Cardiac Imaging and Management of Cardiac Disease in Asymptomatic Renal Transplant Candidates: A Current Update.

Given the high cardiovascular risk accompanying end-stage kidney disease, it would be of paramount importance for the clinical nephrologist to know which screening method(s) identify high-risk patients and whether screening asymptomatic transplant candidates effectively reduces cardiovascular risk in the perioperative setting as well as in the longer term. Within this review, key studies concerning the above questions are reported and critically analyzed. The lack of unified screening criteria and of a prognostically sufficient screening cardiovascular effect for renal transplant candidates sets the foundation for a personalized patient approach in the near future and highlights the need for well-designed studies to produce robust evidence which will address the above questions

The characteristics, dynamics and risk of death in COVID-19 positive dialysis patients in London, UK

Background: Dialysis patients, with frequent co-morbidities, advanced age and frailty, visiting treatment facilities frequently are perhaps more prone to SARS-Cov-2 infection and related death - the risk-factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in SARS-CoV-2 infected dialysis patients. Methods: Data on 224 hemodialysis patients between 02/29/2020 and 05/15/2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using competing risk regression model assessed by sub-distribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case fatality ratio of 22.7(95%CI(17.3-28.3)%) overall but that varies across age groups from 11.4(95%CI(0.9-9.2)) in 80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days indicating a rapid deterioration towards death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in more frail (WHO performance status 3-4) [SHR=2.16(1.25-3.74);p=0.006)], ischemic heart disease [SHR=2.28(1.32-3.94),p=0.003], cerebrovascular disease [SHR=2.11(1.20-3.72),p=0.010], smoking history [SHR=2.69(1.33-5.45),p=0.006], and (completely or partially) hospitalized patients [SHR=10.26.(3.10-33.94),p<.001]; and in patients with high CRP [SHR=1.35(1.10-1.67)] and high neutrophil:lymphocyte ratio [SHR=1.03(1.01-1.04),p<0.001]. Our data did not support differences in the risk of death associated with gender, ethnicity, dialysis vintage or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, and 12.9% being affected, revealed that non-Caucasians (62% vs. 52% in all patients, p=0.001) and diabetic patients (54% vs. 22%, p<0.001) were disproportionately affected. Conclusion: This report discusses the outcomes of a large cohort of dialysis patients with SARS-CoV-2, infection affecting more diabetics and non-Caucasians; with a high case fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP and neutrophil:lymphocyte ratio at presentation

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

The effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiometabolic profile; beyond the hypoglycaemic action

Type 2 diabetes mellitus (T2DM) has growing prevalence worldwide and major clinical implications, chiefly cardiovascular (CV) and renal disease burden. Sodium-glucose co-transporter (SGLT)2 inhibitors are a new drug class in the management of T2DM with a mechanism of action independent of insulin. In addition to their hypoglycaemic effect, SGLT2 inhibitors appear to have haemodynamic and nephroprotective effects. Studies have consistently showed a modest but significant blood pressure (BP) reduction. Metabolic benefits are also attributed to SGLT2 inhibitors with a modest but consistent body weight decrease recorded along with improvements in lipid profile and uric acid levels. Remarkable findings of significant cardioprotective effects came from the recent EMPA-REG study with a particular focus on heart failure. In the kidney, SGLT2 inhibitors reduce hyperfiltration, a precipitant of diabetic nephropathy

High-density lipoprotein and low-density lipoprotein therapeutic approaches in acute coronary syndromes

Background: Low-density lipoprotein cholesterol (LDL), and especially its oxidized form, renders the atherosclerotic plaque vulnerable to rupture in acute coronary syndromes (ACS). On the other hand, high-density lipoprotein (HDL) is considered an anti-atherogenic molecule. The more recent HDL-targeted drugs may prove to be superior to those used before. Indeed, delipidated HDL and HDL mimetics are efficient in increasing HDL levels, while the apoA-I upregulation with RVX-208 appears to offer a clinical benefit which is beyond the HDL related effects. HDL treatment however has not shown a significant improvement in the outcomes of patients with ACS so far, studies have therefore focused again on LDL. In addition to statins and ezetimibe, novel drugs such as PSCK9 inhibitors and apolipoprotein B inhibitors appear to be both effective and safe for patients with hyperlipidemia. Conclusion: Data suggest these could potentially improve the cardiovascular outcomes of patient with ACS. Yet, there is still research to be done, in order to confirm whether ACS patients would benefit from LDL- or HDL-targeted therapies or a combination of both. © 2017 Bentham Science Publishers

Paraoxonase-1: Characteristics and role in atherosclerosis and carotid artery disease

Paraoxonase-1 (PON-1) is a calcium-dependent enzyme that is synthesized in the liver and then secreted in blood where it is bound to High Density Lipoprotein (HDL). PON-1 is a hydrolase with a wide range of substrates, including lipid peroxides. It is considered responsible for many of the antia-therogenic properties of HDL. PON-1 prevents Low Density Lipoprotein (LDL) oxidation, a process that is considered to contribute to the initiation and development of atherosclerosis. PON-1 activity and levels are influenced by gene polymorphisms; of the 2 common variants, one is in position 192 (Q192R) and one in position 55 (M55L). Also, many drugs affect PON-1 activity. The role of PON-1 in carotid atherosclerosis is inconsistent. Some studies show an association of PON-1 polymorphisms with carotid plaque formation, whereas others do not. The aim of this review is to summarize the characteristics of PON-1, its interactions with drugs and its role in atherosclerosis and especially its relationship with carotid artery disease. © 2019 Bentham Science Publishers

Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting an increasing percentage of general population worldwide. Patients with T2DM are frequently characterized by impaired renal function, primarily as a result of diabetic kidney injury, but also by other contributing factors, such as hypertension, atherosclerosis, and medications. Sodium‐glucose cotransporter (SGLT)‐2 inhibitors have emerged as a new, promising class of antidiabetic agents with actions that seem to extend beyond their hypoglycemic effect

Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting an increasing percentage of general population worldwide. Patients with T2DM are frequently characterized by impaired renal function, primarily as a result of diabetic kidney injury, but also by other contributing factors, such as hypertension, atherosclerosis, and medications. Sodium‐glucose cotransporter (SGLT)‐2 inhibitors have emerged as a new, promising class of antidiabetic agents with actions that seem to extend beyond their hypoglycemic effect

Crescentic glomerulonephritis associated with vascular endothelial growth factor (VEGF) inhibitor and bisphosphonate administration

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, has been widely used in a variety of malignancies offering substantial clinical benefit. Hypertension and proteinuria are the most commonly reported manifestations of bevacizumab-related nephrotoxicity with the risk increasing along with the dose and with the concomitant use of bisphosphonates. We describe the first case of a patient with small-cell lung cancer who developed diffuse extracapillary necrotizing crescentic glomerulonephritis, temporarily necessitating haemodialysis, following administration of bevacizumab and zolendronate. Renal function improved without any specific treatment and the patient remained off dialysis after withdrawal of bevacizumab-zolendronate. Special caution is required when VEGF inhibitors are combined with bisphosphonates. Such a combination can cause crescentic necrotizing glomerular lesions. Withdrawal of the offending medications may be adequate for the alleviation of this severe glomerulonephritis