Red blood cell distribution width (RDW) is an index measurement of erythrocyte volume variability and is routinely reported as a part of a complete blood cell count [1], [2]. Elevated RDW reflects increased size variations of red blood cells, which indicates altered erythrocyte life span or dysfunctional erythrocytes. For a long time, RDW has been regarded as a useful index to differentiate the etiology of anemia, such as thalassemia and megaloblastic anemia, as well as iron deficiency–related anemia [3].

In recent years, it was observed that high RDW levels were associated with an increased risk of adverse outcomes in the general population [4], severe sepsis [5], heart failure [6], coronary artery disease [7], stroke [8], acute kidney injury that required renal replacement therapy [9], and kidney transplant recipients [10]. In addition, it was reported that high RDW is associated with early failure of arteriovenous fistula for hemodialysis access [11]. The exact mechanisms causing elevated RDW in these diverse conditions are unknown; however, it is assumed to be related to inflammatory processes that might interfere with the process of erythropoiesis [12]. A few authors reported that increased RDW is a predictor of mortality in end-stage renal disease (ESRD) patients [13], [14].

However, there are only a few studies that have investigated the association between RDW and adverse outcomes in patients on peritoneal dialysis. Therefore, we investigated the association between increased RDW and all-cause mortality in patients on peritoneal dialysis (PD).

RDW, routinely reported as part of a complete blood cell count, is a simple laboratory test that is used to evaluate variability in the size and form of red blood cells [1], [2]. Several studies have recently shown that elevated RDW is a predictor of morbidity and mortality in CV diseases, such as acute and chronic congestive heart failure, acute myocardial infarction, pulmonary hypertension, peripheral artery disease, and stroke [6], [7], [8], [15]. In addition, high RDW has emerged as a risk factor in clinical nephrology, including hemodialysis patients and patients with acute kidney injuries that require continuous renal replacement therapy. Yoon et al [13] reported that a progressive rise in RDW predicts mortality and CV events in ESRD. In our study, the RDW value was also higher in nonsurvivors than in survivors, and it was an independent risk predictor for all-cause mortality.

The US Renal Data System (USRDS) and ANZDATA Registry reported that the most common cause of death is cardiovascular disease, in which infectious disease was the second leading cause [16], [17], [18]. However, Choi et al [19] reported that infection was the most common cause of death in Korean patients on PD. Of the 14 patients that died during this study period, 10 of them were attributable to infectious diseases, such as sepsis. It has also been reported that RDW is associated with inflammatory and infectious conditions. Ku et al [20] and Braun et al [21] reported that RDW is an independent predictor of mortality among patients with gram-negative bacteremia and community-acquired pneumonia. The 2 primary causes of death in PD patients in this study were infection and CV disease, and we believe that RDW could be an additive predictor for all-cause mortality in patients on PD.

Previous literature has reported that RDW is a predictor of CV mortality in various populations [22]. However, only a few reports have discussed the relevance of RDW and CV mortality and morbidity in ESRD patients [7], [8]. Recently, Yoon et al [13] reported that a progressive rise in RDW predicts mortality and CV events in ESRD patients. Peng et al [23] also reported that a high baseline RDW value was associated with CV mortality in incidental PD patients. However, high RDW was not associated with CV mortality in our study. We believe that this finding might be due to different causes of death such as infection in our study. In addition, although patients with high RDW levels showed significantly more frequent nonfatal CV events than patients with low RDW levels, the RDW was not a significant predictor in the present study. Therefore, to clarify the association between RDW and CV mortality, large prospective controlled studies are needed.

Although the mechanism underlying the association between higher RDW and adverse outcomes in PD patients is not completely understood, several mechanisms can be postulated. First, increasing RDW may indicate impaired iron metabolism and is assumed to be related to inflammation which might interfere with the process of erythropoiesis [12], [24]. Impaired iron metabolism is reported to be associated with heart failure [25]. In the present study, TIBC was higher in the high-RDW group than in the low-RDW group and was the independent risk predictor for all-cause mortality. In addition, inflammatory response plays a critical role in the development and progression of heart failure [26], [27] and inhibits erythrocyte maturation and accelerates the migration of reticulocytes into the peripheral circulation, thereby increasing RDW [28]. Therefore, RDW may bridge the relationship between inflammation and poorer heart failure prognosis. In this study, C-reactive protein, which is regarded as an inflammatory marker, was also higher in the high-RDW group than in the low-RDW group. We think that such findings might contribute to the lower event-free survival rate for nonfatal CV events and all-cause mortality in the high-RDW group.

Second, a mechanism that could be involved in such a process is the release of cytokines in response to inflammatory stress. These cytokines might block the activity of erythropoietin, inhibit erythrocyte maturation, and cause production of ineffective red blood cells and elevated RDW [12]. The expansion of proinflammatory cytokines may increase susceptibility to infections [29]. In addition, Duranay et al [30] reported that oxidative stress seems to increase peritonitis in continuous ambulatory peritoneal dialysis patients. In our study, no patients expired because of PD-associated peritonitis; however, infection was an important cause of death. Four patients of 10 who expired because of infection experienced sepsis because of pneumonia within 6 months after starting PD.

Our study has some limitations. First, this is a retrospective study and the study population comprised only Asian people. Second, despite a single measurement of RDW levels that could have reflected acute changes in RDW induced by blood loss or hemolysis, we did not evaluate fluctuations in RDW levels and thus could not account for possible variation over time.

In our study, RDW, albumin, and total leukocyte counts when patients started PD were associated with the incidence of mortality. RDW is a widely available and inexpensive test performed as part of the complete blood cell count. Therefore, measuring the RDW at initiation of PD is helpful for predicting all-cause mortality in patients on PD.

All authors have no conflicts of interest to declare.