title: Endogenous erythropoietin and the association with inflammation and mortality in diabetic chronic kidney disease.
abstract: OBJECTIVE
  Anemia and inflammation are prevalent in diabetic patients with chronic kidney disease (CKD). The role of endogenous erythropoietin (EPO) in the pathophysiology of anemia in chronic diseases and its relationship to clinical outcomes remain uncertain. In this cohort study, we aimed to identify factors associated with endogenous EPO levels and investigate their relation to all-cause mortality.
  
  
  METHODS
  Between 2004 and 2005, 215 patients with type 2 diabetes were enrolled. Exclusion criteria included stage renal disease ESRD and any form of anemia therapy. The association of EPO levels with clinical and laboratory variables was investigated by linear regression modeling. Predictors of all-cause mortality were evaluated by Cox proportional hazards analyses.
  
  
  RESULTS
  Patients (median age, 67 years; 52% men; median duration of diabetes, 10 years; median estimated GFR, 49 ml/min per 1.73 m²) were followed for up to 7.0 years. Forty-one patients died. Elevated EPO levels were independently associated with elevated C-reactive protein, low ferritin, and hypertension, in a multivariate model that also included age, cardiovascular disease, kidney function, albumin, cholesterol, and hemoglobin. Higher EPO levels were independently predictive for mortality, as were age, low levels of albumin, and cardiovascular disease.
  
  
  CONCLUSIONS
  In diabetic patients with CKD, elevated endogenous EPO levels were predictive for mortality and were related mainly to markers of inflammation, independent of kidney function, and despite low hemoglobin levels. Understanding the phenomenon of EPO resistance and iron dysregulation caused by inflammation is crucial for effective and safe treatment of anemia in patients with CKD.
authors: Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany. wagner_m@klinik.uni-wuerzburg.de
authors: Martin
authors: M
authors: Wagner
authors: Ahsan
authors: A
authors: Alam
authors: Josef
authors: J
authors: Zimmermann
authors: Katharina
authors: K
authors: Rauh
authors: Angelika
authors: A
authors: Koljaja-Batzner
authors: Ulrike
authors: U
authors: Raff
authors: Christoph
authors: C
authors: Wanner
authors: Lothar
authors: L
authors: Schramm
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000740:Anemia / Q000097:blood / Q000209:etiology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000401:mortality; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005858:Germany; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D004921:Erythropoietin; D002097:C-Reactive Protein