Does decreased mean platelet volume predict inflammation in chronic renal failure, dialysis, and transplanted patients?

Abstract

Objectives: Increased platelet activation contributes to cardiovascular mortality in chronic kidney disease patients (CKD). Larger platelets are more active and this increased activity had been suggested as a predictive biomarker for cardiovascular disease. In this study, we aimed to evaluate mean platelet volume (MPV) as an inflammatory marker in a broadened group of CKD patients. Our study is unique in literature as it covers all types of CKD including renal replacement therapies. Materials and methods: 200 patients (50 renal transplanted, 50 hemodialysis, 50 peritoneal dialysis, 50 chronic renal failure stages 3–4) were investigated who were between 18 and 76 years of age. The collected data included demographic properties, platelet count, MPV, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and hemoglobin. All of the patients had at least 12 month of therapy of either renal replacement modality. Results: The mean CRP value was detected statistically significantly higher in hemodialysis (HD) patients compared to the resting three groups of patients (p < 0.01). Mean CRP level was detected significantly higher in the pre-dialysis group compared to transplanted and peritoneal dialysis (PD) patients (p < 0.01). There is no statistically significant difference detected among the mean MPV values of all patient groups (p > 0.05). Conclusions: ESR and CRP were significantly increased in hemodialysis patients compared to the other groups. We did not detect a significant difference among MPV between the groups. ESR was detected lowest in transplanted patients. Transplantation is coming forward as the favorable choice of renal replacement therapy which decreases inflammation.

• Chronic kidney disease
• dialysis
• inflammation
• mean platelet volume
• renal transplantation

Introduction

Chronic Renal Failure (CRF) is related to high cardiovascular mortality and morbidity. Nearly half of the mortality of hemodialysis patients is related to cardiovascular diseases.1 The extracorporeal circuit is blamed for increased platelet activation in chronic renal failure patients treated with hemodialysis. Increased platelet activation contributes to cardiovascular mortality in the case of chronic kidney disease patients treated with hemodialysis. Thrombocyte has a pivotal role in atherothrombosis and it was at the center of the arterial occlusion.2,3 Mean Platelet Volume (MPV), which can be easily evaluated by hematological analyzers, is a convenient marker of platelet functions and activation. Larger platelets are metabolically and enzymatically more active and this increased activity had been suggested as a predictive biomarker for cardiovascular disease in a recent meta-analysis.4 There are also conflicting studies that conclude there is no relation with MPV and the severity of coronary artery disease.5 As many of the studies that investigate MPV, cardiovascular disease, renal failure, and platelet activation were retrospective, the results were conflicting and controversial. In this study, we aimed to evaluate MPV in a broadened group of Chronic Kidney Disease (CKD) patients that include hemodialysis, peritoneal dialysis, stage 3–4 chronic kidney disease, and transplanted patients. Our study is unique in literature as it covers all type of renal replacement therapies.

Materials and methods

In this study, we investigated 200 CKD patients between 18 and 76 years of age who visited Atatürk University Medical Faculty outpatient clinic of the Nephrology department. All of the patients were Caucasians. The study protocol was approved by the local ethics committee. Patients were grouped as 50 hemodialysis patients, 50 peritoneal dialysis patients, 50 CKD stage 3–4 patients, and 50 renal transplanted patients. Data were collected from the patient records. The collected data included demographic properties, platelet count, MPV, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and body mass indexes. The patient groups were matched in age and sex. All of the patients had at least 12 month of either therapy of renal replacement modality. Chronic renal failure stage 3–4 patients were also selected from the patients whose estimated Glomerular Filtration Rate (GFR) between 15 and 60 mL/minute per 1.73 m² for at least 12 months on two different measurements. GFR was calculated according to Modification of Diet in Renal Disease (MDRD) Study equation in stage 3–4 patients of the study group. MPV was calculated as fentoliter from whole blood samples that were drawn in 2 mL EDTA tubes from forearm vein in the morning during fasting, and complete blood counts were obtained within 30 minutes by Beckman Coulter LH 750 Analyzer (Brea, CA).

Patients with active documented infection in any site of the body, any hormone replacement (sex steroids, thyroid hormone, or corticosteroid), documented coronary artery disease or thromboembolic accident, cancer, and autoimmune disorders were all excluded from the study. Patients who had medicated anticoagulant or anti-aggregate agents were also excluded from the study. Patients who had anemia were all normochromic, normocytic anemia associated with renal failure; patients with other causes of anemia were excluded from the study.

Statistical analysis

SPSS for Windows 18.0 (SPSS Inc., Chicago, IL) was used in analyzing the data. Parametric tests were applied to data with normal distribution, whereas nonparametric tests were applied to data with non-normal distribution. Chi-square tests were applied for categorical variables. One-way ANOVA test and Kruskal–Wallis One-Way Analysis of Variance on Ranks Test were applied to determine the difference between the four independent groups. In addition, Tukey HSD and Dunn’s Post Hoc Tests were applied to check the differences. The relationships among the variables were evaluated using Pearson and Spearman’s rho correlation analysis. Results were expressed as mean ± SD and median (interquartile range), and p value <0.05 was considered statistically significant.

Results

Patient characteristics, mean MPV, and CRP of the patient groups are presented in Table 1. Each patient group was composed of 50 patients of transplanted, chronic renal disease stage 3–4, hemodialysis, or peritoneal dialysis patients. The mean age of the patients was 47.04 ± 15.3. The calculated mean GFR of CKD patients were 35.42 ± 15.46 mL/min. The mean age of transplanted patient group was statistically significantly lower (36.4 ± 11.9, p < 0.000) than the other groups, as expected. There is no statistically significant difference resting three patient groups (CKD, HD, PD) among the mean patient age (accordingly, 52.98 ± 12.25, 49.88 ± 13.2, 48.8 ± 17.99, p > 0.05). The calculated body mass indexes of transplanted, CKD, HD, and PD groups were 25.07 ± 4.20, 27.74 ± 5.73, 23.01 ± 3.86, 22.56 ± 5.10 kg/m² in orderly. There is no statistically significant difference between the each groups among white blood cell count, MPV, monocyte percent (p > 0.05).

Table 1. Characteristics of chronic kidney disease, dialysis, and renal transplanted patients.

Parameter	CKD	HD	PD	RTx
Patient (n)	50	50	50	50
Sex ratio (F/M)	1 (25/25)	0.92 (24/26)	1.3 (28/22)	1 (25/25)
Average age	52.9 (18–72)	49.8 (22–75)	48.8 (37–76)	36.4 (18–61)
Mean CRP (mg/dL)	7.62 ± 8.63	14.09 ± 17.2*	4.31 ± 3.22	5.99 ± 6.88
Mean ESR (mm/h)	42.71 ± 27.60	45.26 ± 29.03	39.92 ± 28.24	25.95 ± 21.51**
Mean PLT (×10^3/mL)	243.5 ± 81.9	220.5 ± 88.1	259.5 ± 79.04	243.9 ± 58.7
Mean MPV (fL)	7.98 ± 1.05	7.92 ± 1.19	7.76 ± 1.18	7.98 ± 0.94
Hb (g/dL)	12.7 ± 2.02	11.6 ± 1.94	10.8 ± 2.18	13.2 ± 2.23*
Ferritin (mg/dL)	216.29 ± 196.1	650.04 ± 557.7*	318.98 ± 342.4	257.2 ± 234.7

Notes: F: Female, M: Male, CRP: C-reactive protein, PLT: Platelet count, MPV: Mean platelet volume, BMI: Body mass index, Hb: Hemoglobin, CKD: patient with chronic renal failure stage 3–4, PD: Peritoneal dialysis patients, RTx: Renal transplanted patients. Statistically significant differences among the groups were marked with p values for each parameter. *, p < 0.001, **, p < 0.01.

The mean CRP value was detected statistically significantly higher in hemodialysis (HD) patients compared to each of the three groups including transplanted, CKD and peritoneal dialysis patients (Mean CRP values accordingly 14.09 ± 17.2, 5.99 ± 6.88, 7.62 ± 8.63, 4.31 ± 3.22 mg/dl, p < 0.000, p = 0.005, p < 0.000). There was no significant difference between the transplanted and PD patient groups among mean CRP value (p > 0.05).

The ESR was detected statistically significantly lower in transplanted patients compared to HD, CKD, and PD patients (in orderly 25.95 ± 21.51, 45.26 ± 29.03, 42.71 ± 27.60, 39.92 ± 28.24 mm/h) (p = 0.01, p = 0.002, p = 0.002, respectively). According to ESR, there is no statistically significant difference between HD, PD, and CKD patients (p > 0.05). The hemoglobin level of the transplanted patient group was statistically significantly higher than HD and PD patients (p = 0.000, p = 0.000, respectively). There is no significant difference in hemoglobin concentration between transplanted and CKD patients (p = 0.248). Peritoneal dialysis patients had a statistically significantly lower hemoglobin level 10.82 ± 2.18 than the other three patient groups (p = 0.000, p = 0.000, p = 0.048, respectively).

The serum ferritin levels of all patient groups were detected higher than normal laboratory reference values. Serum ferritin level of HD patient group was significantly higher than transplanted, CKD, and PD patient groups (p < 0.000, p < 0.000, p < 0.000, respectively). There is no statistically significant difference in serum ferritin between the transplanted patient group, PD and CKD patient groups (p = 0.59, p = 0.47, p = 0.17, respectively).

Discussion

MPV is an automatically calculated number according to the average size of the platelets in automated blood count systems and it is affected by numerous situations including genetic factors, inflammation, atherosclerosis, anemia, medication, hormone replacement, and even in acute appendicitis.6–8 There are numerous studies that investigate MPV and various inflammatory clinical states. Levin and Bessman9 investigated correlation of MPV in hematological malignancies and they concluded that MPV does not correlate with platelet age and activation in hematological malignancies. Suvak and colleagues10 investigated MPV in cirrhotic patients and detected that MPV was significantly decreased in patients with ascitic fluid infection of cirrhotic patients. They conclude that MPV is a useful indicator for systemic infection in this patient group. Beata and colleagues investigated MPV in an autoimmune disorder named colitis ulcerosa and reported that there is a negative correlation between MPV and active inflammation.11 Conversely, Arevalo-Lorido and colleagues reported that there is a significant correlation with MPV and atherothrombotic carotid artery disease, and an increase in MPV can be used as an activity marker.12 In our study, we primarily aimed to detect presence of any difference in MPV between renal replacement groups and CKD stage 3–4 patients. We secondarily aimed to define the possible relation of MPV and inflammation in the same groups of the patients.

Chronic renal failure is a prothrombogenic state and it is related to high cardiovascular morbidity and mortality, actually cardiovascular disease is the leading cause of mortality in CRF patients.13 Thromboembolic accidents are increased in renal failure state. Increased cardiovascular risk and thromboembolic accident rate are present in all stages of chronic renal failure including the patients treated with renal replacement therapies. Cardiovascular morbidity and mortality further increase in hemodialysis patients.14 Patients with known active cardiovascular disease were excluded from this study because it was speculated that active cardiovascular disease, inflammation, and hormone replacement therapies affect the thrombocyte activation and as a result of this activation it became more spherical and MPV increases.3,11

Increased platelet activation in HD patients is related to many instances in various clinical land laboratory studies. Presence of arteriovenous fistula, venipuncture, extracorporeal blood circuit, and increased platelet activation due to dialysate concentration were all assumed to have increased thrombogenicity and cardiovascular mortality. CRP is a well-documented laboratory marker used to detect the inflammatory state of the patient. It was correlated with cardiovascular mortality and morbidity.15,16 In our study, we detected that CRP was statistically significantly higher in HD patients compared to CKD, PD, and transplanted patients. In our study, although HD patients had detected statistically significantly increased inflammatory state according to CRP, ESR, and ferritin levels, there is no statistically significant difference in MPV of HD patients and other groups.

In dialysis patients with chronic renal failure, CRP levels are known to be a good indicator of the presence of chronic inflammation.17,18 The correlation between MPV and inflammation was investigated in several chronic inflammatory diseases.19 In accord with the literature, in our study chronic inflammatory state of HD, PD, and CKD stage 3–4 was detected with a significantly increased CRP compared to the renal transplantation group in which CRP was close to the normal range. CRP, which implies the presence of a chronic inflammatory situation, was detected statistically significantly lower than HD and CKD patients. We did not detect an inverse correlation with CRP and MPV in an inflammatory state of chronic kidney disease including renal transplanted ones. The significantly lower CRP levels of PD patients may result from longstanding residual renal function of the native kidney in PD patients. Although our results are not correlated with the literature, many previous studies were done in smaller groups of patients and different clinical situations. Our study is unique for enrolling all types of chronic kidney disease patients including transplanted ones.

In conclusion, to our knowledge our study is the first study that investigates the relationship between MPV and inflammation in all types of renal replacement patients including transplanted ones. We did not detect a significant difference among MPV between the transplanted, pre-dialysis, and dialysis patients. CRP which is a universal indicator of inflammation was detected significantly higher in HD compared to CKD stage 3–4, transplanted patients. ESR was detected lowest in transplanted patients. Transplantation is coming forward as a favorable choice of renal replacement therapy which decreases inflammation. To our knowledge, CKD and dialysis patients had an increased inflammatory state. We speculated that MPV does not have a predictive value for increased inflammation in CKD patients. Further larger-scale studies may be required to shade more light on the possible predictive value for increased inflammation in CKD patients.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes

*This study was presented at the 50th ERA-EDTA Congress, Istanbul, Turkey, 18–21 May, 2013.