Original Article

Relationship between red blood cell distribution width and early-stage renal function damage in patients with essential hypertension Zhan-Zhan Li a, Lizhang Chen a, Hong Yuan b, Tao Zhou c, and Ze-Min Kuang d

Background: Red cell distribution (RDW) has been suggested to be associated with cardiovascular mortality and mortality. However, few studies have yet investigated the possible association between RDW and early-stage renal function damage in patients with primary hypertension without receiving drug treatment. Accordingly, the aim of the present study was to evaluate early-stage renal function status in patients with RDW levels. Results: The study included 513 primary hypertension patients (319 men and 194 women) without receiving drug treatment. Significant positive correlation was observed between albumin-to-creatinine ratio (ACR) and RDW in hypertensive patients (r ¼ 0.531, P < 0.001). In multivariate line regression analysis, night-time SBP (B ¼ 0.042, P < 0.001), ACR (B ¼ 0.005, P < 0.001), and uric acid (B ¼ 0.001, P ¼ 0.022) were positive predictors of RDW independent of age, sex, hemoglobin, and other indexes, whereas daytime SBP (B ¼ 0.019, P < 0.001) was inversely associated with RDW. The receiver operating characteristics curves (ROC) explored the relationship between renal function status and RDW, estimated glomerular filtration rate (eGFR), serum creatinine, and high-sensitivity C-reactive protein. The area under the curve was 0.81 (95% CI: 0.77–0.85; P < 0.001), 0.45 (95% CI: 0.39–0.50; P ¼ 0.049), 0.49 (95% CI: 0.43– 0.54; P ¼ 0.583), and 0.49 (95% CI: 0.44–0.55; P ¼ 0.811), respectively. Using a cutoff point of 12.8, the RDW predicted renal function status (ACR) with a sensitivity of 76% and a specificity of 70%. Conclusion: RDW, as an easy and quick measurable index, can predict early-stage renal function damage in essential hypertensive patients without receiving drug treatment. Keywords: hypertension, RDW, red blood cell distribution width, renal function damage Abbreviations: ACR, albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate; Hs-CRP, high-sensitivity C-reactive protein; RBC, red blood cell; RDW, red blood cell distribution width; ROC, receiver operating characteristics

INTRODUCTION

A

s a component of routine blood cell count, the red blood cell distribution (RDW), which is a measure of the variability in size of the erythrocytes in the circulation, not only is used to differentiate the types of anemia, but also has been suggested as an independent predictor of mortality in patients with heart failure [1], stroke [2], pulmonary arterial hypertension [3,4], and acute kidney injury [5]. However, it is still unclear whether erythrocytes might be the cause or a simple epiphenomenon of an underlying disease, such as inflammation, impaired renal function, and oxidative damage, or perhaps an element of both. The correlation between RDW and hypertension has been explored in a number of studies [6,7]. In this sense, RDW is elevated in prehypertension and hypertension patients when compared with normotensive individuals. The recent study also demonstrated that RDW is a useful marker in predicting inadequate reduction in nighttime BP in essential hypertension. RDW values are closely related with inflammation in nondipper hypertensive patients [8]. Hypertension is an important public health problem, which could cause subclinical organ damages [9–11]. According to the 2013 European Society of Hypertension and European Society of Cardiology guidelines [12], the presence of subclinical organ damage is a fundamental important factor in determining the estimated cardiovascular risk with proposed scale. The renal function damage is one of common subclinical organ damages caused by hypertension [13]. Renal dysfunction is associated with poor cardiovascular outcome. A recent study found that reduced estimated glomerular filtration rate (eGFR) is strongly and

Journal of Hypertension 2014, 32:2450–2456 a Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan Province, bDepartment of Cardiology, the Third Xiangya Hospital , Central South University, Changsha, cDepartment of Cardiology, the Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong Province and dDepartment of Hypertension, Beijing Anzhen Hospital of Capital Medical University, Bejing, PR China

Correspondence to Ze-min Kuang, PhD, Department of Hypertension, Beijing Anzhen Hospital of Capital Medical University, 10029, Beijing, PR China. Tel: +86 0731 8883 6996; fax: +86 0731 8883 6162; e-mail: [email protected] Received 23 April 2014 Revised 17 July 2014 Accepted 17 July 2014 J Hypertens 32:2450–2456 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0000000000000356

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Red blood cell distribution and renal function damage

independently associated with poor cardiovascular outcome, following high-risk myocardial infarction. In these patients, the combination of older age and poor left ventricular systolic function is associated with an increased risk of adverse events [14]. Hence, early identification of those patients is of importance, as renal function damage might be a risk factor of future adverse cardiovascular events, especially for hypertension patients. In clinical practice, many hematological and inflammatory biomarkers (mean platelet volume and high-sensitivity C-reactive protein) have been used to explore renal function in patients with hypertension. However, few studies have yet investigated possible association between RDW and early-stage renal function damage in patients with primary hypertension without receiving drug treatment. Accordingly, the aim of the present study was to evaluate early-stage renal function status in patients with RDW levels.

METHODS The present study was conducted at the Beijing Anzhen Hospital between November 2012 and October 2013. Patients registered with this hospital with first-ever hypertension during this period were considered potential candidates for inclusion in this study. The protocol of the present study was reviewed and approved by the local Ethics and Research Committee (CTXY-13004). The study population gave informed consent before physical examination and blood sampling.

The overall study population consisted of 513 hypertensive outpatients 35–64 years of age, who were admitted to the hospital for a health examination. Patients with complete, available medical records were selected according to the following inclusion and exclusion criteria; Hypertension was defined as SBP at least 140 mmHg or a DBP at least 90 mmHg and no use of antihypertensive drug therapy [15]. No patients with secondary hypertension, heart failure, diabetes mellitus, renal or hepatic dysfunction, clinical evidence of cancer, systemic inflammatory disease, hematological system disorder, and known coronary artery or cerebrovascular disease were included. Patients with secondary hypertension (by history, physical examination, current laboratory tests, or having resistant hypertension) were excluded. Most of the study group had been investigated for secondary causes of hypertension previously in our hospital or elsewhere. The selection process is shown in Fig. 1. The patients’ clinical and demographic characteristics encompassing age, sex and smoking habits were obtained by a standardized questionnaire. Hematologic testing was performed on the ADVIA 120 (Bayer Diagnostics, Newbury, Berkshire, UK) automated hematology analyzer, which measures hemoglobin photometrically, including white blood cell counts, platelet counts, hemoglobin, mean corpuscular volume and RDW, optical laser light scattering for cell enumeration, flow cytometer, and laser diffraction for red blood cell (RBC) counts. Serum creatinine (Scr) was measured on a Roche/Hitachi Modular System P (Roche

712 consecutive untreated hypertension screened8

42 patients who refused to participate in the study.8

670 patients for further screening8

113 patients with secondary or primary chronic progressive disease

557 patients for final selection.8

26 patients with diabetes mellitus, renal or hepatic dysfunction, 18 patients with inflammatory disease.8

513 eligible patients included in the study.8

FIGURE 1 Flow diagram of the patients’ selection process.

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Li et al.

Diagnostics GmbH, Mannheim, Germany) by creatinine Jaffe rate blanked and compensated assay. Serum uric acid, creatinine, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol concentrations were measured using standard enzymatic methods. Plasma renin activity, angiotensin II, and aldosterone were measured by specific radioimmunoassay. Ultrasensitive C-reactive protein (CRP) was measured by particle-enhanced immunoturbidimetric assay. Kidney function was estimated by glomerular filtration rate using the following equation: 186  SCr1.154  age in years0.203  1.210 (if black)  0.742 (if women) [16]; for this study, early-stage renal function damage was defined as ACR greater than 30 mg/g because the eGFR from the study population was more than 60 ml/min per 1.73 m2. In addition, fasting blood glucose level, creatinine level, and fasting serum lipid status, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels, were also recorded. BMI was calculated as weight (kg) divided by height squared (m2). LVMI ¼ LVM/BSA (body surface area, BSA).

Statistical analysis Continuous variables are reported as mean  SD or median. Categorical variables are reported as frequencies and percentage. RDW was examined as a continuous variable and also categorized into quartiles using the following cutoffs: less than 12.2%, 12.2–12.7%, 12.7–13.2% and greater than 13.2%. The x2 test or one-way ANOVA was used for

continuous factors between different categories of RDW. Multivariate linear regression was used to determine the factors that were associated with baseline RDW. The receiver operating characteristics (ROC) curves explored the relationship between early-stage renal function damage and RDW. Statistical analysis was performed using SPSS version 17.0 (SPSS Inc, Chicago, Illinois, USA), and the level of statistical significance was defined as P less than 0.05.

RESULTS Baseline characteristics of the study population are provided in Table 1. Cumulative results of RDW, estimated GFR, hemoglobin, serum creatinine, and ACR were retrieved for 513 (319 men and 194 women) outpatients greater than 35 years old. In the entire participants, mean values for RDW, age, eGFR, hemoglobin, serum creatinine, and ACR were 12.7  0.8% (range 11.0–18.0%), 46.8  7.8 (range 35–64 years old), 105.0  24.6 (range 61.6–268.0), 150.0  15.9 (range 85.0–195.0), 70.0  13.0 (range 42.0– 97.0), and 37.8  45.2 (range 0.0–295.7), respectively. Overall, no one had chronic kidney disease (estimated GFR

Relationship between red blood cell distribution width and early-stage renal function damage in patients with essential hypertension.

Red cell distribution (RDW) has been suggested to be associated with cardiovascular mortality and mortality. However, few studies have yet investigate...
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