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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 687-692

Prevalence of mineral bone disorders among hemodialysis patients in Menoufia Governorate, Egypt


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Nephrology, Al-Shohadaa Central Hospital, Menoufia, Egypt

Date of Submission01-Aug-2016
Date of Acceptance23-Oct-2016
Date of Web Publication15-Nov-2017

Correspondence Address:
Ahmed F Abd-Elsattar Saif
Department of Nephrology, Al-Shohadaa Central Hospital, Al-Shohadaa, Menoufia, 32841
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.218276

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  Abstract 

Objective
The aim of this study was to determine the prevalence of mineral bone disorders (MBDs) among hemodialysis (HD) patients in Menoufia Governorate.
Background
As kidney function declines, there is progressive deterioration in mineral homeostasis manifesting as disruption of serum and tissue concentrations of phosphorus and calcium (Ca), as well as changes in circulating levels of hormones such as parathyroid hormone (PTH). These mineral and endocrine functions are critically important in the regulation of both bone modeling and bone remodeling. Chronic kidney disease-MBD describes a broad clinical syndrome that develops as a systemic disorder of mineral and bone metabolism because of chronic kidney disease.
Patients and methods
This study was carried out on 100 patients with end-stage renal disease on regular HD in Menoufia Governorate. After obtaining informed consent, the included patients underwent the following examination: complete blood count, blood sugar level, lipid profile, blood urea level, serum creatinine level, albumin level, uric acid level, Ca level, phosphate level, alkaline phosphatase level, and PTH level.
Results
Hyperparathyroid bone disease was prevalent in 55% of the studied patients and low bone turnover in 30% of the studied patients, and both of the two groups showed highly significant association with serum Ca and phosphate levels. Suggestive MBD-related symptoms were prevalent in both high bone turnover and low bone turnover (60 and 70%, respectively). Hypocalcemia and hyperphosphatemia were observed in 64 and 74% of the studied patients, respectively.
Conclusion
The prevalence of MBD among the studied HD patients was 85% depending on abnormal PTH levels (55% of patients with high PTH level and 30% with low PTH levels). Most of patients with high PTH level (high bone turnover) had low serum Ca with high serum phosphorus levels (83.6 and 81.8%, respectively), whereas most of patients with low PTH levels (low bone turnover) had normal serum Ca with high serum phosphorus levels (60 and 63.3% respectively).

Keywords: chronic kidney disease-mineral bone disorder, hyperparathyroid, mineral bone disorder, renal bone disease


How to cite this article:
Ahmed HA, Elzorkany KM, Yasein YS, Abd-Elsattar Saif AF. Prevalence of mineral bone disorders among hemodialysis patients in Menoufia Governorate, Egypt. Menoufia Med J 2017;30:687-92

How to cite this URL:
Ahmed HA, Elzorkany KM, Yasein YS, Abd-Elsattar Saif AF. Prevalence of mineral bone disorders among hemodialysis patients in Menoufia Governorate, Egypt. Menoufia Med J [serial online] 2017 [cited 2019 Dec 10];30:687-92. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/687/218276


  Introduction Top


Chronic kidney disease (CKD) is a progressive loss in renal function over a period of months or years. As kidney function declines, there is progressive deterioration in mineral homeostasis manifesting as disruption of serum and tissue concentrations of phosphorus and calcium (Ca), as well as changes in circulating levels of hormones such as parathyroid hormone (PTH). These mineral and endocrine functions are critically important in the regulation of both initial bone formation during growth (bone modeling) and bone structure and function during adulthood (bone remodeling) [1].

CKD-mineral bone disorder (CKD-MBD) describes a broad clinical syndrome that develops as a systemic disorder of mineral and bone metabolism because of CKD that can be manifested by any one or a combination of the following: abnormalities of Ca, phosphorus, PTH, and vitamin D metabolism and abnormalities of bone turnover, mineralization, volume, linear growth, and strength, in addition to vascular or soft tissue calcification [2].

The major factors in the pathogenesis of CKD-MBD include renal insufficiency–associated secondary hyperparathyroidism with the associated phosphorus retention (hyperphosphatemia), as renal glomerular filtration rate decreases, and a decrease in calcitriol levels, as metabolically active renal mass is reduced [3].

A national survey in Egypt showed that renal bone disease prevails among 33.3% of dialysis patients [4]. In Poland, a study of renal bone disease among uremic children showed a prevalence of adynamic bone disease in 27%, normal bone histology in 37%, osteomalacia in 2%, mixed lesion in 10%, and hyperparathyroidism in 24%. There was no difference in prevalence between children on continuous ambulatory peritoneal dialysis and hemodialysis (HD) [5]. In the Czech Republic, the prevalence of renal bone disease was reported to be 57% among patients with uremia [6]. In Thailand, adynamic bone disease was found in 41.1%, hyperparathyroidism in 28.6%, mixed type in 19.6%, mild lesion in 5.4%, osteomalacia in 3.6%, and osteosclerosis in 1.8% [7]. In Ibero-America, among 1209 bone biopsies from five different countries (Brazil, Uruguay, Argentina, Portugal, and Spain), it was shown that low-turnover osteomalacia and mixed uremic osteodystrophy were common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. Aluminum was implicated in a large percentage of low bone remodeling lesions in Ibero-America [8]. In Singapore, skeletal survey was positive for renal bone disease in 24.4% of patients [9]. In Turkey, among children with chronic renal failure undergoing continuous ambulatory peritoneal dialysis, high-turnover renal osteodystrophy was the most common bone disease (47%), with low turnover bone disease in 29%, and 24% had mixed renal osteodystrophy [10].

The present study was aimed to study the prevalence of MBD among HD patients in Menoufia Governorate, Egypt.


  Patients and Methods Top


This study was carried out on 100 patients with end-stage renal disease (ESRD) on regular HD in four HD centers in Menoufia Governorate (Shebin El-Koom, Al-Shohadaa, Menouf, Albagour), Egypt. Informed consent was taken from all included patients, and the study was approved from the medical ethical committee of all included centers. This study was done during the period from November 2014 to August 2015. The study excludes patients having acute infections, connective tissue disease, malignancy, chronic liver disease, thyroid gland dysfunctions, recent myocardial infarction, recent trauma in preceding 6 months, and postmenopausal female patients.

All studied patients were subjected to full history taking, general and local examination, and laboratory investigations including complete blood count, blood sugar level, serum lipids, serum albumin level, serum uric acid level, blood urea level, serum creatinine level, total Ca level, serum phosphate level, serum alkaline phosphatase level, and serum PTH level. Plain radiographs on vertebral spines, forearm, hands, and skull were performed in 22 patients who agreed to undergo a radiological examination. The radiologist who reported the radiological findings was blinded to the laboratory data.

The diagnosis of MBD among the studied patients was made according to the following: suggestive MBD–related symptoms (bone pain, muscle weakness, and combination of both symptoms), MBD-related radiological findings (salt and pepper skull, periarticular osteopenia, rugger-jersey vertebrae, and pathological fractures), and MBD-related laboratory indicators (serum PTH, serum Ca, serum phosphorus, and serum alkaline phosphatase levels).

The studied patients were divided into three groups according to serum PTH level: the first group had 30 patients with PTH level less than 150 pg/ml (low bone turnover), the second group had 15 patients with PTH level between 150 and 300 pg/ml (normal bone turnover), and the third group had 55 patients with PTH level more than 300 pg/ml (high bone turnover).

Blood samples for determination of biochemical parameters were collected before the beginning of the dialysis session. Venous blood samples were drawn from suitable veins with loose-fitting tourniquet. After centrifugation, blood was aliquoted in cryovials. Samples for complete blood count were collected in tubes containing EDTA-K2·2H2O. Blood urea, serum creatinine, albumin, Ca, phosphate, alkaline phosphatase, blood sugar, lipids, and uric acid were measured using standard laboratory techniques. Serum PTH assay was performed using electrochemiluminescence immunoassay on the fully automated VIDAS (Biomerieux, Marcy l'Etoile, France). The samples were centrifuged, and then the serum was frozen at −40° until assessment.

Statistical analysis

Data were collected, tabulated, and statistically analyzed with a personal computer using SPSS, version 20 (IBM Corporation, Armonk, New York, USA). Student's t-test was used for continuous quantitative parametric variables and Mann-Whitney U-test for nonparametric variables. Fisher's exact test was used to compare between two groups or more regarding one qualitative variable. c2-Test was used to study statistical relation between different variables. Partial correlation coefficients for testing association between variables was, also, applied. P up to 0.05 was considered statistically significant.


  Results Top


Hyperparathyroid bone disease was prevalent in 55% and low bone turnover in 30% of the studied patients, and both of the two groups showed highly significant association with serum Ca and phosphate levels. Hyperparathyroid group showed 46 (83.6%) patients with hypocalcemia (serum Ca levels <8.5 mg/dl) [Table 1]. Suggestive MBD-related symptoms were prevalent in both high bone turnover and low bone turnover (60 and 70%, respectively) [Table 2].
Table 1: Distribution of laboratory data (serum calcium, inorganic phosphate, and alkaline phosphatase) of the studied patients (n=100) according to serum parathyroid levels

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Table 2: Distribution of suggestive mineral bone disorder-related symptoms in the studied patients (n=100) according to serum parathyroid levels

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Hypocalcemia and hyperphosphatemia were observed in 64 and 74% of the studied patients, respectively [Table 3].
Table 3: Distribution of the studied patients according to laboratory mineral bone disorder indicators

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Positive significant correlation between PTH and ALP and blood urea and negative significant correlation between serum Ca and blood urea were observed [Figure 1], [Figure 2], [Figure 3].
Figure 1: Correlation between parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels in the studied patients.

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Figure 2: Correlation between parathyroid hormone (PTH) and blood urea levels in the studied patients.

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Figure 3: Correlation between serum calcium (Ca) and blood urea levels in the studied patients.

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According to radiological examination of 22 patients of the included 100 patients, renal bone disease was prevalent in 68.2% (15/22) of patients [Table 4] and [Table 5].
Table 4: Distribution of studied 22 patients with radiological examination according to radiological findings

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Table 5: Distribution of radiological findings in the studied 22 patients with radiological examination according to serum parathyroid hormone levels

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  Discussion Top


The nature and type of renal bone disease vary from one patient to another, and several factors may account for this variation [11]. The two major disorders of bone disease in CKD are high-turnover hyperparathyroid and low-turnover bone disorders. Serum PTH level is considered an adequate screening tool to separate these two diseases [11],[12]. Despite bone biopsy being the gold standard for diagnosis of renal bone disease [13], its invasive nature as well as its cost and overall complexity has withdrawn it from the clinical practice. Hence, serum markers of bone turnover have been used to evaluate bone turnover in patients with CKD [14]. Consequently, serum PTH level has taken the leading position among the noninvasive tools for assessing renal bone disease [15]. Measurement of serum PTH has long been considered the principal biochemical marker for diagnosis and monitoring therapy of renal bone disease [14]. In 1986, Andress and colleagues [16] suggested that intact parathyroid hormone (iPTH) could be a good predictor of osteitis fibrosa in patients undergoing maintenance HD.

The K/DOQI guidelines suggested that iPTH should be maintained in a target range between 150 and 300 pg/ml for patients with stage 5 CKD [11].

According to the laboratory criteria used in this study, 55 (55%) patients had laboratory evidence of hyperparathyroid bone disease (iPTH >300 pg/ml) and 30 (30%) patients had low-turnover bone disease (iPTH <150 pg/ml), resulting in a total prevalence of 85% in our studied patients. In a similar study by Buargub et al. [17] in Libya, 28.1% of the patients had laboratory evidence of hyperparathyroid bone disease and 27% patients had low-turnover bone disease, resulting in a renal osteodystrophy total prevalence of 55.3%. Agarwal [18] found hyperparathyroidism in 39.4% of patients with CKD stage 5. Among Indian studies, Jabbar et al. [19] observed prevalence of hyperparathyroidism in 60% of their patients of CKD stages 4 and 5, taking a cutoff of iPTH more than 300 pg/ml for both stages. In another Indian study in 2013, Jabbar et al. [20] reported 61% of patients with hyperparathyroidism. In Ile-Ife, Nigeria, Sanusi et al. [21] reported 11.8% of patients with ESRD with secondary hyperparathyroidism. In Senegal, Seck et al. [22] found that 57 cases (of total 118 cases) showed high-turnover disease (secondary hyperparathyroidism), and 22 cases showed low-turnover bone disease.

In this study, the mean serum iPTH level among the patients in the hyperparathyroid group was 837.5 ± 504.5 pg/ml, and they could be further subdivided into three groups. The first group included two (3.6%) patients with high serum Ca (>9.5 mg/dl), the second group included 46 (83.6%) patients with low serum Ca levels (<8.5 mg/dl), and the third group included seven (12.7%) patients with serum Ca levels between 8.5 and 9.5 mg/dl. In the first group, with high levels of both PTH and Ca, it is likely that therapy with vitamin D was not effective, and evaluation for the use of other vitamin D analogues and the possible need of surgical intervention of the parathyroid glands have to be considered. In the other group with high PTH and low serum Ca levels, the lack of vitamin D effectiveness could be either undertreatment with vitamin D or poor patient compliance [17].

In this study, patients with low bone turnover disease had higher mean serum Ca level compared with the mean serum Ca levels in both the hyperparathyroid bone disease group and the patients with no laboratory evidence of bone disease. This was agreed in the study by Buargub et al. [17].

In this study, the target serum level of iPTH was achieved in only 15% of the patients. Only 28% of the patients had serum Ca levels within the target range. Buargub et al. [17] found that the target serum level of iPTH was achieved in only 17.4% of the patients, and only 30% of the patients had serum Ca levels within the target range. In 2013, Jabbar et al. [20] reported only 9% patients within normal iPTH range.

The study also showed that control of anemia, the other major problem of CKD, was not satisfactory as 64% of studied patients had hemoglobin levels less than 10 g/dl. Buargub et al. [17] found 50% of the studied patients had hemoglobin levels less than 10 g/dl. Hyperparathyroidism is thought to contribute to renal anemia and serves as a possible cause for the impaired response to recombinant human erythropoietin in patients with renal disease [23].

This study demonstrated hypocalcemia and hyperphosphatemia in 64 and 74% of the studied patients, respectively. This is in agreement with the findings of reports from University of Benin Teaching Hospital in Nigeria where Onyemekeihia found hypocalcemia and hyperphosphatemia in 71 and 79% of patients with chronic renal failure, respectively [24]. Also in Ile-Ife, Nigeria, Sanusi et al. [21] reported hypocalcemia and hyperphosphatemia in 59.3 and 75% of patients with ESRD, respectively. Agarwal [18] described hypocalcemia in 49.6% and hyperphosphatemia in 41.8% of patients with CKD stage 5. LaClair et al. [25] found hypocalcemia (Ca <8.5 mg/dl) in 28% and hyperphosphatemia (PO4 >4.5 mg/dl) in 50% of patients with CKD stage 5. Thus, the Western data showed a lower prevalence of hypocalcemia in comparison with the data of Agarwal from India, although both showed a high prevalence of hyperphosphatemia in CKD stage 5. However, our study showed much higher prevalence of hypocalcemia and hyperphosphatemia even in comparison with the findings by Agarwal. In a recent study by Valson et al. [26] 66.3% were hypocalcemic and 59% were hyperphosphatemic.

The radiological survey, which was performed on 22 of the studied patients, revealed that 15 patients had radiological evidence of renal bone disease, and seven patients are radiologically free. Buargub et al. [17] performed radiological survey on 30 of the studied patients (total number = 103) and founded that 14 patients had evidence of bone resorption suggestive of hyperparathyroid bone disease, 10 patients had generalized osteoporosis and osteosclerosis, and six patients had findings suggestive of osteomalacia.


  Conclusion Top


The prevalence of MBD among the studied HD patients was 64% depending on symptoms and 85% depending on abnormal PTH levels (55% of patients with high PTH level and 30% with low PTH levels). Most of patients with high PTH level (high bone turnover) had low serum Ca with high serum phosphorus levels (83.6 and 81.8%, respectively), though most of patients with low PTH levels (low bone turnover) had normal serum Ca with high serum phosphorus levels (60 and 63.3%, respectively).

According to radiological examination of 22 patients of the included 100 patients, MBD was prevalent in 68.2% (15/22) of patients. All the 15 patients had high serum alkaline phosphatase levels and 86.7% (13/15) had high PTH levels with low serum Ca levels.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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