• Users Online: 149
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 44  |  Issue : 4  |  Page : 170-175

Relation between intact parathyroid hormone and hemoglobin level in chronic kidney disease patients on hemodialysis


1 Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission01-Nov-2016
Date of Acceptance21-Dec-2016
Date of Web Publication8-Mar-2017

Correspondence Address:
Rabab A Keshk
Department of Internal Medicine, Faculty of Medicine, Tanta University, 9 Dar Elsalam, Albahr St, Tanta, 31512
Egypt
Login to access the Email id


DOI: 10.4103/tmj.tmj_37_16

Rights and Permissions
  Abstract 

Background Chronic kidney disease (CKD) is associated with many kinds of metabolic changes caused by the kidney disease itself and by dialysis treatment. Secondary hyperparathyroidism is a major complication of CKD; it describes a complex alteration in bone and mineral metabolism that occurs as a direct result of CKD. In addition, anemia is a common complication of CKD.
Aim The aim of this work was to assess the relation between level of intact parathyroid hormone (IPTH) and hemoglobin (Hb) level in CKD patients on hemodialysis with the difference between patients under erythropoietin (EPO) and without EPO.
Patients and methods The present study was carried out on 40 patients and 10 healthy individuals as controls. Patients were classified into the following groups − group I included 30 patients with CKD on hemodialysis, which was further divided into the following: group Ia − 10 patients with anemia and under EPO hormone; group Ib − 10 patients with anemia and not receiving EPO hormone; and group Ic − 10 patients on hemodialysis without anemia. Group II included 10 patients with iorn deficiency anemia and without renal impairment. Group III included 10 healthy individuals as a control group matched for age and sex. Laboratory investigations such as IPTH, serum phosphorus, serum calcium, serum creatinine, blood urea, complete blood count, serum ferritin, and transferrin saturation were performed for all participants.
Results There was a statistically significant negative correlation between IPTH and serum Hb in group I and the other two groups.
Conclusion Increased level of IPTH level in chronic hemodialysis patients may cause resistant anemia to EPO therapy in spite of iron load in their blood.

Keywords: chronic kidney disease, hemoglobin, intact parathyroid hormone


How to cite this article:
Keshk RA, Esheba NE, Salah W, El shall N. Relation between intact parathyroid hormone and hemoglobin level in chronic kidney disease patients on hemodialysis. Tanta Med J 2016;44:170-5

How to cite this URL:
Keshk RA, Esheba NE, Salah W, El shall N. Relation between intact parathyroid hormone and hemoglobin level in chronic kidney disease patients on hemodialysis. Tanta Med J [serial online] 2016 [cited 2017 Oct 18];44:170-5. Available from: http://www.tdj.eg.net/text.asp?2016/44/4/170/201726


  Introduction Top


Chronic kidney disease (CKD) is a term that encompasses all degrees of decreased renal function, from damaged − at risk through mild, moderate, and severe chronic kidney failure [1].

Lack of vitamin D leads to reduced calcium absorption by the intestine, leading to hypocalcemia and increased parathyroid hormone (PTH) secretion. This increases bone resorption. In chronic renal failure, the problem is more specifically failure to convert vitamin D to its active form in the kidney [2].

The currently accepted test for PTH is ‘intact parathyroid hormone (IPTH)’, which is intended to detect only relatively intact and biologically active PTH molecules. Older tests often detected other, inactive fragments [3]. Although anemia is not as common in earlier stages of CKD, patients with stage III disease have a prevalence of concurrent anemia of 5.2%, whereas those with stage IV disease have a prevalence of concurrent anemia of 44.1% [4].

Several factors are involved in conditioning renal anemia, and a critical role is attributed to PTH oversecretion, which has some direct effects on endogenous erythropoietin (EPO) synthesis, bone marrow erythroid progenitors, and red cell survival. Indirect effects are mainly based on the induction of bone marrow fibrosis [5].

Indirect evidence of the role of PTH is based on the observation that parathyroidectomy, when performed in uremic patients, is often followed by restoration of the hematocrit [6].


  Patients and methods Top


This study was carried out on 40 patients and 10 healthy individuals matched for age and sex as controls. They were selected from outpatient clinic and inpatient wards of Internal Medicine Department and Hemodialysis Unit in Tanta University Hospital during the period from September 2014 to March 2015. All participants provided informed written consent, and the study was approved by Tanta Faculty of Medicine Ethical Committee.

The participants were divided into the following groups:


  1. Group I: 30 patients with CKD on hemodialysis. They were further divided into following:



    1. Group Ia: 10 patients with anemia and under EPO hormone therapy.


    2. Group Ib: 10 patients with anemia and not receiving EPO hormone.


    3. Group Ic: 10 patients on hemodialysis without anemia.


  2. Group II: 10 patients with anemia with iron deficiency and without renal impairment.


  3. Group III: 10 healthy individuals as a control group matched for age and sex.


Inclusion criteria

Patients diagnosed to have CKD on hemodialysis were included in this study.

Exclusion criteria

Patients taking angiotensin-converting enzyme inhibitors, NSAIDs, patients with external blood loss, patient with systemic lupus, or patients with decompensated hepatic were excluded from the study.


  Methods Top


All participants in this study were subjected to thorough history taking; full clinical examination; and laboratory investigations in the form of IPTH, serum phosphorus, serum calcium, serum creatinine and blood urea, complete blood count, serum ferritin, and transferrin saturation (TSAT).

Sampling and laboratory investigations

Sampling and all laboratory investigations were done in Clinical Pathology Department, Tanta University Hospitals. Seven milliliters of venous blood was collected from each participant by the use of disposable sterilized plastic syringes. The needle of the syringe was then removed and each sample was divided as follows:


  1. Five milliliters of blood was allowed to pass gently along the wall of a clean dry centrifuge tube labeled with the patient name. The blood was allowed to clot for half an hour in a water bath at 37°C, and then it was centrifuged for 15 min at 3000 rpm for separation of serum by means of a clean dry Pasteur pipette. The serum was fractionated into two clean dry tubes for measuring the following:



    1. IPTH: samples were frozen and the sera were stored at −20°C until analysis by Tosoh AIA-360 Automated Immunoassay Analyzer (Tosoh, Tokyo, Japan).


    2. Serum phosphorus, serum calcium, serum creatinine, and blood urea were assessed by commercial kits available and measured by spectrophotometry. Serum ferritin and TSAT were estimated by chemiluminescence immunoassay [7].


  2. Two milliliters of blood was put on EDTA (1 mg/ml blood) and mixed thoroughly to perform complete blood picture by Erma Automated Blood Count Machine (Tokyo, Japan) [8].


Statistical analysis

Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 [9]. Quantitative data were described using range (minimum and maximum), mean, SD, and median. The distributions of quantitative variables were tested for normality using Kolmogorov–Smirnov test, Shapiro–Wilk test, and D’Agstino’s test. If it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, nonparametric tests were used. For normally distributed data, comparisons between more than two populations were analyzed by F-test (analysis of variance) and post-hoc test (least significant difference). For abnormally distributed data, Kruskal–Wallis test was used to compare between different groups and pair-wise comparison was assessed using Mann–Whitney test. Significance of the obtained results was judged at P value of less than 0.05.


  Results Top


While comparing the three groups, there was no significant difference in all of the following: sex, age, white blood cell (WBC) count, and platelet count. There was a significant difference in the three groups in all of the following: serum urea, serum creatinine, PO4, ionized calcium (ICa), TSAT, IPTH, and serum ferritin (P<0.0001 for all) ([Table 1]).
Table 1 Demographic and laboratory data of the three studied groups

Click here to view


While comparing the three subgroups, there was no significant difference in all of the following: sex, age, WBC, platelet count, serum urea, serum creatinine, PO4, TSAT, IPTH, and serum ferritin. There was a significant difference in the three subgroups in the following: hemoglobin (Hb) level and ICa (P<0.0001, 0.002, respectively) ([Table 2]).
Table 2 Demographic and laboratory data of the three subgroups of chronic kidney disease patients

Click here to view


The correlation between serum IPTH (pg/ml) and serum ICa (mmol/l), serum PO4 (mg/dl), serum ferritin (ng/ml), TSAT (%), serum urea (mg/dl), serum creatinine (mg/dl), Hb (g/dl), platelet (×103/mm3), and WBCs (×103/mm3) in groups I, II, and III showed that there was a statistically significant correlation and negative relation between IPTH (pg/ml) and serum Hb in group I (P=0.005) and serum urea (mg/dl) in group II (P=0.043), and that there was no statistically significant correlation between IPTH and other parameters in the three groups, as shown in [Table 3].
Table 3 Correlation of intact parathyroid hormone with different parameters

Click here to view


The correlation between serum IPTH (pg/ml), serum ferritin (ng/ml), TSAT (%), and Hb (g/dl) in groups Ia, Ib, and Ic showed that there was a statistically significant correlation between IPTH and serum Hb in group Ia (P=0.008) and group Ic (P=0.003) and that there was no statistically significant correlation between IPTH and other parameter in three subgroups, as shown in [Table 4].
Table 4 Correlation of intact parathyroid hormone with different parameters

Click here to view



  Discussion Top


CKD is an important focus of healthcare planning in the developing and developed country [10].

Secondary hyperparathyroidism is a major complication of CKD [11], and it describes a complex alteration in bone and mineral metabolism that occurs as a direct result of CKD [12].

As regards anemia in patients with CKD, normochromic normocytic anemia mainly develops from decreased renal synthesis of EPO. The anemia becomes more severe as the glomerular filtration rate progressively decreases [13].

The aim of this study was to assess the relation between level of IPTH and Hb level in CKD.

In the present study, the mean Hb level was significantly lower in groups I and II in comparison with controls. These results were in accordance with those of Ali et al. [14], who performed their study on patients on hemodialysis in comparison with healthy individuals as a control group, and there was a statistically significant difference between the two groups. This indicates that anemia remains prevalent in patients receiving dialysis [15].

As regards serum PO4, there was a significant increase in PO4 level in group I in comparison with the other two groups (P<0.001). The mean of PO4 in group Ia was lower than that of group Ib but with no statistically significant value (P=0.217).

The results of this work were in accordance with those of Warade and Kavitha [16], who reported that the mean of PO4 in the hemodialysis patients was significantly higher than in the control group (P<0.001), and Deborah et al. [17] reported that there was no statistically significant difference in the mean of PO4 in patients with erythropoietin-stimulating agent (ESA) and in patients without ESA (P=0.634).

As regards serum ICa, there was a significant decrease in ICa level in group I in comparison with group II and group III (P=0.04 and <0.001, respectively); also, there was a significant decrease in ICa in group II in comparison with group III (P<0.001). In addition, there was a significant decrease in ICa in group Ib in comparison with group Ia (P=0.012).

The results of this work were in accordance with those of Sliem et al. [18], who reported that the mean of ICa in the hemodialysis patients was 2.05±1.05 mmol/l and in the control group it was 2.34±0.7 mmol/l, with a statistical significance (P<0.01). On the contrary, the results of this work were opposite to the result of Deborah et al. [17], who reported that the mean of ICa in patients with ESA was 2.3±0.8 mmol/l, and in patients without ESA it was 2.3±0.7 mmol/l, with no statistical significance (P=0.53).

As regards serum IPTH in group I, there was a significant increase in IPTH in group I in comparison with groups II and III (P<0.001).

The results of this work were similar to those of Warade and Kavitha [16], who reported that the mean of serum IPTH in the hemodialysis patients was significantly higher when compared with the control group (P<0.001). In addition, in the study performed by Sliem et al. [18] the mean of serum IPTH in the hemodialysis patients was 296.3±56.1 pg/ml, and in the control group it was 51.9±8.7 pg/ml, with a statistical significance (P<0.001).

As regards serum ferritin, there was a significant decrease in serum ferritin level in group II in comparison with the other two groups (P<0.001). The serum ferritin might be elevated in group I, as it is considered as one of the acute-phase reactants. No statistically significant difference was detected in the subgroups (P=0.375).

Sliem et al. [18] reported similar results, as the mean of serum ferritin in the hemodialysis patients was significantly higher when compared with the control group (P<0.001). In addition, Ali et al. [14] reported similar results (P<0.001).

In the study by Adam et al. [19] on hemodialysis patients, serum ferritin with ESA was 520.59±255.85 ng/ml and without ESA it was 627.4±327.8 ng/ml, with no statistical significance (P=0.278).

As regards TSAT, there was a significant decrease in TSAT level in group II in comparison with the other two groups (P<0.001). Comparison between group Ia and Ib showed no statistically significant values (P=0.069).

These results were in agreement with the result of Adam et al. [19], who reported that TSAT level showed no statistically significant difference in patients receiving ESA when compared with patients not receiving ESA (P>0.05).

Concerning the correlation between IPTH (pg/ml) and serum Hb (g/dl) in group I and the other two groups, there was a statistically significant negative correlation between IPTH and serum Hb (P=0.005). This was in agreement with the study by Sliem et al. [18], who reported statistically significant negative correlation between IPTH and serum Hb among hemodialysis patients and the control group (P=0.01).

Concerning the correlation between serum IPTH (pg/ml) and Hb (g/dl) in the three studied subgroups, there was a statistically significant negative correlation between IPTH and serum Hb in group Ia (P=0.008) and group Ic (P=0.003). In addition, Penne et al. [20] reported a statistically significant correlation between IPTH and serum Hb among patients on hemodialysis (P=0.003). Although Adhikary et al. [21] reported a weak negative correlation between Hb and IPTH among hemodialysis patients, it did not reach statistical significance (P=0.334).

Concerning the correlation between serum ferritin (ng/ml) and Hb (g/dl) in the three studied groups, there was a statistically significant positive correlation between serum ferritin and Hb level in group II (P=0.047). Turgut et al. [22] reported similar results in their study carried out on iron deficiency anemia patients compared with healthy people as the control group, which showed positive significant correlation between serum ferritin and Hb level (P<0.001).

This might be because of the effect of hyperparathyroidism on bone marrow, as it causes bone marrow fibrosis; also, it was reported that increased IPTH might cause resistance of anemic hemodialysis patients to EPO.

The discrepancies between the results of this work and the result of the other studies may be attributed to differences in case selection criteria of patients and the smaller sample size in this study.


  Conclusion Top


These findings suggest that increased level of IPTH level in chronic hemodialysis patients may cause resistant anemia to EPO therapy in spite of iron load in their blood.

Recommendations

Future studies including larger number of patients and longer duration are required to better clarify the exact role of IPTH in chronic hemodialysis patient.

Acknowledgements

The authors thank all participants who helped during this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Hsu Y, Chertow M. Chronic renal confusion: insufficiency, failure, dysfunction, or disease. Am J Kidney Dis 2000; 36:415–418.  Back to cited text no. 1
    
2.
Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001; 22:477–501.  Back to cited text no. 2
    
3.
Souberbielle C, Friedlander G, Cormier C Practical considerations in PTH testing. Clin Chim Acta 2006; 366:81–89.  Back to cited text no. 3
    
4.
Zarychanski R, Houston D. Anemia of chronic disease: a harmful disorder or an adaptive, beneficial response? CMAJ 2008; 179:333–337.  Back to cited text no. 4
    
5.
Arabi A, El Rassi R, El-Hajj Fuleihan G. Hypovitaminosis D in developing countries: prevalence, risk factors and outcomes. Nat Rev Endocrinol 2010; 6:550–561.  Back to cited text no. 5
    
6.
Bamgbola F. Pattern of resistance to erythropoietin-stimulating agents in chronic kidney disease. Kidney Int 2011; 80:464–474.  Back to cited text no. 6
    
7.
Wright M, Royston P. Calculating reference intervals for laboratory measurements. Stat Methods Med Res 1999; 8:93–112.  Back to cited text no. 7
    
8.
Worwood M. Iron deficiency anaemia and iron overload [chapter 7]. In: Mitchell S, Barbara J, Bates I. Dacie and Lewispractical haematology. US: Elsevier 2006. pp. 132–155.  Back to cited text no. 8
    
9.
Verma J. Statistics computer programs [chapter 4]. In: Kirkpatrick A, Feeney C, editors. A simple guide to IBM SPSS statistics for version 20.0. Belmont, CA, USA: Wadsworth Cengage Learning; 2013. pp. 80–100.  Back to cited text no. 9
    
10.
Barsoum S. Chronic kidney disease in the developing world. N Engl J Med 2006; 354:997–999.  Back to cited text no. 10
    
11.
Shigematsu T, Kazama J, Yamashita T, Fukumoto S, Hosoya T, Gejyo F et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis 2004; 44:250–256.  Back to cited text no. 11
    
12.
Levin A, Bakris L, Molitch M, Smulders M, Tian J, Williams A et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007; 71:31–38.  Back to cited text no. 12
    
13.
Stauffer E, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One 2014; 9:e84943.  Back to cited text no. 13
    
14.
Ali T, Genina A, Abo-Salem O. The determinants of hepcidin level in chronic kidney disease and hemodialysis Saudi patients. Beni-Suef Univ J Basic Appl Sci 2014; 3:133–139.  Back to cited text no. 14
    
15.
Locatelli F, Pisoni L, Akizawa T, Cruz M, DeOreo B, Lameire H et al. Anemia management for hemodialysis patients: Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines and Dialysis Outcomes and Practice Patterns Study (DOPPS) findings. Am J Kidney Dis 2004; 44:27–33.  Back to cited text no. 15
    
16.
16.Warade P, Kavitha R. Secondary hyperparathyroidism in chronic kidney disease. IAIM 2015; 2:42–48.  Back to cited text no. 16
    
17.
Deborah L, Joel D, Csaba P, Ryan D, Charles J, Aronovitz J et al. Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol 2006; 17:1181–1191.  Back to cited text no. 17
    
18.
Sliem H, Tawfik G, Moustafa F, Zaki H. Relationship of associated secondary hyperparathyroidism to serum fibroblast growth factor-23 in end stage renal disease: a case control study. Indian J Endocrinol Metab 2011; 15:105–109.  Back to cited text no. 18
    
19.
Adam E, Premila B, Gregory A, Matthew G. TSAT is a better predictor than ferritin of hemoglobin response to epoetin alfa in US dialysis patients. Hemodia Int 2014; 18:38–46.  Back to cited text no. 19
    
20.
Penne L, Neelke C, Muriel P, Grooteman A, Marinus A, Menso J. Role of residual renal function in phosphate control and anemia management in chronic hemodialysis patients. Clin J Am Soc Nephrol 2011; 6:281–289.  Back to cited text no. 20
    
21.
Adhikary P, Pokhrel A, Yadava K, Khadka D, Thakur R. Relation between serum intact parathyroid hormone level and hematocrit in chronic kidney disease patients. Kathmandu Univ Med J 2015; 13:220–223.  Back to cited text no. 21
    
22.
22.Turgut S, Hacıoğlu S, Emmungil G, Turgut G, Keskin A. Relations between iron deficiency anemia and serum levels of copper, zinc, cadmium and lead. Polish J Environ Stud 2009; 18:273–277.  Back to cited text no. 22
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed108    
    Printed0    
    Emailed0    
    PDF Downloaded40    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]