The prevalence of chronic kidney disease (CKD) in Thailand is high and kidney disease progression remains a problem. Empagliflozin has been known to be used to slow CKD progression, but its accessibility remains limited. This study aimed to assess the cost-utility of empagliflozin for CKD progression in Thailand.

A state-transition model was developed consisting of eight health states: five eGFR health states (G2, G3a, G3b, G4, and G5), dialysis, kidney transplantation, and death. Empagliflozin 10 mg was assessed as an add-on treatment to standard of care (SoC). The efficacy of empagliflozin was derived from the EMPA-KIDNEY trial, while other inputs were obtained from a comprehensive literature review. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) was calculated. A probabilistic sensitivity analysis (PSA) was performed to explore uncertainties.

Empagliflozin could improve QALYs by 0.62 and 0.71 for patients with CKD without and with diabetes mellitus (DM) compared with SoC, respectively. However, it required higher total lifetime costs of 77,966 Thai baht (THB) and 59,454 THB for patients with CKD without and with DM, respectively. The ICER for CKD without DM was 126,201 THB/QALY, while the ICER for CKD with DM was 83,473 THB/QALY. The PSA indicated that empagliflozin had a 64.00% probability of being cost-effective for CKD without DM and an 89.18% probability for CKD with DM.

An important limitation was that the treatment effects of empagliflozin were derived from the EMPA-KIDNEY, which was conducted in DM patients and assumed to be the same for non-DM patients because of the limited evidence in non-DM patients.

At the current willingness-to-pay threshold of 160,000 THB/QALY, empagliflozin was cost-effective for treating patients with CKD without or with DM.

Chronic kidney disease (CKD) is the leading cause of kidney failure, end-stage kidney disease (ESKD), and cardiovascular (CV) events in patients with type 2 diabetes (T2D). The FIDELIO-DKD trial demonstrated that finerenone lowered the risk of renal and CV events in patients with CKD and T2D, regardless of cardiovascular disease history. This study evaluated the cost-effectiveness of finerenone added to background treatment (finerenone + BT) versus background treatment (BT) alone in patients with CKD and T2D from the perspective of the National Health Service in England and Wales.

A lifetime Markov model assessed the indicated usage of finerenone for the treatment of stage 3 or 4 CKD with albuminuria associated with T2D in adults, as per the relevant marketing authorization. The model structure considered kidney disease progression and CV risk, with health states encompassing patients' kidney disease stage and CV event profiles, using patient-level data from the FIDELIO-DKD trial. Model outcomes were life years, quality-adjusted life years (QALYs), per-patient costs, incremental costs, and incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analysis were performed, including an analysis exploring the impact of real-world data which suggests more frequent sodium-glucose co-transporter-2 (SGLT2) inhibitor use in the United Kingdom since FIDELIO-DKD.

Patients receiving finerenone experienced kidney and CV benefits, including reduced rates of nonfatal CV events and CV deaths, translating to improvements in survival and quality-adjusted life years (QALYs) of 6.11 and 5.97 per patient for finerenone + BT versus BT, respectively. Total discounted per-patient costs were £48,940 for finerenone + BT and £47,716 for BT alone, resulting in an incremental cost-effectiveness ratio of £8,808 per QALY gained for finerenone + BT versus BT.

Sensitivity and scenario analyses, including more frequent SGLT2 inhibitor use consistent with real-world data, indicate a robust ICER that remains within the bounds of what is typically considered cost-effective.

Sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) medications reduce the risk of cardiovascular and renal complications among patients with type 2 diabetes but are underutilized. There are numerous barriers to prescribing including insurance coverage, medication availability, comfort with prescribing, and diffusion of responsibility of prescribing across specialists. Methods are needed to support prescribing in primary care.

This was a pragmatic, randomized controlled trial testing interventions to increase appropriate SGLT2i and GLP-1RA prescribing. Primary care providers (PCPs) were randomized to 1 of 3 arms: (1) peer champion support (2) peer champion support and information on insurance coverage, or (3) usual care (no intervention). PCPs in both intervention arms received a welcome email and electronic health record (EHR) messages before visits with patients who had sub-optimally controlled diabetes and an indication for 1 of these medications. In the peer champion support only arm the EHR messages included prescribing tips. In the arm that provided peer champion support and information on insurance coverage, EHR messages contained information on medications in each class that would be most affordable for the patient based on their insurance coverage and offered support for prior authorizations if needed. The primary outcome was prescriptions for an SGLT2i or GLP-1RA medication, beginning 3 days before the targeted visit and continuing through 28 days, in each intervention arm compared to control.

191 primary care providers were included in the study. 1,389 patients had at least 1 visit scheduled with their PCP during the 6-month intervention period; of these 1,079 patients attended at least 1 of these visits and will be included in the primary outcome analysis. 66 providers (484 patients) received the peer champion intervention alone, 63 providers (446 patients) received the peer champion intervention and information on insurance coverage, and 62 providers (459 patients) received usual care. On average, patients were 66 years old, 46% were female, 61% were white, and 16% were Hispanic. There were small differences between groups with regards to patient sex, race, ethnicity, partner status, and percent with Medicare insurance.

These medication classes have the potential to reduce cardiovascular and kidney disease among patients with type 2 diabetes. This study tests interventions to support prescribing of these medications in primary care.

Clinicaltrials.gov. Unique identifier: (NCT, Registered: NCT05463705).

The effects of Sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiac outcomes, cardiovascular mortality (CVM), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients have been reported heterogeneously in different studies.

PubMed, Scopus, Embase, Cochrane Library, and Scholar databases were searched with relevant MeSH terms from January 1, 2010, to November 14, 2023. The study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes in all trials included the risk of ACM, CVM, hospitalization for heart failure (HHF), myocardial infarction (MI), and cerebrovascular accidents (CVA) in T2DM patients who were treated with one of the SGLT-2 inhibitors. Heterogeneity between studies was evaluated using Cochran's Q and I2 tests. The Egger's test was used to check for publication bias.

Eighteen studies, including 70,830 participants, were included. A pooled estimate showed that SGLT-2 inhibitor treatment was significantly associated with reduced ACM (OR: 0.82, 95% CI: 0.75-0.90, p-value: 0.001, I2: 35.1%), CVM (OR: 0.88, 95% CI: 0.80-0.96, p-value: 0.001, I2: 0%), MI (OR: 0.88, 95% CI: 0.79-0.98, p-value: 0.001, I2: 0%), and HHF (OR: 0.67, 95% CI: 0.58-0.77, p-value: 0.001). SGL-2 inhibitor treatment had no significant relationship with CVA (stroke) (OR: 0.95, 95% CI: 0.8-1.10, p-value: 0.896). Subgroup analysis showed that the effect of SGLT-2 inhibitor treatment on outcomes varied based on the type of SGLT-2 inhibitor.

SGLT-2 inhibitor treatment significantly reduced CVM, ACM, MI, and HHF. Empagliflozin, Canagliflozin, and Dapagliflozin significantly reduced ACM. Canagliflozin was significantly associated with a reduction in CVM. All SGLT-2 inhibitor treatments were associated with a reduction in HHF.

Anemia is a common comorbidity in heart failure (HF) patients, often leading to worsened outcomes. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors represent a novel approach for anemia management, yet their efficacy and safety in HF patients remain unclear. We aimed to conduct a systematic review and meta-analysis of studies on the effects of HIF-PH inhibitors on hemoglobin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), or estimated glomerular filtration rate (eGFR) in HF patients with chronic kidney disease (CKD).

The search of electronic databases identified four studies including 98 patients. Among the included studies, two were conducted prospectively, while two were retrospective in design. No studies were identified that compared HIF-PH inhibitors with erythropoiesis-stimulating agents or placebo. In cases of significant heterogeneity (I2 > 50 %), data were pooled using a random-effects model; otherwise, a fixed-effects model was used. In pooled analyses, hemoglobin levels increased at one (weighted mean difference [WMD]: 0.697 [0.473, 0.920] g/dL; Pfix < 0.001; I2 = 24 %) and three months (WMD: 0.760 [0.443, 1.076] g/dL; Pfix < 0.001; I2 = 31 %) after the use of HIF-PH inhibitors. NT-proBNP levels showed a modest decrease at one month but no significant changes at three months. eGFR remained unchanged, and no severe adverse events were reported.

This meta-analysis suggests that HIF-PH inhibitors effectively improve anemia in HF patients with CKD without notable changes in renal or HF-related biomarkers. However, the small number of included studies and the absence of a comparator group underscore the need for cautious interpretation of the findings.

Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.

The approval of sodium-glucose cotransporter (SGLT2) inhibitors has revolutionized the management of patients with diabetes, heart failure and especially those with chronic kidney disease (CKD). Beyond development of CKD, patients with autoimmune disorders have an increased cardiovascular morbidity and mortality. Therefore, this patient population would benefit the most from effective therapies to reduce this burden, and secondly, slowing of CKD progression to reduce the frequency of kidney failure. Patients with systemic autoimmune disorders, such as systemic lupus erythematosus with lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis were excluded from the DAPA-CKD trial, and higher doses of glucocorticoids or intravenous use of immunosuppression within 3 months were exclusion criteria of the EMPA-KIDNEY trial. Thus, these agents remain untested in patients with active autoimmune kidney diseases in a systematic way, and this gap is unlikely to be filled by high-quality randomized clinical trials. Beyond having nephro- and cardioprotective effects, SGLT2i have shown in vivo and in vitro efficacy to manage autoimmunity in SLE, LN and rheumatoid arthritis (RA). These effects need to be confirmed in humans, but might provide a further rationale for the use of these potent drugs. The safety profile is in general favourable, but "sick day rules" need to be followed in order to avoid serious side effects.

Youth under the age of 18 years represent a distinct subset of the population living with chronic kidney disease (CKD). The etiology of CKD differs greatly between children and adults, and young people with CKD face an extended lifetime living with their disease. Few rigorous randomized controlled trials in CKD have included people under the age of 18 years. As such, the recent success of CKD trials with sodium glucose co-transporter 2 inhibitors, mineralocorticoid antagonists, dual endothelin agonists, and hypoxia-induced factor prolyl hydroxylase inhibitors have largely not extended to children and adolescents. There are many reasons to believe these medications could prove as transformative in youth as they have in older adults, but trial data are missing. Innovative strategies are required to ensure that trials of recent, and future, agents in youth with CKD are successful.

Managing type-2 diabetes (T2D) in chronic kidney disease (CKD) patients requires consideration of kidney function, and many drugs have not been investigated thoroughly. Clinical studies have demonstrated Glargine U300 (Gla-300) supports achievement of adequate glycemic control at low hypoglycemia risk.

This cross-sectional study analysed routine data of 21 359 T2D patients with CKD (1786 using Gla-300; 19 568 without any insulin) from the prospective Diabetes-Patienten-Verlaufsdokumentation (DPV) registry to evaluate patient characteristics and safety of Gla-300 use across different CKD stages.

Patients on Gla-300 had T2D onset at an earlier age (median age 55.1 vs. 62.3 years), longer diabetes duration (17.3 vs. 11.3 years), higher body weight (91.3 vs. 83.9 kg) and HbA1c levels (7.3% vs. 6.7%) than non-insulin patients (all p < 0.001). Gla-300 usage increased from CKD stage 1-4 (median dose 44 vs. 55 units) with higher baseline HbA1c levels (7.2% vs. 7.4%). Although severe hypoglycemia rates were low, a slight increase (0.01%/PY vs. 0.04%/PY) was observed with decreasing estimated glomerular filtration rate levels. Compared to others, stage 5 CKD patients had a distinct profile with lower HbA1c levels (6.9%), body weight (90 kg) and higher Gla-300 usage (50 units). Metformin, SGLT-2 inhibitors and GLP-1 RA were common concomitant drugs with diminished usage in advanced CKD stages, while Gla-300 was common at all stages.

Despite variations in patient profiles, Gla-300 is widely used across all CKD stages, particularly in advanced stages with a low rate of severe hypoglycemia, suggesting its safe administration in CKD patients.

Hypertension and chronic kidney diseases (CKDs) are known risk factors for the development or worsening of heart failure. In last years, several new therapeutic approaches for the management of people with diabetic and nondiabetic CKD and hypertension have been investigated. In this brief review, the most recent findings regarding the ability of SGLT-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) and GLP-1 receptor agonists to prevent heart failure in patients with hypertension and CKD will be discussed.

In the last 3 years, several large clinical trials involving very large numbers of CKD patients have been published showing that these new therapeutic approaches significantly reduce the risk of heart failure events and hospitalizations in patients with diabetic and nondiabetic nephropathies and hypertension as well as in patients with heart failure without nephropathy. Moreover, these drugs retard the progression of CKD towards end-stage kidney disease.

These observations already have a major impact on the management of people with hypertension and CKD. SGLT-2 inhibitors are now recommended as first-line therapy in people with diabetes, CKD and heart failure. The use of nsMRA is increasing and could replace spironolactone over time in heart failure as well as in early CKD stages.

Chronic kidney disease (CKD) is a major global health burden that affects more than 10% of the adult population. Current treatments, including dialysis and transplantation, are costly and not curative. Kidney fibrosis, defined as an abnormal accumulation of extracellular matrix in the kidney parenchyma, is a common outcome in CKD, regardless of disease aetiology, and is a major cause of loss of kidney function and kidney failure. For this reason, research efforts have focused on identifying mediators of kidney fibrosis to inform the development of effective anti-fibrotic treatments. Given the prominent role of the transforming growth factor-β (TGFβ) family in fibrosis, efforts have focused on inhibiting TGFβ signalling. Despite hopes raised by the efficacy of this approach in preclinical models, translation into clinical practice has not met expectations. Antihypertensive and antidiabetic drugs slow the decline in kidney function and could slow fibrosis but, owing to the lack of technologies for in vivo renal imaging, their anti-fibrotic effect cannot be truly assessed at present. The emergence of new drugs targeting pro-fibrotic signalling, or enabling cell repair and cell metabolic reprogramming, combined with better stratification of people with CKD and the arrival of nanotechnologies for kidney-specific drug delivery, open up new perspectives for the treatment of this major public health challenge.

The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.

Patients with chronic kidney disease and diabetes are at high risk of cardiovascular disease, including heart failure. Risk mitigation requires a comprehensive approach with lifestyle modifications, blood pressure management, renin-angiotensin blockade, and sodium-glucose cotransporter 2 inhibitors. Recent trials have shown that nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) should also be components of this approach. This review will discuss the comprehensive approach to mitigating risk in these high-risk patients and highlight the recent trials of ns-MRAs and GLP-1 RA.

In recent years, large, randomized controlled trials of ns-MRA and GLP-1 RA have shown benefit in kidney and cardiovascular outcomes for patients with chronic kidney disease and diabetes.

The substantial benefits and overall favorable safety profiles for ns-MRA and GLP-1 RA in patients with chronic kidney disease and diabetes demonstrate that these medications should be considered as a part of a comprehensive approach to cardiovascular risk reduction in this high-risk population. Future studies should consider different combination therapies and guide how and when to initiate these therapies.

In clinical practice, sodium-glucose transporter 2 inhibitor (SGLT2i) reduces the composite renal outcomes in patients with diabetic kidney disease (DKD). However, its effect on regulating renal mitochondria remains unclear. Mitochondrial quality control (MQC) has been identified as a key factor in DKD. Peroxiredoxin3 (Prdx3) serves as a primary antioxidant protein in mitochondria. In this study, we investigated the expression of Prdx3 in patients with DKD, diabetic mice and HK-2 cells exposed to high glucose and explored SGLT2i potential mechanism of action. The results also showed that empagliflozin (Empa) treatment improved proteinuria and ameliorated renal pathological damage. We observed that Empa has an impact on the expression of Prdx3 in diabetic mice and HK-2 cells exposed to high glucose, so does the mitochondrial dynamic proteins and mitophagy-related proteins Mfn2, Drp1, PINK1, Parkin, LC3II, and P62. In vitro experiments after transfected with pcDNA3.1(+)-Prdx3 and siPrdx3 the expression of Mfn2, Drp1, PINK1, Parkin, LC3II, and P62 changed. The expression of PINK1 decreased after the knockdown of Prdx3. Furthermore, the knockdown of PINK1 accelerated the MQC damage and weakened the protective effect of Empa. Because Empa has impacts on Prdx3, which plays a protective role by influencing MQC, we investigated the latent impact of Prdx3 deficiency on renal injury and its molecular mechanism in vivo and in vitro in DKD. Herein, we demonstrate that Empa treatment modulates MQC potentially via Prdx3 through interacting with PINK1.

To investigate the efficacy of SGLT2 inhibitors on multiple cardiorenal outcomes across different racial/ethnic groups and regions.

We searched PubMed, Cochrane Library, Web of Science, and Embase databases in April 2024 for a systematic review and meta-analysis. Owing to inconsistencies in the reporting of the racial/ethnic and regional demographics, participants were grouped into three racial groups (Asian, Black, and White) and four regional (Asia, Central/South America, Europe, North America) groups. We compared the efficacy of SGLT2 inhibitors among these racial/ethnic and regional groups by calculating the ratio of hazard ratios (RHR). We evaluated the composite of cardiovascular death or hospitalization for heart failure (HHF), cardiovascular death, HHF, all-cause death, major adverse cardiac events, and cardiorenal composite outcomes.

We included 14 randomized placebo-controlled trials with 94,445 participants. Across the three racial/ethnic groups, SGLT2 inhibitors showed comparable efficacy. Compared with White patients, the efficacy of SGLT2 inhibitors on HHF was more pronounced in Black patients (RHR, 0.64; 95 % confidence interval [CI], 0.44-0.94), and a numerically lower risk was associated with Asian patients (RHR, 0.62; 95 % CI, 0.38-1.01). A consistent reduction in cardiovascular events with SGLT2 inhibitors was observed across all regions, while the efficacy of SGLT2 inhibitors on HHF was more pronounced in Asia than in other regions (RHR, 0.52; 95 % CI, 0.33-0.81).

SGLT2 inhibitors showed generally consistent efficacy across various racial/ethnic and regional groups, with some differences noted in specific populations. Ensuring adequate representation of diverse populations in clinical trials would be key to addressing healthcare disparities.

Glucagon-like peptide 1 (GLP-1) receptor agonists improve cardiac and kidney outcomes in patients with diabetes; however, their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1 receptor agonists on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).

Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024.

Adult participants in RCTs with baseline eGFR<60mL/min/1.73m2.

RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of<60mL/min/1.73m2, that compared GLP-1 receptor agonists with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR<60mL/min/1.73m2 were included.

Two independent investigators extracted the data.

Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system.

The analyses included 17,996 RCT participants with baseline eGFR<60mL/min/1.73m2. GLP-1 receptor agonists were significantly associated with a reduced risk of the composite kidney outcome (OR, 0.85 [95% CI, 0.77-0.94]; P=0.001) with low heterogeneity (I2<0.01%). GLP-1 receptor agonists were also associated with a reduced the risk of a>30% eGFR decline (OR, 0.78; P=0.004), a>40% decline (OR, 0.76; P=0.01), and a>50% decline (OR, 0.72; P<0.001). Risk of all-cause mortality was also lower in the GLP-1 receptor agonist group (OR, 0.77 [95% CI, 0.60-0.98], P=0.03), though there was high heterogeneity (I2=71.6%). Composite CV outcomes were also lower with the use of a GLP-1 receptor agonist (OR, 0.86 [95% CI, 0.74-0.99], P=0.03; I2=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits.

Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias.

GLP-1 receptor agonists improved kidney and CV outcomes, and survival in patients with CKD enrolled in an array of clinical trials.

Registered at PROSPERO with identification number CRD42023449059.

Glucagon-like peptide 1 (GLP-1) receptor agonists reduce body weight and improve glycemic control. They also have been shown to protect the heart and kidney in people with diabetes. However, the extrapolation of these findings to those with chronic kidney disease (CKD) is uncertain. This study meta-analyzed data from clinical trials focusing on patients with CKD and noted that GLP-1 receptor agonists may slow kidney disease progression and lower the risk of heart disease, stroke, and death. These findings suggest that GLP-1 receptor agonists offer multiple kidney and cardiovascular benefits to people with CKD.

Anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for diabetic macular oedema (DMO); however, unmet needs remain. This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in treating DMO.

This multicentre randomised open-label trial included 60 patients with DMO who were eligible for anti-VEGF therapy. Patients were randomised to receive luseogliflozin or glimepiride. Ranibizumab was administered initially to the target eye, with additional doses per protocol. The number of ranibizumab doses up to week 48, and re-admission rates were evaluated. Fellow eye injections were also assessed.

Sixty participants, mostly with diabetic retinopathy and half previously treated with anti-VEGF therapy, were included. SGLT2i and sulfonylurea (SU) groups achieved equivalent glycated haemoglobin, central retinal thickness (CRT), and best-corrected visual acuity improvements. Injection frequency for the target eye was similar between groups (SGLT2i vs. SU: 3.9 ± 0.7 vs. 4.7 ± 0.7 times, p = 0.36). Re-administration rates were decreased significantly after the fourth injection in the SGLT2i group (p = 0.030, hazard ratio: 0.45, 95% confidence interval: 0.22-0.92). Fellow eyes in the SGLT2i group showed significant CRT reduction and fewer injections compared with those in the SU group (1.3 ± 0.6 vs. 3.4 ± 0.8, p = 0.016).

Although the overall number of anti-VEGF injections in the target eye showed no significant difference, some patients responded favourably to SGLT2i and required fewer injections. The reduction in fellow eye injections suggests SGLT2i's efficacy in treating early-stage DMO.

University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961); Japan Registry of Clinical Trials (jRCTs031180210).

Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality.

We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output.

This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases-one with dapagliflozin and one with placebo-will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency.

Dapagliflozin's pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.

Renal fibrosis, a key progression of chronic kidney disease (CKD), remains a major challenge in nephrology, with no FDA-approved drugs specifically targeting this condition. Interleukin-11 (IL-11) has emerged as a potential therapeutic target for renal fibrosis. In this study, we identified the antifibrotic effects of a recombinant human IL-11 analogue, IL-11-6M, in a mouse model of unilateral ureteral obstruction (UUO). We generated additional IL-11-6M variants via an optimized Escherichia coli expression system, with one variant (D46C) exhibiting comparable efficacy. Further modified through cysteine-specific PEGylation, analogue 13 demonstrated similar potency to IL-11-6M with an IC50 value of 61.5 ± 26.2 nM and maintained strong binding affinity to IL-11Rα (KD = 3.0 nM). Notably, analogue 13 exhibited a prolonged half-life and showed significant therapeutic effects in the UUO-induced renal fibrosis model. These findings suggest analogue 13 should be a promising candidate for the treatment of renal fibrosis.

This study aimed to evaluate the causal effect of sodium-glucose cotransporter protein 2 (SGLT2) inhibition on primary open-angle glaucoma (POAG) and explore potential mechanisms. A drug-targeted Mendelian randomization (MR) study was conducted using genetic variation related to SGLT2 inhibition, based on SGLT2 gene expression and glycated hemoglobin levels. Genetic summary statistics for POAG were obtained from the FinnGen consortium and a multi-ancestry genome-wide association study. Glaucomatous endophenotype data were also incorporated. A two-step MR analysis was performed to examine whether pathways related to obesity, blood pressure, lipid levels, oxidative stress, and inflammation mediated the association between SGLT2 inhibition and POAG. Genetically predicted SGLT2 inhibition was associated with a reduced risk of POAG (OR: 0.28; 95% CI: 0.12 to 0.63; P = 2.22 × 10- 3), confirmed in a multi-ancestry validation cohort. It was also associated with decreased optic cup area, reduced vertical cup-disc ratio, and increased optic disc area. Mediation analysis indicated that the effect of SGLT2 inhibition on POAG was partly mediated by diastolic blood pressure (4.8%). This study suggests that SGLT2 inhibition is a promising therapeutic target for POAG. However, further large-scale randomized controlled trials are required to confirm these findings.

To describe temporal changes in the characteristics of medication-initiator cohorts in persons with chronic kidney disease (CKD) and type 2 diabetes (T2D).

Adults with CKD and T2D initiating sodium-glucose cotransporter-2 inhibitors (SGLT-2i) or glucagon-like peptide-1 receptor agonists (GLP-1RA) were identified in the Japan Chronic Kidney Disease Database Extension in each of the two study periods (Period I: 1 January 2014-30 June 2021; Period II: 1 July 2021-31 December 2022). For each cohort, baseline characteristics and the standard mean differences (SMD) between periods I and II were assessed.

During study periods I and II, 1157 and 1122 SGLT-2i, and 329 and 369 GLP-1RA new users were identified, respectively. All four cohorts had similar age, sex and comorbidity patterns, with a mean age spanning 66.1-69.5 years and 60%-70% being male. More than 80% of persons had hypertension and 60% had congestive heart failure. In the SGLT-2i cohorts, we observed a decrease in prior metformin and dipeptidyl peptidase-4 inhibitor use (SMD ≥0.5 and <0.8), and an increase in the number of persons with no T2D medications other than insulin between periods (SMD >0.8). In the GLP-1RA cohorts, there was a medium decrease in persons using insulin.

With the introduction of new treatments and emerging evidence supporting cardio-renal protective effects in people with CKD and T2D, notable changes in baseline treatment were observed in the medication-initiator cohort characteristics. These findings suggest the earlier use of cardio-renal protective medications in the course of T2D.

Aortic valve calcium (AVC) is associated with increased risk of mortality, cardiovascular disease (CVD), non-CVD such as dementia. Traditional atherosclerotic CVD risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown.

To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of CVD.

We examined 6346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m2. AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m2 accompanied with an at least 40 % decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable adjusted Cox proportional hazard regression models to examine the association between AVC (categorical and log-transformed) and incident CKD.

Participants had a mean age 62.2 ± 10.1 years, 53 % were women, and AVC >0 was present in 795 (12 %) participants. During a median follow-up time of 16.9 years, 982 (15 %) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95 % CI: 1.02-1.10]; p = 0.005). Kaplan-Meier models showed a higher cumulative incidence for CKD with higher AVC levels. In the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95 % CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score (p = 0.024), Lp(a) (p = 0.004), and the APOE-ε4 genotype (p = 0.004).

In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD. Further work is needed to understand the multidirectional relationship between AVC, CKD, and atherosclerosis.

The proteinuria is closely related to the prognosis of IgA nephropathy (IgAN) patients. Finerenone has been demonstrated to reduce proteinuria in diabetic kidney disease (DKD). However, the role of finerenone in IgAN has not been reported. This study is to analyze the efficacy and safety of finerenone in IgAN.

This retrospective study analyzed IgAN patients' data post-finerenone treatment, with groups defined by treatment plans at baseline. It observed changes in the urinary albumin-to-creatinine ratio (UACR), the estimated glomerular filtration rate (eGFR), and serum potassium (sK+) levels over a 3-6 months follow-up.

Totally 49 patients had follow-up data at 3 months, and 21 of which had data at 6 months. The median UACR at baseline was 494.25 mg/g. At 1 month, the median UACR decreased by 113 mg/g. At 3 months, the median UACR further decreased by 236.19 mg/g, and the median decrease percentage was 42.29%. At 6 months, the median UACR decreased by 203.88 mg/g, with the median decrease percentage of 41.86%. The average eGFR at baseline was 64.14 ± 19.74 mL/min/1.73 m2. At 6 months, the eGFR showed a minor increase, although it was not statistically significant. The sK+ levels remained within the normal range from 3 to 6 months.

This real-world study demonstrated the efficacy and safety of finerenone treatment in IgAN patients during a 3-6 months follow-up period, providing clinical evidence to support its use in IgAN. However, further prospective research is needed to prove these findings.

Chronic kidney disease (CKD) and heart failure (HF) are two globally prevalent, independent, long-term conditions, which often coexist in an individual and display a bidirectional yet interconnected relationship. The presence of CKD often leads to the development of HF and vice versa, which propagates the worsening of each disease, reflecting an intertwined disease cycle. Both HF and CKD share common risk factors, such as increasing age, diabetes, high blood pressure, obesity and smoking. Data show that approximately half of all people with HF also have CKD, which impacts patient burden and quality of life due to a significantly greater risk of hospitalization and death, compared with those that have either CKD or HF. To maximize treatment effectiveness in individuals with both HF and CKD, healthcare professionals should recognize that these two diseases are systemic conditions, representing organ-specific manifestations of similar underlying processes. It is also essential to understand the role of renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, the nonsteroidal mineralocorticoid receptor antagonist finerenone, and glucagon-like peptide-1 receptor agonists in managing these conditions. Lifestyle modifications should also be recommended. This review discusses factors contributing to the interplay between HF and CKD and the key role of healthcare professionals in providing appropriate treatment for the co-existing diseases.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, characterized by podocyte injury and lipid accumulation, which contribute to high morbidity and mortality. Current treatments primarily alleviate symptoms, underscoring the need for targeted therapies to address the underlying mechanisms of DKD progression. This study explores the protective effects of dapagliflozin (DAPA), a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on podocyte lipotoxicity and its regulatory role in the estrogen-related receptor alpha (ERRα)-acyl-CoA oxidase 1 (ACOX1) axis. Using db/db mice and streptozotocin-induced DKD models, we demonstrate that DAPA significantly reduces the urinary albumin-to-creatinine ratio (ACR) and improves renal pathology by alleviating glomerular hypertrophy, mesangial matrix expansion, and podocyte foot process effacement. DAPA also decreases triglyceride and free fatty acid accumulation in glomeruli, as evidenced by Oil Red O and BODIPY staining. Mechanistically, DAPA upregulates ERRα and ACOX1 expression in podocytes, enhancing fatty acid oxidation (FAO) and mitigating lipidtoxicity. Loss of ERRα exacerbates lipid-induced podocyte injury, while ERRα overexpression confers protective effects. These findings highlight DAPA's renoprotective effects via modulation of the ERRα-ACOX1 axis, suggesting that targeting ERRα could be a promising therapeutic strategy for DKD.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent one of the main cornerstones of heart failure treatment. Nevertheless, while the cardiovascular beneficial effects of these drugs have been clearly demonstrated by several clinical trials, in clinical practice, it remains challenging to identify the appropriate timing to start SGLT2 inhibitors. The potential risk of side effects, like genito-urinary infections and interaction with other drugs, may often lead to delay the prescription of these drugs in the acute setting. However, several studies have demonstrated the safety and the prognostic impact of SGLT2 inhibitors in the hospitalized patient, suggesting that treatment initiation during hospitalization or early post-discharge may represent an ideal therapeutic option. In this review, we discuss the main trials on early administration of SGLT2 inhibitors in acute heart failure supporting early introduction of SGLT2 inhibitors to optimize heart failure treatment. The efficacy and safety of these drugs in patients with acute myocardial infarction are also discussed. Based on the review of existing evidences, a practical flowchart on early administration of SGLT2 inhibitors in the acute setting is proposed.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To evaluate the relative benefits and harms of therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), and their combination in adults with type 2 diabetes mellitus. Secondary objectives To determine the relative rankings of GLP-1RA, SGLT2i, and their combination, according to their comparative efficacy for the critical outcomes identified in this review through a network meta-analysis.

We investigated factors associated with early and long-term changes in renal function after initiating dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with moderate-to-advanced chronic kidney disease (CKD).

A total of 124 patients (mean age, 70.0 ± 13.1 years; 93 men and 31 women) were retrospectively evaluated after 12 months of 10 mg dapagliflozin treatment based on changes in estimated glomerular filtration rate (eGFR). All patients had moderate-to-advanced CKD (mean eGFR: 36.8 ± 11.4 mL/min/1.73 m2; stage G3, n = 86; G4, n = 36; G5, n = 2). We used a multiple linear regression analysis to determine the independent factors associated with changes in eGFR during the administration of 12 months and first 1 month following dapagliflozin treatment.

Systolic blood pressure (SBP) (standard coefficient (β) =  - 0.499, probability (p) = 0.002) was independently correlated with change in eGFR during the administration of dapagliflozin. SBP (β =  - 0.265, p = 0.040), change in eGFR during the 12 months before dapagliflozin administration (β =  - 0.453, p < 0.001), and urinary protein-to-creatinine ratio (β =  - 0.282, p = 0.028) were independently correlated with the change in eGFR during the first 1 month of dapagliflozin administration.

SBP was associated with long-term change in eGFR after initiating dapagliflozin treatment in moderate-to-advanced CKD patients; SBP, urinary protein-to-creatinine ratio, and eGFR change before dapagliflozin administration were associated with early change in eGFR following dapagliflozin treatment in these patients.

The growing morbidity, mortality, and health care costs related to heart failure (HF) underscore the urgent need to prioritize its primary prevention. Whereas a risk-based approach for HF prevention remains in its infancy, several key opportunities exist to actualize this paradigm in clinical practice. First, the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guidelines provided recommendations, for the first time, on the clinical utility of multivariable risk equations to estimate risk of incident HF. Second, the American Heart Association recently developed the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations, which not only enable prediction of incident HF separately, but also include HF in the prediction of total cardiovascular disease. Third, the predominant phenotype of HF risk has emerged as the cardiovascular-kidney-metabolic syndrome. Fourth, the emergence of novel therapies that prevent incident HF (eg, sodium-glucose cotransporter-2 inhibitors) and target multiple cardiovascular-kidney-metabolic axes demonstrate growing potential for risk-based interventions. Whereas the concept of risk-based prevention has been established for decades, it has only been operationalized for atherosclerotic cardiovascular disease prevention to date. Translating these opportunities into a conceptual framework of risk-based primary prevention of HF requires implementation of PREVENT-HF (Predicting Risk of Cardiovascular Disease Events-Heart Failure) equations, targeted use of cardiac biomarkers (eg, natriuretic peptides) and echocardiography for risk reclassification and earlier detection of pre-HF, and definition of therapy-specific risk thresholds that incorporate net benefit and cost-effectiveness. This scientific statement reviews the current evidence for accurate risk prediction, defines strategies for equitable prevention, and proposes potential strategies for the successful implementation of risk-based primary prevention of HF.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy. In addition to glycemic control and the osmotic diuretic effect, the inhibition of SGLT2 improves endothelial function and vasodilation, optimizing myocardial energy metabolism and preserving cardiac contractility. Moreover, SGLT2 inhibitors may exhibit anti-inflammatory properties and attenuate acute myocardial ischemia/reperfusion injury, thereby reducing cardiac infarct size, enhancing left ventricular function, and mitigating arrhythmias. These pleiotropic effects have demonstrated efficacy across various cardiovascular conditions, ranging from acute to chronic coronary syndromes and extending to arrhythmias, valvular heart disease, cardiomyopathies, cardio-oncology, and cerebrovascular disease. This review provides an overview of the current literature on the potential mechanisms underlying the effectiveness of SGLT2 inhibitors across a wide range of cardiovascular diseases beyond HF.

As the population ages, factors affecting prognosis after dialysis initiation in very elderly patients remain unclear. We aimed to develop a prognostic score to predict short-term survival in this group.

This retrospective cohort study included 116 patients aged 85 or older who initiated hemodialysis at our hospital between 2010 and 2023, out of a total of 2279 patients. Using a Cox regression model, we analyzed factors affecting 3-year all-cause mortality. Based on these analyses, a prognostic scoring system was developed to predict patient outcomes.

Baseline factors independently associated with mortality (hazard ratio (HR), 95% confidence interval (CI)) included body mass index (BMI) < 18.5 (2.14, 1.17-3.91), cardiovascular disease (2.16, 1.10-4.22), advanced cancer (4.65, 1.73-12.5), impaired walking (2.33, 1.17-4.64), emergency dialysis without fistula (1.88, 1.03-3.44), fluid overload (2.70, 1.43-5.07), serum albumin < 3.0 g/dL (2.32, 1.25-4.32), and C reactive protein (CRP) > 0.5 mg/dL (3.87, 1.85-8.10). A scoring system was developed, assigning 1 point each for BMI < 18.5, cardiovascular disease, impaired ambulation, emergency dialysis without fistula, fluid overload, and serum albumin < 3.0 g/dL, and 2 points for advanced cancer and CRP > 0.5 mg/dL. The score demonstrated an area under the ROC curve of 0.83. The hazard ratios for 3-year mortality for scores of 4-5 and 6 or higher, compared to 0-3, were 2.55 (95% CI: 1.04-6.23) and 7.10 (3.36-15.0), respectively (P for trend < 0.001). Subgroup analyses confirmed the score's robustness.

The prognostic score for 3-year mortality in very elderly patients who initiate dialysis should be validated in different populations and is expected to inform decisions regarding dialysis initiation.

The optimal timing for prescribing guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) during acute decompensated heart failure (ADHF) remains uncertain. This study evaluated the real-world impact of early in-hospital quadruple GDMT prescription in ADHF patients with HFrEF.

In this retrospective cohort study using the Institutional aCute descompensAted heaRt failUre regiStry (ICARUS), we analysed 2051 HFrEF patients (71% male, median age 68 years) hospitalized for ADHF between June 2022 and March 2024. Early quadruple therapy was defined as the prescription of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) within 48 h of admission. Among included patients, 898 (43.8%) received early quadruple therapy. Using optimal full matching propensity score methodology, early quadruple therapy was associated with lower 30 day mortality/rehospitalization [relative risk (RR) 0.73; 95% confidence interval (CI) 0.55-0.97, P = 0.028], reduced in-hospital mortality (RR 0.29; 95% CI 0.15-0.56, P < 0.001) and shorter hospital stay (β = -2.65 days; 95% CI -3.67 to -1.63, P < 0.001). Patients receiving early quadruple therapy showed higher rates of GDMT continuation at discharge (RR 3.82; 95% CI 3.01-4.86, P < 0.001).

In this HFrEF cohort, early initiation of comprehensive GDMT during ADHF hospitalization was associated with improved clinical outcomes. Future randomized trials including patients across the full spectrum of ejection fraction are needed to validate these findings and determine their applicability to other heart failure phenotypes.

Chronic kidney disease (CKD) is a progressive, irreversible impairment of kidney function due to various etiologies. Numerous studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD, due to their pleiotropic effects. Therefore, there has been an increase in interest in their effects not only on kidney function but also on other parameters in patients with CKD. The aim of the study was to examine the effects of SGLT2i on serum lipid values and kidney function in patients with CKD undergoing SGLT2i treatment.

This study was a retrospective data analysis of 75 patients with CKD on SGLT2i treatment. We compared the values of biochemical parameters, renal function outcomes, and blood pressure at two time points: baseline and 24 months after.

Total cholesterol (Chol) significantly decreased in all patients, while triglyceride (Tg) and low-density lipoprotein cholesterol (LDLc) levels also decreased in all patients. High-density lipoprotein cholesterol (HDLc) levels increased, but this increase was not significant. Creatinine clearance (Ccr) significantly decreased, and serum urea (Sur) significantly increased in all patients. The proteinuria (Prt) levels did not change significantly. The results showed that the diastolic blood pressure (DBP) significantly decreased in all patients.

This study showed that the use of SGLT2i reduced total Chol in all patients with CKD during the 24-month follow-up, regardless of diabetes mellitus (DM) status. No significant differences were observed for the Tg, LDLc, and HDLc values.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart-failure admission among high-risk patients. However, most patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been excluded from randomized trials.

We conducted this randomized, controlled trial in Spain to evaluate the efficacy of dapagliflozin (at a dose of 10 mg once daily) as compared with standard care alone in patients with aortic stenosis who were undergoing TAVI. All the patients had a history of heart failure plus at least one of the following: renal insufficiency, diabetes, or left ventricular systolic dysfunction. The primary outcome was a composite of death from any cause or worsening of heart failure, defined as hospitalization or an urgent visit, at 1 year of follow-up.

A total of 620 patients were randomly assigned to receive dapagliflozin and 637 to receive standard care alone after TAVI; after exclusions, a total of 1222 patients were included in the primary analysis. A primary-outcome event occurred in 91 patients (15.0%) in the dapagliflozin group and in 124 patients (20.1%) in the standard-care group (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P = 0.02). Death from any cause occurred in 47 patients (7.8%) in the dapagliflozin group and in 55 (8.9%) in the standard-care group (hazard ratio, 0.87; 95% CI, 0.59 to 1.28). Worsening of heart failure occurred in 9.4% and 14.4% of the patients, respectively (subhazard ratio, 0.63; 95% CI, 0.45 to 0.88). Genital infection and hypotension were significantly more common in the dapagliflozin group.

Among older adults with aortic stenosis undergoing TAVI who were at high risk for heart-failure events, dapagliflozin resulted in a significantly lower incidence of death from any cause or worsening of heart failure than standard care alone. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT04696185.).

Individuals with prediabetes have a higher risk of cardiovascular events and diabetes mellitus. Therefore, the prevention or delay of prediabetes progression to diabetes via lifestyle modification and medications is an important measure to reduce morbidity and mortality in this population. Based on the American Diabetes Association (ADA) guidelines, metformin is the only recommended drug for prediabetes. A growing body of evidence has shown the beneficial effects of sodium-glucose transporter 2 (SGLT-2) inhibitors in prediabetes. These drugs offer cardiovascular mortality benefits over metformin. This review aimed to summarize current evidence about the clinical effects of SGLT-2 inhibitors in prediabetes.

To determine the prevalence and characteristics of chronic kidney disease (CKD) in a cross-sectional population of people with type 2 diabetes treated at internal medicine clinics in Spain.

We collected data from 25 hospitals that recruited 354 people with type 2 diabetes in an observational study carried out in May 2024. Information collected included demographic data, comorbidities, nutritional status, presence of sarcopenia and frailty, as well as laboratory data and therapy administered.

We included a total of 314 subjects, of whom 185 (58.9%; 95% confidence interval: 53.4-64.3%) had CKD. Compared with people with no CKD, those with CKD were older (77.4 ± 9.7 vs. 65.9 ± 12.5 years; p < 0.001), more often male (53.1% vs. 46.9%; p = 0.021), with more prevalence of ischemic heart disease (22.4% vs. 10.9%; p = 0.006) and longer duration of diabetes disease (14.1 ± 8.6 vs. 10.0 ± 7.0 years; p < 0.001). Malnutrition (37.3% vs. 25%; p = 0.017), sarcopenia (24.6% vs. 11.2%; p = 0.003), and frailty (74.3% vs. 59%; p = 0.006) were more often associated in people with CKD compared with those without CKD.

Internal medicine specialists treat a significant number of people with diabetes and CKD. These people are characteristically elderly, with high proportion of cardiovascular disease showing malnutrition, sarcopenia, and frailty, which could determine the target for metabolic control.

An estimated 37 million people currently live with chronic kidney disease in the US, which places them at increased risk for kidney disease progression, cardiovascular disease, and mortality. This review discusses current standard-of-care management of patients with chronic kidney disease, identifies key gaps in care, and briefly highlights how pharmacists can address gaps in care as members of the multidisciplinary care team.

Recent advances in guideline-directed medical therapies for patients with chronic kidney disease, including agents from the sodium-glucose cotransporter, glucagon-like peptide-1 receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes, can dramatically improve cardiovascular-kidney-metabolic care and outcomes. Unfortunately, gaps in screening, diagnosis, and implementation of recommended therapies persist. Team-based models of care-inclusive of the person with chronic kidney disease-have the potential to significantly improve care and outcomes for people with chronic kidney disease by addressing current gaps in care.

As members of the multidisciplinary care team, pharmacists can play a critical role in addressing current gaps in care, including optimized use of guideline-directed medical therapies, in patients with chronic kidney disease.