Responsiveness to an erythropoiesis-stimulating agent is correlated with body composition in patients undergoing chronic hemodialysis

Abstract

BackgroundResistance to erythropoiesis-stimulating agents (ESA) is associated with adverse outcomes in patients undergoing chronic hemodialysis. However, the impact of body composition on ESA response remains uncertain. This study retrospectively investigated whether there is an association between the ESA resistance index (ERI) and body composition in patients undergoing chronic hemodialysis.MethodsMultifrequency bioelectrical impedance analysis was used to measure body composition every six months. The ERI was calculated by dividing the weekly body weight-adjusted erythropoietin dose by the hemoglobin concentration. The ERI values were recorded every three months.ResultsA total of 123 patients were followed up for 24 (interquartile range 5, 75) months. The ERI was negatively correlated with body mass index, arm circumference, arm muscle circumference, body fat percentage, and visceral fat area (P = 0.057, 0.001, 0.017, 0.063, and 0.041, respectively). Patients with a higher mean ERI during the study period had an increased risk of all-cause mortality, cardiovascular events, and infection requiring hospitalization than those with a lower mean ERI (P = 0.027, 0.021, and 0.037, respectively). We also evaluated the association between the slope of body composition parameters and the ERI trend over time and found that the ERI increased over time in patients who had an increased ratio of extracellular water to total body water (P = 0.002) as well as decreased arm circumference, arm muscle circumference, visceral fat area, and phase angle (P = 0.001, P < 0.001, P = 0.036, and 0.002).ConclusionESA responsiveness appears to be associated with body composition in patients undergoing chronic hemodialysis. Therefore, measures improving body composition, such as nutrition and exercise, may have a favorable effect on the response to ESA.

Hypoxia‐inducible factor prolyl hydroxylase domain inhibitors may mitigate loss of skeletal muscle mass in haemodialysis patients

“…Recent studies have reported that ESA resistance is associated not only with higher risk of cardiovascular events and mortality but also with lower SMM in haemodialysis patients. [8][9][10]55,56 In addition, increased risk of mortality associated with ESA resistance has been shown to be related to higher doses of ESAs and known underlying causes of ESA resistance such as inadequate haemodialysis, nutritional deficiencies, chronic inflammation, and bone marrow disorders. [57][58][59] Iron deficiency is associated with lower SMM and function in community-dwelling individuals.…”

“…The majority of HIF‐PHI users in this study displayed hyporesponsiveness to ESAs, given that they needed the switches from ESAs to HIF‐PHIs when the dose of ESAs was at least 30 μg of darbepoetin equivalent per week. Recent studies have reported that ESA resistance is associated not only with higher risk of cardiovascular events and mortality but also with lower SMM in haemodialysis patients 8–10,55,56 . In addition, increased risk of mortality associated with ESA resistance has been shown to be related to higher doses of ESAs and known underlying causes of ESA resistance such as inadequate haemodialysis, nutritional deficiencies, chronic inflammation, and bone marrow disorders 57–59 .…”

“…7 Erythropoiesis-stimulating agents (ESAs) have been used as treatment of renal anaemia for over 30 years, but recently, several cross-sectional studies have reported that hyporesponsiveness or ESA resistance is associated with decreased SMM in patients receiving haemodialysis, suggesting a close relationship between renal anaemia and sarcopenia. [8][9][10] However, pathophysiological involvement of ESA resistance in sarcopenia is unclear.…”

“…Renal anaemia is one of the major CKD complications that develops due to relative erythropoietin (EPO) deficiency in relation to haemoglobin levels as the glomerular filtration rate (GFR) declines below 50 mL/min/1.73 m 2 7 . Erythropoiesis‐stimulating agents (ESAs) have been used as treatment of renal anaemia for over 30 years, but recently, several cross‐sectional studies have reported that hyporesponsiveness or ESA resistance is associated with decreased SMM in patients receiving haemodialysis, suggesting a close relationship between renal anaemia and sarcopenia 8–10 . However, pathophysiological involvement of ESA resistance in sarcopenia is unclear.…”

Comparison of Patient Survival According to Erythropoiesis-Stimulating Agent Type of Treatment in Maintenance Hemodialysis Patients

“…González-Ortiz et al showed a positive association between protein–energy wasting and ERI in HD patients [ 27 ]. Other studies have shown that the geriatric nutritional risk index, body composition, and sex are associated with ERI in HD patients [ 28 , 29 , 30 ]. Comorbidities have variable effects on the responsiveness of ESA, which are mediated through the inflammatory response and leads to increases in ERI [ 30 ].…”