Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD. Methods: We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30–90 ml/min per 1.73 m², who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results: Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m²; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was –19.6% (95% confidence interval [CI], –34.3 to –1.5), –33.7% (95% CI, –46.1 to –18.5), and –53% (95% CI, –61.7 to –42.4; P<0.001 versus dapagliflozin; P=0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (r=–0.13; P=0.47; r=–0.08; P=0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n=8; 17.4%) compared with dapagliflozin (n=0; 0%) or dapagliflozin-eplerenone (n=2; 4.3%; P _{between-groups}=0.003). Conclusions: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. Clinical Trial registry name and registration number: European Union Clinical Trials Register, EU 2017–004641–25.

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress–induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. Conclusions MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

Adipose tissue accumulation in specific body compartments has been associated with diabetes, hypertension and dyslipidemia. Perirenal fat (PRF) may lead to have direct lipotoxic effects on renal function and intrarenal hydrostatic pressure. This study was undertaken to explore the association of PRF with cardiovascular risk factors and different stages of chronic kidney disease (CKD). We studied 103 patients with CKD of different stages (1 to 5). PRF was measured by B-mode renal ultrasonography in the distal third between the cortex and the hepatic border and/or spleen. The PRF thickness was greater in CKD patients with impaired fasting glucose than in those with normal glucose levels (1.10 ± 0.40 cm vs. 0.85 ± 0.39 cm, P < 0.01). Patients in CKD stages 4 and 5 (glomerular filtration rate [GFR] < 30 mL/min/1.73 m2) had the highest PRF thickness. Serum triglyceride levels correlated positively with the PRF thickness; the PRF thickness was greater in patients with triglyceride levels ≥ 150 mg/dL (1.09 ± 0.40 cm vs. 0.86 ± 0.36 cm, P < 0.01). In patients with a GFR < 60 mL/min/1.73 m2, uric acid levels correlated positively with the PRF thickness (P < 0.05). In CKD patients, the PRF thickness correlated significantly with metabolic risk factors that could affect kidney function.