI were at increased risk of new or progressive CKD (HR 2.67, 95% CI 1.99-3.58; 17.76 versus 7.59 cases per 100 person-years), ESKD (HR 4.81, 95% CI 3.04-7.62; 0.47 versus 0.08 cases per 100 person-years), and death (HR 1.80, 95% CI 1.61-2.02; 13.19 versus 7.26 deaths per 100 person-years). A gradient of risk across increasing AKI stages was demonstrated for all outcomes. For mortality, the magnitude of risk was also modified by clinical setting, baseline kidney function, diabetes, and coronary heart disease. These findings establish the poor long-term outcomes of AKI while highlighting the importance of injury severity and clinical setting in the estimation of risk.

Patient reported barriers are associated with low physical and mental well-being in patients with co-morbid diabetes and chronic kidney disease.

BACKGROUND: Little is known about how patient reported barriers to health care impact the quality of life (HRQoL) of patients with comorbid disease. We investigated patient reported barriers to health care and low physical and mental well-being among people with diabetes and chronic kidney disease (CKD). METHODS: Adults with diabetes and CKD (estimated Glomerular Filtration Rate < 60 ml/min/1.73m2) were recruited and completed a questionnaire on barriers to health care, the 12-Item HRQoL Short Form Survey and clinical assessment. Low physical and mental health status were defined as mean scores < 50. Logistic regression models were used. RESULTS: Three hundred eight participants (mean age 66.9 ± 11 years) were studied. Patient reported 'impact of the disease on family and friends' (OR 2.07; 95% CI 1.14 to 3.78), 'feeling unwell' (OR 4.23; 95% CI 1.45 to 12.3) and 'having other life stressors that make self-care a low priority' (OR 2.59; 95% CI 1.20 to 5.61), were all associated with higher odds of low physical health status. Patient reported 'feeling unwell' (OR 2.92; 95% CI 1.07 to 8.01), 'low mood' (OR 2.82; 95% CI 1.64 to 4.87) and 'unavailability of home help' (OR 1.91; 95% CI 1.57 to 2.33) were all associated with higher odds of low mental health status. The greater the number of patient reported barriers the higher the odds of low mental health but not physical health status. CONCLUSIONS: Patient reported barriers to health care were associated with lower physical and mental well-being. Interventions addressing these barriers may improve HRQoL among people with comorbid diabetes and CKD.

Debate: Should dialysis at home be mandatory for all suitable ESRD patients?: home-based dialysis therapies are the second choice after transplantation.

Since their inception in the 1960s, home-based dialysis therapies have been viable alternatives to conventional thrice weekly in center hemodialysis. In spite of this, uptake of these therapies has been steadily declining over past decades with utilization varying globally; dependent on training support, funding models, and prevailing Nephrologist beliefs. In the Australian context, home dialysis (predominantly peritoneal dialysis and extended hours nocturnal hemodialysis) is now again increasing in popularity--with enthusiasm driven not only by evidence of an array of physiological and psychological patient benefit but also significant economic advantage: critical in the current climate where dialysis therapies in Australia take approximately $1 billion dollars per year from the healthcare budget. When assessing the significant advantages of home-based therapies, it is important to consider not only the increasing body of evidence around improved survival but also that for dramatically better health-related quality of life, decreased economic burden and the overall benefits of undertaking treatment in the home. With patient-centered care an increasingly important aspect of our decision making paradigm, home-based dialysis should be considered as the default option in all patients transitioning to renal replacement therapy.

Estimated Glomerular Filtration Rate versus Albuminuria in the Assessment of Kidney Function: What's More Important?

Clinical practice guidelines state that any evaluation of kidney disease requires the assessment of (1) kidney function in the form of the estimated glomerular filtration rate (eGFR) and (2) kidney damage by a quantitative assessment of proteinuria, preferably by the determination of the urine albumin-to-creatinine ratio. This review discusses the relative merits of each measurement, focusing on the strengths of each measurement in relationship to all-cause and cardiovascular mortality risk prediction as well as the prediction of kidney disease progression with loss of kidney function over time and the progression to end-stage kidney disease treated by dialysis or kidney transplantation.

Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

Lateral lumbar X-ray assessment of abdominal aortic calcification in Australian haemodialysis patients.

AIM: Vascular calcification is prevalent in patients with chronic kidney disease. Abdominal aortic calcification (AAC) can be detected by X-ray, although AAC is less well documented in anatomical distribution and severity compared with coronary calcification. Using simple radiological imaging we aimed to assess AAC and determine associations in prevalent Australian haemodialysis (HD) patients. METHODS: Lateral lumbar X-ray of the abdominal aorta was used to determine AAC, which is related to the severity of calcific deposits at lumbar vertebral segments L1 to L4. Two radiologists determined AAC scores, by semi-quantitative measurement using a validated 24-point scale, on HD patients from seven satellite dialysis centres. Regression analysis was used to determine associations between AAC and patient characteristics. RESULTS: Lateral lumbar X-ray was obtained in 132 patients. Median age of patients was 69 years (range 29-90), 60% were male, 36% diabetic, median duration of HD 38 months (range 6-230). Calcification (AAC score ≥ 1) was present in 94.4% with mean AAC score 11.0 ± 6.4 (median 12). Independent predictors for the presence and severity of calcification were age (P = 0.03), duration of dialysis (P = 0.04) and a history of cardiovascular disease (P = 0.009). There was no significant association between AAC and the presence of diabetes or time-averaged serum markers of mineral metabolism, lipid status and C-reactive protein. CONCLUSIONS: AAC detected by lateral lumbar X-ray is highly prevalent in our cohort of Australian HD patients and is associated with cardiovascular disease, increasing age and duration of HD. This semi-quantitative method of determining vascular calcification is widely available and inexpensive and may assist cardiovascular risk stratification.

Are traditional risk factors valid for assessing cardiovascular risk in end-stage renal failure patients?

AIM: Cardiovascular diseases (CVD) are the major cause of morbidity and mortality in end-stage renal failure (ESRF). Establishing whether traditional risk factors are valid predictors of CVD in ESRF is important in order to devise preventive and interventional strategies for the ESRF populations. METHODS: In this retrospective cohort study, a cohort of patients on dialysis were examined between September 2000 and February 2001. Only those without previous CVD events at baseline were included. For each individual, 5 year CVD risk was calculated using the New Zealand 5 year CVD risk prediction charts based on the Framingham Heart Study prognostic algorithm. The subsequent 5 year CVD outcome for each patient was determined and the observed rate of first CVD events was compared to the predicted risk. Relation of individual risk factors with the CVD outcome was also assessed. RESULTS: Of the patients, 274 were without previous CVD events at baseline and 27% experienced CVD events during the subsequent 5 years. Observed CVD risk was more than twofold that of predicted risk although there was a linear correlation between the two. Among individual risk factors, increasing age, diabetes and smoking were significantly related to the incidence of the CVD events but, unlike in the general population, systolic blood pressure, total cholesterol/high-density lipoprotein ratio and body mass index were not significantly related to CVD events. CONCLUSION: The very high incidence of CVD in ESRF patients suggest that non-traditional risk factors present in the uraemic state are independent risk factors for CVD in ESRF patients. Nevertheless, the application of traditional cardiovascular risk profiles does allow risk stratification of the ESRF population.