Advances in the Pathogenesis of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is both a frequent complication of diabetes mellitus (DM) [...].

Epidemiology and Risk Factors for Stroke in Chronic Kidney Disease: A Narrative Review.

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the present review we aim to discuss the impact of CKD on the risk of stroke and stroke-related consequences, and explore the pathophysiology underpinning the increased risk of stroke in patients with CKD. We cover the clinical association between renal dysfunction and cerebrovascular disease including stroke, silent brain infarct, cerebral small vessel disease, microbleeds, and white matter hyperintensity, and discuss the underlying mechanisms.

The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. The pathogenesis of DKD is multifactorial, with several molecular pathways implicated. Recent data suggest that histone modification plays an important role in the development and progression of DKD. Histone modification appears to induce oxidative stress, inflammation and fibrosis in the diabetic kidney. In the present review, we summarize the current knowledge on the association between histone modification and DKD.

Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Markers of Vascular Damage.

BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular morbidity and delay the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underpinning these benefits are not entirely clear. More specifically, it is uncertain whether these agents exert cardiorenal protective effects through a direct action on the vascular wall. The aim of the present study was to evaluate the effects of SGLT2 inhibitors on markers of subclinical vascular damage. METHODS: In total, 40 adult patients with T2DM and glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 and age- and gender-matched patients with T2DM and GFR > 60 mL/min/1.73 m2 were consecutively enrolled. Indices of arterial stiffness (pulse wave velocity, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (Alx@75) and central systolic, diastolic, pulse and mean pressure), carotid atherosclerosis (stenosis, intima-media thickness (cIMT) and maximal plaque thickness) and peripheral arterial disease (ankle brachial index (ABI)) were determined. The chi-squared and Mann-Whitney U-test were used to detect differences in categorical and continuous variables between groups, respectively. RESULTS: In total, 15 patients were treated with SGLT2 inhibitors and 25 patients were not receiving these agents. Serum low-density lipoprotein cholesterol levels were lower in the former whereas other cardiovascular risk factors, the prevalence of established cardiovascular disease, anthropometric and demographic characteristics, and vital signs did not differ between the 2 groups. The AIx was lower in patients treated with SGLT2 inhibitors (21.9 ± 11.3 vs. 29.7 ± 12% in patients not treated with SGLT2 inhibitors; p < 0.05). The AIx@75 was also lower in the former (21.3 ± 10.9 and 32.6 ± 11.3%, respectively, p < 0.005). Other markers of arterial stiffness were similar in the 2 groups. In addition, markers of carotid atherosclerosis and the ABI did not differ between patients treated and not treated with SGLT2 inhibitors. CONCLUSIONS: Treatment with SGLT2 inhibitors appears to reduce arterial stiffness. Accordingly, these agents might improve cardiovascular outcomes not only in patients with T2DM and established cardiorenal disease but also in lower-risk patients.

Pharmacological Management of Obesity in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. A substantial proportion of patients with PCOS are either overweight or obese, and excess body weight aggravates the hormonal, reproductive and metabolic manifestations of PCOS. In recent years, several studies evaluated the role of various pharmacological agents in the management of obesity in this population. Most reports assessed glucagon-like peptide-1 receptor agonists and showed a substantial reduction in body weight. More limited data suggest that sodium-glucose cotransporter-2 inhibitors and phosphodiesterase-4 inhibitors might also be effective in the management of obesity in these patients. In the present review, we discuss the current evidence on the safety and efficacy of these agents in overweight and obese patients with PCOS.

Evaluation of Subclinical Vascular Disease in Diabetic Kidney Disease: A Tool for Personalization of Management of a High-Risk Population.

Background: Patients with diabetic kidney disease (DKD) are at increased risk for cardiovascular events but traditional risk factors do not fully explain this association. Evaluation of subclinical vascular disease might improve risk stratification and management of these patients. The aim of the study was to compare the prevalence of markers of arterial stiffness, carotid atherosclerosis and peripheral arterial disease between patients with DKD and patients with type 2 diabetes mellitus (T2DM) and preserved kidney function. Methods: We prospectively enrolled patients with DKD and age- and gender-matched patients with T2DM but without DKD (estimated glomerular filtration rate < and ≥60 mL/min/1.73 m2, respectively). The presence of arterial stiffness was evaluated by measuring pulse wave velocity (PWV), augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx@75) and central systolic, diastolic, pulse and mean blood pressure. The presence of carotid atherosclerosis was evaluated by measuring carotid stenosis, carotid intima-media thickness and maximal plaque thickness. The presence of PAD was evaluated with the measurement of ankle-brachial index (ABI). Results: Forty patients with T2DM were included in the study (mean age 71.6 ± 8.9 years). The prevalence of cardiovascular risk factors was similar in patients with and without DKD. PWV was higher in the former (9.8 ± 5.5 and 6.6 ± 4.4 m/s, respectively; p < 0.05) and carotid stenosis of the left carotid artery was also greater in patients with DKD (36.5 ± 12.6 and 22.1 ± 17.2%, respectively; p < 0.05). Other markers of arterial stiffness and carotid atherosclerosis and ABI did not differ between patients with DKD and those without DKD. Conclusions: Patients with DKD appear to have more pronounced arterial stiffness and carotid atherosclerosis than patients with T2DM and preserved kidney function despite the similar prevalence of traditional cardiovascular risk factors in the two groups. Therefore, evaluating the presence of subclinical vascular disease in these patients could be a useful tool for the personalization of their management.

The Predictive Role of the Triglyceride/Glucose Index in Patients with Hypercholesterolemia and Acute Ischemic Stroke.

Background: The triglyceride/glucose index (TyG) reflects insulin resistance and predicts the risk of acute ischemic stroke (aIS). However, it is uncertain if this index predicts the severity and outcome of aIS because studies that addressed this question are few and all were performed in Asian subjects. Moreover, there are no studies that focused on patients with hypercholesterolemia. Methods: We studied 997 Caucasian patients who were hospitalized for aIS and had hypercholesterolemia. aIS severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS) and severe aIS was defined as NIHSS ≥ 21. The outcome was assessed with the functional outcome at discharge and with in-hospital mortality. An unfavorable functional outcome was defined as modified Rank in scale (mRs) at discharge between 3 and 6. Results: The TyG index did not correlate with the NIHSS at admission (r = 0.032, p = NS) and was similar in patients with severe and non-severe aIS (8.7 ± 0.6 and 8.6 ± 0.6, respectively; p = NS). Risk factors for severe aIS were age, female gender, atrial fibrillation (AF) and diastolic blood pressure (DBP) at admission. The TyG index also did not correlate with the mRs(r = 0.037, p = NS) and was similar in patients who had unfavorable and favorable functional outcome (8.7 ± 0.6 and 8.6 ± 0.5, respectively; p = NS). Risk factors for unfavorable functional outcome were age, previous ischemic stroke, body mass index and the NIHSS at admission. The TyG index was similar in patients who died during hospitalization and patients who were discharged (8.7 ± 0.6 and 8.7 ± 0.6, respectively; p = NS). Risk factors for in-hospital mortality were AF and DBP and NIHSS at admission. Conclusions: The TyG index does not appear to be associated with the severity or the outcome of aIS. Nevertheless, since there are few relevant data in Caucasians and the TyG index is an inexpensive and widely available biomarker, more studies in this ethnic group are required to determine the predictive role of this index in patients with aIS.

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease.

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.