Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients

Introduction: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. Methods: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. Results: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40–3.52) and 1.85 (95% CI 1.16–2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. Conclusions: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

[1]  L. Belo,et al.  Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis , 2021, Scientific Reports.

[2]  K. Hong,et al.  C-reactive protein-to-albumin ratio and 8‐year incidence of type 2 diabetes: the Korean genome and epidemiology study , 2021, Acta Diabetologica.

[3]  P. Ridker Inhibiting Interleukin-6 to Reduce Cardiovascular Event Rates: A Next Step for Atherothrombosis Treatment and Prevention. , 2021, Journal of the American College of Cardiology.

[4]  M. Yesin,et al.  Assessment of the relation between C-reactive protein to albumin ratio and the severity and complexity of peripheral arterial disease , 2020, Vascular.

[5]  Lei Jiang,et al.  Serum C-reactive protein to albumin ratio and mortality associated with peritoneal dialysis , 2020, Renal failure.

[6]  Wenjin Liu,et al.  Cardiovascular Disease in Chronic Kidney Disease , 2019, Chronic Kidney Disease.

[7]  P. Stenvinkel,et al.  Chronic inflammation in end-stage renal disease and dialysis , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  P. Libby,et al.  Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) , 2018, European heart journal.

[9]  P. Stenvinkel,et al.  Serum albumin, inflammation, and nutrition in end‐stage renal disease: C‐reactive protein is needed for optimal assessment , 2018, Seminars in dialysis.

[10]  P. Libby,et al.  All roads lead to IL-6: A central hub of cardiometabolic signaling. , 2018, International journal of cardiology.

[11]  P. Stenvinkel,et al.  The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease , 2018, PloS one.

[12]  Yifan Xiang,et al.  C-reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer. , 2017, Oncology letters.

[13]  S. Kaçar,et al.  Predictive value of C-reactive protein/albumin ratio in acute pancreatitis. , 2017, Hepatobiliary & pancreatic diseases international : HBPD INT.

[14]  Te-Chih Wong,et al.  Ratio of C-Reactive Protein to Albumin Predicts Muscle Mass in Adult Patients Undergoing Hemodialysis , 2016, PloS one.

[15]  P. Stenvinkel,et al.  Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. , 2016, Clinical journal of the American Society of Nephrology : CJASN.

[16]  Sang Hoon Han,et al.  The C-Reactive Protein/Albumin Ratio as an Independent Predictor of Mortality in Patients with Severe Sepsis or Septic Shock Treated with Early Goal-Directed Therapy , 2015, PloS one.

[17]  Patrick Royston,et al.  Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome , 2013, BMC Medical Research Methodology.

[18]  Carmine Zoccali,et al.  When do we need competing risks methods for survival analysis in nephrology? , 2013, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[19]  Peter Stenvinkel,et al.  Serum albumin as predictor of nutritional status in patients with ESRD. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[20]  N. Panizo,et al.  Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease , 2012, Renal failure.

[21]  Z. Massy,et al.  Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. , 2010, Kidney international.

[22]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[23]  C. Zoccali,et al.  Dissecting inflammation in ESRD: do cytokines and C-reactive protein have a complementary prognostic value for mortality in dialysis patients? , 2006, Journal of the American Society of Nephrology : JASN.

[24]  A. Garg,et al.  Chronic kidney disease and mortality risk: a systematic review. , 2006, Journal of the American Society of Nephrology : JASN.

[25]  G. Beck,et al.  C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. , 2005, Kidney international.

[26]  B. Psaty,et al.  Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. , 2005, JAMA.

[27]  C. Zoccali,et al.  Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD: searching for the best risk marker by multivariate modeling. , 2005, Journal of the American Society of Nephrology : JASN.

[28]  J. Manson,et al.  Kidney dysfunction, inflammation, and coronary events: a prospective study. , 2004, Journal of the American Society of Nephrology : JASN.

[29]  R. Foley,et al.  Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease. , 1996, Journal of the American Society of Nephrology : JASN.

[30]  E. Jones Disease , 2020, Palgrave Studies in Economic History.