Contemporary management of anaemia, erythropoietin resistance and cardiovascular risk in patients with advanced chronic kidney disease: a nationwide analysis

Background. Optimal management of chronic kidney disease (CKD) anaemia remains controversial and few studies have evaluated real-world management of anaemia in advanced CKD in the context of guideline recommendations. Methods. We performed an observational study from the Swedish Renal Registry evaluating the epidemiology and treatment patterns of anaemia across Stages 3b-5 in non-dialysis (ND) and dialysis-dependent (DD) CKD patients during 2015. Logistic regression and Cox models explored the associations between anaemia treatments, inflammation, erythropoietin resistance index (ERI) and subsequent 1-year risk of major adverse cardiovascular events (MACEs). Results. Data from 14 415 (ND, 11 370; DD, 3045) patients were included. Anaemia occurred in 60% of ND and 93% of DD patients. DD patients used more erythropoiesis-stimulating agents (ESAs; 82% versus 24%) and iron (62% versus 21%) than ND patients. All weekly ESA doses were converted to a weight-adjusted weekly epoetin equivalent dose. The prescribed ESA doses were low to moderate [median 48.2 IU/kg/week (ND), 78.6 IU/kg/week (DD)]. Among ESA-treated patients, 6-21% had haemoglobin (Hb) >13 g/dL and 2-6% had Hb <9 g/dL. Inflammation (C-reactive protein >5 mg/L) was highly prevalent and associated with ERI and higher ESA doses. Higher (>88 IU/kg/week) versus lower (<44 IU/kg/week) ESA doses were associated with a higher risk of MACEs [{ND hazard ratio [HR] 1.36 [95% confidence interval (CI) 1.00-1.86]; DD HR 1.60 [95% CI 1.24-2.06]}. There was no association between iron use and inflammation or MACEs. Conclusions. Anaemia remains highly prevalent in advanced CKD. Patients with anaemia received moderate ESA doses with a relatively low prevalence of iron use. Higher doses of ESA were associated with inflammation and a higher risk of MACE.