Anemia as a risk factor for all-cause mortality: obscure synergic effect of chronic kidney disease

BackgroundAnemia is common in chronic kidney disease (CKD) and may be associated with mortality in CKD patients. However, few studies have examined this relationship in Asian populations.MethodsA total of 62,931 Japanese people (age 64.0 ± 8.0 years; men 38.5%) were followed up from 2008 to 2012. Participants were divided into six groups in accordance with their estimated glomerular filtration rate (eGFR) (<45, 45–59, ≥60 mL/min/1.73 m2) and by hemoglobin levels (13.0 g/dL for men; 12.0 g/dL for women). Hazard ratio and confidence interval (CI) for mortality with a combination of eGFR and anemia were calculated. After matching using propensity score (PS) for anemia, survival analysis between anemic and non-anemic people, independent from some variables, including eGFR, was performed.ResultsA total of 828 (1.3%) participants died (non-anemic vs. anemic, 1.2 vs. 2.3%, p < 0.01). Multivariable Cox analysis showed that, independent of eGFR levels, anemic people had significantly higher mortality. Anemic people were found to have significantly poorer survival than non-anemic people as per a log-rank test (p < 0.01) for the PS-matching cohort. Further stratified logistic analysis using PS in the overall cohort odds ratio (95% CI) showed 2.25 (1.89–2.67) with p < 0.01.ConclusionThe results of the present study showed that anemia was an independent risk factor of all-cause mortality.

[1]  J. Pascual,et al.  Regression of left ventricular hypertrophy after partial correction of anemia with erythropoietin in patients on hemodialysis: a prospective study. , 1991, Clinical nephrology.

[2]  V. Vaccarino,et al.  Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. , 2003, Kidney international.

[3]  J. Griffith,et al.  Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease. , 2005, Journal of the American Society of Nephrology : JASN.

[4]  V. Prasad.  Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease , 2007 .

[5]  Yasuo Ohashi,et al.  U-shaped association between body mass index and proteinuria in a large Japanese general population sample , 2014, Clinical and Experimental Nephrology.

[6]  Hirokazu Honda,et al.  Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. , 2006, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  E. Movilli,et al.  Reversal of left ventricular hypertrophy following recombinant human erythropoietin treatment of anaemic dialysed uraemic patients. , 1991, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  H. Cohen,et al.  Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. , 1999, The American journal of medicine.

[9]  K. Iseki,et al.  Mortality risk among screened subjects of the specific health check and guidance program in Japan 2008–2012 , 2017, Clinical and Experimental Nephrology.

[10]  Yasuhiko Tomino,et al.  Revised equations for estimated GFR from serum creatinine in Japan. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[11]  Y. Ohashi,et al.  Cardiovascular events and death in Japanese patients with chronic kidney disease. , 2017, Kidney international.

[12]  Y. Yano,et al.  Glycohemoglobin not as predictive as fasting glucose as a measure of prediabetes in predicting proteinuria. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[13]  M. Rothstein,et al.  Effect of recombinant human erythropoietin on endothelial cell apoptosis. , 1999, Kidney international.

[14]  T. Ohkubo,et al.  Impact of metabolic syndrome on the risk of cardiovascular disease mortality in the United States and in Japan. , 2014, The American journal of cardiology.

[15]  A. Go,et al.  Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL. , 2005, Kidney international.

[16]  M. Correia,et al.  The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. , 2003, Clinical nutrition.

[17]  A. Sniderman,et al.  Regression of left ventricular hypertrophy in dialysis patients following correction of anemia with recombinant human erythropoietin. , 1990, The Canadian journal of cardiology.

[18]  Y. Ohashi,et al.  Significance of estimated glomerular filtration rate in predicting brain or heart attacks in obese and non-obese populations , 2015, Clinical and Experimental Nephrology.

[19]  H. Burger,et al.  Normalization of hemoglobin level in patients with chronic kidney disease and anemia. , 2006, The New England journal of medicine.

[20]  N. Powe,et al.  Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. , 2004, JAMA.

[21]  E. Beutner,et al.  Report of a WHO Scientific Group (Part 3 of 3) , 1973 .

[22]  D. Fliser,et al.  Erythropoietin regulates endothelial progenitor cells. , 2004, Blood.

[23]  P. van der Harst,et al.  Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. , 2007, European heart journal.

[24]  G. Rossi,et al.  Diagnosis and Classification of Diabetes Mellitus The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classification of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diabetes Care 26:3160–3167, 2003). , 2008, Diabetes Care.

[25]  W. Weintraub,et al.  Association of high serum creatinine and anemia increases the risk of coronary events: results from the prospective community-based atherosclerosis risk in communities (ARIC) study. , 2003, Journal of the American Society of Nephrology : JASN.