Background While sodium-glucose cotransporter-2 (SGLT2) inhibitors provide major benefits across multiple chronic diseases, clinician prescription and patient adherence rates remain low. Objective To explore perspectives of clinician and patient stakeholders regarding barriers and facilitators for SGLT2 inhibitor use. Design Semi-structured interviews, conducted as part of a larger project examining the type 2 diabetes mellitus (T2DM) standard of care. Setting Australia. Participants Clinicians involved in the care of people with T2DM, including primary care clinicians, endocrinologists, nephrologists, cardiologists, diabetes educators, and pharmacists; and adults with T2DM. Methods Barriers and facilitators of SGLT2 inhibitor implementation were explored through the Consolidated Framework for Implementation Research. Analysis of interview transcripts was conducted in duplicate using a combination of framework and thematic analysis. Results A total of 24 clinicians, and four people with T2DM, were interviewed between November 2021 and August 2023, including four primary care clinicians, four endocrinologists, four nephrologists, four cardiologists, four diabetes educators, and four pharmacists. Key findings included that clinicians miss opportunities to prescribe due to competing priorities and therapeutic inertia, and may find it difficult to educate and engage patients about SGLT2 inhibitor use. Patients require detailed education to understand benefits and adverse effect prevention, ideally with multimodal resources and staggered over time, and would benefit from general adherence coaching. Some clinicians were concerned about the risk of urinary tract infections despite reassuring safety data, and few provided genital hygiene advice to reduce SGLT2 inhibitor-associated genital mycotic infections. Better health system support could be achieved through additional cost reimbursement and support for multidisciplinary care access. Limitations Most participants were from a single Australian state, New South Wales, which may not fully reflect experiences across Australia. Participation bias may under-represent those less engaged in SGLT2 inhibitor use. Conclusions Clinicians are convinced about SGLT2 inhibitor benefits but require support to deliver evidence-based care, including effective patient education and engagement. These insights can help inform the design of interventions to maximise societal benefit from these effective medications.

Purpose of program This conference report describes findings from activities to reposition the Canadian Chronic Kidney Disease (CKD) Clinic Network by identifying research priorities and actionable steps aligned with the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The initiative aimed to identify priority actions to integrate clinical research and care through collaborative dialogue and community-driven planning. Sources of information The 2024 KDIGO Clinical Practice Guideline for CKD served as the foundation to assess and prioritize relevant research areas. Insights were gathered through a national survey and a participatory workshop using World Café methodology. Methods An anonymized online semi-structured survey was distributed to members of the Canadian CKD Clinic Network from April 4-14, 2025 to assess the perceived relevance and importance of the 2024 KDIGO CKD guideline research recommendations. This was followed by an in-person World Café workshop in May 2025 involving patients, clinicians, researchers, and administrators. Data collection included live graphic recording, table notes, and Post-it reflections, which were thematically analyzed. Key findings The survey yielded responses from 80 network members, representing a 24% response rate. Survey results prioritized the need for research on: the impact of newer medications (SGLT2i, non-steroidal mineralocorticoid receptor antagonists) in patients intolerant of ACEi/ARB, implementation science to ensure uptake of proven therapies and symptom management, essential components for transition clinics for young people, tools for health literacy in different populations, strategies to prevent hyperkalemia, impact of medication deprescribing, effects of dietary restriction, and symptom identification, classification, and control. Attendees of the World Café (n=19) identified several network strengths, including its established relationships that drive national collaboration, willingness in knowledge sharing, and inclusion of the patient voice. Feedback emphasized the need for collaborative implementation and context-sensitive application of guidelines. The workshop also aligned the network’s future direction with Learning Health System principles, which embed research into routine care delivery, supporting goals with provincial and national CKD strategies, deepening patient engagement, shared measurement tools, and local-to-national learning loops. Actionable steps identified included enhancing visibility through a public-facing website, anchoring activities to sustainable national platforms, and exploring additional partnerships and collaborative research opportunities. Limitations Only 24% of the CKD Clinic Network responded to the survey, and 19 members were present at the World Café, reflecting perspectives from only a small portion of the network. Therefore, the results may overlook key challenges or opportunities that did not surface due to missing perspectives of others within the kidney care community. Implications This initiative demonstrates how engaging diverse perspectives can inform network transformation and future strategic research directions. The CKD Clinic Network is well-positioned to evolve into a responsive, patient-centred platform that drives learning and improvement in health care delivery across Canada’s kidney care system.

Diabetes mellitus is the leading cause of chronic kidney disease and kidney failure worldwide, and diabetic kidney disease (DKD) is associated with excess cardiovascular and all-cause mortality. The pathophysiology of DKD is complex and multifactorial, characterized by physiologically redundant haemodynamic, metabolic and inflammatory pathways that promote maladaptive renal remodelling and accelerate disease progression. Current management of DKD centres around four key pillars of guideline-directed medical therapy (GDMT): renin–angiotensin–aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, non-steroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. These therapies are increasingly used in combination for cardiorenal protection in DKD. However, substantial residual cardiorenal risk persists even among patients receiving optimal GDMT. Next-generation therapies for DKD that are currently in development include various incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory agents. These therapies are expected to complement current GDMT and further improve kidney and cardiovascular outcomes in patients with DKD. In this Review, the authors discuss guideline-directed medical therapy for diabetic kidney disease and the evolving clinical evidence for next-generation therapies, including incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory therapies.

Introduction:We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada. Methods:This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years. Results:A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94). Conclusion:CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed for their glucose-lowering effects and have shown a modest glycaemic benefit in people with type 2 diabetes mellitus (T2DM). In the past decade, a series of large, robust clinical trials of these therapies have demonstrated striking beneficial effects for various care goals, transforming the chronic disease therapeutic landscape. Cardiovascular safety studies in people with T2DM demonstrated that SGLT2 inhibitors reduce cardiovascular death and hospitalization for heart failure. Subsequent trials in participants with heart failure with reduced or preserved left ventricular ejection fraction demonstrated that SGLT2 inhibitors have beneficial effects on heart failure outcomes. In dedicated kidney outcome studies, SGLT2 inhibitors reduced the incidence of kidney failure among participants with or without diabetes. Post hoc analyses have suggested a range of other benefits of these drugs in conditions as diverse as metabolic dysfunction-associated steatotic liver disease, kidney stone prevention and anaemia. SGLT2 inhibitors have a generally favourable adverse effect profile, although patient selection and medication counselling remain important. Concerted efforts are needed to better integrate these agents into routine care and support long-term medication adherence to close the gap between clinical trial outcomes and those achieved in the real world. Here, the authors discuss the beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors for a range of clinical outcomes beyond glucose lowering, including kidney and cardiovascular protection. They also discuss the need for implementation and adherence initiatives to help translate the benefits of these agents into real-world clinical outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of kidney disease progression in people with or without diabetes as well as the risk of acute kidney injury and hyperkalaemia.SGLT2 inhibitors reduce the risk of cardiovascular death and heart failure hospitalization among people with type 2 diabetes mellitus and have beneficial effects on key heart failure outcomes irrespective of diabetes status or left ventricular ejection fraction.SGLT2 inhibitors modestly lower systolic and diastolic blood pressure without a significant increase in risk of hypotensive episodes and have modest benefits for weight loss.Other benefits of SGLT2 inhibitors include improvements in liver outcomes in people with metabolic dysfunction-associated steatotic liver disease, reduced risk of symptomatic kidney stone events, improvements in anaemia outcomes and potential reductions in the risk of new-onset atrial fibrillation and new-onset diabetes.SGLT2 inhibitors have a generally favourable adverse effect profile but are associated with increased risk of genital mycotic infections and a small increased risk of diabetic ketoacidosis; they should be used with caution in people with unstable volume status owing to the risk of hypovolaemia.Prescription of SGLT2 by clinicians and patient adherence are suboptimal despite strong evidence for the efficacy and cost-effectiveness of these therapies.

Background. The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods. Patients with CKD aged >= 18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 <= 40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results. Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions. KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

AIM:To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. MATERIALS AND METHODS:A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end-stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all-cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. RESULTS:The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59-0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. CONCLUSIONS:Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups.

Abstract BACKGROUND AND AIMS Type 2 diabetes mellitus (T2DM) is associated with comorbidities, such as chronic kidney disease (CKD) and peripheral vascular disease (PVD), which may increase risk of cardiovascular (CV) and kidney events. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, reduced the risk of CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trial, respectively. The effects of canagliflozin on CV and kidney outcomes in patients with CKD with and without PVD remain unknown. METHOD This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of canagliflozin compared with placebo on CV and kidney outcomes were assessed in patients with CKD with and without PVD at baseline. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and PVD was defined based on investigator classification on the electronic case report form without requirement for specific clinical evaluation or imaging. Propensity score (PS) matching was used to balance patient demographics and baseline clinical characteristics between groups. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox regression models. RESULTS A total of 14 543 participants from the CANVAS Program (N = 10 142) and CREDENCE (N = 4401) were included. Of these, 3514 had CKD alone (canagliflozin, n = 1792; placebo, n = 1722; mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 49%; insulin use, 64%) and 1156 had CKD + PVD (canagliflozin, n = 626; placebo, n = 530; mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 96%; insulin use, 74%) at baseline. Canagliflozin was associated with a reduced risk of major adverse cardiovascular events (MACE), the composite of hospitalization for heart failure (HHF) or CV death (HHF/CV death), doubling of serum creatinine (dSCr), end-stage kidney disease (ESKD) and the composite of ESKD or dSCr compared with placebo in patients with CKD with and without PVD (Figure 1A). After matching, 3210 patients had CKD alone (mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 49%; insulin use, 64%) and 966 had CKD + PVD (mean eGFR, 46 mL/min/1.73 m2; symptomatic CV disease history, 98%; insulin use, 74%), with equal numbers in the canagliflozin and placebo groups. In the PS-matched groups, canagliflozin was associated with a reduced risk of MACE, HHF/CV death, dSCr, ESKD and the composite of ESKD or dSCr compared with placebo in patients with CKD with and without PVD (Figure 1B). CONCLUSION Canagliflozin significantly reduced the risk of MACE, HHF/CV death, dSCr, ESKD, and the composite of ESKD or dSCr in patients with CKD with and without PVD, suggesting that the beneficial effects of canagliflozin on CV and kidney outcomes are consistent and can be seen in patients regardless of these comorbidities.

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Background: Care gaps remain in modern health care despite the availability of robust, evidence-based medications. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated profound benefits in improving both cardiovascular and kidney outcomes in patients, the uptake of these medications remain suboptimal, and the causes have not been systematically explored. Objective: The purpose of this study was to use the Consolidated Framework for Implementation Research (CFIR) to describe the barriers and facilitators faced by clinicians in British Columbia, Canada, when prescribing an SGLT2 inhibitor. To achieve this, we conducted semistructured interviews using the CFIR with practicing family physicians, nephrologists, endocrinologists, and cardiologists in British Columbia. Design: Semistructured interviews. Setting: British Columbia, Canada. Participants: Actively practicing family physicians, nephrologists, endocrinologists, and cardiologists in British Columbia. Methods: Twenty-one clinicians were interviewed using questions derived from the CFIR. The audio recordings were transcribed verbatim, and each transcription was individually analyzed in duplicate using thematic analysis. The analysis focused on identifying barriers and facilitators to using SGLT2 inhibitors in clinical practice and coded using the CFIR constructs. Once the transcriptions were coded, overarching themes were created. Results: Five overarching themes were identified to the barriers and facilitators to using SGLT2 inhibitors: current perceptions and beliefs, clinician factors, patient factors, medication factors, and health care system factors. The current perceptions and beliefs were that SGLT2 inhibitors are efficacious and have distinct advantages over other agents but are underutilized in British Columbia. Clinician factors included varying levels of knowledge of and comfort in prescribing SGLT2 inhibitors, and patient factors included intolerable adverse events and additional pill burden, but many were enthusiastic about potential benefits. Multiple SGLT2 inhibitor related adverse events like mycotic infections and euglycemic diabetic ketoacidosis and the difficulty in obtaining reimbursement for these medications were also identified as a barrier to prescribing these medications. Facilitators for the use of SGLT2 inhibitors included consensus among colleagues, influential leaders, and peers in support of their use, and endorsement by national guidelines. Limitations: The experience from the clinicians regarding costs and the reimbursement process is limited to British Columbia as each province has its own procedures. There may be responder bias as clinicians were approached through purposive sampling. Conclusion: This study highlights different themes to the barriers and facilitators of using SGLT2 inhibitors in British Columbia. The identification of these barriers provides a specific target for improvement, and the facilitators can be leveraged for the increased use of SGLT2 inhibitors. Efforts to address and optimize these barriers and facilitators in a systematic approach may lead to an increase in the use of these efficacious medications.

Non-adherence to medications is a critical challenge in the management of people with chronic kidney disease (CKD). This review explores the complexities of adherence in this population, the unique barriers and enablers of good adherence behaviours, and the role of emerging digital health technologies in bridging the gap between evidence-based treatment plans and the real-world standard of care. We present the current evidence supporting the use of digital health interventions among CKD populations, identifying the key research questions that remain unanswered, and providing practical strategies for clinicians to support medication adherence in a digital age.

This review on sex, gender, and cardiovascular diseases in chronic kidney disease attempts to summarize what we know and what we do not know about the effects of sex and gender on cardiovascular disease in chronic kidney disease. We discuss and define the terminology of sex and gender, and the underlying physiology for differences observed. We explore how sex and gender affect specific cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, cardiovascular mortality, and pre-eclampsia. We conclude with a review of recent randomized controlled trials and highlight the pharmacokinetic and pharmacodynamic differences in both sexes.

The exponential growth in digital technology coupled with the global coronavirus disease 2019 pandemic is driving a profound change in the delivery of medical care and research conduct. The growing availability of electronic monitoring, electronic health records, smartphones and other devices and access to ever greater computational power provides not only new opportunities, but also new challenges. Artificial intelligence (AI) exemplifies the potential of this digital revolution, which also includes other tools such as mobile health (mHealth) services and wearables. Despite digital technology becoming commonplace, its use in medicine and medical research is still in its infancy, with many clinicians and researchers having limited experience with such tools in their usual practice. This article, derived from the 'Digital Health and Artificial Intelligence' session of the Kidney Disease Clinical Trialists virtual workshop held in September 2020, aims to illustrate the breadth of applications to which digital tools and AI can be applied in clinical medicine and research. It highlights several innovative projects incorporating digital technology that range from streamlining medical care of those with acute kidney injury to the use of AI to navigate the vast genomic and proteomic data gathered in kidney disease. Important considerations relating to any new digital health project are presented, with a view to encouraging the further evolution and refinement of these new tools in a manner that fosters collaboration and the generation of robust evidence.