Association between red cell distribution width and mortality in patients undergoing continuous ambulatory peritoneal dialysis

www.nature.com/scientificreports OPEN received: 15 August 2016 accepted: 02 March 2017 Published: 03 April 2017 Association between red cell distribution width and mortality in patients undergoing continuous ambulatory peritoneal dialysis Yao-Peng Hsieh1,2,3,4, Shr-Mei Tsai5, Chia-Chu Chang1,4, Chew-Teng Kor1 & Chi-Chen Lin6 Although red cell distribution width (RDW) has emerged as a biomarker of clinical prognostic value across a variety of clinical settings in the last two decades, limited evidence is available for its role in end-stage renal disease. We enrolled 313 incident patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in this retrospective observational study from 2006 to 2015. In the fully adjusted model of Cox regression analysis, the adjusted hazard ratios for the high RDW group versus the low RDW group were 2.58 (95% confidence interval (CI) = 1.31–5.09, p = 0.006) and 3.48 (95% CI = 1.44–8.34, p = 0.006) for all-cause and cardiovascular disease (CVD)-related mortality, respectively. Based on area under the receiver operating characteristic curve (AUC) analysis, RDW (AUC = 0.699) had a stronger predictive value for all-cause and CVD-related mortality than other biological markers including hemoglobin (AUC = 0.51), ferritin (AUC = 0.584), iron saturation (AUC = 0.535), albumin (AUC = 0.683) and white blood cell count (AUC = 0.588). Given that RDW is a readily available hematological parameter without the need for additional cost, we suggest that it can be used as a valuable index to stratify the risk of mortality beyond a diagnosis of anemia. The health burden of chronic kidney disease (CKD) is increasing globally, especially for those with advanced CKD. Peritoneal dialysis (PD) is one of the accepted renal replacement therapies for patients reaching end-stage renal disease (ESRD). A total of 27,522 ESRD patients were treated with PD in 2009 according to the 2011 US Renal Data System report1. Despite an increased understanding of pathophysiological processes in patients undergoing PD and subsequent improvements in management strategies, the mortality rate associated with PD is still high. The leading cause of mortality is cardiovascular disease (CVD), accounting for 40–50% of all deaths2. Anemia is prevalent in CKD patients, mainly because of decreased erythropoietin production by dysfunctional kidneys, and this has also been associated with CVD-related mortality in patients undergoing PD3. Red cell distribution width (RDW), an index of quantitative measurements of erythrocyte volume variability, is routinely reported as part of a complete blood cell count (CBC). It is calculated by dividing the standard deviation of the mean corpuscular volume (MCV) by the MCV of erythrocytes. Traditionally, RDW is used along with MCV for the differential diagnosis of anemia, especially in iron deficiency anemia4. However, it has also emerged as a biomarker of clinical prognostic value across a variety of clinical settings in the last two decades5–9. An elevated RDW level, even in the reference range, has also been associated with an increased risk of mortality10–12. The exact mechanism explaining the association between RDW and mortality is unknown. In CKD patients, RDW has been reported to be closely associated with renal function status13. However, limited evidence is available for the predictive role of RDW in the risk of mortality in patients with CKD, particularly those treated with PD. Therefore, the aim of this retrospective investigation was to investigate the association between RDW and the risk of both all-cause and CVD-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) between 2006 and 2015 in a medical center in Taiwan. 1 Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. 2Ph.D. program in translational medicine, College of Life Science, National Chung Hsing University, Taichung, Taiwan. 3 School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 5Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan. 6Institute of Biomedical Sciences, College of Life Science, National Chung Hsing University, Taichung, Taiwan. Correspondence and requests for materials should be addressed to Y.-P.H. (email: ) Scientific Reports | 7:45632 | DOI: 10.1038/srep45632 1 www.nature.com/scientificreports/ Results Patient characteristics. The study cohort included 313 patients undergoing CAPD from 2006 to 2015. The baseline characteristics of these patients stratified by median RDW value (15.3%) are shown in Table 1. The mean age was 54.5 ± 15.9 years, and 164 (52.4%) were male. The three leading causes of ESRD were chronic glomerulonephritis (34.1%), diabetes mellitus (28.1%) and hypertension (17.8%). Most of the patients (248, 79.2%) had pre-dialysis CKD before initiating PD. At baseline, the patients in the higher RDW group (>15.3%) were older, had lower urine output and lower residual renal function. With regards to laboratory examinations, the patients in the high RDW group had lower levels of albumin, calcium, hemoglobin, and cholesterol, and higher levels of alkaline phosphate, ferritin and blood urea nitrogen (BUN) compared to the lower RDW group (≦15.3%). With regards to pharmacotherapy, more patients in the low RDW group used iron preparations. Association of RDW with all-cause and CVD-related mortality. During the study period, 27 patients (17.4%) died in the low RDW group and 64 patients (40.5%) died in the high RDW group (p < 0.001). Of these 91 patients, 48 died of CV events, which was the leading cause of mortality. There was also a significant difference in CVD-related mortality rate between the two groups, with 14 patients (9%) in the low RDW group and 34 (21.5%) in the high RDW group (p = 0.003). Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality rates compared to the low RDW group (Figs 1 and 2; p <  0.001, p < 0.001, respectively). In the unadjusted and adjusted Cox proportional regression models, the high RDW group was associated with an increased risk of all-cause and CVD-related mortality compared with the low RDW group (Table 2). In the fully adjusted model (model 5), the adjusted HRs for the high RDW group versus the low RDW group were 2.58 (95% CI =  1.31–5.09, p = 0.006) and 3.48 (95% CI =  1.44–8.34, p = 0.006) for all-cause and CVD-related mortality, respectively. Subgroup analyses showed that the patients with higher RDW levels had higher rates of all-cause and CVD-related mortality in the adjusted models compared to those with lower RDW levels (Figs 3 and 4). Sensitivity analysis. Three levels of sensitivity testing were performed as shown in Table 2. In the fully adjusted model, a higher RDW level was associated with a higher risk of overall and CVD-related mortality in all of the thre (...truncated)