|Year : 2021 | Volume
| Issue : 1 | Page : 58-62
Evaluation of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as markers of diabetic kidney disease in Bangladeshi patients with type 2 diabetes mellitus
A BM Kamrul-Hasan1, Marufa Mustari2, Md Asaduzzaman3, Md Abu Jar Gaffar4, Palash Kumar Chanda1, Mohammad Motiur Rahman5, Mohammad Abdul Hannan6, Farhana Akter7, Mohammad Saifuddin8, Shahjada Selim2
1 Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
2 Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
3 Department of Endocrinology, Shaheed Sheikh Abu Naser Specialized Hospital, Khulna, Bangladesh
4 Department of Physiology, Naogaon Medical College, Naogaon, Bangladesh
5 Department of Medicine, Rajshahi Medical College Hospital, Rajshahi, Bangladesh
6 Department of Endocrinology, North East Medical College, Sylhet, Bangladesh
7 Department of Endocrinology, Chittagong Medical College, Chittagong, Bangladesh
8 Department of Endocrinology, Dhaka Medical College, Dhaka, Bangladesh
|Date of Submission||13-Jan-2020|
|Date of Decision||14-Mar-2020|
|Date of Acceptance||22-Apr-2020|
|Date of Web Publication||25-Dec-2020|
Dr. A BM Kamrul-Hasan
Department of Endocrinology, Mymensingh Medical College, Mymensingh 2200.
Source of Support: None, Conflict of Interest: None
Background: The roles of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as novel surrogate markers of diabetic kidney disease (DKD) are promising. Objective: The aim of this study was to evaluate whether NLR and PLR can predict DKD in type 2 diabetes mellitus (T2DM). Subjects and Methods: This cross‑sectional study was conducted from July 2018 to June 2019, among 312 patients with T2DM recruited from eight tertiary hospitals throughout Bangladesh. Complete blood count (CBC) was performed in fully automated hematology analyzers, and NLR and PLR were calculated. The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. The diagnosis of DKD was made based on the presence of albuminuria (ACR ≥30 mg/g) and/or reduced estimated glomerular filtration rate (eGFR <60mL/min/1.73 m2) in the absence of signs or symptoms of other primary causes of kidney damage. Results: Among 312 study subjects, 150 (48.1%) had DKD. The mean age (51.9 ± 11.9 vs. 48.6 ± 9.6 years), fasting plasma glucose (10.3 ± 4.1 vs. 9.2 ± 3.0 mmol/L), 2-h postprandial plasma glucose (14.6 ± 5.6 vs. 12.8 ± 4.5 mmol/L), glycated hemoglobin (HbA1c) (9.2 ± 2.1 vs. 8.4 ± 1.9%), and serum triglyceride (213.6 ± 109.9 vs. 185.5 ± 100.8) were higher (P ≤0.05 in each instance) in subjects with DKD in comparison to those without DKD. DKD group had higher mean absolute neutrophil count (6.0 ± 2.0 vs. 5.4 ± 1.9 ×109/L, P = 0.022), platelet count (310.4 ± 87.3 vs. 287.0 ± 78.7 ×109/L, P = 0.013), NLR (2.16 ± 1.1 vs. 1.92 ± 0.96, P = 0.040), and PLR (115.45 ± 57.07 vs. 101.02 ± 40.06, P = 0.010). The levels of hemoglobin, total leukocyte count, absolute lymphocyte count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width were similar in the two groups. Conclusion: In this study, we found higher NLR and PLR in subjects with DKD than those without DKD. NLR and PLR may be considered as cheap, readily available alternative markers of DKD in resource-poor settings.
Keywords: Albuminuria, diabetic kidney disease, diabetic nephropathy, neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, type 2 diabetes mellitus
|How to cite this article:|
Kamrul-Hasan A B, Mustari M, Asaduzzaman M, Gaffar MA, Chanda PK, Rahman MM, Hannan MA, Akter F, Saifuddin M, Selim S. Evaluation of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as markers of diabetic kidney disease in Bangladeshi patients with type 2 diabetes mellitus. J Diabetol 2021;12:58-62
|How to cite this URL:|
Kamrul-Hasan A B, Mustari M, Asaduzzaman M, Gaffar MA, Chanda PK, Rahman MM, Hannan MA, Akter F, Saifuddin M, Selim S. Evaluation of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as markers of diabetic kidney disease in Bangladeshi patients with type 2 diabetes mellitus. J Diabetol [serial online] 2021 [cited 2021 Jan 25];12:58-62. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/1/58/304353
| Introduction|| |
Diabetic kidney disease (DKD) is one of the microangiopathic complications of diabetes mellitus (DM) and is one of the most common causes of end‑stage renal disease (ESRD). Increased urinary albumin excretion is the hallmark of DKD. Existing data suggest a potential role for inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM). Previous studies exploring the relationship between systemic inflammation and cardiovascular disease discovered that chronic inflammation promotes the development and acceleration of microangiopathy and macroangiopathy in patients with DM., DKD in T2DM is known to have an inflammatory pathology. Many inflammatory markers are found to be related to DKD, such as interleukin‑1 (IL1), IL6, IL8, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor‑alpha (TNF‑α), and cytokines. High cost, lack of availability, and difficulty in their assay standardization limit their use in routine clinical practice for this purpose., Total white blood cell (WBC) count is a crude but cheap, readily available, and sensitive indicator of inflammatory status; WBCs are positively associated with inflammation, particularly in cardiovascular diseases. An increase in the number of neutrophils is associated with thrombus formation and ischemic injury. Among the multiple parameters of complete blood count (CBC), the neutrophil–lymphocyte ratio (NLR) and the platelet–lymphocyte ratio (PLR) have been studied extensively as inflammatory markers in cardiac and noncardiac diseases; NLR has been suggested as a prognostic marker in acute myocardial infarction, heart failure, and stroke., Worldwide, many investigators have evaluated the value of NLR and PLR as markers of DKD, and these have been identified as novel surrogate markers of DKD by them.,,,,,,,,,
Bangladesh has a high prevalence of diabetes, and T2DM is the most common type of diabetes here. Previous data suggest that the Asian Indian population has more prevalence of DKD as compared to the Caucasian population. Using a cheap, widely available marker of DKD is of paramount importance in a developing country such as Bangladesh. No studies have evaluated the value of NLR and PLR as surrogate markers of DKD in T2DM in this area. This study, therefore, aimed to evaluate whether NLR and PLR have roles in predicting DKD in Bangladeshi patients with T2DM.
| Subjects and Methods|| |
This cross‑sectional study was conducted from July 2018 to June 2019, in the endocrine outpatient departments (OPDs) of eight tertiary hospitals in Bangladesh. Previously diagnosed patients with T2DM attending the OPDs were included in the sample. Type 2 diabetes was defined as a clinical diagnosis with onset at ≥25 years, without initiation of insulin therapy within 1 year, and/or who needed insulin initially due to very high blood glucose, but subsequently, insulin could be stopped, and blood glucose could be managed by non-insulin agents for at least 1 year after that and had no ketoacidosis at diagnosis. The study protocol was explained to the patients, and those who gave informed written consent were included in the study. Patients with type 1 DM; patients with infections or history of infections in the past 1 month; patients with systemic disorders such as stroke, myocardial infarction, chronic liver disease, blood disorders, autoimmune disorders, malignancy, and poisoning; patients on anti‑inflammatory drugs, systemic or topical steroids, angiotensin‑converting enzyme inhibitors, angiotensin II receptor blockers, and alcohol; patients with severely uncontrolled blood pressure (BP) (i.e., ≥160/100mm Hg); patients having diseases affecting urinary protein excretion as nephrotic syndrome, urolithiasis, renal artery stenosis, dehydration state, and urinary tract infections (UTI); and patients having low glomerular filtration rate (GFR) without albuminuria were excluded from the study.
Information was collected from the patients on their age, gender, duration of T2DM, treatment history for diabetes and other medical conditions, comorbidities, and known complications of diabetes. Data were collected on the anthropometric parameters (height, weight, body mass index [BMI], and waist circumference) and BP. BMI categories applicable to the Asian Indians were used to define the obesity status, and waist circumference ≥90cm and ≥80cm was used to define abdominal obesity for men and women, respectively., Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
Laboratory data included fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2H-PPPG), glycated hemoglobin (HbA1c), serum creatinine, urine routine examination, and fasting lipid profile; all the centers used fully automatic biochemistry analyzers for biochemical tests. Plasma glucose was measured by glucose oxidase method, and HbA1c was measured by methods suggested by the National Glycohemoglobin Standardization Program (NGSP) in all centers. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate the estimated GFR (e-GFR). CBC was carried out in fully automated hematology analyzers in all the centers. The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. The presence of albuminuria was confirmed by testing the urine sample again after a 1-week follow-up; only those having persistent albuminuria on both the testing were finally selected for the study. Urinary ACR cutoff ≥30 mg/g was used to define albuminuria. The diagnosis of DKD was made based on the presence of albuminuria (ACR ≥30 mg/g) and/or reduced eGFR (<60mL/min/L.73 m2) in the absence of signs or symptoms of other primary causes of kidney damage.
Statistical analysis: Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, version 23.0 (IBM, Armonk, New York) software. The categorical variables were represented as percentages and the measurable variables as mean ± standard deviation (SD). Student’s t test and chi-square test were performed for comparing the variables between different groups as appropriate. P value ≤0.05 was considered to be statistically significant.
| Ethical Clearance|| |
Ethical approval for this study (MMC/IRB/2018/165) was provided by the Institutional Review Board of Mymensingh Medical College, Mymensingh, Bangladesh, on 04 June 2018.
| Results|| |
Among 312 study subjects, 150 (48.1%) had DKD. The comparison of demographic and laboratory parameters of the study subjects with and without DKD is given in [Table 1]. The subjects with DKD had higher mean age, FPG, 2H-PPPG, HbA1c, and triglyceride (TG) in comparison to those without DKD. No differences were observed in the two groups in gender, family history of T2DM, smoking status, duration of DM, BMI, waist circumference, BP, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).
|Table 1: Comparison of demographic and laboratory parameters of the study subjects with and without diabetic kidney disease|
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The comparison of the renal function parameters between DKD and no-DKD groups is shown in [Table 2]; the DKD group had higher mean serum creatinine, lower eGFR, and higher urinary ACR than the no-DKD group.
|Table 2: Comparison of renal function parameters of the study subjects with and without diabetic kidney disease|
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The hematological parameters of the two groups are compared in [Table 3]. DKD group had higher mean absolute neutrophil count (ANC), platelet count, NLR, and PLR. The levels of hemoglobin, total leukocyte count (TLC), absolute lymphocyte count (ALC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width–coefficient of variation (RDW-CV) were similar in the two groups.
|Table 3: Comparison of hematological parameters of the study subjects with and without diabetic kidney disease|
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| Discussion|| |
This study, conducted at several tertiary hospitals of Bangladesh, observed that NLR and PLR were significantly higher in patients of T2DM with DKD than those in patients of T2DM without DKD. This is the first study in Bangladesh to assess the relationships between NLR and PLR with DKD.
Though the exact pathogenesis of DKD is largely unknown, renal inflammation is known to play a critical role. A cascade of pathological events (with glomerular damage being an early sign, which gives rise to proteinuria, followed by progressive renal damage, fibrosis, inflammation, and finally loss of functional nephrons) is known to play an important role in the development and progression of DKD. WBC count and its subtypes are among the readily available and inexpensive classic inflammatory markers. NLR and PLR are the proportions of absolute neutrophil to lymphocyte and platelet to lymphocyte counts retrieved from the CBC test. NLR stands out as a novel marker of chronic inflammation that reflects a counterbalance between two complementary components of the immune system; neutrophils, being the active nonspecific mediator of inflammation, forming the first line of defense, whereas lymphocytes acting as the protective or regulatory component of inflammation. Platelets can interact with various cell types, including endothelial cells, T-lymphocytes, neutrophils, and mononuclear phagocytes, in which earlier investigations strongly suggested that chronic inflammation may contribute to the development of atherosclerosis. Besides, PLR was found to be higher in some inflammatory conditions. Multiple studies have established that inflammatory markers, such as neutrophilia and relative lymphocytopenia, are independent markers of many diseases, especially complications of DM, such as DKD. However, establishing a diagnosis based on WBC, neutrophil, or lymphocyte counts has its own biases individually, unlike NLR and PLR, which are dynamic parameters having higher prognostic values.,
In our study, the mean NLR in patients with DKD was significantly higher than that in those without DKD. In concordance with our results, Huang et al. also found that NLR values were significantly higher in patients of diabetes with nephropathy than those in patients of diabetes without nephropathy and in healthy controls. Moreover, a recent study in Egyptian patients has shown that NLR values were significantly higher not only in patients who are diabetic with nephropathy but also those having retinopathy and neuropathy than those without any microvascular complications and healthy controls. Fawwad et al. also found NLR to be an important predictor for the existence of microvascular complications in subjects with T2DM. Another study by Kahraman et al. in Turkish patients with diabetes also showed that NLR levels significantly increased in parallel to albuminuria levels. The findings of Khandare et al., Chittawar et al., Afsar, Akbas et al., and Abdelaziz et al. also support our study result.
We observed no difference in TLC between the two groups. Khandare et al., Kahraman et al., and Akbas et al. had similar observations. In contrast, Fawwad et al. observed that TLC was higher in subjects with T2DM with at least one microvascular complication than those without microvascular complications. Differences in differential counts of individual white cells also have been observed in previous research. Subjects with DKD had higher ANC and lower ALC in studies conducted by Khandare et al., Kahraman et al., Akbas et al., and Abdelaziz et al. Fawwad et al. observed higher ANC and lower ALC in subjects with T2DM with at least one microvascular complication than those without microvascular complications. Besides, ANC and ALC were also found to correlate with DM in the study performed by Huang et al. Though ANC was significantly higher in patients with DKD, no difference in ALC between DKD and no-DKD groups was observed in our study.
Platelet count was higher in subjects with DKD than those without DKD in our study. Similar to ours, patients with diabetes with macroalbuminuria had higher total platelet count than normoalbuminuric ones in studies conducted by Fawwad et al. and Akbas et al. Similar differences in platelet counts in DKD and no-DKD groups were observed by Kahraman et al. and Huang et al.
PLR is also a novel inflammatory biomarker used as prognostic factors in various diseases. Abdelaziz et al. observed a higher PLR in subjects with DM with macroalbuminuria in comparison to those with microalbuminuria and normoalbuminuria. Akbas et al. and Alsayyad and Abd Alsamie also had similar observations. PLR was higher in subjects with DKD than that in those without DKD according to our study result. On the contrary, Onalan et al. observed no differences in PLR between subjects of diabetes with and without DKD.
The strengths of this study were the large sample size and its multicenter design throughout the country. The major limitation was that any conclusive causal associations between NLR and DN could not be investigated due to its cross-sectional design. This study was performed among a preselected high-risk population; hence the issue of selection bias could not be ignored.
| Conclusion|| |
NLR and PLR may be used as a marker of DKD, according to our study findings. These are easy to calculate from CBC, which is almost a routine test. So, in resource-poor settings, these may serve as an alternative to other costly markers and predictors of DKD and other diabetic microangiopathies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]