To evaluate the characteristics of anemia and reticulocyte indices in patients with non-dialysis dependent stage III - V chronic kidney disease.
Journal of military pharmaco-medicine no9-2019 SURVEY OF ANEMIA CHARACTERISTICS AND SOME RETICULOCYTE INDICES IN PATIENTS WITH STAGES III TO V CHRONIC KIDNEY DISEASE Nguyen Trung Kien1; Nguyen Thi Hien Hanh1; Nguyen Khanh Van1 Ta Viet Hung1; Thai Danh Tuyen1; Le Viet Thang1 SUMMARY Objectives: To evaluate the characteristics of anemia and reticulocyte indices in patients with non-dialysis dependent stage III - V chronic kidney disease Subjects and methods: A descriptive, cross-sectional study on 81 patients with stage - chronic kidney disease who did not receive renal replacement therapy and treated at Nephrology and Hemodialysis Department, 103 Military Hospital from October 2017 to October 2018 Results: The prevalence of anemia in the study was 95.1% (mild 27.3%, moderate 36.4% and severe 36.4%) Up to 13% of patients had microcytic, hypochromic anemia The mean value of reticulocyte percentage (RET%) was 2.05 ± 0.73%; absolute reticulocyte count (RET#) was 0.07 ± 0.02 T/L and hemoglobin reticulocyte equivalent (RET-He) was 30.38 ± 3.69 pg The mean value of RET% in women was significantly higher than in men (p < 0.05) There was no difference in mean value of RET# and RET-He between men and women (p > 0.05) The higher the age, the lower RET%, RET# and RET-He However, this difference was not statistical significance with p > 0.05 Conclusion: Anemia was a common manifestation in patients with chronic kidney disease in which most of them were moderate and severe anemia The reticulocyte indices in patients with chronic kidney disease were not significantly difference between men and women and between age groups * Keywords: Chronic kidney disease; Anemia; Reticulocytes INTRODUCTION Anemia is a very common complication of chronic kidney disease (CKD) and can develop in the early phases of the disease and contributes to poor quality of life [1] In patients with stages - CKD, severe anemia is associated with increased hospitalization duration, costs and mortality rate [2] Reticulocytes are the final stage in the differentiation process of red blood cells Peripheral reticulocytes are considered to be the presence of erythropoiesis in the bone marrow An increasing peripheral reticulocytes means that the erythropoiesis of bone marrow is normal, while a decrease in peripheral reticulocytes mean that the erythropoiesis of bone marrow is inhibited Therefore, reticulocyte tests are used clinically as an indicator to diagnose the causes of anemia We conducted this study for the aim: Assessing the anemia characteristics and reticulocyte indices in patients with stages III to V CKD who did not receive any renal replacement therapy 103 Military Hospital Corresponding author: Nguyen Trung Kien (bs ntkien@gmail.com) Date received: 10/10/2019 Date accepted: 21/11/2019 222 Journal of military pharmaco-medicine no9-2019 SUBJECTS AND METHODS Subjects 81 adult patients with stage III - V CKD, who did not receive any renal replacement therapy, attended to the Department of Nephrology and Hemodialysis, 103 Military Hospital from October 2017 to October 2018 * Inclusion criteria: Patients with age of 16 years and above, stages III - V CKD (eGFR < 60 mL/min), did not receive any renal replacement therapy and consented to participate in research were selected to our research * Exclusion criteria: Patients on renal replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplant), parenteral iron therapy or blood transfusion within months, EPO therapy within weeks, evidence of active bleeding or infection or blood transfution previously diagnosed of non-renal causes of anemia, various comorbidities such as malignancy, end-stage liver disease, and collagen vascular disease (systemic lupus erythematosus and rheumatoid arthritis) were excluded from our study Methods * Study design: A descriptive crosssectional study * Testing performances: Complete blood count and reticulocyte indices on Sysmex XN1000 automated hematology analyzer (Japan) * Diagnostic criteria: - Diagnosis and staging of CKD: According to the National Kidney Foundation/Kidney Disease Outcome Quality Initiative (NKF/KDOQI) (2002) classification criteria [3] - Anemia diagnosis: According to WHO (2011) [4] * Statistical analysis: The data were analyzed by SPSS software (version 20.0) manufactured by International Business Machine (IBM) RESULTS Characteristics of anemia 4.9% 95.1% Normal Anemia Chart 1: Anemia proportion of study group (n = 81) The majority of patients was suffered from anemia (95.1%) 223 Journal of military pharmaco-medicine no9-2019 * The severity of anemia (n = 77): The proportion of patients with mild, moderate and severe anemia was 27.2%, 36.4% and 36.4%, respectively * Morphological type of anemia (n = 77): Microcytic anemia: 10 patients (13.0%); normocytic anemia: 67 patients (87.0%); macrocytic anemia: patient (0%) * Anemia characteristics (n = 77): In our study, there were 37.7% (29 patients) of anemia patients with hypochromic anemia 48 patients (62.3%) had normochromic anemia Chart 2: The proportion of patients with microcytic-hypochromic anemia (n = 77) There was up to 13% of anemia patients with microcytic-hypochromic anemia Table 1: Characteristics of reticulocyte indices by gender (n = 81) Gender RET% (%) RET# (T/L) RET-He (pg) All (n = 81) 2.05 ± 0.73 0.07 ± 0.02 30.38 ± 3.69 Male (n = 57) 1.94 ± 0.60 0.07 ± 0.02 30.48 ± 4.05 Female (n = 24) 2.3 ± 0.93 0.07 ± 0.03 30.15 ± 2.69 < 0.05 > 0.05 > 0.05 p The mean value of RET% in women was significantly higher than in men (p < 0.05) There was no difference in mean value of RET# and RET-He between men and women (p > 0.05) 224 Journal of military pharmaco-medicine no9-2019 Table 2: Characteristics of reticulocyte indices by aging group (n = 81) Aging group RET% (%) RET# (T/L) RET-He (pg) < 30 (n = 12) 2.4 ± 1.18 0.08 ± 0.04 30.26 ± 1.48 30 - 39 (n = 12) 2.2 ± 0.83 0.07 ± 0.02 31.69 ± 4.1 40 - 49 (n = 14) 2.06 ± 0.47 0.08 ± 0.01 31.61 ± 3.04 50 - 59 (n = 9) 1.95 ± 0.41 0.07 ± 0.009 28.7 ± 3.46 ≥ 60 (n = 34) 1.89 ± 0.62 0.06 ± 0.02 29.9 ± 4.22 > 0.05 > 0.05 > 0.05 p The higher of age, the lower of the mean value of reticulocyte indices However, the difference was not statistically significant with p > 0.05 DICUSSIONS Anemia characteristics in patients with stages III to V chronic kidney disease who did not receive any renal replacement therapy In this study, we used WHO criteria to diagnose anemia, in which the evaluation criteria were based on hemoglobin (HGB) Anemia was defined as HGB levels < 130 g/L for adult male and < 120 g/L for female without pregnancy In our study, the proportion of anemia was up to 95.1%, in which mild anemia accounted for only 27.2%, moderate and severe accounted for 36.4% The proportion of anemia in our study was consistent with several previous studies Li Y et al (2016) studied 2,420 patients with CKD in Shanghai (China) indicated that the proportion of anemia in patients with stage III CKD was 51.1% This proportion in patients with stage IV and stage V CKD was 79.2% and 90.2%, respectively [5] This result was similar to the study by Salman M et al (2016) with the anemia proportion in CKD patients was 75.8% (stage IIIa was 41.9%, stage IIIb was 63.4%, stage IV was 85.4% and stage V was 97.4%) [6] Anemia is a common manifestation of CKD The incidence of anemia usually increases together with the severity of CKD This reflects the pathogenetic mechanism of CKD, when the renal function is sharply reduced, it leads to the progression of metabolic and endocrine disorders, including erythropoietin secretion In addition, the acidosis balance disorder and the increase in free radicals and inflammatory cytokines inhibit erythroblast in the bone marrow which causes hemolysis, reducing erythropoiesis, and reducing the life-span of red blood cells that lead to the worsening of anemia Many subsequent studies had made it possible to understand the causes and mechanisms of anemia in CKD All three mechanisms of anemia including decreased red blood cell production, increased red cell destruction and the bleeding had been seen in patients with CKD 225 Journal of military pharmaco-medicine no9-2019 In all anemia patients, the vast majority of patients had normocytic anemia (87%) Microcytic anemia patients accounted for 13% There were no patients with macrocytic anemia About anemia characteristics, there was 37.7% of anemia patients with hypochromic anemia The majority of anemia patients had normochromic anemia (62.3%) This was up to 13% of anemia patients with microcytic-hypochromic anemia Afshar R et al (2010) studied patients with chronic renal failure with and without hemodialysis The results showed that 80% of patients had normocytic-normochromic anemia, 15% of patients had microcytic anemia and 5% of patients had macrocytic anemia This study also showed that the incidence of hypochromic anemia in patients without hemodialysis was higher than that in patients with hemodialysis and the proportion of macrocytic anemia in patients with hemodialysis was higher than those without hemodialysis (5.2% compared with 4.8%) [7] The high proportion of hypochromic anemia in our study can be explained by chronic medical conditions, nutritional deficiencies, absolute or functional iron deficiency, protein loss in the urine, metabolic disorders, gastrointestinal damage by high blood urea Characteristics of reticulocyte indices in patients with stages III to V CKD who did not receive any renal replacement therapy Cell kinetic studies had shown that approximately 1% of peripheral red blood cells are replaced by new reticulocytes 226 These new cells will mature within 24 hours to take on the role of red blood cells In acute or chronic anemia, stimulation factors such as hypoxiainducible factor (HIF 1) affect fibroblasts around the renal tubules leading to an increasing expression of EPO synthesis genes CKD damages the number and function of cells responsible for EPO secretion, as well as disruption of stimulation, communication, and gene expression, resulting in erythropoietin deficiency and anemia As the results of table 1, the mean value of reticulocyte percentage (RET%) was 2.05%, of reticulocyte count (RET#) was 0.07 T/L and of RET-He was 30.38 pg The mean value of RET% in women was significantly higher than in men (p < 0.05) There was no difference in the mean value of RET# and RET-He between men and women (p > 0.05) The percentage and absolute count of reticulocytes in our study were higher than that of Maconi M et al’ (2009) when studied over 200 hemodialysis patients (1.45% and 0.05 T/L, respectively) However, RET-He in our study was lower than in this study (30.38 pg compared to 33.9 pg) [6] This can be explained by differences in the study subjects Our study group had not been received any renal replacement or iron therapy, so the proportion of patients with anemia due to iron deficiency in our study was higher than above study Our results in table also indicated that the higher the age, the lower RET%, RET# and RET-He However, these differences were not statistically significant with p > 0.05 Journal of military pharmaco-medicine no9-2019 CONCLUSIONS In our study, anemia was a common manifestation in patients with CKD, in which most of them were moderate and severe anemia (27.2% and 36.4%, respectively) There was up to 13% of anemia patients with microcytic-hypochromic anemia The mean value of reticulocyte percentage was 2.05 ± 0.73%, of reticulocyte count was 0.07 ± 0.02 T/L and of reticulocyte hemoglobin equivalent was 30.38 ± 3.69 pg The reticulocyte indices in patients with CKD were not significantly difference between men and women and between age groups REFERENCES Eknoyan G et al The burden of kidney disease: Improving global outcomes Kidney 2004, 66 (4), pp.1310-1314 Dowling T.C Prevalence, etiology, and consequences of anemia and clinical and economic benefits of anemia correction in patients with chronic kidney disease: An overview American Journal of Health-System Pharmacy 2007, 64 (13 Supplement 8), pp.S3-S7 K/DOQI K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification Am J Kidney Dis, 2002, 39 (2 Suppl 1), pp.S1-266 WHO Haemoglobin for the diagnosis of anemia and assessment of severity Vitamin and Mineral Nutrition Information System 2011, pp.1-6 Li Y et al Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study Medicine (Baltimore) 2016, 95 (24), p.e3872 Maconi M et al Erythrocyte and reticulocyte indices in iron deficiency in chronic kidney disease: Comparison of two methods Scand J Clin Lab Invest 2009, 69 (3), pp.365-370 Afshar R et al Hematological profile of chronic kidney disease (CKD) patients in Iran, in pre-dialysis stages and after initiation of hemodialysis Saudi Journal of Kidney Diseases and Transplantation 2010, 21 (2), pp.368- 371 227 ... Afshar R et al Hematological profile of chronic kidney disease (CKD) patients in Iran, in pre-dialysis stages and after initiation of hemodialysis Saudi Journal of Kidney Diseases and Transplantation... metabolic and endocrine disorders, including erythropoietin secretion In addition, the acidosis balance disorder and the increase in free radicals and inflammatory cytokines inhibit erythroblast in. .. About anemia characteristics, there was 37.7% of anemia patients with hypochromic anemia The majority of anemia patients had normochromic anemia (62.3%) This was up to 13% of anemia patients with