Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

Abstract Background Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. Methods This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. Results 29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

Abstract Background Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. Methods This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. Results 29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

Optimizing the medical management of patients with chronic kidney disease and end-stage renal disease

Chronic kidney disease (CKD) prevalence is high and constantly increasing over the last years across the world. CKD is associated with higher incidence of cardiovascular disease, as well as premature mortality. There is an urgent unmet need for more data on novel treatment strategies that may prevent further renal function decline and appropriately treat cardiovascular complications in patients with CKD. Cardiac and renal interactions remain complex and poorly understood. As we show in the first publication, there is significant overlap between acute kidney injury or acutely decompensated heart failure and progression of chronic kidney disease or congestive heart failure. Involvement of both organs portends worse clinical outcomes. In the ESRD population, hemodialysis itself probably exerts detrimental effects on heart function through worsening myocardial perfusion that seems to be caused by excessive ultrafiltration rates, as we show in the second publication. The third article summarizes available clinical evidence and suggests beneficial effects of mineralocorticoid receptor antagonists, spironolactone or eplerenone, when added to an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker in patients with diabetic nephropathy. Although albuminuria that was examined in this study is a surrogate marker for hard renal outcomes, further blockade of renin-angiotensin-aldosterone system looks promising, at least in patients with diabetes mellitus. Atrial fibrillation is a common problem in CKD and is associated with significant morbidity. It has recently been shown that vitamin K antagonists may not be as effective in this population and there is increasing interest on direct oral anticoagulants in CKD. The fourth article examines the pharmacokinetics of apixaban in patients on hemodialysis. This article demonstrates that steady state levels are far higher than levels obtained after a single dose of the drug and may be supratherapeutic with the full dose (5 mg twice daily). Furthermore, it shows that apixaban is not removed by hemodialysis. The fifth article examines platelet reactivity in stable outpatients with cardiovascular disease and CKD. In contrast to what has been shown in patients undergoing percutaneous coronary intervention, CKD is not associated with higher platelet reactivity or lower antiplatelet drug responsiveness in stable outpatients. Furthermore, there is no interaction between CKD status and high platelet reactivity for major adverse cardiovascular events in this population

Traitements anticoagulants: inconvénients des régimes actuels et promesses pour le futur

La maladie thromboembolique veineuse constitue une cause majeure de morbidité et de mortalité et le traitement anticoagulant est la pierre angulaire de sa prévention et de sa prise en charge. Les anticoagulants actuellement utilisés ont fait preuve d'une incontestable efficacité mais présentent également certains inconvénients. L'héparine non fractionnée, les héparines de bas poids moléculaire et le fondaparinux doivent être administrés en parentéral ce qui rend leur utilisation problématique au long cours. Les anti-vitamines K ont un début d'action lent et nécessitent un traitement initial par un agent parentéral. Etant donné leur effet anticoagulant variable, un monitoring fréquent est nécessaire dans le but d'ajuster la posologie. A la recherche d'un anticoagulant idéal qui ne présenterait pas ces inconvénients, plusieurs molécules ont été développées. Celles qui sont actuellement à un stade avancé de développement sont les trois inhibiteurs directs oraux du facteur Xa, le rivaroxaban, l'apixaban et l'edoxaban, et un inhibiteur direct de la thrombine, le dabigatran. Ces dernières années, de nombreuses études ont évalué leur place dans la prévention et le traitement de la maladie thromboembolique veineuse ou la fibrillation auriculaire avec des résultats prometteurs. Leurs propriétés pharmacologiques se rapprochent du profil de l'anticoagulant idéal : administration orale, pas de monitoring, dosage unique, interactions médicamenteuses limitées. Leur emploi permettra de simplifier la prise en charge de la maladie thromboembolique veineuse et de la fibrillation auriculaire

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome

Effect of eplerenone and ramipril on an experimental model of diabetic nephropathy

We studied the effect of the combined treatment with an angiotensin converting enzyme inhibitor (ramipril) and eplerenone, compared with ramipril alone in the streptozocin-induced diabetic rat. Wistar rats were divided into four groups: non diabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg), and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produces early stage diabetic nephropathy. Diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance), and histopathological evidence of renal injury, including glomerular hypertrophy and mesangial expansion. Ramipril and to a lesser extent ramipril combined with eplerenone reduced proteinuria. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration. A decrease in nitric oxide levels was detected in the cortex of diabetic rats that is reversed by combined treatment with eplerenone and ramipril but not with ramipril alone. Eplerenone in addition to an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker may provide more complete interruption of the renin angiotensin aldosterone system and may be helpful in slowing the nephropathy progression. Clinical trials testing eplerenone at an early stage of diabetic nephropathy are eagerly awaited.O σκοπός της διατριβής είναι η σύγκριση του συνδυασμού επλερενόνης-ραμιπρίλης με τη ραμιπρίλη ως μονοθεραπεία σε επίμυες που κατέστησαν διαβητικοί μετά τη χορήγηση στρεπτοζοκίνης. Για τη διεξαγωγή του πειράματος χρησιμοποιήθηκαν άρρενες επίμυες Wistar ηλικίας 10 εβδομάδων. Οι επίμυες έγιναν διαβητικοί με άπαξ ενδοπεριτοναϊκή έγχυση στρεπτοζοκίνης (50 mg/kg). Οι επίμυες αυτοί τυχαιοποιήθηκαν σε τρεις ομάδες (n=6), αφού προηγουμένως προσδιορίστηκε το βάρος τους. Η ομάδα D δεν έλαβε αγωγή, η ομάδα R έλαβε ραμιπρίλη (1 mg/kg), ενώ η ομάδα R+E έλαβε το συνδυασμό ραμιπρίλης (1 mg/kg) και επλερενόνης (100 mg/kg). Έξι μη διαβητικοί άρρενες επίμυες, της ίδιας ηλικίας, αποτέλεσαν την ομάδα ελέγχου (ομάδα C). Η διάρκεια του πειράματος ήταν 8 εβδομάδες. Οι επίμυες που κατέστησαν διαβητικοί από τη στρεπτοζοκίνη ανέπτυξαν τις τυπικές αλλοιώσεις διαβητικής νεφροπάθειας αρχικού σταδίου. Η μελέτη μας έδειξε ότι η αναστολή του μετατρεπτικού ενζύμου από τη ραμιπρίλη έχει ως αποτέλεσμα την ελάττωση της πρωτεϊνουρίας και την αναστολή της σπειραματικής υπερτροφίας. Οι ευεργετικές αυτές επιδράσεις παρατηρήθηκαν επίσης κατά τη χορήγηση του συνδυασμού ραμιπρίλης-επλερενόνης. Διαπιστώσαμε ακόμη ότι ο συνδυασμός επλερενόνης-ραμιπρίλης αναστέλλει τη σπειραματική υπερδιήθηση, πράγμα που δεν ισχύει για τη μονοθεραπεία με ραμιπρίλη. Αντιθέτως, δεν παρατηρήσαμε κάποια σημαντική επίδραση στην υπερπλασία του μεσαγγείου, τόσο με τη ραμιπρίλη, όσο και με το συνδυασμό της με την επλερενόνη. Διαπιστώσαμε ακόμη ότι η συγκέντρωση του ΝΟ στο νεφρικό φλοιό ελαττώνεται στους διαβητικούς επίμυες. Ο συνδυασμός ραμιπρίλης-επλερενόνης αποτρέπει την ελάττωση αυτή της συγκέντρωσης του ΝΟ, πράγμα που δεν επιτυγχάνει η μονοθεραπεία με ραμιπρίλη. Ο συνδυασμός ενός αναστολέα του μετατρεπτικού ενζύμου της αγγειοτασίνης με έναν αποκλειστή των υποδοχέων της αλδοστερόνης υπόσχεται ενθαρρυντικά αποτελέσματα στην κλινική πράξη και θα μπορούσε να μελετηθεί σε ασθενείς με διαβητική νεφροπάθεια αρχικού σταδίου με σκοπό την αναστολή της επιδείνωσης της νεφροπάθειας

Mineralocorticoid receptor antagonists in patients with chronic kidney disease

Mineralocorticoid receptor antagonists (MRA) can reduce cardiovascular morbidity and mortality in patients with heart failure and ischemic heart disease. In addition, these agents have been used in patients with diabetic nephropathy to control proteinuria and slow down chronic kidney disease (CKD) progression. Current guidelines recommend against the use of MRAs in patients with advanced CKD. However, there is growing interest on their use in this population that has unmet needs (high cardiovascular morbidity and mortality) and unique challenges (risk of acute kidney injury or hyperkalemia). This narrative review discusses the emerging role of MRAs for the management of cardiovascular disease and/or the prevention of CKD progression, highlighting results from randomized controlled trials and presenting real-world data from available registries. Results from recent trials in patients on maintenance dialysis are also discussed

Bivalirudin in ST-segment-elevation myocardial infarction: for better or worse?

Bivalirudin and heparin are the major available parenteral anticoagulants for percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction. Even though hard clinical outcomes are comparable with both drugs, bivalirudin appears to be safer (less bleeding events) at the expense of lower short-term efficacy (more acute stent thrombosis events). The selection of anticoagulation during PCI in ST-segment-elevation myocardial infarction should be individualized, taking into account the patient's ischemic and bleeding risk. In patients with increased bleeding risk, bivalirudin might be preferable to heparin, whereas in complex PCI with increased risk for stent thrombosis, heparin is preferable. Further clinical studies are needed to elucidate the role of these drugs in PCI for ST-segment-elevation myocardial infarction in the era of radial approaches, new potent antiplatelet agents and the use of glycoprotein IIb/IIIa inhibitors

Bivalirudin in stable angina and acute coronary syndromes

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes