AIMS:In FIDELITY, finerenone improved kidney and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines categorise CKD progression risk based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This FIDELITY post hoc subanalysis investigated KDIGO risk category changes associated with finerenone. METHODS:Improvement or worsening in KDIGO risk category was defined by variation from baseline, with specified eGFR and UACR changes. Association of these category changes with a CV composite outcome was assessed. RESULTS:Finerenone therapy led to a higher likelihood of KDIGO risk category improvement (odds ratio [OR], month 36: 1.47; 95% confidence interval [CI], 1.31-1.65; p < 0.0001) and lower likelihood of worsening (OR, month 36: 0.83; 95% CI, 0.77-0.90; p < 0.0001) vs. placebo. Risk category improvement reduced the CV composite outcome risk (hazard ratio [HR]: 0.82; 95% CI, 0.68-0.99; p = 0.043) while worsening increased this risk (HR: 1.29; 95% CI, 1.06-1.56; p = 0.01). CONCLUSIONS:Finerenone therapy is associated with greater improvement and less worsening in KDIGO risk vs. placebo. The category changes are associated with lower risk of CV events in patients with CKD and T2D. TRIAL REGISTRATION NUMBER:FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) are registered with ClinicalTrials.gov (funded by Bayer AG).

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD), though their potential to prevent the development of CKD in type 2 diabetes needs to be examined. Purpose: Evaluate SGLT2 inhibitors for the primary prevention of CKD in people with type 2 diabetes. Data Sources: PubMed and Cochrane CENTRAL were searched through October 2025. Data Synthesis: Randomized controlled trials (RCTs) of SGLT2 inhibitors compared to placebo or other glucose-lowering agents in people with type 2 diabetes without baseline CKD were included. Outcomes were eGFR decline and incident albuminuria (i.e., UACR ≥30 mg/g). Random-effects meta-analyses were performed, and heterogeneity was assessed with I2. Certainty of evidence was evaluated with GRADE. PROSPERO CRD420251130722. Results: Eight RCTs were included: 5 cardiovascular outcomes trials comparing SGLT2 inhibitors and placebo (24072 participants) and 3 trials comparing SGLT2 inhibitors and sulfonylureas (2889 participants). Compared to placebo, SGLT2 inhibitors reduced the risk of incident albuminuria (3 trials, hazard ratio [HR]: 0.82, 95% CI (0.77-0.88), I2=0%, high certainty) and slowed eGFR decline based on chronic eGFR slope (5 trials, mean difference [MD]: 0.95 (0.84-1.07) ml/min/1.73 m2/year, I2=19%, high certainty) and total eGFR slope (4 trials, MD: 0.76 (0.50-1.03) ml/min/1.73 m2/year, I2=88%, moderate certainty). Compared to sulfonylureas, SGLT2 inhibitors slowed eGFR decline based on chronic eGFR slope (3 trials, MD: 2.43 (1.72-3.13) ml/min/1.73 m2/year, I2=55%, moderate certainty). Conclusions: In people with type 2 diabetes without CKD, SGLT2 inhibitors slow eGFR decline compared to both placebo and sulfonylureas and prevent incident albuminuria compared to placebo. Article Highlights (111/130 words) · Why did we undertake this study? To evaluate the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the primary prevention of chronic kidney disease (CKD) in people with type 2 diabetes. · What is the specific question(s) we wanted to answer? Can SGLT2 inhibitors prevent the onset of CKD in people with type 2 diabetes who do not have evidence of CKD at baseline? · What did we find? In people with type 2 diabetes without baseline CKD, SGLT2 inhibitors prevent incident albuminuria and slow eGFR decline. · What are the implications of our findings? Evidence supports the use of SGLT2 inhibitors for the primary prevention of CKD in people with type 2 diabetes.

BACKGROUND AND HYPOTHESIS:Chronic kidney disease (CKD) is a global health and economic burden, particularly among individuals with type 2 diabetes (T2D). According to Kidney Disease: Improving Global Outcomes guidelines, key CKD indicators include urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Although independent genetic loci for these traits have been reported, their shared genetic architecture remains insufficiently understood. We hypothesized that there are shared genetic markers of kidney function (eGFR) and albuminuria generally, but also specific to the T2D population. METHODS:We conducted a cross-sectional observational study including 432 451 UK Biobank participants of primarily European descent (94%), with a subgroup of 16 265 with T2D after data quality control. We examined whether 423 single-nucleotide polymorphisms previously associated with eGFR in a large genome-wide association study meta-analysis were associated with (a) eGFR estimated using the 2021 race-free CKD-Epidemiology Collaboration creatinine equation (eGFR2021) and (b) UACR. Multiple linear regression models were adjusted for systolic blood pressure, age, sex, and the first 10 genetic principal components to account for population stratification. Analyses were performed using Python and R. Bonferroni correction (BC) was performed. For the T2D subgroup, the models were additionally adjusted for body mass index and glycated hemoglobin. RESULTS:In the overall population, 422 loci were nominally associated with eGFR2021, of which 75 were nominally associated with UACR (p≤0.05); 12 remained significant after BC (Pb ≤ [Formula: see text]). In the T2D subgroup, 76 loci nominally associated with eGFR2021, six also associated nominally with UACR (p≤0.05), and one remained significant after BC (Pb ≤ [Formula: see text]). Two pleiotropic loci (GSTA2, USP2-AS1) suggested diabetes-specific effects. CONCLUSION:This study identifies several shared genetic loci underlying eGFR and UACR in both general and T2D European populations. These findings highlight common pathobiological pathways between albuminuria and reduced kidney function and provide a genetic map that may inform future CKD risk stratification and towards the development of therapeutic targets.

Objective: To evaluate whether the efficacy and safety of finerenone varied by baseline hemoglobin A1c (HbA1c) levels, a proxy of glycemic control, and diabetes duration in people with type 1 diabetes and chronic kidney disease (CKD). Research Design and Methods: Adults with type 1 diabetes, urinary albumin-to-creatinine ratio (UACR) 200−<5000 mg/g and estimated glomerular filtration rate (eGFR) 25−<90 mL/min/1.73 m2 were randomized (1:1) to finerenone or placebo. UACR change from baseline over 6 months by baseline HbA1c and diabetes duration was analyzed. Results: Baseline HbA1c was available for 240/242 participants; mean (SD) HbA1c, diabetes duration, and eGFR were 7.6% (1.1; 60 [12] mmol/mol), 32.0 (14.2) years, and 58.9 (19.2) mL/min/1.73 m2, respectively. At 6 months, HbA1c (95% CI) remained unchanged (finerenone: +0.03% [–0.14, 0.20]; placebo: 0.00% [–0.12, 0.11]; between-group difference +0.04% [–0.17, 0.24]; P=0.74). Over 6 months, median UACR decreased from 574.6 to 373.5 mg/g with finerenone and from 506.4 to 475.6 mg/g with placebo, corresponding to a –25% placebo-corrected change (95% CI –35, –13; P=0.0001). Treatment effects were consistent across HbA1c tertiles (<7.1%, ≥7.1%−≤8.1%, and >8.1%), with placebo-corrected UACR changes (95% CI) of –17% (–40, 13), –18% (–39, 10), and –37% (–55, –13), respectively (P interaction=0.41). Effects were similarly consistent across diabetes duration tertiles (P interaction=0.70). Overall safety and incidence of hyperkalemia were similar across HbA1c tertiles. Conclusions: In adults with type 1 diabetes and CKD, finerenone reduced UACR and was well-tolerated irrespective of HbA1c levels or diabetes duration.

Several psychological and emotional aspects have been identified in people with diabetic foot disease (DFD). Currently, the scope of evidence on the topic is unclear. The aim of this scoping review is to identify and map the literature on psychological and emotional aspects of DFD. A systematic search was conducted on the 6th of May 2024, in MEDLINE, Embase, CINAHL and PsycInfo. Search results were screened based on predefined eligibility criteria. Data charting followed predefined extraction sheets, adapted for quantitative or qualitative studies. Out of 1,838 unique records identified from the database search and 1,819 from backwards citation search, 118 studies were deemed eligible for inclusion. Five categories of foot outcomes were identified. Qualitative studies revealed psychological and emotional impacts, primarily through individual interviews and various methods of analysis. Quantitative studies reported 25 different psychological and emotional concepts, utilizing 53 distinct tools. Most common concepts were depression, anxiety, and illness perception. Existing research on psychological and emotional aspects of DFD is diverse, using a wide variety of study designs, concepts, and tools. Most studies focus on quantitative psychological factors. This highlights the need for further exploration of other relevant aspects to enhance patient support.

Importance:Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has improved outcomes in type 2 diabetes (T2D) and CKD. Objective:To evaluate the efficacy and safety of finerenone across CKM stages, and to examine the effects of finerenone on CKM syndrome progression and regression over time. Design, Setting, and Participants:This study is a post hoc pooled analysis of 2 randomized, double-blind, placebo-controlled, phase 3 multinational, multicenter clinical trials (FIDELITY) and was conducted across 48 countries. Patients with T2D and CKD with estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2 or higher, serum potassium 4.8 mmol/L or less, and taking maximally tolerated renin angiotensin system inhibitor therapy were included and classified into CKM syndrome stages, using American Heart Association criteria. These data were analyzed from September 2025 and March 2026. Intervention:Participants in the pooled trials were randomly assigned to either finerenone or placebo. Main Outcomes and Measures:Cardiovascular composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization and a kidney composite outcome of kidney failure, a sustained 57% or more decrease in eGFR from baseline over 4 weeks or more, or death from kidney failure. Results:Among 12 990 participants (mean [SD] age, 64.8 [9.5] years; 3932 women [30%] and 9058 men [70%]) in FIDELITY, 3864 were classified as CKM stage 2 (30%), 3275 stage 3 (25%), and 5851 stage 4 (45%). After a median follow-up of 3 years, stage 4 was associated with a higher incidence of cardiovascular events (adjusted hazard ratio [aHR], 1.87; 95% CI, 1.56-2.24) and kidney events (aHR, 1.96; 95% CI, 1.43-2.69) when compared with stage 2. Finerenone consistently reduced cardiovascular (P for interaction = .86) and kidney (P for interaction = .65) events, irrespective of baseline CKM stage. Absolute rate reductions for the composite cardiovascular outcome were -1.1 per 100 person-years for stage 4 and -0.4 per 100 person-years for stage 2. After 3 years, participants randomized to finerenone were more likely to experience CKM syndrome regression (11.4% vs 7.4%; adjusted odds ratio [aOR], 1.66; 95% CI, 1.30-2.13; P < .001) and less likely to experience CKM syndrome progression (aOR, 0.89; 95% CI, 0.79, 1.00; P = .05) vs placebo. Conclusions and Relevance:Among patients with T2D and CKD in this study, finerenone reduced risks of cardiovascular and kidney events across CKM stages and led to greater CKM syndrome regression, and lesser CKM syndrome progression, over time. Trial Registration:ClinicalTrials.gov Identifier: NCT02540993 and NCT02545049.

BACKGROUND:We recently developed and validated a hierarchical composite endpoint (HCE) for chronic kidney disease (CKD) progression combining time-to-event kidney outcomes with the rate of estimated glomerular filtration rate (eGFR) decline (eGFR slope). The CKD progression HCE is an informative endpoint for clinical trials in rare kidney diseases, such as focal segmental glomerulosclerosis (FSGS), where event-driven trials are often infeasible. METHODS:We applied a HCE for CKD progression to the subset of patients with FSGS from the DAPA-CKD trial, a randomized double-blind, placebo-controlled clinical trial, to assess the effects of the sodium glucose co-transporter 2 inhibitor dapagliflozin on CKD progression in 4304 participants. We compared treatment effects for the primary composite endpoint (sustained 50% eGFR decline, kidney failure, or death due to kidney or cardiovascular causes), eGFR slope, and CKD progression HCE. We also compared statistical power for these outcomes using a bootstrap sampling procedure to evaluate the impact on trial efficiency. RESULTS:Overall, 115 participants were included (mean age, 54 years; 68% male; median urinary albumin-to-creatinine ratio, 1283 mg/g; mean eGFR, 42 mL/min/1.73m2). The effect of dapagliflozin on the primary composite endpoint (hazard ratio 0.45 [95% confidence interval [CI]: 0.13, 1.49]) and total eGFR slope (0.9 mL/min/1.73m2 (95%CI: -0.6, 2.3) were consistent with the overall trial results but the 95% CI crossed unity. The win-odds for the CKD progression HCE suggested benefits for dapagliflozin and the 95%CI did not cross unity (win-odds: 1.52 [95%CI: 1.01, 2.28]). Power calculations suggested that for a given sample size, statistical power was higher for the CKD progression HCE compared with the primary composite endpoint or eGFR slope. CONCLUSION:Our findings suggest that a CKD progression HCE, which integrates established CKD endpoints and eGFR slope, provides a sensitive and efficient measure to assess treatment effects in patients with FSGS. Validation of the HCE in prospective clinical trials will support its implementation.

Urinary epidermal growth factor (uEGF) and clusterin (uCLU) are emerging biomarkers in chronic kidney disease (CKD), but rigorous analytical validation is required before clinical implementation. We evaluated intra-individual variability and long-term storage stability of uEGF and uCLU in CKD. In the prospective, multicenter UVALID study, 60 adults with CKD stages 2-4 underwent urine sampling at three visits over 8 weeks. First-morning and 24-h urine samples were collected to assess intra-individual variability over 24 h, 3 days and 8 weeks. Biomarkers were measured in duplicate by ELISA and normalized to urinary creatinine (/Cr). Inter-laboratory performance was assessed using quality control samples. Stability after 12 and 15 months of storage at -20 °C and -80 °C and the influence of pH were evaluated. Over 24 h, 3 days, and 8 weeks, uEGF/Cr demonstrated low variability and remained stable after long-term storage at both temperatures. In contrast, uCLU/Cr showed greater variability and pronounced instability at -20 °C, whereas stability was preserved at -80 °C. Samples with pH > 6 partially preserved uCLU stability at -20 °C. Inter-laboratory reproducibility was acceptable for uEGF but suboptimal for uCLU at low concentrations. Thus, uEGF showed robust analytical performance, supporting its potential clinical applicability in CKD, whereas uCLU exhibited important analytical and pre-analytical limitations, warranting further assay optimization. These findings underscore the need for rigorous validation to facilitate biomarker implementation in clinical practice.

INTRODUCTION:Population-based surveillance is essential for quantifying the burden of diabetes and monitoring temporal changes. In Denmark, nationwide health registers enable long-term surveillance of type 1 diabetes (T1D) and type 2 diabetes (T2D). We aimed to estimate trends in prevalence, incidence, mortality and years of life lost to diabetes in Denmark from 1996 to 2024. RESEARCH DESIGN AND METHODS:We conducted a nationwide register-based cohort study from 1996 to 2024. We used an updated national diabetes register integrating hospital, prescription, clinical, and laboratory data to identify diabetes type and date of onset. Prevalence was estimated annually using a binomial model. Incidence, mortality and standardized mortality ratios (SMR) were analyzed using age-period-cohort models. Analyses were stratified by sex and diabetes type. A multistate model was used to assess the lifetime risk and years of life lost to diabetes. RESULTS:As of January 1, 2025, a total of 366 174 individuals (6.1% of the population) had diabetes identified through national healthcare registers; of these, 8.2% had T1D and 91.8% had T2D. Since 1996, diabetes prevalence more than tripled, largely driven by an overall annual increase in T2D of ~4.1%. T1D prevalence remained stable, with increases in individuals aged <40 years and decreases in older age groups. From 1996 to 2024, a total of 567 510 incident diabetes cases were recorded, of which 4.6% were T1D. T1D incidence declined on average by 1.1% annually, with increasing rates at younger ages and declining rates at older ages. T2D incidence showed a non-linear pattern, with a decline from 2010 to 2015 followed by an increase in recent years, resulting in an overall upward trend from 1996 to 2024. Men had higher T2D incidence than women across age and calendar years. Mortality declined for T1D after 2008 and for T2D until 2012, then stabilized. SMRs decreased for T1D after 2008 but increased for T2D, converging by 2025. CONCLUSIONS:In Denmark, diabetes prevalence and incidence increased markedly since 1996, largely driven by T2D. Although mortality declined, particularly for T1D, excess mortality remains, emphasizing the need for continued surveillance and prevention efforts.

Both sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have demonstrated kidney benefits in adults with chronic kidney disease (CKD) with type 2 diabetes (T2D) and overweight/obesity. However, questions remain regarding the optimal positioning, combination and sequencing of the two drug classes. This systematic literature review (SLR) identified evidence on comparisons, combinations or sequencing of SGLT2is and GLP-1 RAs in this population. Databases were searched in May 2025. Relevant congresses between 2023 and 2025, SLR bibliographies and ClinicalTrials.gov were hand-searched. Articles were screened by two independent reviewers. Kidney and composite kidney outcomes were prioritised as the most clinically relevant for a population with CKD; additional safety, cardiovascular, HbA1c and weight endpoints were also extracted. Electronic databases identified 922 records, with an additional 117 records from hand searches. In total, 48 publications were included reporting on 38 unique studies; comprising 11 meta-analyses (MAs) and 27 primary publications. Findings from MAs consistently favoured SGLT2is over GLP-1 RAs for composite kidney outcomes. Primary research studies showed no clear direction of benefit for change in estimated glomerular filtration rate (eGFR) or albuminuria from baseline, or eGFR decline. However, progression of kidney disease, where reported, was consistently reduced with SGLT2is versus GLP-1 RAs. In the absence of head-to-head trials, the evidence identified supports the use of SGLT2is as a foundational therapy in adults with CKD and T2D, offering kidney protection, metabolic and cardiovascular benefits, with GLP-1 RAs positioned as a complementary adjunct. CRD420251053598.

Despite unprecedented advances in the treatment of non-diabetic chronic kidney disease (CKD) and CKD in type 2 diabetes mellitus in the past decade, no new drugs have been approved for CKD in type 1 diabetes mellitus. Urgent action is needed to develop new therapies and improve outcomes for this population.

The optimal positioning and sequencing of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with chronic kidney disease (CKD) with type 2 diabetes (T2D) and overweight/obesity is unclear. This Delphi panel aimed to establish expert consensus on the foundational versus adjunctive role of SGLT2is and GLP-1 RAs in this adult population. A total of 114 participants across 10 countries participated in a two-round Delphi panel (9.7

Who should read this plain language summary? This article may help people with chronic kidney disease, their families and other caregivers, patient advocates, and healthcare professionals to understand the effects of taking vicadrostat, given with or without empagliflozin, in people with chronic kidney disease. What is chronic kidney disease? Chronic kidney disease (or CKD) is a condition where the kidneys are damaged and cannot filter blood properly. The most common causes of CKD are diabetes and hypertension. CKD varies in its severity and usually gets worse over time. CKD can progress to kidney failure in the most severe cases, although this does not happen in everyone with CKD. Further information on CKD, its diagnosis, and treatment options are shown below. Where can I find more information on CKD? National Institute of Diabetes and Digestive and Kidney Diseases (US): https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd National Institute of Diabetes and Digestive and Kidney Diseases (US; Spanish language): https://www.kidney.org/es/kidney-topics/pruebas-para-revisar-la-salud-renal National Kidney Foundation (US): https://www.kidney.org/kidney-topics/chronic-kidney-disease-ckd Kidney Care (UK): https://kidneycareuk.org/kidney-disease-information/kidney-conditions/ckd-chronic-kidney-disease/

Peri- and epicardial adipose tissue (PEAT) is a metabolically active fat depot surrounding the heart and coronary arteries that may contribute to vascular dysfunction and inflammation in type 2 diabetes (T2D). We examined associations between PEAT volume, coronary calcification (CACS), myocardial flow reserve (MFR), and systemic inflammation (hsCRP). Cross-sectional analysis of adults with T2D without overt CVD recruited 2020–2023. PEAT was quantified on non-contrast CT; CACS was calculated by the Agatston method; MFR was measured by rubidium-82 PET/CT; hsCRP assessed systemic inflammation. Associations were tested using multivariable regression adjusting for cardiovascular risk factors. Among 887 participants (mean age 65 years; 70