INTRODUCTION:Patients with advanced stages of chronic kidney disease (CKD) and dialysis-dependent kidney failure are at a greater risk of cardiovascular events and mortality than those with early stages of CKD. There are no completed definitive randomized trials on the safety and efficacy of anticoagulant therapy in this patient population. METHODS:Treatment of cardiovascular disease with low-dose Rivaroxaban in Advanced Chronic Kidney disease (TRACK) is a multi-center, randomized, placebo-controlled trial (NCT03969953), designed to enrol 1886 adult participants with CKD stage 4 or 5 (estimated glomerular filtration rate 29 mL/min/1.73 m2) or dialysis-dependent kidney failure and high cardiovascular risk (defined as at least one of the following risk factors; coronary artery disease, non-hemorrhagic non-lacunar stroke, peripheral artery disease [PAD], diabetes mellitus, or age 65 years). Participants are randomized to rivaroxaban 2.5 mg twice daily or matching placebo. The primary efficacy outcome is a composite of cardiovascular death, myocardial infarction, stroke, or PAD event. The primary safety outcome is major bleeding, defined as a composite of fatal bleeding, bleeding leading to hospitalization, or symptomatic bleeding in a critical area or organ. From January 2021 through July 2025, 1458 eligible participants (mean age 63.2 years, 700 [48%] age 65 years, 432 [29.6%] women, 715 [49%] dialysis-dependent kidney failure and 743 [51%] CKD stage 4 or 5, 1125 [77.2%] diabetes mellitus, 674 [46.2%] treated with aspirin at baseline) underwent randomization. CONCLUSION:TRACK will evaluate the effect of low dose rivaroxaban on major adverse cardiovascular events in participants with CKD stages 4 and 5 and dialysis-dependent kidney failure, and elevated cardiovascular risk.

AIMS:GLP-1 medicines provide substantial cardio-renal benefits for type 2 diabetes (T2D) and are increasingly used for weight loss. Most high-income countries subsidize access for T2D with restrictions; use outside of these restrictions occurs through private prescriptions. Despite strong consumer demand, the extent of private access to GLP-1 medicines remains poorly quantified. METHODS:We used national pharmaceutical sales data to quantify population use of GLP-1 medicines listed for T2D in Australia, May 2020-April 2025. We used Pharmaceutical Benefits Scheme (PBS) dispensing claims to measure subsidized access; we estimated private access as the difference between sales and PBS dispensings. We measured GLP-1 medicine use as number of units sold/dispensed and defined daily dose (DDD)/1000 population/day. RESULTS:Since May 2020, total sales of GLP-1 medicines indicated for T2D increased almost 10-fold. Most growth was in private access, driven by semaglutide and rapid uptake of tirzepatide. Supply dropped by 79% during periods of global shortage and primarily accessed through subsidized care. In the year May 2024-April 2025, the majority of GLP-1 medicines used were semaglutide (63.3%) and tirzepatide (30.7%). Half (47.8%) were accessed privately (26.9% of semaglutide; all tirzepatide). In this year, we estimate approximately 483 000-502 000 people accessed GLP-1 medicines each month, with 180 000-240 000 people accessing privately. CONCLUSIONS:Use of GLP-1 medicines indicated for T2D has increased dramatically, accessed by approximately half a million Australians each month, almost half of which is private. Our findings highlight demands outside of subsided care, equity concerns for access and pressures for health systems in meeting this demand.

Importance:Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective:To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions:Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures:The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results:Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance:In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration:ClinicalTrials.gov Identifier: NCT03969953.

Background:The objective of this study was to evaluate the clinical outcomes and patient satisfaction of a new nurse practitioner chronic kidney disease (CKD) clinic. Methods:This was a prospective cohort study of all patients who had their first appointment with the early CKD nurse practitioner from October 2023 to October 2024, with data extracted on 1 April 2025. The outcomes were assessed across three domains: (domain 1) change in clinical outcomes of kidney function, albuminuria and blood pressure, (domain 2) prescription of guidelines concordant medications and (domain 3) patient satisfaction with care as assessed by a survey. Results:There were 95 patients with a median age of 63 years [interquartile interval (IQI) 51-76], and 45.3% were female. Cardio-metabolic comorbidity was common; 82.8% of patients had hypertension, 55.6% diabetes and 25.2% cardiovascular disease. At referral the median urine albumin-creatinine ratio was 32.3 mg/mmol (IQI 11.2-53.5) and this was lower at discharge, 12.4 mg/mmol (IQI 2.9-25.3, P < .001). Systolic and diastolic blood pressure were lower at discharge [mean difference mmHg (95% confidence interval, P-value): 10.1 (6.58-13.54, <.001) and 5.2 (2.6-7.7, <.001), respectively]. There was no change in median estimated glomerular filtration rate. More patients at discharge were on a renin-angiotensin system inhibitor (88.4% versus 76.8%), sodium-glucose cotransporter 2 inhibitor (53.6% versus 28.4%), mineralocorticoid receptor antagonist (23.1% versus 5.2%) and glucagon-like peptide-1 receptor agonist (23.1% versus 9.6%). The survey response rate was 51.6% with patients reporting high satisfaction with the service. Conclusion:The CKD nurse practitioner clinic was effective at implementing guideline-directed medical therapies for early CKD and associated with improvements in blood pressure and albuminuria.

AIMS:Prevalence of chronic kidney disease (CKD) differs between females and males across the disease spectrum. Data on whether management of CKD also varies according to sex are limited. This study aimed to understand sex-related differences in CKD monitoring and cardiovascular risk management in Australian primary care. MATERIALS AND METHODS:Retrospective cohort study of adults attending general practices in Australia between 1 January 2011 and 30 June 2020 and met diagnostic criteria for CKD. Sex differences in CKD monitoring and management were assessed within 18 months of meeting CKD diagnostic criteria. Core monitoring was defined as ≥1 measurement of all of blood pressure, estimated glomerular filtration rate, urine albumin creatine ratio, lipids and, in patients with diabetes, haemoglobin A1c (HbA1c). Cardiovascular risk management comprised angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) and statin prescriptions, blood pressure target achievement, and lipid control. Adjusted modified Poisson regression determined the relative risk (RR) of outcomes in females versus males, and sex-specific analyses explored associations between patient characteristics and outcomes. RESULTS:Of 140 774 patients with CKD, 51.4% were female. Females were older (mean age: 75.8 vs. 72.7 years) and had less prevalent cardiovascular disease and diabetes. Females were less likely than males to receive core monitoring in models adjusted for clinical and sociodemographic characteristics (RR [95% CI], 0.96 [0.95-0.98]), ACEi/ARB prescription (0.96 [0.95-0.97]; no difference in statin prescription), blood pressure targets (<140/90 mmHg: 0.96 [0.95-0.97]), and LDL <2 mmol/L (0.82 [0.80-0.84]). Differences persisted with advancing age, higher CKD risk, and co-morbidity subgroups. Sex-specific analyses found similar associations between patient characteristics and CKD care in both females and males. CONCLUSIONS:Females with CKD were less likely to receive CKD monitoring and cardiovascular risk management compared to males. Findings were not explained by differences in sociodemographic and clinical characteristics, with findings persisting in both high-risk subgroups and adjusted models. Further research is required to understand reasons for disparities in care.

Diabetes is a leading cause of kidney failure, and individuals with both diabetes and chronic kidney disease (CKD) experience significantly higher rates of complications and mortality. The international guideline developer Kidney Disease: Improving Global Outcomes (KDIGO) has produced clinical practice guidelines that reflect recent advances in pharmacotherapy for this population, extending beyond glycaemic control to include cardio-renal benefits. However, these guidelines were developed without specific consideration of the healthcare systems, access issues and population needs in Australia and New Zealand. In response, the Caring for Australians and New Zealanders with Kidney Impairment (CARI) Guidelines Working Group has provided a regional commentary on the KDIGO 2022 guideline. This commentary highlights key recommendations and contextualises their implementation within the Australian and New Zealand healthcare environments. It addresses issues such as medication access, equity for Indigenous populations and the importance of shared decision-making, aiming to support clinicians in delivering evidence-based, locally relevant care for people living with diabetes and CKD.

BACKGROUND:Clinical practice guidelines recommend the initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors when the estimated glomerular filtration rate (eGFR) is ≥20 mL/min/1.73 m2. Although continuing SGLT2 inhibitors when the eGFR falls to <20 mL/min/1.73 m2 is recommended, data on the efficacy and safety of SGLT2i in this setting are limited. METHODS AND RESULTS:In this post-hoc analysis of the CREDENCE trial, we used time-updated Cox proportional hazards models to assess the association between deterioration in eGFR to <20 mL/min/1.73 m2, efficacy and safety outcomes, and treatment with canagliflozin. Among 4401 randomized participants, 443 (10.1%) experienced eGFR deterioration to <20 mL/min/1.73 m2 at least once in follow-up. These participants experienced a higher risk of the primary composite outcome (hazard ratio [HR] 10.68, 95% confidence interval [CI] 8.50-13.41, P < .001). Canagliflozin compared with placebo was associated with a lower risk of the primary outcome among participants who did (HR 0.87, 95% CI 0.61-1.25) and did not (HR 0.69, 95% CI 0.57-0.84) experience deterioration of the eGFR to <20 mL/min/1.73 m2 (PInteraction = .18). Although the incidence of adverse outcomes was higher among participants whose eGFR fell to <20 mL/min/1.73 m2, event rates remained similar between treatment groups irrespective of an eGFR decline to <20 mL/min/1.73 m2. CONCLUSIONS:In patients with type 2 diabetes and chronic kidney disease whose eGFR fell to <20 mL/min/1.73 m2, continuation of canagliflozin was associated with a persistent benefit for kidney and cardiovascular outcomes with no additional safety concerns. These data support current guideline recommendations to continue SGLT2 inhibitors until dialysis or transplantation.

AIMS:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly withheld during hospitalisation because of concerns about diabetic ketoacidosis. We examined whether hospitalisation was associated with discontinuation of SGLT2i and compared patterns with another anti-hyperglycaemic medicine without similar inpatient safety concerns: dipeptidyl peptidase-4 inhibitors (DPP-4i). MATERIALS AND METHODS:We conducted a retrospective new-user cohort study using linked, population-level data for adult residents of New South Wales, Australia. Adults aged ≥ 40 years initiating SGLT2i or DPP-4i (separate cohorts) between 2016 and 2020 were followed until death, mid-2021, or treatment discontinuation (gap of ≥ 90 days without a dispensing of the index medicine). We used Cox proportional hazards models to estimate the association between hospitalisation and discontinuation, adjusting for demographic and clinical characteristics. We treated the 'hospitalisation period' (the inpatient stay plus the 90 days following discharge) as a time-dependent exposure. RESULTS:Among people initiating SGLT2i (n = 106 098), the median age was 63 years and 61% were male. Overall, 35.1% were hospitalised during follow-up, and discontinuation was substantially more frequent during the hospitalisation period (56.4 per 100 person-years) compared with other follow-up times (37.6 per 100 person-years). This association remained significant after adjustment (HR: 1.83; 95% CI: 1.79-1.87). Similar patterns were observed among DPP-4i treated people (HR: 1.55; 95% CI: 1.51-1.58). CONCLUSIONS:Hospitalisation is a strong risk factor for discontinuation of SGLT2i and DPP-4i therapy. Strategies to support re-initiation of SGLT2i during transitions from hospital to community care are needed to prevent harm and maximise cardiorenal protective effects of these medicines.

Importance: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. Objective: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. Interventions: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. Results: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). Conclusions and Relevance: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. Trial Registration: ClinicalTrials.gov Identifier: NCT03969953.

BACKGROUND:Polypharmacy in chronic kidney disease (CKD) is substantial. Clinicians and patients are often reluctant to add medications to already complex regimens, partly due to concerns about diminishing efficacy and increased adverse effects. We assessed whether efficacy and safety of canagliflozin is modified by polypharmacy status in patients with type 2 diabetes and CKD. METHODS:We conducted a post-hoc analysis of the CREDENCE trial, which evaluated the effects of canagliflozin on outcomes in patients with type 2 diabetes and CKD. Participants were categorized as no polypharmacy (0-4 medicines), polypharmacy (5-9 medicines), or hyperpolypharmacy (≥10 medicines). We assessed the relative effects of canagliflozin on clinical and safety outcomes by polypharmacy status using Cox proportional hazards models. We assessed absolute benefits using Poisson regression. The primary outcome was a composite of doubling of serum creatinine, kidney failure or death due to cardiovascular or kidney disease. RESULTS:Among 4401 participants, 612 (14%), 2404 (55%), and 1385 (31%) were categorized as no polypharmacy, polypharmacy and hyperpolypharmacy, respectively. Mean number of medications was 8.3 (SD 3.77). The effect of canagliflozin on kidney and cardiovascular outcomes was consistent irrespective of polypharmacy status, with no interaction observed for safety outcomes (all P-interaction > 0.06). Rates of treatment discontinuation increased with medication burden, but were lower with canagliflozin versus placebo, regardless of polypharmacy status (P-interaction = 0.16). Incidence of all-cause hospitalization, and heart failure hospitalization or cardiovascular death increased with higher medication burden, thus absolute risk reductions were estimated to be substantially greater in patients with polypharmacy and hyperpolypharmacy. CONCLUSION:Among patients with type 2 diabetes and CKD, the efficacy and safety of canagliflozin appears consistent regardless of polypharmacy status, with larger estimated absolute reductions in hospitalizations and cardiovascular events in those experiencing polypharmacy or hyperpolypharmacy. These findings suggest that polypharmacy alone should not preclude consideration of SGLT2 inhibitor therapy in patients with CKD and type 2 diabetes for whom treatment is otherwise indicated.

RATIONALE & OBJECTIVE:Chronic kidney disease (CKD) is a global public health concern, but its burden in Africa is poorly defined. This study estimated CKD prevalence across the African continent. STUDY DESIGN:Systematic review and individual participant data meta-analysis. SETTING & STUDY POPULATION:Populations residing in Africa. SELECTION CRITERIA:Eligible studies enrolled ≥300 adults, were observational, used community-based designs, and reported CKD prevalence or data necessary to calculate it. SEARCH STRATEGY:Studies, both published and unpublished, through May 31, 2024, identified through systematic searches of major databases and through networks within the CKD-Africa Collaboration. DATA EXTRACTION:Data were systematically extracted and verified by the authors. Extracted information included study and publication details, CKD diagnostic criteria, and participant characteristics. ANALYTICAL APPROACH:Pooled prevalence estimates were calculated using random-effects meta-analysis. RESULTS:Sixty-seven studies, comprising 91,723 participants from 19 countries, were included. High- and moderate-quality studies accounted for 37% and 52%, respectively, and 6% were unpublished. Pooled CKD prevalence (stages 1-5) was 13.7% (95% CI, 11.0-16.4), and 5.1% (95% CI, 4.3-5.8) for stages 3-5. Regional variation was evident (I2 >98%; P < 0.001), with higher prevalence in western Africa compared to southern Africa. Estimates using aggregated data and individual participant data were consistent. LIMITATIONS:Variations in the quality of the study data and substantial heterogeneity in prevalence estimates. Lack of assessment of chronic CKD. Reliance on aggregated data for 55% of the sample. Gaps in geographic representation may limit the generalizability of findings. CONCLUSIONS:Approximately 14% of African adults had CKD, highlighting its public health burden. The precision of this finding was augmented by the use of individual participant data. REGISTRATION:Registered at Prospero with identification number CRD42019143370. PLAIN-LANGUAGE SUMMARY:Chronic kidney disease (CKD), a long-term condition in which the kidneys gradually lose their ability to filter waste and fluids from the blood, is an increasing health problem in Africa, but prevalence data have been limited. Previous studies relied on only summaries of studies' data. This analysis combined individual-level and summary data from multiple African countries to provide a more accurate and precise estimate of CKD prevalence. It found that CKD affects a substantial proportion of adults, with rates varying across regions. These findings highlight the potential value of early detection given the availability of effective clinical strategies to manage CKD.

AIM:The KDIGO 2021 Glomerular Disease Guidelines provide updated recommendations on the management of glomerular diseases (GD), with substantial advances made in diagnosis, treatment, and improvement of outcomes for people with GD. METHODS:The Caring for Australians and New Zealanders with kidney Impairment (CARI) Guidelines commentary contextualises the updated guidelines for the Australian and New Zealand setting. RESULTS:Kidney biopsy remains central to diagnosis, with validated scoring systems available. However, genetic testing for suspected monogenic kidney disease is now accessible in Australia, enabling earlier diagnosis and management, particularly in situations where a kidney biopsy is considered high risk or contraindicated. The guideline emphasises timed urine collections for protein excretion over spot tests and we suggest the use of the CKiD u25 eGFR equation for people under 25. For IgA nephropathy (IgAN) and IgA vasculitis (IgAV), emerging therapies such as targeted-release budesonide and sparsentan demonstrate promise but await approval and public subsidy in our region. For membranous nephropathy, the guideline highlights the differences in adult and paediatric management. In nephrotic syndrome, tacrolimus is used as first-line therapy and rituximab as a second-line agent for steroid-dependent or frequently relapsing disease. Minimal change disease recommendations include glucocorticoid tapering after remission, while focal segmental glomerulosclerosis incorporates genetic classifications and advocates for next-generation sequencing. CONCLUSION:Our commentary underscores the need for increased participation in clinical trials to validate regional applicability and improve long-term outcomes for people with GD in Australia and New Zealand. Clinical trials of new medications have led to more treatment options that are awaiting approval.