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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 7  |  Issue : 1  |  Page : 24-29

Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios and their association with atherogenic index of plasma in sickle cell nephropathy


1 Department of Medical Laboratory Science, School of Basic Medical Sciences, University of Benin, Benin City, Nigeria
2 Department of Medicine, Nephrology Unit, Faculty of Medical Sciences, Bayero University, Aminu Kano Teaching Hospital, Kano, Nigeria
3 Department of Haematology and Transfusion Science, Aminu Kano Teaching Hospital, Kano, Nigeria

Date of Web Publication25-Apr-2016

Correspondence Address:
Mathias Abiodun Emokpae
Department of Medical Laboratory Science, School of Basic Medical Sciences, University of Benin, Benin City
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-5127.181109

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  Abstract 

Background/Objectives: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) were introduced as cheap and readily assessed biologic markers of subclinical inflammation. There are few studies that have evaluated NLR and PLR as prognostic markers of proteinuria in sickle cell anemia (SCA) patients. This study seeks to evaluate NLR and PLR in SCA patients with proteinuria, impaired kidney function and to ascertain whether there exist relationship between the leukocyte ratios and atherogenic index of plasma. Materials and Methods: The NLR, PLR, and atherogenic index were calculated from full blood count and lipid profile parameters determined from fasting blood specimens collected from 200 confirmed SCA patients and 100 control subjects with normal hemoglobin (Hb). Results: The NLR and PLR values were significantly higher (P < 0.001) in SCA patients compared with control subjects with normal Hb. Similarly, NLR and PLR values were significantly higher (P < 0.001) in SCA patients with proteinuria and those with impaired kidney function than without proteinuria and normal controls. A significantly positive association was observed between NLR and atherogenic index of plasma (AIP) in SCA patients with proteinuria (P < 0.05) and those with impaired kidney function (P < 0.02) while significant association was observed between PLR and AIP in SCA with impaired kidney function (P < 0.05). Conclusion: The leukocyte ratios may be useful as prognostic markers for the presence of proteinuria in SCA patients and impaired kidney function as well as cardiovascular risk event. The need to have reference cut-off values of NLR and PLR is hereby suggested to better identify those patients at risk in the management SCA patients.

Keywords: Atherogenic index of plasma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, sickle cell disease


How to cite this article:
Emokpae MA, Abdu A, Gwaram B A. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios and their association with atherogenic index of plasma in sickle cell nephropathy. J Appl Hematol 2016;7:24-9

How to cite this URL:
Emokpae MA, Abdu A, Gwaram B A. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios and their association with atherogenic index of plasma in sickle cell nephropathy. J Appl Hematol [serial online] 2016 [cited 2018 Jan 22];7:24-9. Available from: http://www.jahjournal.org/text.asp?2016/7/1/24/181109


  Introduction Top


The kidneys of sickle cell anemia (SCA) patients may be adversely affected by chronic hemodynamic alterations and adverse consequences of vaso-occlusive episodes in the renal medulla.[1] Abnormalities of the structure and function take place with increasing age of the SCA patients. The pathogenesis of SCA involves chronic polymerization of sickled red blood cells (RBCs) in reduced oxygen tension and could lead to hemolytic anemia, vaso-occlusion of microvascular vessels and infarction.[2] In the kidney, these events could result in injury to the glomerular tissues with proteinuria as one the manifestations. Proteinuria in SCA is an indication of ongoing renal insufficiency and a progression factor in chronic kidney disease.[3] Oxidative stress has been shown to occur in sickle cell nephropathy arising from increased secretion of pro-oxidants and decreased antioxidant systems.[4],[5] This increased oxidative stress has been reported to be one of the pathogenic mechanisms in the development of cardiovascular complications in SCA patients.[6] Studies have shown that white blood cells particularly neutrophils may be involved in the initiation and propagation of vaso-occlusive event.[7] Adhesion of activated neutrophils to endothelium in SCA may lead to endothelial damage because neutrophils do not lyse easily as RBCs do, thereby leading to obstruction of blood flow within the microcirculation.[8],[9] Abnormalities of vascular endothelium are important factors associated with end organ disease. Recently, Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) have been introduced as biologic markers of subclinical inflammation. Studies have associated elevated NLR and PLR with clinical outcomes in cardiovascular disease [CVD],[10] cancers [11],[12] as well as renal and gastrointestinal diseases.[13],[14],[15] There are very few studies that have evaluated NLR and PLR (and their association with proteinuria) in SCA with nephropathy. In a study that evaluated NLR in 79 SCA patients and fifty age-matched hemoglobin AA (HbAA) controls, there was no significant correlation between NLR and proteinuria observed.[16] However, one of the limitations of that study was the small population size which the authors agreed may have affected the observed result. This study seeks to evaluate NLR and PLR in SCA patients with and without proteinuria and impaired kidney function (defined in this study as estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m 2). It also aimed at evaluating whether there is any relationship between the leukocyte ratios and atherogenic index of plasma (AIP).


  Materials And Methods Top


Study Population

A total of 200 confirmed SCA patients were consecutively recruited between January 2005 and December 2006; the patients were in steady clinical state enrolled during their routine visit to the clinic with some having impaired kidney function. One hundred age-matched subjects with normal HbAA were selected from among staff and students of the university. A structured questionnaire was administered to obtain demographic and medical history of the participants.

Ethical Consideration

The study protocol was reviewed and approved by the Ethic Committee of Aminu Kano Teaching Hospital, Kano, Nigeria. All participants had given informed consent before they were enrolled.

Sample Preparation

Five milliliters of fasting blood specimen was collected from each participant and dispensed into dipotassium ethylenediaminetetraacetic acid container. This was used for full blood count using Coulter counter cell dye 3700 auto-analyzer. The sample was thereafter centrifuged at 3000 rpm for 10 min and plasma separated carefully to avoid hemolysis. The plasma was then kept frozen at − 20°C until analyzed. Random urine specimen was collected from each participant and urine protein determined using dipstick technique (Medi-test Combi-9), Macherey-Nagel, GmbH and Co., Duren, Germany.

Those with positive dipstick proteinuria were repeated at least once on a separate visit to confirm and quantitated using 25% sulfosalicylic acid turbidimetric method. The plasma was used for lipid profile assay by colorimetric method using reagents supplied by Randox Laboratories, UK. The NLR and PLR were derived by dividing the absolute Neutrophil and Platelet counts by absolute lymphocyte count. The AIP was derived by mathematical calculation of log (triglyceride [TG]/high-density lipoprotein-cholesterol [HDL-c]).[17]

Statistical Analysis

Data were expressed as mean ± standard error of mean. Analysis was performed using SPSS version 16 (SPSS Inc., Chicago, IL, USA). The measured hematological indices and lipid profile parameters were compared among the groups with controls using Students' t-test. Pearson correlation coefficient was used to calculate the association of NLR, PLR with AIP in the various sub-groups. P < 0.05 was considered as statistically significant.


  Results Top


The findings from this study are as indicated in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]. [Table 1] shows the comparison of the measured hematological parameters in SCA patients with control subjects with normal Hb. Statistically significant higher (P < 0.001) levels of platelet count, NLR and PLR were observed in SCA patients while significant lower (P < 0.001) levels of hematocrit, Hb, and RBCs count were observed in SCA patients compared with controls. There were 56 (28%) patients with proteinuria and 15 (7.5%) patients with impaired kidney function. [Table 3] shows the comparison of hematological parameters in SCA patients with proteinuria and without proteinuria. In SCA patients with proteinuria, NLR (P < 0.001), PLR (P < 0.001), absolute eosinophil count (P < 0.001), and mean cell volume (MCV) (P < 0.002) were significantly higher while platelet count (P < 0.05) and monocyte count (0.001) were significantly lower than those without proteinuria. In SCA with impaired kidney function, age, MCV, absolute neutrophil count, NLR, and PLR were significantly higher (P < 0.001) while Hb (P < 0.005) and absolute lymphocyte count (0.002) were lower than SCA patients with no impaired kidney function [Table 4]. Plasma urea, creatinine, TG, total cholesterol were significantly higher (P < 0.001) while eGFR and HDL-c were lower (P < 0.001) in SCA patients with impaired kidney function compared to those with or without proteinuria [Table 5]. The AIP increased significantly from 0.15 ± 0.01 in SCA patients without proteinuria to 0.22 ± 0.01 in SCA patients with proteinuria and 0.46 ± 0.01 in those with impaired kidney function. The NLR correlated positively with AIP (r = 0.595; P < 0.02) in SCA patients with impaired kidney function and (r = 0.310; P < 0.05) in SCA patients with proteinuria but not in SCA patients without impaired kidney function (r = 0.142; P = 0.20). Similarly, PLR correlated positively (r = 0.498; P < 0.05) in SCA patients with impaired kidney function but no association was observed in SCA patients with proteinuria and those with no proteinuria (r = 0.293; P = 0.2; r = 0.145; P = 0.10), respectively [Figure 1], [Figure 2], [Figure 3], [Figure 4].
Table 1: Comparison of neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and other hematological indices in sickle cell anemia patients with control subjects with normal hemoglobin genotype

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Table 2: Correlation of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with atherogenic index of plasma in sickle cell anemia patients with nephropathy, and in those with normal kidney function

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Table 3: Comparison of neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios and other hematological indices in sickle cell anemia patients without proteinuria and with proteinuria

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Table 4: Comparison of hematological indices in sickle cell anemia patients with nephropathy and those with normal kidney function

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Table 5: Comparison of biochemical parameters and atherogenic index of plasma in sickle cell anemia patients with, without nephropathy

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Figure 1: Correlation between neutrophil-to-lymphocyte ratio and atherogenic index of plasma in subjects with impaired renal function

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Figure 2: Correlation between platelet-to-lymphocyte ratio and atherogenic index of plasma in subjects with impaired renal function

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Figure 3: Correlation between neutrophil-to-lymphocyte ratio and atherogenic index of plasma in sickle cell disease patients with proteinuria

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Figure 4: Relationship between platelet-to-lymphocyte ratio and atherogenic index of plasma in sickle cell disease patients without proteinuria

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  Discussion Top


The data presented in this study showed that NLR and PLR values in SCA patients were significantly higher (P < 0.001) in SCA patients compared with control subjects with normal Hb. Similarly, NLR and PLR values were significantly higher (P < 0.001) in SCA patients with nephropathy in this study referred to as those with proteinuria and those with impaired kidney function than those without proteinuria and HbAA controls. This study also demonstrated a positive association between NLR and AIP in SCA patients with nephropathy.

The use of the leukocyte ratios may be useful and superior to individual absolute leukocytes in assessing inflammatory status in SCA because the ratios are relatively stable and may not be easily affected by physiological, pathological, and physical events.[18],[19],[20] Neutrophil represents the active nonspecific inflammatory mediator of cellular immunity (innate) while lymphocytes mediate the adaptive or protective aspect of inflammation.[21],[22] Elevated NLR and PLR values may be used to distinguish patients who do not have physiological capacity to withstand the inflammatory injury and low survival outcomes.[23] Studies that have evaluated NLR and PLR ratios in SCA patients are very few. In a study that assessed NLR in SCA patients with nephropathy there was no observed association between NLR and macroalbuminuria but however reported a nonsignificant increased of NLR in SCA with macroalbuminuria compared with those without macroalbuminuria.[16] The observation which they attributed to the fact that the disease process was not fully developed in SCA patients with macroalbuminuria and concluded that macroalbuminuria was not a sensitive marker of nephropathy.[16] The data we presented in this study did not agree with their finding. The means NLR increased from 1.28 in SCA patients with normal renal function to 2.07 in SCA patients with proteinuria and 2.33 in SCA patients with impaired kidney function. In the same vein, the mean PLR increased from 102.6 in SCA patients with normal kidney function to 122 in those with proteinuria and 158 in SCA patients with impaired kidney function. Our finding is consistent with that of Binnetoglu et al.[14] who reported that NLR and PLR correlated positively with proteinuria in impaired kidney function patients. It was suggested that leukocyte ratios may be used as predictive markers for the presence and degree of proteinuria.[14] We previously reported a high prevalence of proteinuria among SCA patients in Nigeria, and it was regarded as a sensitive marker of renal insufficiency, a condition that increase with increasing age of patients.[3] Our finding is also consistent with others who reported raised NLR and PLR as predictors of poor clinical outcomes in cancers,[11] CVD [10] and critically ill patients.[23] However, these studies used arbitrary mean values in the assessment of these ratios in the different disease conditions. The ratios were reported to vary with race, lower in African Americans compared to Hispanics and Caucasians even in apparently healthy population.[24] The need to determine local reference cut-off points in distinguishing those at risk is therefore suggested.

In this study, association between the calculated ratios and AIP was observed and is in agreement with those which reported high Neutrophil counts and relative lymphopenia in patients with acute heart failure.[25],[26] Similarly, peripheral blood leukocyte counts have been associated with inflammation in relationship to CVD, which is also common in SCA patients with renal insufficiency.[27] Studies have reported association between CVD and elevated NLR and PLR. CVD is common in SCA and dyslipidemia significantly contribute to its pathogenesis. AIP has been used in the assessment of CVD risk, and it has proven to correctly distinguish subjects at risk even though the lipid profile parameters were not markedly deranged.[28] The association of NLR and PLR with AIP observed in this study is in agreement with previous studies.[10],[29],[30],[31],[32] In a study that evaluated the leukocyte ratios as predictor of all-cause mortality in patient with coronary artery disease, the elevated ratio was associated with coronary heart disease.[10] Gary et al.[29] observed that in patients with peripheral artery occlusive disease, PLR ratio of > 150 could be used to identify patients with high risk for critical limb ischemia. Others have observed that elevated leukocyte ratios may indicate risk for thrombosis of prosthetic valves [30] and myocardial infarction.[31]


  Conclusion Top


The NLR and PLR were higher in SCA patients with Nephropathy compared to SCA patients with normal kidney function and those with normal Hb. Association was observed between the ratios and AIP in SCA patients with nephropathy. The need to have reference cut-off values of NLR and PLR is hereby suggested to better identify those patients at risk in the management SCA patients.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

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Emokpae MA, Uadia PO, Kuliya-Gwarzo A. Antioxidant enzymes and acute phase proteins correlate with marker of lipid peroxide in adult Nigerian sickle cell disease patients. Iran J Basic Med Sci 2010;13:177-82.  Back to cited text no. 4
    
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Osadnik T, Wasilewski J, Lekston A, Strzelczyk J, Kurek A, Gonera M, et al. The platelet-to-lymphocyte ratio as a predictor of all-cause mortality in patients with coronary artery disease undergoing elective percutaneous coronary intervention and stent implantation. J Saudi Heart Assoc 2015;27:144-51.  Back to cited text no. 10
    
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Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: A systematic review and meta-analysis. J Natl Cancer Inst 2014;106:dju124.  Back to cited text no. 11
    
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Kumar R, Geuna E, Michalarea V, Guardascione M, Naumann U, Lorente D, et al. The neutrophil-lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials. Br J Cancer 2015;112:1157-65.  Back to cited text no. 12
    
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Uthamalingam S, Patvardhan EA, Subramanian S, Ahmed W, Martin W, Daley M, et al. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol 2011;107:433-8.  Back to cited text no. 13
    
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Binnetoglu E, Sengül E, Halhalli G, Dindar S, Sen H. Is neutrophil lymphocyte ratio an indicator for proteinuria in chronic kidney disease? J Clin Lab Anal 2014;28:487-92.  Back to cited text no. 14
    
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Shimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, et al. High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer 2010;13:170-6.  Back to cited text no. 15
    
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John CA, Adegbola OA, Emmanuel CO, Christian EO, Nancy CI, Muheez DA. Neutrophil-to-lymphocyte ratio in sickle cell anaemia patients with nephopathy. Br J Med Res 2015;10:1-6.  Back to cited text no. 16
    
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29.
Gary T, Pichler M, Belaj K, Hafner F, Gerger A, Froehlich H, et al. Platelet-to-lymphocyte ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. PLoS One 2013;8:e67688.  Back to cited text no. 29
    
30.
Gürsoy OM, Karakoyun S, Kalçik M, Gökdeniz T, Yesin M, Gündüz S, et al. Usefulness of novel hematologic inflammatory parameters to predict prosthetic mitral valve thrombosis. Am J Cardiol 2014;113:860-4.  Back to cited text no. 30
    
31.
Yildiz A, Yuksel M, Oylumlu M, Polat N, Akyuz A, Acet H, et al. The utility of the platelet-lymphocyte ratio for predicting no reflow in patients with ST-segment elevation myocardial infarction. Clin Appl Thromb Hemost 2015;21:223-8.  Back to cited text no. 31
    
32.
Zouridakis EG, Garcia-Moll X, Kaski JC. Usefulness of the blood lymphocyte count in predicting recurrent instability and death in patients with unstable angina pectoris. Am J Cardiol 2000;86:449-51.  Back to cited text no. 32
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


This article has been cited by
1 Relationship between Neutrophil-to-Lymphocyte Ratio and Inflammatory Markers in Sickle Cell Anaemia Patients with Proteinuria
Mathias Emokpae,Austin Aruomaren,Evarista Osime
Medical Sciences. 2016; 4(3): 11
[Pubmed] | [DOI]



 

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