High Erythropoiesis Resistance Index Is a Significant Predictor of Cardiovascular and All-Cause Mortality in Chinese Maintenance Hemodialysis Patients

Abstract

Background. Renal anemia is a common complication of hemodialysis patients. Erythropoietin (EPO) hyporesponsiveness has been recognized as an important factor to poor efficacy of recombinant human erythropoietin in the treatment of renal anemia. More importantly, increased erythropoiesis resistance index (ERI) may be associated with inflammation and increased mortality. Objective. The objective of this research was to investigate correlated factors of EPO responsiveness and to clarify the relationships between EPO hyporesponsiveness and cardiovascular mortality and all-cause mortality among maintenance hemodialysis patients. Methods. This prospective cohort study enrolled 276 maintenance hemodialysis patients for a 55-month follow-up to investigate the factors related to ERI and its relationship to all-cause mortality and cardiovascular mortality. Results. ERI was positively correlated with predialysis serum high-sensitivity C-reactive protein ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>r</a:mi> <a:mo>=</a:mo> <a:mn>0.234</a:mn> </a:math> , <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>p</c:mi> <c:mo>&lt;</c:mo> <c:mn>0.001</c:mn> </c:math> ), alkaline phosphatase ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>r</e:mi> <e:mo>=</e:mo> <e:mn>0.134</e:mn> </e:math> , <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo>=</g:mo> <g:mn>0.028</g:mn> </g:math> ), and ferritin ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>r</i:mi> <i:mo>=</i:mo> <i:mn>0.155</i:mn> </i:math> , <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>p</k:mi> <k:mo>=</k:mo> <k:mn>0.010</k:mn> </k:math> ) and negatively correlated with albumin ( <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>r</m:mi> <m:mo>=</m:mo> <m:mo>−</m:mo> <m:mn>0.206</m:mn> </m:math> , <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>p</o:mi> <o:mo>&lt;</o:mo> <o:mn>0.001</o:mn> </o:math> ) and creatinine ( <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>r</q:mi> <q:mo>=</q:mo> <q:mo>−</q:mo> <q:mn>0.232</q:mn> </q:math> , <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>p</s:mi> <s:mo>&lt;</s:mo> <s:mn>0.001</s:mn> </s:math> ). As multiple linear regression showed, predialysis serum albumin, high-sensitivity C-reactive protein, ferritin, and creatinine were independent correlated factors of ERI ( <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>p</u:mi> <u:mo>&lt;</u:mo> <u:mn>0.05</u:mn> </u:math> ). Kaplan–Meier curves showed that the cumulative incidences of both cardiovascular mortality and all-cause mortality were significantly higher in patients with <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mtext>ERI</w:mtext> <w:mo>&gt;</w:mo> <w:mn>11.04</w:mn> <w:mtext> </w:mtext> <w:mtext>IU</w:mtext> <w:mo>/</w:mo> <w:mtext>kg</w:mtext> <w:mo>/</w:mo> <w:mtext>w</w:mtext> <w:mo>/</w:mo> <w:mtext>g</w:mtext> <w:mo>/</w:mo> <w:mtext>dL</w:mtext> </w:math> (both <y:math xmlns:y="http://www.w3.org/1998/Math/MathML" id="M13"> <y:mi>p</y:mi> <y:mo>&lt;</y:mo> <y:mn>0.01</y:mn> </y:math> ). The high ERI group was significantly associated with higher risk for all-cause mortality (OR 1.781, 95% CI 1.091 to 2.910, <ab:math xmlns:ab="http://www.w3.org/1998/Math/MathML" id="M14"> <ab:mi>p</ab:mi> <ab:mo>=</ab:mo> <ab:mn>0.021</ab:mn> </ab:math> ) and cardiovascular mortality (OR 1.972, 95% CI 1.139 to 3.417, <cb:math xmlns:cb="http://www.w3.org/1998/Math/MathML" id="M15"> <cb:mi>p</cb:mi> <cb:mo>=</cb:mo> <cb:mn>0.015</cb:mn> </cb:math> ) after adjusting for confounders. Conclusions. Predialysis serum albumin, high-sensitivity C-reactive protein, ferritin, and creatinine were independent correlated factors of EPO responsiveness among maintenance hemodialysis patients. Patients with higher ERI values had a higher all-cause mortality rate and cardiovascular mortality rate.