Heart Failure in Patients with Chronic Kidney Disease

Abstract

The function of the kidney is tightly linked to the function of the heart. Dysfunction/disease of the kidney may initiate, accentuate, or precipitate of the cardiac dysfunction/disease and vice versa, contributing to a negative spiral. Further, the reciprocal association between the heart and the kidney may occur on top of other entities, usually diabetes, hypertension, and atherosclerosis, simultaneously affecting the two organs. Chronic kidney disease (CKD) can influence cardiac function through altered hemodynamics and salt and water retention, leading to venous congestion and therefore, not surprisingly, to heart failure (HF). Management of HF in CKD is challenging due to several factors, including complex interplays between these two conditions, the effect of kidney dysfunction on the metabolism of HF medications, the effect of HF medications on kidney function, and the high risk for anemia and hyperkalemia. As a result, in most HF trials, patients with severe renal impairment (i.e., eGFR 30 mL/min/1.73 m² or less) are excluded. The present review discusses the epidemiology, pathophysiology, and current medical management in patients with HF developing in the context of CKD.

Keywords: angiotensin receptor/neprilysin inhibitor; chronic kidney disease; heart failure; renin-angiotensin aldosterone system inhibitors; sodium glucose cotransporter 2 inhibitor; β-blockers.

Figure 1

Stages of chronic kidney disease (CKD) according to KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease and cardiovascular mortality risk [7]. CKD can be diagnosed if glomerular filtration rate (GFR) is less than 60 mL/min per 1.73 m² or albuminuria is greater than 30 mg/24 h, both persisting for more than 3 months. Categories are defined by GFR and albuminuria measures (e.g., CKD category G3A3). Green, low risk; yellow, increased risk; orange, high risk; red, very high risk.

Figure 2

The “cardiovascular death triangle” comprised of atherosclerosis, chronic kidney disease, and heart failure and associated risk factors. Notably, atherosclerosis, chronic kidney disease, and heart failure share many common risk factors, the most important being hypertension and diabetes. Abbreviations: CKD, chronic kidney disease; HF, heart failure.

Figure 3

Mechanisms contributing to cardiac and renal fibrosis. With permission from ref. [26]. Abbreviation: ER stress, endoplasmic reticulum stress.

Figure 4

Inflammation, oxidative stress, neurohormonal overactivity, and sodium and water retention contribute both to adverse renocardiac interactions and anemia development. The latter contributes to a further deterioration of renal and cardiac function.

Figure 5

Management of heart failure according to the stage of chronic kidney disease. GFR, glomerular filtration rate; MRA, mineralocorticoid receptor antagonist; Sac/Val, sacubitril/valsartan; SGLT-2i, sodium glucose cotransporter 2 inhibitor; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker. Red, advanced renal disease necessitating nephrology consultation.