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Chronic kidney disease (CKD) is a major public health issue and an independent risk factor for cardiovascular and all-cause mortality. Diabetic kidney disease develops in 30-50% of diabetic patients and it is the leading cause of end-stage renal disease in the Western world. Strict blood pressure control and renin-angiotensin system (RAS) blocker use are the cornerstones of CKD treatment; however, their application in everyday clinical practice is not always ideal and in many patients CKD progression still occurs. Accumulated evidence in the past few years clearly suggests that sodium-glucose co-transporter-2 (SGLT-2) inhibitors present potent nephroprotective properties. In clinical trials in patients with type 2 diabetes mellitus, these agents were shown to reduce albuminuria and proteinuria by 30-50% and the incidence of composite hard renal outcomes by 40-50%. Furthermore, their mechanism of action appears rather solid, as they interfere with the major mechanism of proteinuric CKD progression, i.e., glomerular hypertension and hyperfiltration. The present review summarizes the current evidence from human trials on the effects of SGLT-2 inhibitors on nephroprotection and discusses their position in everyday clinical practice.

Renovascular hypertension (RVH) remains among the most prevalent and important, but also potentially reversible, causes of secondary hypertension. The predominant causes of renal artery stenosis (RAS) are atherosclerotic renovascular arterial stenosis (ARAS) and renal fibromuscular dysplasia. This condition can lead to progressive renal injury, cardiovascular complications and ‘flash pulmonary edema’. Duplex Doppler ultrasonography, computed tomographic angiography and magnetic resonance angiography are the most commonly used diagnostic methods. There are three therapeutic options available: medical therapy including renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, percutaneous angioplasty with or without stent placement and surgical revascularization. Three large trials failed to demonstrate the superiority of renal artery revascularization over pharmaceutical therapy in controlling blood pressure and preserving renal function. For this reason, today revascularization is only recommended for patients with progressive worsening of renal function, recurrent ‘flash pulmonary edema’ and rapid increase in antihypertensive requirement in patients with previously well-controlled hypertension. However, more properly designed trials are needed in order to identify which patient populations would probably benefit from renal revascularization.

Background: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin–angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. Methods: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by −24.55% (95% CI −29.57 to −19.53%), urine protein-to-creatinine ratio (UPCR) by −53.93% (95% CI −79% to −28.86%) and 24 h albumin excretion by −32.47% (95% CI −41.1 to −23.85%). MRAs also reduced UACR by −22.48% (95% CI −24.51 to −20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of −2.38 ml/min per 1.73 m2 (95% CI −3.51 to −1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16–0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69–4.08) compared with placebo/active control. Conclusion: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels. Sin financiación 4.171 JCR (2019) Q1, 13/65 Peripheral Vascular Disease 1.365 SJR (2019) Q1, 42/186 Physiology, 65/362 Cardiology and Cardiovascular Medicine, 21/139 Internal Medicine No data IDR 2019 UEM

Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) -25.39%, 95% confidence interval (CI) -34.17 to -16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD -40.78%, 95% CI -63.21 to -18.34) or severely increased albuminuria (WMD -36.40%, 95% CI -51.53 to -21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI -5.24 to -3.63) and 1.81 mmHg (95% CI -2.38 to -1.23), respectively.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on CTA, MRA and/or catheter-based angiography were eligible.Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46±16 years (12% ≥65yo), 86% were hypertensive, 72% had multifocal and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65yo had more often multifocal FMD, lower eGFR and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management and follow-up of FMD. TRANSLATIONAL PERSPECTIVE: Fibromuscular dysplasia (FMD) is nowadays considered as a systemic arterial disease, warranting brain-to-pelvis vascular imaging in all patients. However, most current evidence is derived from a limited number of expert centres. Furthermore, one size may not fit all. Based on analysis of the first thousand patients enrolled in the European/International FMD registry (46 centres; 22 countries) we characterized distinct patient profiles according to FMD subtype, age and gender and identified predictors of widespread disease, aneurysms and dissections, paving the way for individualized management and follow-up. Further studies will allow refining patient characterization according to ethnicity, genetic profile and imaging biomarkers.

Background: During the past decades, the prevalence of diabetes (DM) has increased significantly, mainly as a result of continuous rise in the incidence of type 2 DM. According to World Health Organization statistics, >422 million adults globally were suffering from DM in 2014 and a continuous rise in DM prevalence is expected. Objective: The present review considers recent epidemiological data providing worldwide estimates regarding the incidence of DM. Methods: A comprehensive literature search was conducted to identify available data from epidemiological studies evaluating the current burden of DM. Results: Over the past few decades the prevalence of DM has risen significantly in nearly all countries and may be considered as a growing epidemic. Urbanization and income status are major factors which influence current rates in the prevalence studies introducing interesting differences between several population groups. Conclusion: Having recognized the global burden of DM, we now realize the urgent need for effective interventions. In order to monitor the public-health strategies and design effective future interventions we need reliable global estimates regarding the prevalence of DM.

Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis. Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH. Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) ( Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate–adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P =0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P P =0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187–2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.

Objective:Diabetic Kidney Disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage-renal-disease in Western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose co-transporter 2