Assessment of Iron Profile in Chronic Kindey Disease Patients Managed Without Dialysis
Assessment of Iron Profile in Chronic Kindey Disease Patients Managed Without Dialysis
Assessment of Iron Profile in Chronic Kindey Disease Patients Managed Without Dialysis
Corresponding Authors: Dr. Dumpa. Srinivasa Reddy M.D. 1*; Dr. Srikar Bharadwaj SPVS2*; Dr. Ballipilli Mohith3*
Abstract:-
Conclusion:
Aim: It is imperative to make every possible attempt to
To assess the Haematological profile and Serum Iron determine the underlying cause of anemia in patients with
indices in non-dialysis Chronic Kidney Disease patients chronic kidney disease (CKD) and to provide appropriate
treatment for the concurrent iron deficient anemia in
Background And Objectives: these individuals. Additionally, it is important to monitor
Anemia is one of the most common condition seen in other hematological parameters in order to identify any
patients with Chronic Kidney Disease. It occurs due to concomitant abnormalities.
reduced production of erythropoietin from Kidney which
is required for production of RBC. As many people are I. INTRODUCTION
landing up with CKD and it is becoming a global issue,
anemia is becoming more prevalent among the Chronic kidney disease (CKD) refers to a range of
population. One of the factor which also contributes to it different processes that cause impaired kidney function and a
is nutritional deficiency such as iron deficiency anemia gradual decrease in glomerular filtration rate (GFR).
which overlaps with reduced production of RBC due to
CKD. Accurately assessing the burden of chronic renal disease
is challenging. The estimated prevalence of chronic kidney
Materials and Methods: disease (CKD) is 800 cases per one million individuals,
It is a cross sectional study conducted over a period whereas the occurrence of end stage renal disease (ESRD) is
of 18 month in out patient department and wards of between 150 and 200 cases per one million individuals.
Department of Nephrology and General Medicine, Katuri Chronic kidney disease (CKD) is a global epidemic that is
Medical College and Hospital, Guntur. A sample size of linked to several other health conditions, making it a disease
100 individuals were considered for the study. Ethical with a high fatality rate.1,2
Clearances were taken and informed consent given about
the same. Patients underwent needed investigations like Anemia of chronic disease is a multifaceted ailment
haematological profile including Serum. Ferritin, Iron influenced by a range of causes. While the main issue is a
and transferrin saturation and Renal Function tests. reduction in the generation of erythropoietin by the kidney,
several additional factors may also have a contributing effect.
Results: For instance, deficiencies in iron, folate, and vitamin B12
Our study's findings indicated that the severity of might occur as a result of inadequate nutrition or increased
chronic renal disease increased along with a low level of blood loss, shorter red blood cell (RBC) lifespan,
hemoglobin and packed cell volume. Anaemia was hyperparathyroidism, moderate chronic inflammation, or
present in all the individuals included in the study cases. aluminum toxicity. Anemia in chronic kidney disease
70% of the individuals exhibited microcytic exacerbates the co-morbidities of diabetes and hypertension,
normochromic anemia, while 10% displayed microcytic leading to unfavorable outcomes and increased mortality
hypochromic anemia. 10 percent of the studied subjects rates, resulting in unfavorable results and elevated fatality
exhibited concurrent occurrences of both forms of rates.
anemia. The observed difference was very statistically
significant (p = 0.0001). Among the Control patients, 32% Untreated chronic anemia can result in several
had normal levels of haemoglobin, whereas the remaining physiological diseases, such as cardiovascular issues, and can
68% presented both kinds of anemia. There were lead to higher rates of death and morbidity. The Kidney
significant differences (p < 0.05) in the TIBC, TSAT %, Disease Outcomes Quality Initiative (KDOQI) guidelines,
and Ferritin values between the study and control cases in published by the National Kidney Foundation in 2002,
terms of serum iron indices. The Ferritin readings did not categorized chronic kidney disease (CKD) into five stages
show any significant differences. based on two factors: glomerular filtration rate (GFR) and
The Following Items are Included: measuring blood sugar levels, renal parameters such as blood
urea and serum creatinine, serum electrolyte levels, and the
Age below 18 years urine spot protein creatinine ratio.
Indications of recent infection or injury during the past
four weeks Serum ferritin levels were measured using an enzyme-
Recent administration of iron injections through non-oral linked immunosorbent assay (ELISA). The iron level was
routes within the past 14 days. assessed using the Ferrozine method without the need for
Recent blood transfusion history during the past month deproteinization.
Hemoglobinopathies
Malignancies The Spectrophotometric Assay was used to assess the
Total Iron Binding Capacity (TIBC).
Recent visible bleeding
Patient undergoing dialysis and post-transplant status.
Transferrin saturation is determined by the formula
(TSAT): TSAT = (serum iron/total iron-binding capacity) ×
IV. METHODS
100.
The Clinical Examination Encompassed
Ethical committee approval : Obtained
Consent : Informed Consent obtained
Assessment of weight, height, and vital statistics.
Examination of Major Systems Financial Support : Nil
Conflict of Interest : Nil
Haematological tests include measurements of
haemoglobin, red blood cell count, white blood cell count, Statistical Tools
haematocrit, differential count, mean corpuscular volume The data gathered on all the cases selected was
(MCV), mean corpuscular haemoglobin (MCH), mean documented in a Master Chart. The data analysis was
corpuscular haemoglobin concentration (MCHC), platelet conducted using the Epidemiological Information Package
count, red cell distribution width (RDW), examination of (EPI 2010), a computer program developed by the Centre for
peripheral smear, and assessment of bleeding time. Tests Disease Control in Atlanta.
were conducted to measure clotting time, ESR (erythrocyte
sedimentation rate), serum ferritin, total iron binding Utilizing this software, calculations were performed for
capacity, and serum iron. Hemogram was conducted using range, frequencies, percentages, means, standard deviations,
automated methods. chi square, and 'p' values. The Kruskal-Wallis chi-square test
was employed to assess the significance of differences
A peripheral blood smear was performed. The between quantitative variables, whereas Yate's chi-square test
erythrocyte sedimentation rate (ESR) was determined using was utilized for qualitative variables. A 'p' value less than
the Wintrobes method. Biochemical studies include 0.05 is considered to indicate a statistically significant link.
The study group had a mean age of 39.68 years with a CKD GROUP CONTROL GROUP
standard deviation of 12.56 years, while the control group had 39.68 40.1
a mean age of 40.1 years with a standard deviation of 13.4
years.
Out of a total of 50 study cases, 34 are males and 16 are Table 3: Duration of Illness Among Patients with Chronic
females. The male population accounts for 68% while the Kidney Disease
female population accounts for 32%. Among the 50 control Table 3: Duration of illness
cases, there are 35 males and 15 girls. The male population Parameter Duration of CKD in Months
comprises 70% while the female population comprises 30%. Range 3-24
Mean 8.42
Sex CKD GROUP CONTROL GROUP SD 4.371008383
Male 34 35
Female 16 15 The duration of disease varied between 3 months and 24
months, with an average of 8.57 months.
Table 4: Glomerular Filtration Rate (GFR) among patients Suffering with Chronic Kidney Disease (CKD) and their Stages
Glomerular Filtration Rate (GFR) / CKD stages
CKD stages /GFR (ml/min/m²) Cases
NO %
Stage 5(<15) 18 36.00%
Stage 4 (15-29) 18 36.00%
Stage 3 (30-59) 14 28.00%
Stage 2 (60-89) _
Stage 1 (≥90) _
Total 50 100.00%
Range 2.09-45
Mean 17.564928
SD 10.97845872
Out of the 50 cases of Chronic Kidney Disease (CKD), CKD Stages Percentage
the Glomerular Filtration Rate (GFR) varied between 2.09 Stage 5 36.00%
and 45 ml/min/m2. The average glomerular filtration rate Stage 4 36.00%
(GFR) was 17.56 milliliters per minute per square meter, with Stage 3 28.00%
a standard deviation of 10.97. None of the selected instances
exhibited stage 1 or stage 2. Among all cases, 28% of patients had Stage 3 sickness,
36% had Stage 4, and the remaining 36% had Stage 5.
48% of the study cases had hypertension, whereas 26% had Diabetes Mellitus.
History of bleeding manifestation (gum bleeding, ecchymosis) was present in 2 cases, motion ova & cyst present in 2 cases
and motion for occult blood was positive in one case.
Upon comparing the data from the study and control and the average packed cell volume (PCV) was 25.50%. The
groups, significant statistical differences were seen in Mean Red Cell Distribution Width was 15.71%. The
Hemoglobin (Hb), RBC count, PCV, and ESR (p<0.005). Erythrocyte Sedimentation Rate was increased in 35 cases,
Hemoglobin, red blood cell count, and packed cell volume accounting for 64.8% of the total.In all cases, the levels of
were lower, whereas erythrocyte sedimentation rate was hemoglobin and packed cell volume were found to be
higher, compared to the control group. low.There were 7 cases with an increase in neutrophil white
blood cells and 3 cases with an increase in lymphocyte white
The average hemoglobin level was 8.01 gm/dl. Among blood cells. There were six patients that exhibited
males, the average hemoglobin level was 8.03 gm/dl, while eosinophilia. None of the patients exhibited symptoms
among females, it was 7.71 gm/dl. The average red blood cell indicative of lymphoma or leukemia. Thrombocytosis was
(RBC) count was 3.17 million per cubic millimeter (mm3), present in 7 individuals.
Table 8: Association between CKD Stages and other Quantiative Haematological Parameters
Parameter Values (Mean±SD) in Cases with P Value Significance
CKD 3 CKD 4 CKD 5 (ANOVA)
Hb (gm/dl) 9.04±1.65 8.6±1.07 6.98±1.59 0.0004 Significant at 0.0005
RBC (million/cumm) 3.41±0.56 3.29±0.75 2.85±0.66 0.0489 Not Significant at 0.0001
PCV % 28.43±3.58 26.2±3.77 22.51±3.93 0.0002 Significant at 0.0002
MCV (fL) 80.96±9.25 84.20±7.26 78.13±21.65 0.4633 Not Significant at 0.0001
MCH (pg) 26.50±5.28 25.38±4.78 25.38±5.47 0.7909 Not Significant at 0.0001
MCHC (g/dL) 31.08±4.03 31.45±3.56 32.27±3.01 0.6136 Not Significant at 0.0001
RDW % 15.83±4.72 15.72±4.35 15.61±2.59 0.9878 Not Significant at 0.0001
Duration (in months) 6.57±2.40 7.77±2.50 10.55±3.11 0.0005 Significant at 0.0005
Significant statistical relationships were found between The p-value is less than 0.0005. As the stage of chronic
the levels of Hb% (p= 0.0005), PCV (p<0.0002), and the kidney disease (CKD) progresses, the level of hemoglobin
length of sickness and the stages of chronic kidney disease and packed cell volume falls. These associations exhibit
(CKD). statistical significance.
Three patients (6%) saw an increase in bleeding time. The clotting time was within the usual range for all patients.
Anaemia was present in all the individuals included in The observed difference was very statistically significant (p
the study cases. 70% of the individuals exhibited microcytic = 0.0001). Among the Control patients, 32% had normal
normochromic anemia, while 10% displayed microcytic levels of haemoglobin, whereas the remaining 68% presented
hypochromic anemia. 10 percent of the studied subjects both kinds of anemia.
exhibited concurrent occurrences of both forms of anemia.
Fig 1: Variations in Peripheral Smear Seen in Patients with Chronic Kidney Disease
Table 11: Relationship between Type of Peripheral Smear and Serum Ferritin (ug/l), Transferrin Saturation %(TSAT)
Peripheral Smear type No of Cases Mean TSAT Mean Ferritin
Normocyctic normochromic 35 30.98 342.88
Microcyctic hypochromic 10 16.62 116.37
Both 5 22.16 170.18
There was a statistically significant correlation between hypochromic anemia exhibited low levels of serum ferritin
the type of peripheral smear and TSAT (p=<0.001), as well and transferrin saturation. The average transferrin saturation
as a substantial correlation between the type of peripheral in cases of normocytic normochromic anemia is 30.98, while
smear and ferritin levels (p=<0.002). Patient with microcytic in cases of microcytic hypochromic anemia it is 16.62. Both
types of anemia are observed in 22.16% of cases. The average anemia is 116.37, and in patients with both types of anemia is
ferritin levels in patients with normocytic normochromic 170.18.
anemia is 342.88, in patients with microcytic hypochromic
Left ventricular hypertrophy was observed in 34% of between the hemoglobin level and LVH. The p-value is less
individuals with chronic kidney disease, specifically in 17 than 0.001.
cases. A statistically significant correlation was observed
There were significant differences (p < 0.05) in the control cases in terms of serum iron indices. The Ferritin
TIBC, TSAT %, and Ferritin values between the study and readings did not show any significant differences.
There was no statistically significant association between serum iron indices, severity of CKD, and serum iron profile.
38% of the study cases have a serum ferritin level below The etiology of anemia in chronic renal disease is
100 micro gm/L. There is no significant correlation between multifaceted. The renal community has long acknowledged
the stage of chronic kidney disease (CKD) and the level of that anemia can detrimentally affect the quality of life of
serum ferritin. 62% of the cases had a serum ferritin level patients and result in irreversible cardiac repercussions.33,34.
more than 100 nano gm/L. (Levy AS et al)
<100 microg/L ≥100 microg/L Anemia, a condition that can be easily reversed in end-
38 62 stage renal disease, is a separate risk factor for both cardiac
disease and death in individuals with end-stage renal
VI. DISCUSSION disease33,34.
Chronic kidney disease is a significant global public The existing evidence clearly indicates that: In order to
health issue and a leading cause of illness and death. The form red blood cells, both iron and erythropoietin are
incidence of early stages of CKD is significantly higher than necessary. Therefore, if there is not enough iron available,
that of advanced stages.However, in clinical practice, the erythropoietin will have limited effectiveness. The TSAT and
prevalence of stage 4 and 5 is higher due to the fact that first serum ferritin are the most reliable indications of the body's
stages are typically asymptomatic, and individuals seek iron status that we currently have, however no tests are
medical attention when the severity of symptoms escalates. completely accurate in assessing iron reserves. The numbers
are 35, 36, and 37. Considering the high occurrence of iron
deficiency in patients with chronic kidney disease (CKD), as
well as the accuracy of TSAT and serum ferritin in identifying
iron deficiency, it may be concluded that there is a significant
probability of iron deficit when TSAT is below 20% and VII. LIMITATION OF THE STUDY
serum ferritin is below 100 ng/mL. Hence, it is imperative to
ensure that the TSAT (Transferrin Saturation) and serum Due to the limited size of the study population, it is
ferritin levels are kept above 20% and 100 ng/mL, necessary to conduct larger investigations in order to confirm
respectively, in all patients with non-dialysis chronic renal the findings of this study. Iron deficiency in chronic kidney
disease. disease (CKD) should be evaluated using alternative and
more recent techniques, such as soluble transferrin receptors,
This study was conducted to examine the hematological zinc protoporphyrin, percentage of hypochromic cells,
profile and determine the prevalence of iron deficiency reticulocyte hemoglobin content, and the most reliable way,
anemia in non-dialysis chronic renal disease patients. bone marrow testing for stainable iron. Hepcidin level was
not measured.
The study group had a mean age of 39.68 years with a
standard deviation of 12.56 years, while the control group had In our patients, the likely factors contributing to iron
a mean age of 40.1 years with a standard deviation of 13.4 deficiency, such as hidden or concealed Upper
years. Out of a total of 50 study cases, 34 are males and 16 gastrointestinal endoscopy did not rule out gastro intestinal
are females. The male population accounts for 68% while the blood loss. Assays for folic acid and vitamin B12 are not
female population accounts for 32%. Among the 50 control conducted.
cases, there are 35 males and 15 girls. The male population
comprises 70% while the female population comprises 30%. Due to the nature of this cross-sectional investigation,
The duration of disease varied between 3 months and 24 we were unable to ascertain the long-term persistence of the
months, with an average of 8.57 months. findings. Ultimately, this study merely demonstrates a
correlation and is unable to establish a causative relationship.
Out of the 50 cases of Chronic Kidney Disease (CKD), Conclusive evidence can only be obtained through
the Glomerular Filtration Rate (GFR) varied between 2.09 interventional research to establish a cause-and-effect link.
and 45 ml/min/m2. The average glomerular filtration rate
(GFR) was 17.56 milliliters per minute per square meter, with VIII. CONCLUSION
a standard deviation of 10.97. None of the selected instances
exhibited stage 1 or stage 2. 48% of the study cases had Our investigation has revealed that chronic renal disease
hypertension, whereas 26% had Diabetes Mellitus. primarily impacts individuals in the middle age
demographic.
History of bleeding manifestation (gum bleeding, All the participants in this study were classified as being
ecchymosis) was present in 2 cases, motion ova & cyst in stage 3, 4, or 5 of Chronic Kidney Disease (CKD).
present in 2 cases and motion foroccult blood was positive in All of our patients had severe anemia, which significantly
one case.In their investigation, Akisola et al.41 observed a contributes to the high rates of death and illness in
25.6% increase in bleeding time. Therefore, it is important to individuals with End Stage Renal Disease (ESRD).
exercise caution during surgical procedures in patients with Hemoglobin and Packed Cell Volume decreased
chronic kidney disease (CKD) who experience increased significantly as the severity of CKD stage increased.
bleeding time. Additionally, correcting anemia may help Three patients (6%) had an increase in bleeding time. The
improve the abnormal bleeding time. clotting time was within the usual range for all patients.
Anaemia was present in all the individuals included in the
Upon comparing the data from the study and control study cases. 70% of the individuals exhibited microcytic
groups, significant statistical differences were seen in normochromic anemia, while 10% displayed microcytic
Hemoglobin (Hb), RBC count, PCV, and ESR (p<0.005). hypochromic anemia. 10 percent of the studied subjects
Hemoglobin, red blood cell count, and packed cell volume exhibited concurrent occurrences of both forms of
were lower, whereas erythrocyte sedimentation rate was anemia. The observed difference was very statistically
higher, compared to the control group. significant (p = 0.0001). Among the Control patients, 32%
had normal levels of haemoglobin, whereas the remaining
The average hemoglobin level was 8.01 gm/dl. Among 68% presented both kinds of anemia.
males, the average hemoglobin level was 8.03 gm/dl, while
There were significant differences (p < 0.05) in the TIBC,
among females, it was 7.71 gm/dl. The average red blood cell TSAT %, and Ferritin values between the study and
(RBC) count was 3.17 million per cubic millimeter (mm3), control cases in terms of serum iron indices. The Ferritin
and the average packed cell volume (PCV) was 25.50%. The
readings did not show any significant differences.
Mean Red Cell Distribution Width was 15.71%. The
Prior to the start of dialysis or erythropoietin therapy, it is
Erythrocyte Sedimentation Rate was increased in 35 cases,
recommended to administer sufficient iron supplements
accounting for 64.8% of the total.
either orally or through the parenteral route in order to
achieve the desired outcomes as per the guidelines
provided by the National Kidney Foundation (NKF).
Efforts must be made to determine the source of anemia [17]. Pickett JL, Theberge DC, Brown WS, et al:
in patients with chronic kidney disease (CKD) and to treat Normalizing haematocrit in dialysis patients improves
the concurrent iron deficiency anemia. Additionally, it is brain function. Am J Kidney Dis 1999; 33(6):1122-
important to monitor other hematological parameters to 1130.
identify any coexisting abnormalities.
REFERENCES