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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA–AFRICA  
Year : 2018  |  Volume : 29  |  Issue : 6  |  Page : 1431-1440
Assessment of iron status in predialysis chronic kidney disease patients in a Nigerian Tertiary Hospital


1 Department of Internal Medicine, University of Benin, Benin City, Edo State, Nigeria
2 Department of Internal Medicine, Kidney Care Center, University of Medical Sciences, Ondo, Ondo State, Nigeria

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Date of Submission18-Oct-2017
Date of Acceptance14-Dec-2017
Date of Web Publication27-Dec-2018
 

   Abstract 

Anemia in chronic kidney disease (CKD) is associated with poor overall outcome if not promptly managed with erythropoietin when indicated. This study assessed iron status and associated factors in predialysis CKD patients in Southern Nigeria. This was a cross-sectional study that assessed and compared iron status in 100 predialysis CKD patients and 90 healthy controls. Mean age of the CKD patients was 49.39 ± 14.84 years. Iron deficiency was present in 14% of CKD patients compared to 3% of the controls (P = 0.021). Among CKD patients with ID, 11 (85.7%) had functional iron deficiency while three (14.3%) had absolute iron deficiency. Serum ferritin was significantly higher in the predialysis CKD patients (P = 0.001). There was no significant gender difference in iron indices among the CKD patients. Functional iron deficiency was present in 11 (11%) of the CKD patients compared to none among the control group (P = 0.003). There was no significant association between iron deficiency and age, gender, etiology, and stage of CKD. Functional iron deficiency was the predominant form of iron deficiency in our predialysis CKD patients, and there was no significant association with age, gender, stage, or etiology of CKD.

How to cite this article:
Iyawe IO, Adejumo OA, Iyawe LI, Oviasu EO. Assessment of iron status in predialysis chronic kidney disease patients in a Nigerian Tertiary Hospital. Saudi J Kidney Dis Transpl 2018;29:1431-40

How to cite this URL:
Iyawe IO, Adejumo OA, Iyawe LI, Oviasu EO. Assessment of iron status in predialysis chronic kidney disease patients in a Nigerian Tertiary Hospital. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jan 17];29:1431-40. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1431/248296

   Introduction Top


Anemia is one of the nontraditional cardiovascular risk factors that commonly occurs in chronic kidney disease (CKD) patients.[1],[2],[3],[4] Causes of anemia in CKD are multifactorial including relative deficiency of erythropoietin (EPO), malnutrition, inflammation, uremic toxins, bone marrow fibrosis, chronic blood loss, reduced red cell life span, and abnormal platelet function.

Anemia contributes significantly to the development of cardiovascular disease (CVD) in CKD patients by causing left ventricular dilatation and hypertrophy.[5] Anemia is also associated with rapid progression to end-stage renal disease, prolonged hospitalization, exercise intolerance, impaired cognitive and sexual function, and reduced quality of life in CKD patients; hence, there is a need for early treatment.[6],[7],[8],[9] Left ventricular hypertrophy may be reversed, and other secondary effects of anemia in CKD may be improved if correction of anemia is instituted early with EPO.[10],[11],[12] However, patients may become unresponsive to EPO treatment in the presence of iron deficiency which may be functional or absolute.[13] Approximately 40% of patients with EPO resistance have iron deficiency. Deficiency of iron which is an integral element in hemoglobin (Hgb) leads to impaired Hgb production.[13],[14] The common causes of iron deficiency in CKD include anorexia, vomiting, reduced intestinal absorption, inflammation, infection, and acute and/or chronic blood loss. CKD patients are also at risk of iron overload if iron therapy is instituted without close monitoring of iron status with possible attendant complications such hospitalization, CVD, and mortality.[15],[16],[17]

Serum iron, ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), percentage hypochromic red cells, reticulocyte Hgb content, zinc protoporphyrin, and soluble transferrin receptors are useful in iron status assessment. However, two most widely available and used tests for assessing iron status are the TSAT and serum ferritin even though they have limitations in terms specificity and specificity in patients with CKD.[18]

There is still limited information on iron status and associated factors in predialysis CKD patients in Nigeria. This study assessed iron status and associated factors in predialysis CKD patients. The findings of this study add to the body of knowledge and also provide information that may be helpful in reviewing and improving local guidelines for anemia management in CKD.


   Methods Top


This was a hospital-based cross-sectional analytical study carried out in the University of Benin Teaching Hospital (UBTH), Benin, Edo State, Nigeria over a period of one year between November 2013 and October 2014. Consecutive predialysis CKD patients who met the inclusion criteria were recruited over one-year period from the nephrology clinic, medical wards, and the emergency unit of the hospital. Controls were recruited from healthy staff of the hospital and patients’ relatives who did not have CKD. The consent of all participants in this study was obtained before recruitment into the study. Ethical clearance for this study was obtained from the Ethics and Research Committee of UBTH on October 2, 2013, with protocol number ADM/E 22/A/ VOL.VII/956.

Sample size

This was calculated using 94% as the prevalence of anemia in CKD patients with the Leslie-Kish formula for sample size determination in a finite population as shown below:[19]



Where

N = Sample size

Z = Value of 95% confidence interval = 1.96

P = Prevalence 94% (0.94)

E = Sampling error = 0.05



N = 1.962 × 0.94 × 0.06/0.052

N= 86.66

N is approximately 87.

The minimum sample size in this study was 96 after including 10% attrition rate.

A total of 100 predialysis CKD patients and 90 age-and sex-matched apparently healthy adults without CKD were involved in the study.

Inclusion criteria were newly diagnosed CKD patients or those on conservative management who were ≥18 years of age and gave informed consent to participate in the study while exclusion criteria were CKD patients on renal replacement therapy (RRT) and those with HIV infection, hemoglobinopathies, chronic infections, malignancy, history of cigarette smoking, use of erythropoiesis-stimulating agents, iron products, or history of blood transfusion in the previous four weeks to the time of evaluation for study.

Ten milliliters of blood was collected from participants of this study for serum creatinine, erythrocyte sedimentation rate (ESR), serum iron, TIBC, ferritin levels, and TSAT. Estimated glomerular filtration rate (eGFR) was calculated using modification of diet in renal disease that has been previously validated in Nigerians.[20]

Definition of terms

Absolute iron deficiency was defined as TSAT <20% and serum ferritin <100 ng/mL while functional iron deficiency was defined as TSAT <20% and serum ferritin >100 ng/mL.[18]

TSAT was calculated using the formula (TSAT) = SI/TIBC × 100;[22]

Where TIBC (pg/dL) = iron level + UIBC and serum iron.

CKD was defined as the presence of markers of kidney damage and/or eGFR of <60 mL/ min/1.73 m2 for at least three months.[20] Predialysis CKD patients were those patients who fulfilled the criteria for the definition of CKD and had not been dialyzed.

CKD stages were defined according to KDIGO as follows: Stage 1, eGFR >90 mL/min/1.73 m2 and/or persistent proteinuria; Stage 2, eGFR of 60–89 mL/min/1.73 m2 and/or persistent proteinuria; Stage 3, eGFR of 30–59 mL/min/1.73 m2; Stage 4, eGFR of 15–29 mL/min/1.73 m2; and stage 5, eGFR <15 mL/min/1.73 m2.[21]


   Statistical Analysis Top


Data entry and analysis were performed using the IBM Corp. Released 2012 (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Data were presented as frequencies, percentages, and means (standard deviation). Chi-square test and Yates correction were used to determine the significance of observed differences for categorical variables where appropriate.

Continuous variables were presented as means and standard deviation for unskewed data and median and interquartile range for skewed data. Student’s t-test was used to compare mean values of the subgroups for those with unskewed data while Mann–Whitney U-test was used to compare skewed data. Pearson’s correlation test was used to find association between continuous variables. P ≤0.05 was considered as statistically signi -ficant for all test conducted.


   Results Top


One hundred predialysis CKD patients and 90 age-matched controls participated in the study with a mean age of 49.39 ± 14.84 years and 52.66 ± 13.90 years, respectively. There were 56 (58.9%) male predialysis patients and 39 (41.1%) male controls while there were 44 (46.3%) female predialysis patients and 51 (53.7%) female controls. The difference was not statistically significant (P = 0.081) [Table 1].
Table 1: Characteristics of the study population.

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Sixty-two (62%) of the CKD patients were young or middle aged. Fifty-one (61.9%) of the control group had a tertiary level of education compared to 32 (38.6%) of the CKD patients. This was statistically significant (P = 0.001). Fourteen (14%) of the CKD patients were in Stage 1, 8(8%) in Stage 2, 29 (29%) in Stage 3, 14 (14%) in Stage 4, and the remaining 16 (16%) were in Stage 5 [Table 1]. The etiology of CKD in the study were hypertension (32%), diabetes mellitus (31%), chronic glomerulonephritis (25%), and obstructive uropathy (12%) [Figure 1]. Among CKD patients with iron deficiency, 85.7% had functional iron deficiency, while 14.3% had absolute iron deficiency [Figure 2].
Figure 1: Etiology of chronic kidney disease in the patients (n = 100).

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Figure 2: Pattern of iron deficiency among iron-deficient predialysis chronic kidney disease patients (n = 14)

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There was a significant difference between Hgb concentration (8.71 ± 2.70 vs. 12.93 ± 8.7, P <0.001) and packed cell volume (26.64 ± 12.17 vs. 38.05 ± 6.11, P <0.001) between the predialysis CKD and control groups. The ESR and serum ferritin levels were significantly higher in the predialysis patients than the controls (P <0.001). There was no statistical difference in the mean values of the serum iron, TSAT, and TIBC between the CKD and control groups [Table 2].
Table 2: Hematological indices of predialysis chronic kidney disease and control groups (n =190).

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The mean serum creatinine was significantly higher in the CKD group compared to the control group (3.28 ± 2.75 mg/dL vs. 0.90 ± 0.78 mg/dL; P <0.001) while the mean eGFR in the CKD patients was significantly lower compared to the control group (35.74 ± 26.26 mL/min/1.73 m2 vs. 114.19 ± 41.24 mL/min/ 1.73 m2; P <0.001) [Table 2]. There was no significant difference in median values of iron indices between male and female predialysis CKD patients [Table 3].
Table 3: Comparisons of iron indices between male and female predialysis chronic kidney disease patients.

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Fourteen (14%) of the predialysis CKD patients had low TSAT compared to 3 (3%) in the control group (P = 0.021). There was no significant difference in proportion of participants who had low ferritin and absolute iron deficiency between the controls and CKD patients. However, functional iron deficiency was present in 11 (11%) of the CKD patients compared to none among the controls. This was significant with a P = 0.003 [Table 4]. There were 14 (14%) predialysis CKD patients found to have iron deficiency which was significantly higher than three (3%) present in the control group (P = 0.021). There was no significant association between age, gender, etiology of CKD, CKD stage, and functional iron deficiency [Table 5].
Table 4: Comparison of TSAT, serum ferritin, and iron deficiency between CKD and control patients.

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Table 5: Association between age, gender etiology, and stage of CKD and iron deficiency among CKD patients.

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There was significant negative correlation between eGFR and TIBC (r = -0.226, P = 0.024) [Table 6]. There was also a significant positive correlation between serum ferritin and ESR (r = 0.312, P = 0.002) [Table 7].
Table 6: Association between GFR and iron indices in CKD patients.

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Table 7: Association between ESR and iron indices in CKD patients.

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   Discussion Top


This study showed that 14% of the pre-dialysis CKD patients were iron deficient, which was higher than 3% found in healthy controls using a cutoff value of >20% and 100 ng/mL for TSAT and serum ferritin, respectively, in the definition of iron deficiency. Functional iron deficiency was the predominant form of iron deficiency in the CKD patients accounting for 85.7% of the CKD patients with iron deficiency.

The prevalence of iron deficiency in our study is lower than 31.2% and 56.1% reported in previous studies by Mohammed[22] and Arogundade et al.[23] However, the variation in the prevalence may be accounted for by differences in methodology used in the various studies. Arogundade et al[23] used a higher cutoff of serum ferritin of >300 ng/mL and TSAT of >25% for definition of normal iron store. Iron status was assessed in all our CKD patients irrespective of Hgb concentration unlike in the study of Arogundade et al[23] where iron status was assessed in those with anemia using a cutoff of Hgb concentration of <11 g/dL. Mohammed found iron deficiency in 31.2% of their study population in a similar study done in Northern Nigeria using the similar cutoff values for defining iron deficiency as done in our study.[22] The higher prevalence of iron deficiency in the study compared to this present study may be related to the fact that the study involved both pre-dialysis CKD and those on maintenance HD.

The predominant form of iron deficiency in this study is functional iron deficiency which is similar to report of some previous studies.[22],[23] However, Lukaszyk et al[24] reported that absolute iron deficiency was more common than functional iron deficiency in their study population. This latter study was done in white patients with a higher proportion (61%) in early CKD Stages 2 and 3. There have been reports of ethnic variations in iron deficiency as reported elsewhere.[25],[26]

Level of inflammation assessed by ESR, a nonspecific inflammatory marker, was significantly higher in the predialysis CKD patients compared to the controls. This may explain why functional iron deficiency whose underlying etiological factor is inflammation was higher. Ferritin which is an acute-phase reactant was the only parameter among the iron indices assessed that showed significant correlation with ESR. Functional iron deficiency is characterized by the presence of adequate body iron store in the reticuloendothelial system, but there is impaired iron release to meet the demand for erythropoiesis.

The mean value of serum ferritin was significantly higher in CKD group than non-CKD control which is similar to findings from previous studies involving either predialysis CKD patients or those already on RRT.[27],[28] The mean value of serum ferritin is similar to that reported by Ifudu et al[29] but lower to that reported by Jairam et al.[28] The higher mean value of ferritin in the latter study may be related to the fact that they studied end-stage renal disease patients who were more likely to have higher degree of inflammation that may raise the level of serum ferritin. This is also corroborated by the positive association observed between ESR and ferritin in this study even though it is a nonspecific inflammatory marker.

There was no significant difference in the mean values of serum iron and TIBC between the control and CKD groups, which is similar to previous report by Mohammed.[22] There was also no significant difference between TSAT values in the CKD patients and controls in our study, which is similar to reports by Oluboyode et al[27] and Deori and Bhuyan;[30] however, Mohammed and Jairam et al[22],[28] reported a significantly lower value in the CKD patients compared to controls in their studies. This may be because our study only included predialysis patients unlike the latter studies that involved end-stage renal disease patients on RRT who were more likely to be iron depleted compared to predialysis patients.

There was no significant difference in iron indices between male and female predialysis CKD patients in this study. Mohammed also reported similar pattern except ferritin that was significantly higher in male CKD patients.[22] There was no significant association between serum iron indices and eGFR except TIBC which showed a positive association. TIBC is the maximum amount of iron needed to saturate plasma transferrin which is the primary iron-transport protein and increased instate of iron deficiency. This may, therefore, imply that with worsening renal function, there is a tendency toward iron deficiency.

There was no significant association between etiology and stage of CKD, age, gender, and iron deficiency. A slightly higher proportion of the female CKD patients had iron deficiency than the male CKD patients. This may be related to additional blood loss that occurs in the females during menstruation for those with mild-to-moderate renal insufficiency who are not amenorrheic. Therefore, iron status should be evaluated in CKD patients before commencing on iron supplementation irrespective of their age, CKD stage, gender, or etiology of CKD.

Limitation of this study was that it was difficult to get equal representation of all stages of CKD because it was carried out in a tertiary hospital setting where most of the patients were likely to present late. Furthermore, underlying inflammation could not be completely ruled out in these patients which could have affected the serum ferritin level.


   Conclusion Top


This study showed that functional iron deficiency is the predominant form of iron deficiency in our predialysis patients, and there was no significant association with age, gender, etiology, or stage of CKD.


   Recommendations Top


  1. All CKD patients should be evaluated for iron deficiency
  2. Initiation of iron therapy and follow-up should be guided by iron status of the patient; hence, iron status should be checked regularly as not all CKD patients may require iron therapy
  3. Multicenter studies to be conducted across Africa to further characterized iron status in our CKD patients.


Conflict of interest: None declared.

 
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Correspondence Address:
Dr Ikponmwosa Osamudiamen Iyawe
Department of Internal Medicine, University of Benin, Benin City, Edo State
Nigeria
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DOI: 10.4103/1319-2442.248296

PMID: 30588977

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