Anemia of cardiorenal syndrome

Abstract

Cardiorenal syndrome includes a spectrum of disorders of the kidneys and heart in which loss of function in one organ contributes to reduced function in the other organ. Cardiorenal syndrome is frequently complicated by comorbid anemia, which leads to reciprocal and progressive cardiac and renal deterioration. The triad of heart failure, chronic kidney disease (CKD), and anemia is termed cardiorenal anemia syndrome (CRAS). There are currently no evidence-based recommendations for managing patients with CRAS; however, the treatment of these patients is multifactorial. Not only must the anemia be controlled, but heart failure and kidney injury must be addressed, in addition to other comorbidities. Intravenous iron and erythropoiesis-stimulating agents are the mainstays of treatment for anemia of CKD, addressing both iron and erythropoiesis deficiencies. Since erythropoiesis-stimulating agent therapy can be associated with adverse outcomes at higher doses in patients with CKD and is not used in routine practice in patients with heart failure, treatment options for managing anemia in patients with CRAS are limited. Several new therapies, particularly the hypoxia-inducible factor-prolyl hydroxylase inhibitors, are currently under clinical development. The hypoxia-inducible factor-prolyl hydroxylase inhibitors have shown promising results for treating anemia of CKD in clinical trials and may confer benefits in patients with CRAS, potentially addressing some of the limitations of erythropoiesis-stimulating agents. Updated clinical practice guidelines for the screening and management of anemia in cardiorenal syndrome, in light of potential new therapies and clinical evidence, would improve the clinical outcomes of patients with this complex syndrome.

Keywords: cardiovascular disease; chronic kidney disease; erythropoiesis-stimulating agents; heart failure; hypoxia-inducible factor–prolyl hydroxylase inhibitor; iron deficiency.

Graphical abstract

Figure 1

A schematic diagram of the mechanisms underlying cardiorenal syndrome.^,,, , Dysfunction in either the heart or kidneys, caused by systemic insults, triggers hemodynamic and nonhemodynamic changes, culminating in cardiorenal syndrome (CRS) and propagating a vicious cycle (double-headed black arrows). Black arrows indicate pathophysiological interactions in CRS; blue arrow, hemodynamic changes; dotted red arrows, consequences of nonhemodynamic changes; and green arrow, mechanism to correct renal function (decompensated). ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; BP, blood pressure; CVP, central venous pressure; GFR, glomerular filtration rate; HF, heart failure; Na⁺, sodium; RAAS, renin-angiotensin-aldosterone system; RBF, renal blood flow; SNS, sympathetic nervous system.

Figure 2

The cycle of damage in cardiorenal anemia syndrome.^,, ∗Medications used in heart failure (HF) associated with anemia include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and β-blockers. ADH, antidiuretic hormone (vasopressin); BNP, brain natriuretic peptide; BP, blood pressure; EC, extracellular; EPO, erythropoietin; Hct, hematocrit; HR, heart rate; LVH, left ventricular hypertrophy; Na⁺, sodium; PV, plasma volume; RAAS, renin-angiotensin-aldosterone system; RBF, renal blood flow; SNS, sympathetic nervous system; SV, stroke volume.