Island medicine longitudinal cohort study: Rapid rise in chronic kidney disease in rural and remote communities.

AIM: To determine the change in incidence and prevalence of chronic kidney disease (CKD) in rural and remote communities over the last decade. METHODS: We examined the change in age-standardized incidence and prevalence in Tasmania between 2010 and 2020, using a linked dataset that included any adult with a creatinine test taken in a community laboratory during the study period (n = 581 513; 87.8% of the state's adult population). We defined CKD as two measures of eGFR <60 mL/min per 1.73 m2, at least 3 months apart. RESULTS: State-wide age-standardized prevalence of CKD increased by 28% in the decade to 2020, from 516 to 659 per 10 000 population. Prevalence in men increased 31.3% and women 24.8%. The greatest increase in age-standardized prevalence was seen in rural or remote communities with an increase of 36.6% overall, but with considerable variation by community (range + 0.4% to +88.3%). The increase in the actual number of people with CKD in the decade to 2020 was 67%, with the number of women increasing by 58% and men by 79%. CONCLUSION: The age-standardized prevalence of CKD in rural and remote regions has increased considerably over the past decade, likely compounded by limited access to primary and secondary healthcare. These findings highlight the need to ensure healthcare resources are directed to areas of greatest need.

Creating an interactive map visualising the geographic variations of the burden of diabetes to inform policymaking: An example from a cohort study in Tasmania, Australia.

OBJECTIVES: To visualise the geographic variations of diabetes burden and identify areas where targeted interventions are needed. METHODS: Using diagnostic criteria supported by hospital codes, 51,324 people with diabetes were identified from a population-based dataset during 2004-2017 in Tasmania, Australia. An interactive map visualising geographic distribution of diabetes prevalence, mortality rates, and healthcare costs in people with diabetes was generated. The cluster and outlier analysis was performed based on statistical area level 2 (SA2) to identify areas with high (hot spot) and low (cold spot) diabetes burden. RESULTS: There were geographic variations in diabetes burden across Tasmania, with highest age-adjusted prevalence (6.1%), excess cost ($2627), and annual costs per person ($5982) in the West and Northwest. Among 98 SA2 areas, 16 hot spots and 25 cold spots for annual costs, and 10 hot spots and 10 cold spots for diabetes prevalence were identified (p<0.05). 15/16 (94%) and 6/10 (60%) hot spots identified were in the West and Northwest. CONCLUSIONS: We have developed a method to graphically display important diabetes outcomes for different geographical areas. IMPLICATIONS FOR PUBLIC HEALTH: The method presented in our study could be applied to any other diseases, regions, and countries where appropriate data are available to identify areas where interventions are needed to improve diabetes outcomes.

Anticoagulation for people receiving long-term haemodialysis.

BACKGROUND: Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. OBJECTIVES: To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). MAIN RESULTS: We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated as high or unclear for most risk domains. Compared to UFH, LMWH had uncertain effects on extracorporeal circuit thrombosis (3 studies, 91 participants: RR 1.58, 95% CI 0.46 to 5.42; I2 = 8%; low certainty evidence), while major bleeding and minor bleeding were not adequately reported. Regional citrate anticoagulation may lower the risk of minor bleeding compared to UFH (2 studies, 82 participants: RR 0.34, 95% CI 0.14 to 0.85; I2 = 0%; low certainty evidence). No studies reported data comparing regional citrate to UFH on risks of extracorporeal circuit thrombosis and major bleeding. The effects of very LMWH, danaparoid, prostacyclin, direct thrombin inhibitors, factor XI inhibitors or heparin-grafted membranes were uncertain due to insufficient data. The effects of different LMWH, different doses of LMWH, and the administration of LMWH anticoagulants using inlet versus outlet bloodline or bolus versus infusion were uncertain. Evidence to compare citrate to another citrate or control was scant. The effects of UFH compared to no anticoagulant therapy or different doses of UFH were uncertain. Death, dialysis vascular access outcomes, blood transfusions, measures of anticoagulation effect, and costs of interventions were rarely reported. No studies evaluated the effects of treatment on non-fatal myocardial infarction, non-fatal stroke and hospital admissions. Adverse events were inconsistently and rarely reported. AUTHORS' CONCLUSIONS: Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes.

Postoperative Outcomes After Gastrointestinal Surgery in Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: This study evaluated the postoperative mortality and morbidity outcomes following the different subtypes of gastrointestinal (GI) surgery over a 15-year period. BACKGROUND: Patients receiving chronic kidney replacement therapy (KRT) experience higher rates of general surgery compared with other surgery types. Contemporary data on the types of surgeries and their outcomes are lacking. KRT was defined as patients requiring chronic dialysis (hemodialysis or peritoneal dilaysis) or having a functioning kidney transplant long-term. METHODS: All incident and prevalent patients aged greater than 18 years identified in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry as receiving chronic KRT were linked with jurisdictional hospital admission datasets between January 1, 2000 until December 31, 2015. Patients were categorized by their KRT modality [hemodialysis (HD), peritoneal dialysis (PD), home hemodialysis (HHD), and kidney transplant (KT)]. GI surgeries were categorized as upper gastrointestinal (UGI), bowel (small and large bowel), anorectal, hernia surgery, cholecystectomy, and appendicectomy. The primary outcome was the rates of the different surgeries, estimated using Poisson models. Secondary outcomes were risks of 30-day/in-hospital postoperative mortality risk and nonfatal outcomes and were estimated using logistic regression. Independent predictors of 30-day mortality were examined using comorbidity-adjusted Cox models. RESULTS: Overall, 46,779 patients on chronic KRT were linked to jurisdictional hospital datasets, and 9,116 patients were identified as having undergone 14,540 GI surgeries with a combined follow-up of 76,593 years. Patients on PD had the highest rates of GI surgery (8 per 100 patient years), with hernia surgery being the most frequent. Patients on PD also had the highest risk of 30-day postoperative mortality following the different types of GI surgery, with the risk being more than 2-fold higher after emergency surgery compared with elective procedures. Infective postoperative complications were more common than cardiac complications. This study also observed a U-shaped association between body mass index (BMI) and mortality, with a nadir in the 30 to 35 kg/m 2 group. CONCLUSIONS: Patients on chronic KRT have high rates of GI surgery and morbidity, particularly in those who receive PD, are older, or are either underweight or moderately obese.

Multi-center, pragmatic, cluster-randomized, controlled trial of standardized peritoneal dialysis (PD) training versus usual care on PD-related infections (the TEACH-PD trial): trial protocol.

BACKGROUND: Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices. METHODS: The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. DISCUSSION: TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816111. Registered on 24 January 2019.

Multicentre registry analysis of incremental peritoneal dialysis incidence and associations with patient outcomes.

BACKGROUND: Incremental peritoneal dialysis (PD) is increasingly advocated to reduce treatment burden and costs, with potential to better preserve residual kidney function. Global prevalence of incremental PD use is unknown and use in Australia and New Zealand has not been reported. METHODS: Binational registry analysis including incident adult PD patients in Australia and New Zealand (2007-2017), examining incidence of and outcomes associated with incremental PD (first recorded PD exchange volume <42 L/week (incremental) vs. ≥42 L/week (standard)). RESULTS: Incremental PD use significantly increased from 2.7% of all incident PD in 2007 to 11.1% in 2017 (mean increase 0.84%/year). Duration of incremental PD use was 1 year or less in 67% of cases. Male sex, Aboriginal and Torres Strait Islander (ATSI) or Maori ethnicities, age 45-59 years, medical comorbidities or treatment at a centre with low use of automated PD or icodextrin was associated with lower incidence of incremental PD use. Low body mass index and higher estimated glomerular filtration rate was associated with higher incidence. After accounting for patient and centre variables, commencing PD with an incremental prescription was associated with reduced peritonitis risk (adjusted hazard ratio 0.73, 95% confidence interval (CI) 0.61-0.86).When kidney transplantation and death were considered as competing risks, the association between incremental PD and peritonitis was not significant (sub-hazard ratio [SHR] 0.91, 95%CI 0.71-1.17, p = 0.5), however cumulative incidence of 30-day transfer to haemodialysis was lower in those receiving incremental PD (SHR 0.73, 95%CI 0.56-0.94, p = 0.01). There was no association between incremental PD and death. CONCLUSIONS: Incremental PD use is increasing in Australia and New Zealand and is not associated with patient harm.

Metabolic Syndrome and Inflammation from Young to Mid-Adulthood and Subclinical Kidney Damage in Middle-Aged Australians.

Background: Relationships between metabolic syndrome (MetS), inflammation, and chronic kidney disease (CKD) have been reported, but long-term follow-up studies are limited. This study aimed to investigate whether MetS and C-reactive protein (CRP) from young adulthood associated with the risk of subclinical kidney damage (SKD), a surrogate measure for CKD, in mid-adulthood. Materials and Methods: One thousand fifteen participants from the Childhood Determinants of Adult Health study aged 26-36 years at baseline (2004-2006) were followed up at age 36-49 (2014-2019). Log-binomial regression was used to determine whether MetS and high CRP in young adulthood and from young to mid-adulthood predicted the risk of SKD (an estimated glomerular filtration rate [eGFR] of 30-60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 with a urine albumin-creatinine ratio ≥2.5 mg/mmol [males] or ≥3.5 mg/mmol [females]) in midlife. Results: Having MetS in young adulthood was associated with an increased risk of SKD in midlife (adjusted relative risk [aRR] = 2.67, 95% confidence interval [CI]: 1.24-5.76). Participants with MetS and high CRP as young adults had a greater risk of having SKD in midlife (aRR = 4.27, 95% CI: 1.61-11.30) compared with those without MetS and high CRP. Furthermore, for participants with persistent MetS, the aRR of SKD in midlife was 4.08 (95% CI: 1.84-9.05) compared with those without MetS from young to mid-adulthood. No significant associations were found between CRP in young adulthood, or change in CRP from young to mid-adulthood, and SKD in midlife. Conclusions: MetS in young adulthood, with and without high CRP, and persistent MetS were associated with an increased risk of SKD in middle midlife.

Childhood modifiable risk factors and later life chronic kidney disease: a systematic review.

BACKGROUND: Relationships between adulthood modifiable risk factors and chronic kidney disease (CKD) are well-established, but associations with childhood risk factors are unclear. This study systematically assesses the published evidence about childhood modifiable risk factors and adulthood CKD. METHODS: We searched MEDLINE, EMBASE, and Web of Science to 6th May 2022. Articles were included if (1) they were population-based longitudinal studies, (2) exposures were potentially modifiable, for example through pharmacological or lifestyle modifications, including clinical conditions/measures (diabetes, blood pressure, adiposity, and dyslipidaemia); health behaviours (smoking, alcohol consumption, physical activity, fitness, and poor nutrition); and socio-economic factors (socio-economic position), and occurred during childhood (ages 2-19 years), and (3) outcome was CKD or surrogate markers of CKD in adulthood (ages 20 years or older). Three reviewers independently extracted the data. RESULTS: 15,232 articles were identified after deduplication; 17 articles met the inclusion criteria, reporting childhood blood pressure (n = 8), adiposity (n = 4), type 2 diabetes (n = 1), socio-economic position (n = 1), famine (n = 1), cardiorespiratory fitness (n = 1), and a healthy lifestyle score (n = 1). The results suggested positive associations of childhood adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females with CKD in adulthood. Findings were inconsistent on associations between childhood BP and CKD in adulthood. Childhood healthy lifestyle score and exposure to famine were not associated with risk of CKD in adulthood. CONCLUSIONS: The limited evidence suggests childhood factors may contribute to the CKD risk in adulthood, particularly adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females. Further high-quality community-based studies are needed with long-term follow-up and investigation of a broader range of modifiable risk factors.

Risk of hospital admission or emergency department presentation due to diabetes complications: a retrospective cohort study in Tasmania, Australia.

Objective To estimate the risk of an emergency department (ED)/inpatient visit due to complications in people with diabetes and compare them to their non-diabetes counterparts. Methods This matched retrospective cohort study used a linked dataset in Tasmania, Australia for the 2004-17 period. People with diabetes (n = 45 378) were matched on age, sex and geographical regions with people without diabetes (n = 90 756) based on propensity score matching. The risk of an ED/inpatient visit related to each complication was estimated using negative binomial regression. Results In people with diabetes, the combined ED and admission rates per 10 000 person-years were considerable, especially for macrovascular complications (ranging from 31.8 (lower extremity amputation) to 205.2 (heart failure)). The adjusted incidence rate ratios of ED/inpatient visits were: retinopathy 59.1 (confidence interval 25.8, 135.7), lower extremity amputation 11.1 (8.8, 14.1), foot ulcer/gangrene 9.5 (8.1, 11.2), nephropathy 7.4 (5.4, 10.1), dialysis 6.5 (3.8, 10.9), transplant 6.3 (2.2, 17.8), vitreous haemorrhage 6.0 (3.7, 9.8), fatal myocardial infarction 3.4 (2.3, 5.1), kidney failure 3.3 (2.3, 4.5), heart failure 2.9 (2.7, 3.1), angina pectoris 2.1 (2.0, 2.3), ischaemic heart disease 2.1 (1.9, 2.3), neuropathy 1.9 (1.7, 2.0), non-fatal myocardial infarction 1.7 (1.6, 1.8), blindness/low vision 1.4 (0.8, 2.5), non-fatal stroke 1.4 (1.3, 1.6), fatal stroke 1.3 (0.9, 2.1) and transient ischaemic attack 1.1 (1.0, 1.2). Conclusions Our results demonstrated the high demand on hospital services due to diabetes complications (especially macrovascular complications) and highlighted the importance of preventing and properly managing microvascular complications. These findings will support future resource allocation to reduce the increasing burden of diabetes in Australia.

The kidney failure risk equation predicts kidney failure: Validation in an Australian cohort.

AIMS: Predicting progression to kidney failure for patients with chronic kidney disease is essential for patient and clinicians' management decisions, patient prognosis, and service planning. The Tangri et al Kidney Failure Risk Equation (KFRE) was developed to predict the outcome of kidney failure. The KFRE has not been independently validated in an Australian Cohort. METHODS: Using data linkage of the Tasmanian Chronic Kidney Disease study (CKD.TASlink) and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), we externally validated the KFRE. We validated the 4, 6, and 8-variable KFRE at both 2 and 5 years. We assessed model fit (goodness of fit), discrimination (Harell's C statistic), and calibration (observed vs predicted survival). RESULTS: There were 18 170 in the cohort with 12 861 participants with 2 years and 8182 with 5 years outcomes. Of these 2607 people died and 285 progressed to kidney replacement therapy. The KFRE has excellent discrimination with C statistics of 0.96-0.98 at 2 years and 0.95-0.96 at 5 years. The calibration was adequate with well-performing Brier scores (0.004-0.01 at 2 years, 0.01-0.03 at 5 years) however the calibration curves, whilst adequate, indicate that predicted outcomes are systematically worse than observed. CONCLUSION: This external validation study demonstrates the KFRE performs well in an Australian population and can be used by clinicians and service planners for individualised risk prediction.

Costs of major complications in people with and without diabetes in Tasmania, Australia.

Objective We set out to estimate healthcare costs of diabetes complications in the year of first occurrence and the second year, and to quantify the incremental costs of diabetes versus non-diabetes related to each complication. Methods In this cohort study, people with diabetes (n = 45 378) and their age/sex propensity score matched controls (n = 90 756) were identified from a linked dataset in Tasmania, Australia between 2004 and 2017. Direct costs (including hospital, emergency room visits and pathology costs) were calculated from the healthcare system perspective and expressed in 2020 Australian dollars. The average-per-patient costs and the incremental costs in people with diabetes were calculated for each complication. Results First-year costs when the complications occurred were: dialysis $78 152 (95% CI 71 095, 85 858), lower extremity amputations $63 575 (58 290, 68 688), kidney transplant $48 487 (33 862, 68 283), non-fatal myocardial infarction $30 827 (29 558, 32 197), foot ulcer/gangrene $29 803 (27 183, 32 675), ischaemic heart disease $29 160 (26 962, 31 457), non-fatal stroke $27 782 (26 285, 29 354), heart failure $27 379 (25 968, 28 966), kidney failure $24 904 (19 799, 32 557), angina pectoris $18 430 (17 147, 19 791), neuropathy $15 637 (14 265, 17 108), nephropathy $15 133 (12 285, 18 595), retinopathy $14 775 (11 798, 19 199), transient ischaemic attack $13 905 (12 529, 15 536), vitreous hemorrhage $13 405 (10 241, 17 321), and blindness/low vision $12 941 (8164, 19 080). The second-year costs ranged from 16% (ischaemic heart disease) to 74% (dialysis) of first-year costs. Complication costs were 109-275% higher than in people without diabetes. Conclusions Diabetes complications are costly, and the costs are higher in people with diabetes than without diabetes. Our results can be used to populate diabetes simulation models and will support policy analyses to reduce the burden of diabetes.

Trends in Rates of Surgery and Postoperative Mortality Among Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: To estimate the incidence and postoperative mortality rates of surgery, and variations by age, diabetes, kidney replacement therapy (KRT) modality, and time over a 15-year period. BACKGROUND: Patients with kidney failure receiving chronic KRT (dialysis or kidney transplantation) have increased risks of postoperative mortality and morbidity. Contemporary data on the incidence and types of surgery these patients undergo are lacking. METHODS: This binational population cohort study evaluated all incident and prevalent patients receiving chronic KRT using linked data between Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admission datasets between 2000 and 2015. Patients were categorized by their KRT modality (hemodialysis, peritoneal dialysis, home hemodialysis, and kidney transplant) for each calendar year. Incidence rates for overall surgery and subtypes were estimated using Poisson models. Logistic regression was used to estimate 30-day/in-hospital mortality risk. RESULTS: Overall, 46,497 patients over a median (interquartile range) follow-up of 6.3 years (3.5-10.2 years) underwent 81,332 surgeries. The median incidence rate of surgery remained stable over this period with a median of 14.9 surgeries per 100 patient-years. Annual incidence rate was higher in older people and those with diabetes mellitus. Patients receiving hemodialysis had a higher incidence rate of surgery compared with kidney transplant recipients (15.8 vs 10.0 surgeries per 100 patient-years, respectively). Overall adjusted postoperative mortality rates decreased by >70% over the study period, and were lowest in kidney transplant recipients (1.7%, 95% confidence interval, 1.4-2.0). Postoperative mortality following emergency surgery was >3-fold higher than elective surgery (8.4% vs 2.3%, respectively). CONCLUSIONS: Patients receiving chronic KRT have high rates of surgery and morbidity. Further research into strategies to mitigate perioperative risk remain a priority.

Childhood cardiorespiratory fitness and the early markers of kidney disease in middle age: A population-based cohort study.

OBJECTIVES: To investigate the relationship of childhood cardiorespiratory fitness with early markers of chronic kidney disease, glomerular hyperfiltration and albuminuria, in midlife. DESIGN: Prospective cohort study. METHODS: This study included 1371 participants aged 36-49 years who participated in the 1985 Australian Schools Health and Fitness Survey when they were 7-15 years of age. Childhood cardiorespiratory fitness was estimated by the time taken to complete a 1.6- km run. Blood and urine samples were collected at follow-up. Log-binomial regression was used to determine the associations of childhood cardiorespiratory fitness with glomerular hyperfiltration [estimated glomerular filtration rate (mL/min/1.73 m2) > 95th percentile standardized for age and sex] and albuminuria (urine albumin-to-creatinine ratio ≥ 2.5 mg/mmol in males or ≥3.5 mg/mmol in females) in midlife. RESULTS: Compared with women with high childhood cardiorespiratory fitness, those with lower childhood cardiorespiratory fitness had a higher risk of glomerular hyperfiltration in midlife after adjusting for childhood age, the duration of follow-up, and midlife smoking status [adjusted relative risk = 2.86, 95% confidence interval, 1.04-7.86 for individuals with moderate childhood cardiorespiratory fitness (P = 0.04), and adjusted relative risk = 3.38, 95% confidence interval, 1.13-10.14 for individuals with low childhood cardiorespiratory fitness (P = 0.03)]. Further adjustment for childhood and midlife body mass index resulted in a slightly attenuated and statistically non-significant association. No significant associations were found with glomerular hyperfiltration in males or albuminuria in either males or females. CONCLUSIONS: Low cardiorespiratory fitness in childhood may increase the risk of glomerular hyperfiltration in midlife in females, possibly via a path through adult cardiorespiratory fitness.

Incremental healthcare expenditure attributable to diabetes mellitus: A cost of illness study in Tasmania, Australia.

AIMS: To quantify the incremental direct medical costs in people with diabetes from the healthcare system perspective; and to identify trends in the incremental costs. METHODS: This was a matched retrospective cohort study based on a linked data set developed for investigating chronic kidney disease in Tasmania, Australia. Using propensity score matching, 51,324 people with diabetes were matched on age, sex and residential area with 102,648 people without diabetes. Direct medical costs (Australian dollars 2020-2021) due to hospitalisation, Emergency Department visits and pathology tests were included. The incremental costs and cost ratios between mean annual costs of people with diabetes and their controls were calculated. RESULTS: On average, people with diabetes had healthcare costs that were almost double their controls ($2427 [95% CI 2322-2543]; ratio 1.87 [95% CI 1.85-1.91]; pooled from 2007-2017). While in the first year of follow-up, the costs of a person with diabetes were $1643 (95% CI 1489-1806); ratio 1.83 (95% CI 1.76-1.92) more than their control, this increased to $2480 (95% CI 2265-2680); ratio 1.69 (95% CI 1.62-1.77) in the final year. Although the incremental costs were higher in older age groups (e.g., ≥70: $2498 [95% CI 2265-2754]; 40-49: $2117 [95% CI 1887-2384]), the cost ratios were higher in younger age groups (≥70: 1.52 [95% CI 1.48-1.56]; 40-49: 2.37 [95% CI 2.25-2.61]). CONCLUSIONS: Given the increasing burden that diabetes imposes, our findings will support policymakers in future planning for diabetes and enable targeting sub-groups with higher long-term costs for possible cost savings for the Tasmanian healthcare system.

Associations of a healthy lifestyle score from childhood to adulthood with subclinical kidney damage in midlife: a population-based cohort study.

BACKGROUND: The relationships of healthy lifestyle scores (HLS) of various kinds in adulthood with the risk of chronic kidney disease (CKD) have been reported, but little is known about the association of childhood lifestyle with later life CKD. This study examined the relationship of HLS from childhood to adulthood with subclinical kidney damage (SKD) in midlife, a surrogate measure for CKD. METHODS: Data were collected in an Australian population-based cohort study with 33 years follow-up. 750 participants with lifestyle information collected in childhood (ages 10-15 years) and midlife (ages 40-50 years), and measures of kidney function in midlife were included. The HLS was generated from the sum scores of five lifestyle factors (body mass index, smoking, alcohol consumption, physical activity, and diet). Each factor was scored as poor (0 point), intermediate (1 point), or ideal (2 points). Log-binomial regression was used to investigate the relationship of HLS in childhood and from childhood to adulthood with SKD defined as either 1) estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73m2 or 2) eGFR> 60 mL/min/1.73m2 with urine albumin-creatinine ratio ≥ 2.5 mg/mmol (males) or 3.5 mg/mmol (females), adjusting for socio-demographic factors and the duration of follow-up. RESULTS: The average HLS was 6.6 in childhood and 6.5 in midlife, and the prevalence of SKD was 4.9% (n = 36). Neither HLS in childhood nor HLS from childhood to adulthood were significantly associated with the risk of SKD in midlife. CONCLUSIONS: A HLS from childhood to adulthood did not predict SKD in this middle-aged, population-based Australian cohort.

Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib-A case report.

BACKGROUND: Combination molecular targeted therapy with dabrafenib plus trametinib has been shown to improve progression-free survival and overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. In general, these agents are well tolerated. Kidney related adverse events are uncommon with only three case reports of acute interstitial nephritis and one case of a serious acute kidney injury. We report another case of interstitial nephritis related to these drugs. CASE: A 37-year-old man diagnosed with metastatic melanoma (BRAF V600E mutation) who developed acute interstitial nephritis 5 years into his treatment with combination dabrafenib plus trametinib therapy. He presented with an asymptomatic acute kidney injury on routine surveillance pathology with a creatinine of 174 µmol/L (from baseline 80 µmol/L) and a corresponding estimated glomerular filtration rate (eGFR) of 42 ml/min/1.73 m2 (from a baseline >90 ml/min/1.73 m2 ) and microalbuminuria (albumin creatinine ratio [ACR] 8.5 mg/mmol). Renal biopsy revealed a granulomatous interstitial nephritis likely drug related. He was treated with prednisolone 1 mg/kg and ceased his targeted therapy with improvement in his renal function. CONCLUSION: Although rare, recognition of acute interstitial nephritis, a possible serious adverse outcome due to dabrafenib and trametinib is important and needs to be incorporated into current Australian cancer therapy guidelines.

Competing risks of death and kidney failure in a cohort of Australian adults with severe chronic kidney disease.

OBJECTIVES: To examine the competing risks of death (any cause) and of kidney failure in a cohort of Australian adults with severe chronic kidney disease. DESIGN: Population-based cohort study; analysis of linked data from the Tasmanian Chronic Kidney Disease study (CKD.TASlink), 1 January 2004 - 31 December 2017. PARTICIPANTS: All adults in Tasmania with incident stage 4 chronic kidney disease (estimated glomerular filtration rate [eGFR], 15-29 mL/min/1.73 m2 ). MAIN OUTCOME MEASURES: Death or kidney failure (defined as eGFR below 10 mL/min/1.73 m2 or initiation of dialysis or kidney transplantation) within five years of diagnosis of stage 4 chronic kidney disease. RESULTS: We included data for 6825 adults with incident stage 4 chronic kidney disease (mean age, 79.3 years; SD, 11.1 years), including 3816 women (55.9%). The risk of death increased with age - under 65 years: 0.18 (95% CI, 0.15-0.22); 65-74 years: 0.39 (95% CI, 0.36-0.42); 75-84 years, 0.56 (95% CI, 0.54-0.58); 85 years or older: 0.78 (95% CI, 0.77-0.80) - while that of kidney failure declined - under 65 years: 0.39 (95% CI, 0.35-0.43); 65-74 years: 0.12 (95% CI, 0.10-0.14); 75-84 years: 0.05 (95% CI, 0.04-0.06); 85 years or older: 0.01 (95% CI, 0.01-0.02). The risk of kidney failure was greater for people with macroalbuminuria and those whose albumin status had not recently been assessed. The risks of kidney failure and death were greater for men than women in all age groups (except similar risks of death for men and women under 65 years of age). CONCLUSIONS: For older Australians with incident stage 4 chronic kidney disease, the risk of death is higher than that of kidney failure, and the latter risk declines with age. Clinical guidelines should recognise these competing risks and include recommendations about holistic supportive care, not just on preparation for dialysis or transplantation.

Methods of analyzing patterns of multimorbidity using network analysis: a scoping review protocol.

OBJECTIVE: The purpose of this review is to summarize the techniques used for network analysis of multimorbidity to inform development of a standard methodology. INTRODUCTION: There is a growing trend of using network analysis to investigate relationships between chronic illnesses in people with multimorbidities. However, there is currently no recommended approach to calculating and displaying networks of chronic health conditions. This review intends to summarize the current literature to further the development of a standard methodology. INCLUSION CRITERIA: Studies will be included if they investigated the relationships between multiple chronic health conditions without referring to an index condition, using network analysis techniques. Studies using both survey and administrative data will be included. Studies including biological or genomic data sets will not be included as they are out of scope. METHODS: Databases searched will include MEDLINE, ScienceDirect, Scopus, and PsycINFO. All relevant publications will be included provided they were published before October 2020. Publications from all languages will be included where an appropriate translation in English can be obtained. Data extracted will include country of origin, type of data used, measure of association, software used, and notes on any specific points of methodological interest relevant to the review question.

BMI Trajectories from Childhood to Midlife are Associated with Subclinical Kidney Damage in Midlife.

OBJECTIVE: This study aimed to investigate the relationship of BMI trajectories from childhood with subclinical kidney damage (SKD) in midlife, a surrogate measure for chronic kidney disease. METHODS: The study followed up 1,442 participants from the 1985 Australian Schools Health and Fitness Survey who were between 7 and 15 years old at the time the survey was conducted and who had BMI measurements in childhood and at least two follow-ups in adulthood. Measures of kidney function for participants 36 to 50 years old were also included. Latent class growth mixture modeling was used to identify the BMI trajectories. Log-binomial regression determined the associations of BMI trajectories with SKD defined as either 1) an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2 or 2) an eGFR > 60 mL/min/1.73 m2 with a urine albumin-creatinine ratio ≥ 2.5 mg/mmol (males) or 3.5 mg/mmol (females), adjusting for childhood age, sex, and duration of follow-up. RESULTS: Relative to the persistently low trajectory (n = 534, 37.0%), being in higher BMI trajectories was associated with greater risk of SKD in midlife (relative risk [RR] = 1.89, 95% CI = 1.10-3.25 for progressing to moderate [n = 633, 43.9%]; RR = 1.91, 95% CI = 0.95-3.81 for progressing to moderate/high [n = 194, 13.5%]; RR = 2.86, 95% CI = 1.03-7.99 for progressing to high/very high [n = 39, 2.7%]; and RR = 2.47, 95% CI = 0.77-7.94 for adult-onset high [n = 35, 2.4%]). CONCLUSIONS: Participants with increasing BMI trajectories from childhood had an increased risk of SKD in midlife.