Standardized Definitions of Changes in Kidney Function in Trials of Heart Failure: JACC Expert Panel From the HF-ARC.

Perturbations in kidney function are frequently encountered in heart failure (HF) across its spectrum in both chronic and acute settings with distinct implications for patient management and prognosis. Lack of consensus on the threshold for clinically meaningful changes in kidney function has led to heterogeneity in the clinical characteristics and background therapies of individuals enrolled in clinical trials, and in multiple aspects of trial design. A meaningful and collaborative interaction among the disciplines of cardiology and nephrology, clinical trialists, industry sponsors, and regulatory agencies is vital to the development of standardized definitions of changes in kidney function across HF settings.

Peak Tricuspid Regurgitation Jet Velocity and Kidney Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Introduction: Although venous congestion secondary to elevated pulmonary artery pressure (PAP) has been hypothesized to worsen kidney function, the association of peak tricuspid regurgitation jet velocity (pTRV), a surrogate of PAP, with kidney outcomes remains uncertain in heart failure (HF) with preserved ejection fraction (HFpEF).

Methods: This analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial analyzed participants with a left ventricular ejection fraction (LVEF) of ≥45% who had pTRV measured by echocardiography at baseline. For the cross-sectional analysis, the association of baseline pTRV with baseline estimated glomerular filtration rate (eGFR) was assessed using linear regression.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy.

Epidemiology and Management of Patients With Kidney Disease and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization.

Association of Longitudinal B-Type Natriuretic Peptide Monitoring With Kidney Failure in Patients With CKD: A Cohort Study.

Rationale & Objective: Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT).

Updates in Cardiorenal Syndrome.

Cardiorenal syndrome is a term that refers to a collection of disorders involving both the heart and kidneys, encompassing multi-directional pathways between the 2 organs mediated through low arterial perfusion, venous congestion, and neurohormonal activation. The pathophysiology is complex and includes hemodynamic and neurohormonal changes, but inconsistent findings from recent studies suggest this is very heterogenous disorder. Management for ADHF remains focused on decongestion and neurohormonal blockade to overcome the intense sodium and fluid avidity of the CRS.

The importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial.

Aims: Previous studies have suggested venous congestion as a stronger mediator of negative cardio-renal interactions than low cardiac output, with neither factor having a dominant role. While the influence of these parameters on glomerular filtration have been described, the impact on diuretic responsiveness is unclear. The goal of this analysis was to understand the hemodynamic correlates of diuretic response in hospitalized patients with heart failure.

Cardiorenal Syndrome in the Hospital.

The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. Upward of 60% of patients admitted for acute decompensated heart failure have CKD, as defined by an eGFR of <60 ml/min per 1.73 m 2 .

Rates of In-Hospital Decongestion and Association with Mortality and Cardiovascular Outcomes Among Patients Admitted for Acute Heart Failure.

Background: Decongestion is an important goal in the management of acute heart failure. Whether the rate of decongestion is associated with mortality and cardiovascular outcomes is unknown.

Methods: Using data from 4133 patients from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we used multivariable Cox regression models to evaluate the association between rates of in-hospital change in assessments of volume overload, including b-type natriuretic peptide (BNP), N-terminal pro b-type natriuretic peptide (NT-proBNP), as well as change in hemoconcentration, with risk of all-cause mortality and a composite outcome of cardiovascular mortality or heart failure hospitalization.

Inferior Vena Cava Diameter Measurement Provides Distinct and Complementary Information to Right Atrial Pressure in Acute Decompensated Heart Failure.

Background: Inferior vena cava (IVC) measurements correlate only modestly with right atrial pressure (RAP). Part of this inaccuracy is due to the high compliance of the venous system, where a large change in blood volume may result in only a small change in pressure. As such, the information provided by the IVC may be different rather than redundant.

Rates of Reversal of Volume Overload in Hospitalized Acute Heart Failure: Association With Long-term Kidney Function.

Rationale & Objective: Achievement of decongestion in acute heart failure (AHF) is associated with improved survival and cardiovascular outcomes but can be associated with acute declines in estimated glomerular filtration rate (eGFR). We examined whether the rate of in-hospital decongestion is associated with longer term kidney function decline.

Study Design: Post hoc analysis of trial data.

FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions.

Background: Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors.

Methods: One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics.

Estimating serum-ionized magnesium concentration in hemodialysis patients.

Introduction: Cardiovascular mortality is significantly increased in kidney failure with replacement therapy (KFRT) patients, which is partly mediated by enhanced vascular calcification. Magnesium appears to have anticalcifying capabilities, and hypomagnesemia has been associated with increased mortality in KFRT patients. Ionized magnesium represents the biologically and physiologically active form.

Acute eGFR declines after intensive BP lowering with RAS blockade and risk of kidney failure.

As guidelines now recommend intensive blood pressure (BP) lowering targets, more patients are being started on intensive BP regimens, which often include renin-angiotensin-aldosterone system (RAS) blockade. Our results suggest that the relation between mild acute estimated glomerular filtration rate (eGFR) declines after starting these regimens and risk of kidney failure was different depending upon BP target intensity, rather than depending upon the inclusion or not of a RAS-blocking agent.

Association of Volume Overload With Kidney Function Outcomes Among Patients With Heart Failure With Reduced Ejection Fraction.

Introduction: In patients with heart failure with reduced ejection fraction (HFrEF), volume overload is associated with mortality. Few studies that have examined the relation between volume and long-term kidney function outcomes in HFrEF.

Methods: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we used multivariable Cox regression models to evaluate the association between volume overload as evaluated by B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a clinical congestion score (scale of 0-12) composed of pedal edema, jugular venous distension, rales, and orthopnea with the occurrence of estimated glomerular filtration rate (eGFR) decline by >40%, and incident chronic kidney disease (CKD) stage ≥4 defined by eGFR of <30 ml/min per 1.

Peritoneal magnesium elimination and its clinical relevance in peritoneal dialysis patients.

Background: Dialysis patients are at increased risk for vascular calcification and cardiovascular disease. Emerging data suggests that magnesium might be protective for the vascular system in peritoneal dialysis (PD) patients as well. However, only limited data is available on the elimination of magnesium through PD treatment.

Intensive BP Control and eGFR Declines: Are These Events Due to Hemodynamic Effects and Are Changes Reversible?

Purpose Of Review: Acute declines in estimated glomerular filtration rate (eGFR) are often observed during intensive blood pressure (BP) lowering. This review focuses on identifying the various mechanisms of eGFR decline associated with intensive BP lowering and evaluates the evidence linking BP control with kidney and cardiovascular (CV) outcomes.

Recent Findings: In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) began recommending treatment of all individuals to a BP target of < 130/80 mmHg.

Acute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure.

Objectives: This study aimed to examine whether incorporation of a comprehensive set of measures of decongestion modifies the association of acute declines in kidney function with outcomes.

Background: In-hospital acute declines in kidney function occur in approximately 20% to 30% of patients admitted with acute decompensated heart failure (ADHF) and may be associated with adverse outcomes.

Methods: Using data from EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan), we used multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with death and a composite outcome of cardiovascular death and hospitalization for heart failure.

Sodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series.

Aims: Diuretic resistance is common in acute decompensated heart failure (ADHF). When loop diuretic monotherapy is ineffective, thiazides are often recommended as adjunctive therapy, but these agents have many side effects and are associated with worsened survival. In contrast, sodium glucose cotransporter 2 inhibitors (SGLT-2i's), initially developed as glucose-lowering medications for type 2 diabetes, improve heart failure outcomes.

Acute declines in estimated glomerular filtration rate on enalapril and mortality and cardiovascular outcomes in patients with heart failure with reduced ejection fraction.

Angiotensin-converting enzyme inhibitors are beneficial in heart failure with reduced ejection fraction but are associated with acute declines in estimated glomerular filtration rate (eGFR). Prior studies evaluating thresholds of eGFR decline while using angiotensin-converting enzyme inhibitors in heart failure with reduced ejection have not taken into account this medication-driven decline. Here we used data from the Studies of Left Ventricular Dysfunction (SOLVD) trial of 6245 patients and performed Cox proportional hazards regression models to calculate hazard ratios of all-cause mortality and heart failure hospitalization-associated with percent eGFR decline at two- and six-weeks after randomization to enalapril versus placebo.