Anemia Management in the Cardiorenal Patient: A Nephrological Perspective

Abstract

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, sharing significant overlap in prevalence and pathophysiological mechanisms. This coexistence, termed cardiorenal syndrome (CRS), often leads to anemia, which exacerbates both HF and CKD, thereby increasing morbidity and death. Managing anemia in CRS is complex due to conflicting guidelines and the multifactorial nature of the condition. Anemia in CRS is influenced by factors such as inadequate erythropoietin production, iron deficiency, reduced red blood cell life span, and chronic inflammation, which inhibit iron absorption and mobilization. This interplay of mechanisms worsens anemia, further aggravating HF and CKD. Anemia significantly impacts the prognosis of both HF and CKD, and recent trials have shown that hemoglobin increases, particularly with sodium-glucose cotransporter 2 inhibitors, can improve outcomes in patients with HF and CKD. Iron deficiency is also prevalent in both patients with HF and patients with CKD and is associated with poorer exercise capacity and a higher mortality rate. Guidelines for diagnosing and treating iron deficiency differ between HF and CKD. Furthermore, treatment of anemia in CRS is controversial: While sodium-glucose cotransporter 2 inhibitors and intravenous iron has shown consistent benefits in patients with CRS, normalization of hemoglobin with erythropoiesis-stimulating agents improves symptoms and quality of life but have not consistently demonstrated cardiovascular benefits. There are no definitive guidelines for anemia management in CRS. Treatment should address HF, CKD, and anemia concurrently. A proposed algorithm includes correcting iron deficiency, initiating sodium-glucose cotransporter 2 inhibitors, and considering erythropoiesis-stimulating agents if hemoglobin remains <10 g/dL. Further research is needed to optimize anemia management strategies in patients with CRS.

Keywords: anemia treatment; cardiorenal syndrome; chronic kidney disease; heart failure; iron deficiency.

Figure 1. Pathophysiology of cardiorenal anemia syndrome.

Anemia associated with heart failure and chronic kidney disease is caused by multiple factors including inadequate erythropoietin synthesis, iron deficiency, shortened life span of red blood cells, the negative impact of uremic toxins and inflammation on erythropoiesis, and disturbances in bone‐mineral disease (such as hyperparathyroidism and increased levels of fibroblast growth factor 23), along with the use of renin‐angiotensin‐aldosterone system inhibitors. ADH indicates antidiuretic hormone; BNP, B‐type natriuretic peptide; CKD, chronic kidney disease; EPO, erythropoietin; IL‐6, interleukin‐6; LV, left ventricular; LVH, left ventricular hypertrophy; RAAS, renin–angiotensin–aldosterone system; RBF, renal blood flow; and SNS, sympathetic nervous system.

Figure 2. Proposed algorithm to treat anemia in patients with cardiorenal syndrome.

*Retest monthly until correct hemoglobin and thereafter every 2 to 3 mo. Hemoglobin >10 and hemoglobin <11.5 continue/titrate ESA, hemoglobin >11.5 reduce ESA dose, hemoglobin >13 g/dL stop ESA. ESA indicates erythropoiesis stimulating agent; Hb, hemoglobin; ID, iron deficiency; IV, intravenous; SGLT2i, sodium glucose cotransporter type 2 inhibitor; and TSAT, transferrin saturation index.