Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

Effect of sodium-glucose cotransporter 2 inhibitors on hemoglobin and hematocrit levels in type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes of patients with type 2 diabetes at high cardiovascular risk and chronic kidney disease. Recent studies showed an increase in hemoglobin and hematocrit after SGLT2i treatment. MATERIALS AND METHODS: We did a systematic review and meta-analysis of randomized, double-blind, placebo-controlled studies of SGLT2i in patients with type 2 diabetes. We searched through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from January 2010 to January 2021. RESULTS: We included seventeen randomized, double-blind, placebo-controlled studies. The total number of evaluated patients was 14,748. The treatment arm consisted of canagliflozin, dapagliflozin, empagliflozin and ipragliflozin. SGLT2i therapy significantly increased hemoglobin levels when compared to placebo (MD 5.60 g/L, 95% CI 3.73-7.47 g/L, P < 0.00001, considerable heterogeneity-I2 = 94%). Each SGLT2i also led to a significant increase in the hematocrit level when compared to placebo (MD 1.32%, 95% CI 1.21-1.44, P < 0.00001, considerable heterogeneity-I2 = 99%). CONCLUSIONS: SGLT2i led to significant increases in hemoglobin and hematocrit levels when compared to placebo. In addition to their cardiovascular effect, SGLT2i also increases hemoglobin and hematocrit levels.

Left atrial strain: A novel "biomarker" for chronic kidney disease patients?

Cardiovascular disease and chronic kidney disease are frequently inter-connected and this association leads to an exponential growth of cardiovascular risk. This risk is currently underestimated by the existing algorithms and there is a constant need for new markers to predict adverse outcomes in this special population. In general population left atrial strain has emerged as an important tool for both the diagnosis and prognostic stratification, but data regarding its role in chronic kidney disease patients is scarce. The purpose of this review is to summarize the current evidence regarding this matter. Left atrial size and function mirror the duration and severity of increased left ventricular filling pressures. Increased left atrial volume index and impaired left atrial strain parameters are independent predictors for adverse cardiovascular events. Left atrial strain is impaired before changes in volume appear, thus being able to predict both diastolic and systolic function in chronic kidney disease patients. Finally, left atrial strain can identify renal patients with impaired exercise capacity and this could have clinical applications in the rehabilitation of this patients.

Coronary artery bypass grafting versus percutaneous coronary intervention in end-stage kidney disease: A systematic review and meta-analysis of clinical studies.

The most significant complication of end-stage kidney disease (ESKD) is cardiovascular disease, mainly coronary artery disease (CAD). Although the effective treatment of CAD is an important prognostic factor, whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for treating CAD in this group of patients is still controversial. We searched Pubmed/Medline, Web of Science, Embase, the Cochrane Central Register of Controlled Trials articles that compared the outcomes of CABG versus PCI in patients with ESKD requiring dialysis. A total of 10 observational studies with 39,666 patients were included. Our analysis showed that when compared to PCI, CABG had lower risk of need for repeat revascularization (relative risk [RR] = 2.25, 95% confidence interval [CI] 2.1-2.42, p < 0.00001) and cardiovascular death (RR = 1.19, 95% CI 1.14-1.23, p < 0.00001) and higher risk for short-term mortality (RR = 0.43, 95% CI 0.38-0.48, p < 0.00001). There was no statistically significant difference between the PCI and CABG groups in the risk for late mortality (RR = 1.05, 95% CI 0.97-1.14, p = 0.25), myocardial infarction (RR = 1.05, 95% CI 0.46-2.36, p = 0.91) or stroke (RR = 1.02, 95% CI 0.64-1.61, p = 0.95). This meta-analysis showed that in ESKD patients requiring dialysis, CABG was superior to PCI in regard to cardiovascular death and need for repeat revascularization and inferior to PCI in regard to short term mortality. However, this meta-analysis has limitations and needs confirmation with large randomized controlled trials.

Role of Klotho in the Development of Essential Hypertension.

Klotho has antiaging properties, and serum levels decrease with physiological aging and aging-related diseases, such as hypertension, cardiovascular, and chronic kidney disease. Klotho deficiency in mice results in accelerated aging and cardiovascular injury, whereas Klotho supplementation slows down the progression of aging-related diseases. The pleiotropic functions of Klotho include, but are not limited to, inhibition of insulin/IGF-1 (insulin-like growth factor 1) and WNT (wingless-related integration site) signaling pathways, suppression of oxidative stress and aldosterone secretion, regulation of calcium-phosphate homeostasis, and modulation of autophagy with inhibition of apoptosis, fibrosis, and cell senescence. Accumulating evidence shows an interconnection between Klotho deficiency and hypertension, and Klotho gene polymorphisms are associated with hypertension in humans. In this review, we critically review the current understanding of the role of Klotho in the development of essential hypertension and the most important underlying pathways involved, such as the FGF23 (fibroblast growth factor 23)/Klotho axis, aldosterone, Wnt5a/RhoA, and SIRT1 (Sirtuin1). Based on this critical review, we suggest avenues for further research.

Colchicine Use in Acute Coronary Syndromes: An Update.

Coronary artery disease is the leading cause of death worldwide, and its main pathological substrate is represented by atherosclerosis. Inflammation is a major promoter of the atherosclerotic process and is involved in both the initiation and progression of atherosclerosis, as well as in the occurrence of fatal complications. Until the present moment, Colchicine Cardiovascular Outcomes Trial is the largest trial to demonstrate a major benefit of low-dose colchicine on major adverse cardiac events in patients with recent myocardial infarction (MI), but the mechanisms behind this relation are not completely known. The purpose of this review is to emphasize the possible pathways through which colchicine improves the clinical outcomes in the acute setting of acute coronary syndromes by referring to the results of the studies published in the past 5 years. Aside from its stated systemic anti-inflammatory effect, colchicine could be a valuable addition to the therapeutic approach of acute MI by reducing the infarct size, stabilizing the coronary plaque, as well as reducing platelet aggregation. Moreover, colchicine may improve endothelial function, reduce the transcoronary release of cytokines, and prevent a rise in inflammatory markers after percutaneous coronary intervention, thus diminishing the residual inflammatory risk.

Effect of Coffee Consumption on Renal Outcome: A Systematic Review and Meta-Analysis of Clinical Studies.

OBJECTIVE: Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, antithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake and chronic kidney disease (CKD) related outcomes. DESIGN AND METHODS: Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa scale was used for quality assessment of included studies. RESULTS: 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P = .01) with a greater decrease in individuals taking ≥2 cups/day compared to those who drank ≤1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in coffee users (HR 0.82, 95% CI 0.72 to 0.94, P = .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81, 95% CI 0.68 to 0.97, P = .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P = .02). CONCLUSION: Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.

Efficiency of Hypertonic Saline in the Management of Decompensated Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies.

INTRODUCTION: Acute decompensated heart failure (ADHF), with an incidence of 1-2%, is a clinical syndrome with significant morbidity and mortality despite therapeutic advancements and ongoing clinical trials. A recent therapeutic approach to patients with ADHF includes combination therapy with hypertonic saline solution (HSS) and furosemide, based on the hypothesis that resistance to loop diuretics occurs because of achievement of plateau in water and sodium excretion in patients receiving long-term loop diuretic therapy. OBJECTIVE: Our aim was to conduct a meta-analysis to evaluate the efficiency of combination HSS plus furosemide therapy in patients with ADHF in terms of mortality, readmissions, length of hospital stay, kidney function, urine output, body weight, and B-type natriuretic peptide (BNP). METHODS: A total of 14 studies-four observational and ten randomized studies (total 3398 patients)-were included in the meta-analysis. RESULTS: Our results demonstrate the superiority of combination HSS plus furosemide therapy over furosemide alone in terms of kidney function preservation (mean creatinine difference - 0.33 mg/dL; P < 0.00001), improved diuresis (mean difference [MD] 581.94 mL/24 h; P < 0.00001) and natriuresis (MD 57.19; P < 0.00001), weight loss (MD 0.99 kg; P < 0.00001), duration of hospital stay (MD - 2.72 days; P < 0.00001), readmissions (relative risk 0.63; P = 0.01), and mortality (relative risk 0.55; P < 0.00001). However, no difference in BNP levels was detected (MD 19.88 pg/mL; P = 0.50). CONCLUSION: Despite the heterogeneity and possible risk of bias among the studies, results appear promising on multiple aspects. A clear need exists for future randomized controlled trials investigating the role of combination HSS plus furosemide therapy to clarify these effects and their possible mechanisms.

Atrial fibrillation and chronic kidney disease conundrum: an update.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and it is frequently encountered in chronic kidney disease (CKD) subjects. CKD patients are already at high risk for cardiovascular (CV) complications and the addition of AF further aggravates the prognosis. Data is missing regarding on how to best approach CKD patients with AF, due to lack of randomized controlled trials (RCTs). AF and CKD have a double edged-sword relationship. On one hand, there are kidney-specific mechanisms which can alter cardiac structure and predispose to AF, and on the other hand the development of AF itself can accelerate the progression of CKD. Furthermore, the synergistic effect of these two entities raises serious issues concerning the balance between bleeding and thrombotic risk. Anticoagulant treatment can be challenging, especially in end stage renal disease (ESRD), where the net clinical benefit is still unclear. The decision of rate vs. rhythm control lies mostly on general consensus, rather than on RCTs. The purpose of this review is to reinforce the symbiotic relationship between AF and CKD, to briefly summarize the current state of the therapeutic approach in this particular population and to highlight novel potential therapeutic strategies.

Cardioprotective apelin effects and the cardiac-renal axis: review of existing science and potential therapeutic applications of synthetic and native regulated apelin.

First described in 1998, apelin is one of the endogenous ligands of the apelinergic receptor. Since its discovery, its possible role in human physiology and disease has been intensively studied. Apelin is a native cardioprotective agent that the body synthesizes to create atheroprotective, antihypertensive, and regenerative effects in the body. By antagonizing the RAA system, apelin could play an important role in heart failure and hypertension. It is also involved in myocardial protection against ischemia/reperfusion injury, post-ischemic remodeling, and myocardial fibrosis. A small number of studies even suggest that serum apelin levels may be involved the development of life-threatening arrhythmias. All this information generated excitement about potential therapeutic effects in patients with heart failure and myocardial infarction. The therapeutic index of apelin is unknown but is anticipated to be favorable based on the small number of studies. In this review, we summarize the mechanisms by which apelin exerts its cardioprotective effects and its connection with the cardiorenal axis. Also, we report the potential therapeutic applications of synthetic and native regulated apelin. If larger studies can be performed, it is possible that apelin-mediated drug treatment may play a major role for a large number of patients worldwide in the future.