The kidney in heart failure: an update

Abstract

Heart and kidney are closely related in the clinical syndrome of heart failure (HF). It is now sufficiently clear that renal dysfunction occurs frequently in all phenotypes of HF, and when present, it is associated with higher mortality and morbidity. While the pathophysiology is multifactorial, the most important factors are a reduced renal perfusion and venous congestion. Recent interest has focused on worsening renal function (WRF), a situation strongly related to mortality, but seemingly only when HF status deteriorates. Unfortunately, to date clinicians are unable to identify specifically those patients with a grim prognosis following WRF. Although much has been learned on cardiorenal interaction in HF, still more questions have been left unanswered. The coming decade should provide us with more dedicated epidemiologic, mechanistic, and controlled trials in HF patients with reduced renal function. An updated classification of the cardiorenal syndrome that incorporates recent evidence and points towards areas of interest and uncertainties, and areas where progress is needed could facilitate this process. Ultimately, this should lead to preventive and treatment strategies that can preserve renal function and associated outcome in patients with HF.

Keywords: Cardiorenal interaction; Heart failure; Renal dysfunction.

Figure 1

History of research in cardiorenal interaction. Overview of some key investigations in cardiorenal research. For reference list, see Supplementary material online, files.

Figure 2

Visual depiction of association between changes in renal function, clinical condition, and mortality risk. AKI, acute kidney injury; GFR, glomerular filtration rate; WRF, worsening renal function. Darker colours indicate higher mortality risk. Suggested cut-off values for WRF (chronic HF): ≥26.5 µmol/L and ≥25% increase in creatinine OR ≥ 20% decrease in eGFR over 1–26 weeks, and AKI (acute HF): increase of 1.5–1.9 times baseline creatinine within 1–7 days before or during hospitalization OR ≥ 26.5 µmol/L increase in creatinine within 48 h OR urine output < 0.5 mL/kg/h for 6–12 h (based on Damman et al.)

Figure 3

Pathophysiologic pathways of cardiorenal interaction. AKI, acute kidney injury; CO, cardiac output; CVP, central venous pressure; DCM, dilated cardiomyopathy; GFR, glomerular filtration rate; HFPEF, heart failure with preserved ejection fraction; HFREF, heart failure with reduced ejection fraction; IL-18, interleukin 18; KIM-1, kidney injury molecule 1; L-FABP, liver type fatty acid binding protein; LVAD, left ventricular assist device; NAG, N-acetyl-β-d-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; NTproBNP, N-terminal pro brain natriuretic peptide; RAAS, renin angiotensin aldosterone system; SNS, sympathetic nervous system; WRF, worsening renal function. The diagram illustrates predisposing factors that can cause both cardiac and renal disease. From both ends of the spectrum, disease of one organ can lead to progressive dysfunction leading to heart and renal failure. Both interact with each other through haemodynamic and (neurohormonal) (mal)adaptive processes, and modulating factors further affect these associations. Further progression of disease is caused by (re)hospitalizations. Eventually, patients enter a vicious circle of mutual organ dysfunction, resulting either in end stage renal disease, end stage heart failure, or a combination of both. Illustrations (adapted from) Servier Medical Art (http://www.servier.com/Powerpoint-image-bank), under the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

Figure 4

Approach to the heart failure patients with renal dysfunction. GFR, glomerular filtration rate; RAAS, renin angiotensin aldosterone system; WRF, worsening renal function. *At least every 6 months, can be individually determined.