[Show abstract][Hide abstract] ABSTRACT: Current goals in the acute treatment of heart failure are focused on pulmonary and systemic decongestion with loop diuretics as the cornerstone of therapy. Despite rapid relief of symptoms in patients with acute decompensated heart failure, after intravenous use of loop diuretics, the use of these agents has been consistently associated with adverse events, including hypokalemia, azotemia, hypotension, and increased mortality. Two recent randomized trials have shown that continuous infusions of loop diuretics did not offer benefit but were associated with adverse events, including hyponatremia, prolonged hospital stay, and increased rate of readmissions. This is probably due to the limitations of congestion evaluation as well as to the deleterious effects linked to drug administration, particularly at higher dosage. The impaired renal function often associated with this treatment is not extensively explored and could deserve more specific studies. Several questions remain to be answered about the best diuretic modality administration, global clinical impact during acute and post-discharge period, and the role of renal function deterioration during treatment. Thus, if loop diuretics are a necessary part of the treatment for acute heart failure, then there must be an approach that allows personalization of therapy for optimal benefit and avoidance of adverse events.
[Show abstract][Hide abstract] ABSTRACT: The term cardiorenal syndrome (CRS) implies acute or chronic injury to the heart and kidneys that often involves a temporal sequence of disease initiation and progression. The classification of CRS is divided into five subtypes. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury (AKI) or accelerated chronic kidney disease (CKD). Types 3 and 4, describe AKI and CKD, respectively, leading primarily to heart failure, although, it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRS type 5 describes a systemic insult to both heart and the kidneys, such as sepsis, where both organs are injured simultaneously in persons with previously normal heart and kidney function at baseline. This manuscript will summarize key issues and future opportunities in challenging patients with CRS. Because most CRS occur in patients with pre-existing myocardial disease or chronic kidney disease, we will emphasize the chronic condition which puts individuals at risk for acute events. In the setting of a hospitalization, acute CRS can occur which have been consistently associated with inpatient complications, longer lengths of intensive care unit and hospital stay, need for renal replacement therapy, rehospitalization and death. While there are several common diagnostic and therapeutic targets for the heart and kidney, there remains considerable opportunity for both in-vitro diagnostics and medicinal therapy to favorably influence the occurrence and natural history of CRS.
[Show abstract][Hide abstract] ABSTRACT: Hyperkalemia is defined as serum potassium concentrations elevated above the upper limit of normal (> 5.0 mEq/L). It has become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad application of drugs that modulate renal elimination of potassium by reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, β-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). The risk of hyperkalemia is a major limiting factor for the use of these disease-modifying drugs in both acute and chronic cardiorenal syndromes. Thus, agents to control the plasma concentration of potassium are needed in the multidrug treatment of cardiorenal disease, including chronic kidney disease, heart failure, and acute kidney injury. Novel oral therapies in development for both acute and extended use in the management of hyperkalemia include patiromer sorbitex calcium and sodium zirconium cyclosilicate. Important biochemical differences between these compounds result in unique product profiles and electrolyte outcomes in patients treated for hyperkalemia. This review highlights the major mechanisms of hyperkalemia and key results from randomized trials in a range of clinical scenarios in patients with, and at risk for, hyperkalemia.
Reviews in cardiovascular medicine 07/2015; 16(2):140-55. · 0.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over the past decade, science has greatly advanced our understanding of interdependent feedback mechanisms involving the heart, lung, and kidney. Organ injury is the consequence of maladaptive neurohormonal activation, oxidative stress, abnormal immune cell signaling, and a host of other mechanisms that precipitate adverse functional and structural changes. The presentation of interorgan crosstalk may include an acute, chronic, or acute on chronic timeframe. We review the current, state-of-the-art understanding of cardio-pulmonary-renal interactions and their related pathophysiology, perpetuating nature, and cycles of increased susceptibility and reciprocal progression. To this end, we present a multidisciplinary approach to frame the diverse spectrum of published observations on the topic. Assessment of organ functional reserve and use of biomarkers are valuable clinical strategies to screen and detect disease, assist in diagnosis, assess prognosis, and predict recovery or progression to chronic disease.
Journal of the American College of Cardiology 06/2015; 189(22). DOI:10.1016/j.jacc.2015.04.024 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.
Internal and Emergency Medicine 05/2015; 10(5). DOI:10.1007/s11739-015-1246-0 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is on the rise due to the increased rate of related comorbidities such as diabetes and hypertension. Patients with CKD are at higher risk of cardiovascular events and atrial fibrillation is more common in this patient population. It is estimated that the prevalence of chronic atrial fibrillation in patients with CKD is two to three times higher than general population. Furthermore, patients with CKD are less likely to stay in sinus rhythm. Atrial fibrillation presents a major burden in this population due to difficult treatment decisions in the setting of a lack of evidence from randomized clinical trials. Patients with CKD have higher risk of stroke with more than half having a CHADS2 score ≥ 2. Anticoagulation have been shown to significantly decrease embolic stroke risk, however bleeding complications such as hemorrhagic stroke is twofold higher with warfarin. Although newer novel anticoagulation drugs have shown promise with lower intracranial hemorrhage risk in comparison to warfarin, lack clinical trial data in CKD and the unavailability of an antidote remains an issue. In this review, we discuss the treatment options available including anticoagulation and the evidence behind them in patients with chronic kidney disease suffering from atrial fibrillation.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to tubular injury. Contrast-induced acute kidney injury (CI-AKI) is associated with adverse outcomes in chronic kidney disease (CKD) patients. We sought to characterize blood NGAL level and the degree of kidney injury in CKD patients who underwent coronary angiography.
This study was a prospective, blinded assessment of blood samples obtained from patients with estimated glomerular filtration rates (eGFRs) between 15 and 90 mL/min/1.73 m2 undergoing elective coronary angiography with iodinated contrast. Blood NGAL and serum creatinine were measured at baseline, 1, 2, 4, 6, 12, 24 and 48 h after contrast administration.
A total of 63 subjects with a mean eGFR of 48.17±16.45 mL/min/1.73 m2 were enrolled. There was a graded increase in baseline NGAL levels across worsening stages of CKD (p=0.0001). Post-procedure NGAL increased from baseline in each stage of CKD. Eight (12.7%) patients were diagnosed with CI-AKI by diagnostic criteria of 2012 KDIGO definition of CI-AKI, and seven (11.1%) patients developed subclinical CI-AKI defined by a twofold or greater rise in NGAL. There was no relationship between baseline eGFR and diabetes on the composite outcome of subclinical and clinical CI-AKI.
Baseline and post-procedure NGAL are progressively elevated according to the baseline stage of CKD. Using a twofold rise in NGAL, 46.7% of composite CI-AKI is detected and complements the 53.3% of cases identified using KDIGO criteria. Traditional risk predictors were not independently associated with this composite outcome.
[Show abstract][Hide abstract] ABSTRACT: This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1-5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3-5 CKD than Stages 1 and 2. There were no differences in clinicians' likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.
PLoS ONE 11/2014; 9(11):e110535. DOI:10.1371/journal.pone.0110535 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute kidney injury complicates decompensated heart failure in ∼33% of cases and is associated with morbidity and mortality, thus, we sought to systematically review this topic in order to summarize novel diagnostic and therapeutic approaches.Methods
Structured PubMed searches on these topics were conducted in February 2014 and relevant literature was identified. The PubMed search identified a total of 192 articles that were individually screened for inclusion in this analysis and 58 were included.ResultsAcute kidney injury, defined by substantial rises in serum creatinine, is consistently associated with prolonged length of stay, rehospitalization, and mortality. Biomarker studies suggested that natriuretic peptides are prognostic for shorter and longer term mortality. Novel proteins indicating kidney damage and albumin in the urine are associated with acute kidney injury. The most promising acute pharmacologic treatment appears to be serelaxin, which has been shown to improve acute heart failure symptoms, hemodynamic parameters, and renal function.Conclusions
The presence of acute kidney injury results in worse clinical outcomes for patients with acute heart failure. Novel biomarkers and therapies hold the promise of improving both cardiac and renal outcomes in these patients.
The American Journal of Medicine 11/2014; 128(3). DOI:10.1016/j.amjmed.2014.10.035 · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary heart disease is highly prevalent in patients with CKD, and survival after acute coronary syndrome (ACS) is worse compared with the general population. Many trials that define guidelines for cardiovascular disease excluded patients with kidney disease, leaving a gap between the evidence base and clinical reality. The underlying pathophysiology of vascular disease appears to be different in the setting of CKD. Patients with CKD are more likely to present with myocardial infarction and less likely to be diagnosed with ACS on admission compared with the general population. Patients with CKD appear to benefit with angiography and revascularization compared with medical management alone. However, the increased risk of in-hospital bleeding and risk of contrast-induced acute kidney injury are 2 factors that can limit overall benefit for some. Thus, judicious application of available therapies for the management of ACS is warranted to extend survival and reduce hospitalizations in this high-risk population. In this review, we highlight the clinical challenges and potential solutions for managing ACS in patients with CKD.
[Show abstract][Hide abstract] ABSTRACT: Background:
A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.
Methods and results:
We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.
Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.
[Show abstract][Hide abstract] ABSTRACT: In patients with heart failure as a result of mechanical and neurohormonal derangements, macrophages secrete galectin-3, which is a paracrine and endocrine factor that stimulates additional macrophages, pericytes, myofibroblasts, and fibroblasts to proliferate and secrete procollagen I, which is irreversibly crosslinked to form fibrotic collagen. Normal plasma concentrations of galectin-3 are < 11.0 ng/mL. Galectin-3 measured in blood has been shown to predict the development of all-cause mortality and heart failure in the general population, identify increased risk for de novo heart failure and progressive loss of renal filtration function in healthy middle-aged adults, predict cardiac failure in patients after acute coronary syndromes, help establish the diagnosis of heart failure with preserved ejection fraction in patients presenting with effort intolerance, and aid in the prognosis of both systolic and nonsystolic heart failure for the outcomes of hospitalization and death. This article presents case discussions of these applications to highlight the importance of galectin-3 measurement across the spectrum of patients at risk for cardiorenal disease.
Reviews in cardiovascular medicine 10/2014; 15(3):197-207. DOI:10.3909/ricm0726 · 0.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth
factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development,
and diagnostic accuracy of two clinical cutoffs for a test using these markers.