Abstract
Aim: The importance of changes about platelet emphasized in most chronically diseases in recent years. Mean platelet volume (MPV) and platelet count can be used as a prognostic biomarker. In this study, clinical importance of the changes of MPV during active and remission phases in children with nephrotic syndrome was investigated. Patients and methods: Fifty-five children with nephrotic syndrome (30 females, 25 males) and 29 healthy children (18 females, 11 males) were included to the study. Patients were divided in two groups (steroid sensitive nephrotic syndrome and focal segmental glomerulosclerosis). Demographic characteristics of the patients, type of nephrotic syndrome were recorded and laboratory parameters in active and remission phases were evaluated. Results: Mean platelet count in the patient group was significantly higher than control group. Mean platelet count of FSGS group was significantly higher than SSNS group. Mean MPV value was significantly lower in active period of nephrotic syndrome when compared with control group. A significant negative relation between mean MPV value and mean platelet count was found. Significant positive correlations between mean platelet count and mean total cholesterol and mean triglyceride levels were demonstrated. Conclusion: MPV in nephrotic syndrome patients can be an easy, cheap and simple method for determine the prognosis of the disease and steroid resistance.
Introduction
An inverse relationship exists between mean platelet volume (MPV) and platelet count in healthy society. Recently MPV has shown that may be a marker of some diseases like as platelet count.Citation1 In childhood, nephrotic syndrome is a common disease and patients with nephrotic syndrome are at increased risk for the development of thromboembolic complications. Increase of platelet count and activation may be important on hypercoagulopathy.Citation2 Early prognosis predictors of the nephrotic syndrome have not been determinate yet.
Our aim was the evaluation of MPV as a prognostic biomarker in patients with nephrotic syndrome. Clinical importance of the changes of MPV during active and remission phases in children with nephrotic syndrome was investigated.
Patients and methods
Fifty-five children (30 girls, 25 boys) with nephrotic syndrome were included in the study. All patients had no history of thrombosis. Patients were divided in two groups (group 1: steroid sensitive nephrotic syndrome (39 patients) and group 2: focal segmental glomerulosclerosis (FSGS) (16 patients). About 29 healthy children (18 girls, 11 boys) were included in the study as control group.
Demographic characteristics of the patients (age, sex, weight, blood pressure), type of nephrotic syndrome were recorded and laboratory parameters including hemoglobin, hematocrit, mean corpuscular volume, red cell distribution width, white blood cell, platelet counts, MPV, prothrombin time, partial thromboplastin time, C-reactive protein, blood urea nitrogen, creatinine, electrolytes, albumin, alanine aminotransferase, and aspartate amino –transferase, and the amount of proteinuria in active and remission phases were evaluated. Baseline laboratory parameters at diagnosis of nephrotic syndrome and remission phase are used in evaluation for avoid the effects of steroids. Baseline values at diagnosis were used for compared SSNS and FSGS groups for avoid the effects of long follow-up time and treatment of FSGS group.
Proteinuria was assessed using 24-h urine protein excretion. Pathological proteinuria was defined as urinary protein excretion >4 mg/m2/h. Values >40 mg/m2/h was considered as nephrotic range proteinuria. Remission has been accepted as proteinuria <4 mg/m2/h and albumin level is within normal limits. Steroid resistance was defined as absence of remission despite therapy with daily prednisolone at dose of 2 mg/kg/day for 6–8 weeks.
Renal biopsy was performed on patients because of the resistance to steroid treatment, and FSGS was proven by biopsy.
Full blood counts (in K3 EDTA) of all patients were measured on a Coulter Abbott Cell-Dyn 3700 system (Abbott Diagnostics, Santa Clara, CA). Ranges of 7–12 fL were considered to be normal for MPV values. Biochemical parameters were measured with spectrophotometric methods on Abbott Arcitec C-8000 (Abbott Diagnostics, Santa Clara, CA) device.
Statistical analysis was performed with SPSS for Windows, version 11.0 (SPSS, Chicago, IL). p Values <0.05 were considered to indicate statistical significance.
Results
Fifty-five children (30 girls, 25 boys) with nephrotic syndrome and 29 healthy children (18 girls, 11 boys) were included to the study. The mean age of patients with nephrotic syndrome was 7:37 ± 4.35 years and the mean age of the control group was 8:52 ± 4.92 years (p > 0.05) ().
Table 1. Demographic data of patient and control groups.
Initial treatment begins with daily prednisolone at dose of 60 mg/day/m2 in divided doses for 4 weeks, followed by 45 mg/day/m2 every second day for 4 weeks and then either tapered over several weeks. Patients who had steroid resistance were treated with pulse intravenous methylprednisolone, cyclosporine A or mycophenolate mofetil. Sixteen patients with FSGS proven by biopsy were included to the study.
Mean platelet count in the patient group (403,112 ± 185,605/μL) was significantly higher than control group (326,896 ± 68,765/μL) (p = 0.02). Mean MPV value was significantly lower in active period of nephrotic syndrome when compared with control group (7.64 ± 1.05 fL, 8.58 ± 1.05 fL, respectively, p = 0.00). Mean MPV value was increased during remission period (7.81 ± 1.06 fL). Although tended to increase during remission, mean MPV value was significantly lower in patients when compared with control group (p < 0.05) ().
Table 2. Platelet parameters of patient during active and remission phases.
A significant negative relation between mean MPV value and mean platelet count was found (r = −0.455, p = 0.003). This negative relation between mean MPV value and mean platelet count could be shown in SSNS and FSGS groups (r = −0.38, p = 0.016, r = −0.51, p = 0.042, respectively). In SSNS and FSGS groups, significant positive correlations between mean platelet count and mean total cholesterol and mean triglyceride levels were demonstrated (r = 0.269, p = 0.045, r = 0.314, p = 0.02, respectively).
Mean creatinine, total protein, triglyceride, LDL, HDL, VLDL, sodium, calcium, CRP, ESR and proteinuria values were similar in 2 nephrotic syndrome groups. Mean albumin level of SSNS (2.38 ± 0.9 g/dL) and FSGS (2.32 ± 0.91 g/dL) groups were similar (p > 0.05) ().
Table 3. Demographic data and biochemical parameters of nephrotic syndrome patients.
Mean platelet count of FSGS group was significantly higher than SSNS group. Mean MPV value of FSGS group was significantly lower than SNSS group (). Mean LDL level of SSNS group has a significant negative correlation with mean MPV value (r = −0.57, p = 0.039), but this relation could not be shown with other lipid parameters.
Table 4. Platelet parameters of patient and control groups.
Discussion
Thromboembolic events are not rare in nephrotic syndrome. Hypercoagulability, hypovolemia, inactivity and infections increase tendency to thrombosis. Increased platelet aggregation and/or thrombocytosis, increased procoagulant factors and fibrinogen levels, decreased coagulation inhibitors such as antithrombin III, protein C and protein S levels increase the risk for thrombosis.Citation3 Increased platelet activity is associated with platelet volume.Citation4 MPV may be an indirect indicator of platelet activation.
The mechanism of increase in platelet count in during nephrotic syndrome has not been lengthily evaluated yet. Hypoalbuminemia and hypercholesterolemia may be responsible for this situation.Citation5 In our study, the platelet count was significantly higher in nephrotic syndrome patients than the control group; also FSGS group had higher platelet count than other groups. We could not show any correlation between platelet count and hypoalbuminemia; although there was a significant relation between mean platelet counts and mean total cholesterol and mean triglyceride levels. Higher mean platelet count of FSGS group could be associated with disease activity.
Recent studies were shown a significant negative correlation between platelet count and MPV in chronic illness.Citation6,Citation7 Thrombocytosis associated with low level – but in normal range – of MPV has been shown in diseases such as inflammatory bowel disease, ulcerative colitis, rheumatoid arthritis and ankylosing spondylitis and these findings is more prominent in the active period of the disease. This finding can be used as an indicator of the disease activity.Citation8–10
A significant negative relation between mean platelet count and MPV was demonstrated in our study. In a recent study, a similar negative correlation in nephrotic syndrome was shown between mean platelet count and mean MPV value.Citation5 This result supports also our study findings. The lowest mean MPV value was detected in FSGS group among the nephrotic syndrome patients. Probable effect of cytokine and growth factors in FSGS patients related to unhindered proteinuria on failure of suppression of platelet hyperactivity can play an important role in the pathogenesis renal failure in long-term period.
An important limitation of our study is the small number of patient. For this reason, we could not consider the possible effect of drugs used for the treatment on the MPV value.
Mean platelet volume in nephrotic syndrome patients can be an easy, cheap and simple method for determine the prognosis of the disease and steroid resistance. A careful follow-up is important, especially for development of FSGS, in patients with low MPV accompanied by thrombocytosis.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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