|Year : 2019 | Volume
| Issue : 2 | Page : 61-66
The spectrum of red blood cell parameters in chronic kidney disease: A study of 300 cases
Indira Shastry, Sushma Belurkar
Department of Pathology, Kasturba Medical College, Manipal, Karnataka, India
|Date of Web Publication||10-Jul-2019|
Dr. Sushma Belurkar
Department of Pathology, Kasturba Medical College, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
AIMS: To analyze various changes in the red blood cell (RBC) parameters in patients with chronic kidney disease (CKD) and to correlate it with the stage of the disease.
MATERIALS AND METHODS: The following parameters were analyzed in 300 diagnosed cases of CKD: RBC count; hemoglobin (Hb); hematocrit; mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); MCH concentration (MCHC); serum iron profile (serum total iron, total iron-binding capacity, and serum ferritin levels); and peripheral smear, blood urea, and serum creatinine levels. The data were retrieved from the laboratory information system, and SPSS version 20 was used for statistical analysis.
RESULTS: The mean age of presentation was 52 ± 14 years. The male-to-female ratio was 4.3:1. The mean RBC count was 3.29 ± 0.79 × 106/μl, and a significant fall was noticed as the stage of CKD progressed. 74% and 60% of patients with Stage 4 and 5 CKD, respectively, showed Hb of <10 g/dl. Correlation of MCV, MCH, and MCHC values with stages of CKD was statistically not significant. One hundred and six (59%) patients had anemia of chronic disease as per the serum iron profile. 94% of patients showed normocytic normochromic RBC picture on peripheral smear and 21% showed features of hemolysis.
CONCLUSION: Anemia is a leading cause of morbidity in patients with CKD and it worsens with the stage of the disease. Evaluation of Hb and RBC parameters in patients with CKD helps in classifying the type of anemia and aids in choosing the correct treatment modalities and avoids unnecessary iron overload in these patients.
Keywords: Anemia, chronic kidney disease, red blood cells
|How to cite this article:|
Shastry I, Belurkar S. The spectrum of red blood cell parameters in chronic kidney disease: A study of 300 cases. J Appl Hematol 2019;10:61-6
| Introduction|| |
Chronic renal failure has attained overriding importance due to associated profound morbidity, mortality, and its impact on lifestyle after the proposal of the Kidney Disease Improving Global Outcomes guidelines for the treatment of patients with chronic kidney disease (CKD). The hematological changes associated with chronic kidney failure are the leading contributing factors for morbidity and mortality. Since the 19th century, because of newer studies and research methodologies, the management and treatment outcome of CKD has changed drastically and hence has a better quality of lifestyle and lesser comorbidities.
The major outcomes of CKD, regardless of the specific diagnosis, include progression to kidney failure and development of cardiovascular complications. Increasing evidence shows that early detection and therapeutic interventions in the earlier stages may prevent or ameliorate some of these complications, as well as slow down the progression to kidney failure.
Renal diseases are associated with a variety of hematological changes, and anemia is the most predominant feature. Pathogenesis of anemia in patients with CKD is multifactorial, but deficiency of erythropoietin (EPO) is the primary cause. Others include hemolysis and shortened red cell survival, iron deficiency, Vitamin B12 and folate deficiency, blood loss (dialyzer, sampling, and gastrointestinal), aluminum toxicity, osteitis fibrosa cystica, anemia of chronic disease due to recurrent infection, and EPO resistance.
Anemia in CKD is usually normocytic normochromic, but sometimes, it can be microcytic hypochromic due to superimposed iron deficiency anemia and hypoproliferative due to reduced EPO activity in the bone marrow. Patients may also show macrocytic anemia due to Vitamin B12/folate deficiency, dialysis-induced changes in red cell volume, and bone marrow suppression. Hematocrit is reduced in these patients due to hemodilution.
Reticulocyte count in these patients is relatively low for the degree of anemia, but peripheral blood smear is often normal with low polychromasia and occasional burr cells and acanthocytes.
Anemia is an independent risk factor for the development of cardiac dysfunctions such as increased cardiac output, cardiac enlargement, left ventricular hypertrophy, and congestive cardiac failure. It may decrease the quality of life and exercising capacity. Cardiovascular diseases account for 40%–50% of all deaths in patients with chronic renal failure.
Epidemiological data by the National Health and Nutrition Examination Survey 3 and the Kidney Early Evaluation Program show an increase in the prevalence of anemia in individuals aged >61 years in the presence of Stage 3 CKD or higher. According to the World Health Organization (WHO), the prevalence of anemia is 43% in patients with CKD. The WHO defines anemia as hemoglobin (Hb) concentration lower than 13 g/dl in men and postmenopausal women and lower than 12 g/dl in younger women.
As renal function deteriorates, slow and progressive decrease in Hb concentration is observed, particularly in patients with glomerular filtration rate (GFR) 30 ml/min/1.73 m2. 75% of uremic patients who require dialysis have hematocrit value of <30% and most of them are transfusion dependent.
Evaluation of anemia in chronic kidney disease
- Complete blood count,,
- Red blood cell (RBC) count, Hb concentration, and hematocrit
- Red blood indices – Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and MCH concentration (MCHC)
- Total and differential white blood cell count
- Platelet count.
- Absolute reticulocyte count
- Serum total iron and TIBC (Total iron binding capacity)
- Serum ferritin to assess iron stores
- Serum transferrin saturation or content of Hb in reticulocytes (CHr) to assess adequacy of iron for erythropoiesis
- Bone marrow (rarely required in unresponsive, idiopathic anemia).
Aims and objectives
- To analyze the changes in various RBC parameters (Hb concentration and hematocrit, RBC count, and RBC indices) in patients with CKD
- To compare the changes in various RBC parameters with different stages of chronic renal failure.
| Materials and Methods|| |
The study was carried out in the clinical laboratory of Kasturba Medical College and Hospital for the duration of 2½ years (November 2011 to June 2014). Three hundred diagnosed cases of CKD were analyzed.
This was a hospital-based retrospective and prospective study (ambispective study). Three hundred diagnosed cases of CKD as per the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative criteria regardless of its primary cause were chosen. GFR was estimated using MDRD study equation.
Estimated glomerular filtration rate = 175 × standardized Scr−1.154 × age−0.203
Multiply by 0.742 for women.
All patients with CKD admitted to Kasturba Hospital were analyzed for the following parameters: RBC count; Hb; hematocrit; MCV; MCH; MCHC; serum iron profile (serum total iron, total iron-binding capacity, and serum ferritin levels); and peripheral smear for type of anemia and features of hemolysis, blood urea, and serum creatinine.
Clinical details were collected from the medical record department, and hematological and biochemical data were retrieved using hospital information system and from research population data for CBC.
Statistical Package for Social Sciences (SPSS), IBM SPSS Statistics 20.0 was used for statistical analysis. Nonparametrical test was used to compare parameters with different stages of renal failure. Spearman's rho correlation study was used for statistical significance and type of correlation (positive or negative). Fisher's exact test was used for categorical data. P < 0.05 was considered statistically significant.
| Results|| |
Three hundred patients with CKD were included in the study. The age distribution of the study population ranged from 18 years to 82 years with a mean age of 52 ± 14 years. Majority of patients were between 51 and 70 years of age. There were 243 (81%) males and 57 (19%) females.
Majority (68.7%) of the patients in the study were in Stage V CKD, followed by Stage IV (22.3%), Stage III (8.7%), and Stage II (0.3%). No cases of Stage I were seen. No cases of Stage I were seen as we have included only the inpatients in the study and Stage I CKD usually do not require hemodialysis and are treated at outpatient department level.
Diabetes was the leading cause of CKD (38.3%), followed by obstructive uropathy (10.3%), hypertension (7.3%), and glomerular diseases (11%) which include chronic glomerulonephritis (4.3%), IgA nephropathy (1.7%), (FSGS) focal segmental glomerulosclerosis (2.7%), membranous nephropathy (1%), and crescentic glomerulonephritis (1.3%) as leading causes of CKD. Rare causes for CKD in the study population included drug-induced renal failure due to nonsteroidal anti-inflammatory drug abuse and ayurvedic medicines (2.3%), chronic tubulointerstitial nephritis due to various etiologies (2.3%), autoimmune diseases such as (SLE) systemic lupus erythematosus (1.7%), renal amyloidosis (1.3%), multiple myeloma (1%), renal artery stenosis (0.7%), and inherited causes such as autosomal dominant polycystic kidney disease (1.7%) and mitochondrial cytopathy (0.3%).
97% of patients with CKD showed deranged renal function test that is blood urea >40 and serum creatinine >1.4.
The RBC count ranged from 1.29 to 4.22 × 103/μl, with a mean of 3.29 ± 0.79. 36.6% of patients showed a decrease in RBC counts of <3 × 106/μl, and 63.4% of patients showed RBC counts of >3 × 106/μl. Majority of patients in Stage 2 and Stage 3 CKD showed RBC counts of >3 × 106/μl. A significant fall in the RBC count was noted as the stage of CKD progressed [Table 1]. Patients with normal RBC counts in advanced CKD were due to treatment with EPO. These findings were statistically significant (P = 0.001).
Hb percentage ranged from 3.6 to 14.2 g/dl with a mean of 9.31 ± 0.52 g/dl. Thirty-three percent of patients showed normal to mildly reduced (>10 g/dl) Hb, and 67% of patients showed decreased Hb <10 g/dl. 60% and 74% of patients with Stage 4 and 5 CKD, respectively, showed Hb of < 10 g/dl. Deviation in Hb percentage is directly proportional to RBC count and hematocrit (PCV). The findings were statistically significant (P = 0.001) [Table 2].
Hematocrit ranged from 11.6% to 42% with a mean of 28.48% ± 7.8%. Thirty-seven percent of patients had normal to mildly reduced hematocrit of >30%, and 63% of patients had hematocrit of <30%. Majority of patients with PCV <30% were in Stage 4 or 5 renal disease. The findings were statistically significant (P = 0.001). On follow-up of patients after hemodialysis, no significant changes were seen in RBC count, Hb, and hematocrit, but in few patients, worsening of anemia was noted.
P values for MCV = 0.576, MCH = 0.392, and MCHC = 0.267 were not found to be statistically significant [Table 3].
|Table 3: Correlation of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration with stage of renal failure|
Click here to view
More than 70% of patients had normal MCV, MCH, and MCHC values.
MCV value ranged from 57 to 132.9 fl with a mean value of 86 ± 7.07 fl. Seventy percent of patients had normal MCV, whereas 27.6% of patients had decreased MCV with microcytes in peripheral smear. Among 6 (2.1%) patients with high MCV, two had macro-ovalocytes with decreased serum B12 and folate levels.
MCH value ranged from 16.7 to 44.8 pg with a mean of 28.4 ± 2.59. MCHC value ranged from 11.8 to 37.1 with a mean value of 32.8 ± 1.71. Correlation of MCV, MCH, and MCHC values with stages of CKD was statistically not significant.
Serum iron profile was available for 177 patients, of which 59 (33.3%) patients showed normal serum iron profile, 7 (3.9%) showed features of iron deficiency, 106 (59%) patients had anemia of chronic disease, and 5 (2.8%) showed iron overload (P = 0.004). Among 106 patients with anemia of chronic disease, 41 cases were associated with infection.
Total serum iron ranged from 12 to 190 μg/dl with a mean of 63.1 ± 38 μg/dl. Decreased total serum iron was seen in 73 (40.3%) cases and increased serum iron was seen in 3 (1.65%) cases. TIBC value ranged from 60 to 531 μg/dl with a mean of 211.9 ± 71.2 μg/dl. Decrease in TIBC was seen in 82 (45.3%) cases and increase in TIBC seen in 3 (1.65%) cases. Serum ferritin ranged from 5 - >2269.0 μg/dl with a mean of 541.2 μg/dl. Increase in serum ferritin was seen in 85 (51.8%) cases and decrease in serum ferritin was seen in 2 (1.21%) cases.
The most frequent peripheral smear picture seen predominantly was normocytic normochromic anemia (94%), followed by microcytic hypochromic anemia in 3.4% of cases and macrocytic anemia in 2.6% of cases. Of the eight cases of macrocytic anemia, serum B12/folate levels were done in only two patients, and it was decreased in both the patients.
Among 10 patients with microcytic hypochromic anemia, only one patient showed serum iron profile suggestive of iron deficiency whereas others showed anemia of chronic disease.
Other significant findings on peripheral smear were polychromasia and anisocytosis. Anisocytosis and polychromasia were mostly seen in patients with normocytic normochromic blood picture with microcytes. Patients with iron deficiency and infections showed anisopoikilocytosis. Echinocytes were seen in only 1 (0.3%) case. As we use the ICSH guidelines for grading of peripheral smears, echinocytes were reported only when they were more than 5% and hence probably the incidence of echinocytes is less in our study [Figure 1].
|Figure 1: Peripheral smear showing sparse distribution of RBC with hypochromasia and anisocytosis (Leishman stain, ×40)|
Click here to view
Features of hemolysis were predominantly seen in patients with Stage 5 CKD and few with Stage 4 disease [Figure 2].
|Figure 2: Peripheral smear showing schistocytes and spherocytes (Leishman stain, ×40)|
Click here to view
Among 300 cases, 44 (14.7%) cases showed spherocytes, fragmented RBC was seen in 28 (9.3%) cases, and schistocytes were seen in 2 (0.7%) cases. Spherocytes were observed in patients with very high blood urea levels (Stage 4 and 5). All the patients with spherocytes showed negative autoimmune serology finding, except in five cases where the cause of renal failure was SLE.
| Discussion|| |
Our study demonstrated a low RBC count in the study population which worsened as the renal function deteriorated. Only those cases who received EPO showed normal RBC counts along with normal Hb and PCV. A statistically significant correlation was observed between the severity of anemia and the stage of renal failure, suggesting that severe anemia is more likely to be associated with Stage V renal failure. On follow-up of these patients after hemodialysis, the severity of anemia worsened. These findings agree with the studies by Suresh et al., Talwar et al., and Singh et al., which also showed low RBC counts, Hb, and hematocrit values associated with CKD patients [Table 4].
|Table 4: Comparison of mean red blood cell count, hemoglobin, and packed cell volume in chronic kidney disease|
Click here to view
In the study by Alghythan and Alsaeed (Saudi Arabia), RBC count, Hb, and PCV levels, although within normal range, were significantly lower when compared with the control population.
Primary cause of decrease in RBC count, Hb, and hematocrit (RBC mass) in chronic renal failure is impaired EPO production and shortened red cell survival, due to the effect of uremic plasma which increases the expression of phosphatidylserine on outer leaflet of red cell membrane and hence increased recognition of the damaged red cells by macrophages leading to their destruction. Other causes for anemia in our study group were iron-deficiency anemia, and few cases showed Vitamin B12/folate deficiency.
Hematocrit provides accurate reflection of the extent of reduction of red cell mass in chronic renal failure. The severity of anemia was found to be directly associated with the stage of renal failure. The findings in the present study agree with the study by Arun et al., which showed lower values of Hb toward lesser values of GFR [Table 5]. Similar studies done by Shittu et al. and Khanam et al. showed decline in the mean RBC count as stage of renal failure progressed.
Majority of patients (>70%) with CKD in our study population showed normal MCV, MCH, and MCHC values. The present study agrees with the studies by Talwar et al., Singh et al., and Alghythan and Alsaeed, in which majority of patients showed normal RBC indices.
A study conducted by Shittu et al. showed comparatively lower MCV and MCH values, but it was not statistically significant because the control population also showed similar values and did not show significant differences in RBC indices in different stages of renal failure. Similarly, in our study, patients in different stages of renal failure did not show significant changes in RBC indices.
Total serum iron in the present study is in accordance with the study by Talwar et al., but the mean serum ferritin values are high because of unequal distribution of values ranging from 5 to >2269. This is also because most of cases in our study had anemia of chronic disease with lower mean TIBC levels.
A study by Singh et al. showed higher mean values for serum iron and lower serum ferritin levels than our study. This is because patients had received EPO therapy, and fall in serum ferritin in these cases indicates iron utilization by replicating erythroid cells. In our study, only few patients had received EPO; therefore, no significant decrease in the mean serum ferritin levels was observed.
In 2010, Jairam et al. showed that 60% of the end-stage renal disease patients in their study had adequate iron stores, most of them had received parenteral iron therapy before presentation to their hospital, and iron deficiency was seen among who had not received intravenous iron. Hence, wide use of parenteral iron and repeated transfusions in cases of CKD had led to iron overload. They also concluded that the use of serum ferritin alone for defining iron overload is faulty, because 2–3-fold elevations in the ferritin (acute phase reactant) levels with inflammatory activation are known, which is common in patients with CKD.
On comparison of peripheral smear, the results in the present study are similar to the studies by Singh et al. and Bhatta et al., where majority of cases showed normocytic normochromic picture [Table 6]. The differences in the smear findings between different studies are due to the variation in the sample size and difference in the study population.
Talwar et al. showed a higher incidence of microcytic hypochromic anemia compared to our study population. Lesser incidence in our study population could be explained by the fact that majority of patients in advanced stages of renal failure receive oral or parenteral iron as prophylactic even before evaluation for iron deficiency.
Normocytic normochromic anemia in renal failure patients is mainly hypoproliferative anemia due to EPO deficiency leading to bone marrow suppression and peripheral destruction.
*In the study by Arun et al., 25% of cases showed features of both normocytic normochromic anemia and microcytic hypochromic anemia, but iron deficiency was associated with only subset of cases.
| Conclusion|| |
Anemia is a leading cause of morbidity in patients with CKD, and it worsens with the stage of the disease. The most common type of anemia is normocytic normochromic anemia due to EPO deficiency and microcytic hypochromic anemia due to iron deficiency. Evaluation of Hb and RBC parameters in patients with CKD helps in classifying the type of anemia and aids in choosing the correct treatment modalities and avoids unnecessary iron overload in the patients.
We acknowledge Dr. Chethan Manohar, Lab in Charge, for granting us permission to do the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Levey AS, Coresh J, Bolton K, Kusek J, Culleton B, Levin A, et al.
NKF-KDOQI clinical practice guidelines for chronic kidney disease. Am J Kidney Dis 2002;39:S11-2.
Robinson BE. Epidemiology of chronic kidney disease and anemia. J Am Med Dir Assoc 2006;7:S3-6.
Zachée P, Vermylen J, Boogaerts MA. Hematologic aspects of end-stage renal failure. Ann Hematol 1994;69:33-40.
Joanne M, Bargman JM, Skorecki K. Disorders of the kidney and urinary tract. In: Harrison's Principle and Practice of Internal Medicine. 17th
ed. Vol. 2. New York: McGraw-Hill; 2008. p. 1761-71.
Tennankore KK, Soroka SD, West KA, Kiberd BA. Macrocytosis may be associated with mortality in chronic hemodialysis patients: A prospective study. BMC Nephrol 2011;12:19.
Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012;23:1631-4.
KDOQI, National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 2006;47:S11-145.
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.
Worwood M, May A. Iron deficiency anemia and iron overload. In: Dacie and Lewis Practical Hematology. 11th
ed. Elsevier; Churchill Livingstone; 2011. p. 176-96.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd
, Feldman HI, et al.
Anew equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12.
Suresh M, Reddy MN, Singh SB, Bandi HK, keerti SG, Chandrashekar M. Hematological changes in chronic renal failure. Int J Sci Res Publ 2012;2:1-4.
Talwar VK, Gupta HL, Narayan S. Clinicohaematological profile in chronic renal failure. J Assoc Physicians India 2002;50:228-33.
Singh NP, Aggarwal L, Singh T, Anuradha S, Kohli R. Anaemia, iron studies and erythropoietin in patients of chronic renal failure. J Assoc Physicians India 1999;47:284-90.
Shittu AO, Chijioke A, Biliaminu S, Makusidi M, Sanni M, Abdul Rehman M, et al
. Hematological profile of patients with chronic kidney disease in Nigeria. J Nephrol Ren Transplant 2013:5;2-10.
Wasti AZ, Iqbal S, Fatima N, Haider S. Haematological disturbances associated with chronic kidney disease and kidney transplant patients. Int J Adv Res 2013;1:48-54.
Alghythan AK, Alsaeed AH. Haematological changes before and after hemodialysis. Sci Res Essays 2012;7:490-7.
Arun S, prabhu VM, Chowta NK, Bengre ML. The haematological pattern of the patients with chronic kidney disease in a tertiary care setup in South India. J Clin Diagn Res 2012;6:1003-6.
Khanam S, Begum N, Begum S, Hoque EA. Changes in haematological indices in different stages of chronic renal failure. J Bangladesh Soc Phyisol 2007;2:38-41. [doi: 10.3329/jbsp.v2i0.983].
Jairam A, Das R, Aggarwal PK, Kohli HS, Gupta KL, Sakhuja V, et al.
Iron status, inflammation and hepcidin in ESRD patients: The confounding role of intravenous iron therapy. Indian J Nephrol 2010;20:125-31.
] [Full text]
Bhatta S, Aryal G, kafle RK. Anemia in chronic kidney disease patients in predialysis and post dialysis stages. J Patholo Nepal 2011;1:26-9.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
|This article has been cited by|
||Traversing Their Path to the Peripheral Smear: The Journey of Traumatized Red Blood Cells
| ||Chethana Mannem, Tuba Saher, Gayathri Bilagali Ramdas |
| ||Journal of Laboratory Physicians. 2023; |
|[Pubmed] | [DOI]|
||Scaling Pharmacodynamics from Rats to Humans to Support Erythropoietin and Romiplostim Combination Therapy to Treat Erythropoietin-Resistant Anemia
| ||Xiaoqing Fan, Wojciech Krzyzanski, Dongyang Liu, Raymond S. M. Wong, Xiaoyu Yan |
| ||Pharmaceutics. 2023; 15(2): 344 |
|[Pubmed] | [DOI]|
||Morphological Types of Anemia Associated with Chronic Renal Diseases
| ||Mazin Razooqi Mohammed, Bushra Mahmood |
| ||Open Access Macedonian Journal of Medical Sciences. 2022; 10(B): 905 |
|[Pubmed] | [DOI]|
||An analysis of laboratory parameters of chronic kidney failure in elderly patients
| ||Edhem Haskovic, Harun Uzunalic, Snežana Uncanin, Safija Herenda, Denis Haskovic, Amina Selimovic |
| ||Acta Facultatis Medicae Naissensis. 2022; 39(4): 459 |
|[Pubmed] | [DOI]|
||Administration of a-Klotho Does Not Rescue Renal Anemia in Mice
| ||Min Young Park, Carole Le Henaff, Despina Sitara |
| ||Frontiers in Pediatrics. 2022; 10 |
|[Pubmed] | [DOI]|
||The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients
| ||Magda Wisniewska,Natalia Serwin,Violetta Dziedziejko,Malgorzata Marchelek-Mysliwiec,Barbara Dolegowska,Leszek Domanski,Kazimierz Ciechanowski,Krzysztof Safranow,Tomasz Golebiowski,Andrzej Pawlik |
| ||International Journal of Environmental Research and Public Health. 2021; 18(12): 6282 |
|[Pubmed] | [DOI]|
||Renalase in Haemodialysis Patients with Chronic Kidney Disease
| ||Magda Wisniewska,Natalia Serwin,Violetta Dziedziejko,Malgorzata Marchelek-Mysliwiec,Barbara Dolegowska,Leszek Domanski,Kazimierz Ciechanowski,Krzysztof Safranow,Andrzej Pawlik |
| ||Journal of Clinical Medicine. 2021; 10(4): 680 |
|[Pubmed] | [DOI]|