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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2006  |  Volume : 17  |  Issue : 3  |  Page : 401-407
Prevalence and Pattern of Renal Osteodystrophy in Chronic Hemodialysis Patients: A Cross Sectional Study of 103 Patients


1 Department of Medicine, Tripoli Central Hospital and at Al-Shat Nephrology and Dialysis Center, Tripoli, Libya
2 Department of Medicine and Endocrinology, Tripoli Central Hospital, Tripoli, Libya

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   Abstract 

This cross sectional study was conducted to determine the prevalence and pattern of renal osteodystrophy (ROD) in patients on maintenance hemodialysis (HD) in Tripoli, Libya. A total of 103 randomly selected patients, of whom 53% were males, were investigated. Their mean age was 47.6 +/-12.5 years. They were on dialysis for a mean duration of 6.2 +/- 4.3 years. Pre-dialysis serum levels of intact parathyroid hormone (iPTH), osteocalcin, alkaline phosphatase, albumin, total calcium and phosphate were measured in all the patients. Depending on serum iPTH levels, the patients were divided into three groups: hyperpara­thyroid bone disease (iPTH > 450 pg/ml), adynamic bone disease (iPTH< 60 pg/ml), and a group with apparently normal bone (iPTH 60 pg/ml to 450 pg/ml). As a whole, the mean serum levels of iPTH, osteocalcin, alkaline phosphatase and corrected total calcium were high in all study patients (373.7 pg/ml, 251.3 ng/ml, 254.9 IU/l, and 9.9 mg/dl respectively). The prevalence of ROD among these patients was 55.3%. Of these, 29 (28.1%) had laboratory evidence of hyperparathyroid bone disease, while 28 patients (27.1%) had laboratory evidence of adynamic bone disease. In only 18 patients, (17.4%) the serum levels of iPTH were within the target range recommended by the K/DOQI guidelines (150-300 pg/ml). This cross sectional study, albeit in a limited number of patients, shows that the prevalence of ROD in our institution is high, possibly because of inadequate patient monitoring and lack of insight into ROD among both patients and physicians.

Keywords: Renal Osteodystrophy, Chronic dialysis, Parathyroid hormone, Adynamic bone disease.

How to cite this article:
Buargub MA, Nabulsi MF, Shafeh TA. Prevalence and Pattern of Renal Osteodystrophy in Chronic Hemodialysis Patients: A Cross Sectional Study of 103 Patients. Saudi J Kidney Dis Transpl 2006;17:401-7

How to cite this URL:
Buargub MA, Nabulsi MF, Shafeh TA. Prevalence and Pattern of Renal Osteodystrophy in Chronic Hemodialysis Patients: A Cross Sectional Study of 103 Patients. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2020 Feb 27];17:401-7. Available from: http://www.sjkdt.org/text.asp?2006/17/3/401/35776

   Introduction Top


Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease (CKD). Histological evidence of renal osteodystrophy (ROD) is apparent in patients with moderate renal failure and progresses as renal failure advances. The overall incidence of ROD in patients with advanced renal failure and those treated with maintenance hemodialysis (HD) is 90 to 100%.[1]

A large body of evidence indicates that these metabolic derangements are associated with an increase in mortality and morbidity; patients may suffer from bone pain, fractures, bone deformity, myopathy, tendon rupture, and growth retardation. In addition, these meta­bolic derangements and/or their therapies may have long-term effects on soft tissue calcification.[2],[3],[4],[5]

The most accurate diagnostic test for detecting the type of bone disease associated with CKD is bone biopsy with histomorpho­metric analysis.[1],[2] This diagnostic tool requires trained personnel for its preparation and interpretation. At the present time, trained personnel are not available in most medical institutions, including ours. Because of this limitation, clinicians depend upon indirect methods to diagnose the presence and the type of bone disease.[2]

Parathyroid hormone (PTH) level is considered a useful test in detecting high and low turnover bone disease.[2] A meta­analysis using PTH to diagnose renal bone disease was performed,[2] which revealed a sensitivity of 93% and a specificity of 77% when using a lower PTH threshold level of 150 to 200 pg/ml to diagnose hyper parathyroid bone disease and a sensitivity of 70% and a specificity of 87% when using an upper PTH threshold level of 60 pg/ml to diagnose adynamic bone disease (ABD). In a study by Qi et al, [6] PTH > 450 pg/ml was 100% specific for high turnover bone disease.

Several other biochemical markers of bone turnover have been studied but the current data are insufficient to assess their diagnostic utility.[2]

The purpose of this study was to describe the prevalence and distribution of different types of ROD in 103 patients selected from a large group of patients attending the two main HD centers in Tripoli and establish risk factors that might have influenced their development.

Serum levels of iPTH, osteocalcin, total calcium, albumin, phosphate, and alkaline phosphatase were measured; some of these patients also underwent radiological skeletal survey to look for pathological changes and compare radiological findings with the laboratory data.


   Patients and Methods Top


A total of 103 patients were randomly selected from the two main HD centers in Tripoli (Al-shat and 2nd of March centers). They included 55 males and 48 females. They were on maintenance HD, which was performed using Fresenius machine 4008S, polysulfone membrane dialyzer, and a dialysate solution containing 32 mmol/L of bicarbonate and 1.75 mmol/L of calcium. All study patients were on dialysis for more than one year and none of them had clinical evidence of active liver disease or any other acute illness during the study period.

Blood samples for determination of bio­chemical parameters were drawn before the beginning of the dialysis session. Serum intact PTH and osteocalcin assays were performed using electro-chemiluminescence immunoassay (ECLIA) on the fully automated immuno­analyzer Elecys 2010 (Roche). The normal values for iPTH and osteocalcin were 15-65 pg/ml and 11-43 ng/ml, respectively.

Measurements of serum albumin, total alkaline phosphatase, total calcium, and phosphate levels were determined by the automated clinical chemistry analyzer Cobas Integra 400 Plus (Roche). Normal values for serum total alkaline phosphatase, total calcium and phosphate, as determined by this analytic method, were 35-129 IU/L, 8.8-10.1 mg/dl and 2.7-4.6 mg/dl, respectively. Total serum calcium was corrected according to the usual formula.

A radiographic skeletal survey was performed in 30 patients who were symptomatic of bone pain and agreed to have a radiological examination performed. The physician who reported the radiological findings was blinded to the laboratory data.

All study patients gave their consent to be included in the study.


   Statistical analysis Top


Statistical analysis was performed using the statistics software SPSS10. Data are repre­sented as means +/- SD. We performed non­parametric analysis on our data. Comparison of the means was performed using an in­dependent sample T-test and Spearman's rank order correlation was used to assess the inter-relationship between various examined markers.

A p value less than 0.05 was considered significant at a two-tailed level.


   Results Top


The demographic and clinical characteristics, as well as, the laboratory results of 103 patients are provided in [Table - 1]. As mentioned, there were 48 females and 55 males and their mean age was 47.6 years +/- 12.5 (range 21 to 75 years).

The underlying disease was diabetic nephro­pathy in 16 patients, chronic glomerulonephritis in 17, rapidly progressive glomerulonephritis in 13, chronic interstitial nephritis in 12, polycystic kidney disease in 4, congenital renal disease in 3, lupus nephritis in 1 while the remaining 37 had unknown etiology. Sixty-nine patients were on thrice-weekly dialysis schedules and 34 were on twice weekly schedules.

The mean values for iPTH, osteocalcin, alkaline phosphatase, and corrected calcium were 373.7 pg/ml, 251.3 ng/ml, 254.9 IU/L, and 9.6 mg/dl, respectively. Hemoglobin levels were lower than 10 g/dl in 52% of the study patients.

According to the criteria used, 57 of the patients (55.3%) had laboratory evidence of renal bone disease (ROD) of which 29 (28.1%) had hyper parathyroid bone disease (serum iPTH > 450 pg/ml), while the other 28 patients (27.1%) had ABD.

Using the independent sample T-test and considering the etiology of CKD, there was a significant statistical association between diabetic nephropathy and lower serum iPTH (mean iPTH 82.2 +/- 9 pg/ml), compared with the other disease groups (iPTH 407 +/- 471 pg/ml, P <0.01), lower serum osteocalcin levels (mean osteocalcin 137.7 +/- 72 ng/ml) compared with 269 +/- 182 ng/ml, P <0.05 in other etiological groups and higher corrected calcium levels. Mean calcium levels are 10.3 mg/dl in diabetics as compared to 9.4 mg/dl among non-diabetics (P< 0.005).

[Table - 2] shows the comparison between patients with ABD and those with hyper­parathyroid bone disease. As seen, ABD had a positive statistical association with high serum calcium (P <0.01) and a negative association with blood osteocalcin and alkaline phosphatase levels (both P < 0.01). In [Table - 3], a comparison between patients with ABD and patients considered to have normal bone is shown. Patients with ABD again had a statistically significant positive association with high serum calcium (P<0.001) and a negative association with both serum albumin and osteocalcin levels (P 0.01 and P<0.004 respectively). The radiological survey, which was performed on 30 of the studied patients, revealed that 14 patients had evidence of bone resorption suggestive of hyperparathyroid bone disease [Figure - 1], 10 patients had generalized osteoporosis and osteosclerosis [Figure - 2] and 6 patients had findings suggestive of osteomalacia. Asso­ciated vascular calcification was reported in seven patients [Figure - 3].


   Discussion Top


The onset of ROD is generally noted when about 50% of kidney function is lost, and by the time dialysis is required almost all patients are affected. [2] The nature and type of ROD varies from one patient to another and several factors may account for this variation.[1],[2] The two most commonly encountered types of ROD are: high turnover hyperparathyroid and low turnover ABD. Serum levels of PTH are considered an adequate screening tool to separate these two diseases.[2]

According to the laboratory criteria used in this study, 29 of the patients (28.1%) had laboratory evidence of hyperparathyroid bone disease (iPTH >450 pg/ml) and 28 patients (27%) had low turnover ABD (iPTH <60 pg/ml) resulting in a ROD total prevalence of 55.3% in our study patients.

The mean serum iPTH level among the patients in the hyperparathyroid group was 1048 ng/ml (range 506-1984) and they could be further subdivided into two groups. The first group included 10 patients with high serum calcium (>9.5 mg/dl) and the other group included five patients with low serum calcium levels (<8.5 mg/dl). In the first group with high levels of both PTH and calcium, 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, has to be considered. In the other group with high PTH and low serum calcium levels, the lack of Vitamin D effective­ness could be either under treatment with vitamin D or poor patient compliance.

We found that patients with ABD had higher serum calcium levels; their mean serum calcium level was 11 mg/dl compared with the mean serum calcium levels in both the hyperparathyroid bone disease group and the patients with no laboratory evidence of bone pathology (8.6 mg/dl (P<0.01) and 9.47 mg/dl (P<0.01), respectively). They also had lower serum osteocalcin and alkaline phosphatase levels (P<0.01); this finding was not unexpected as both osteocalcin and alkaline phosphatase are considered markers of bone formation [Table - 2],[Table - 3].

We found a significant statistical association between diabetic nephropathy and lower levels of serum iPTH and osteocalcin and higher corrected calcium levels (P< 0.01). This may be due to the fact that ABD is more common in diabetic patients probably due to a deficiency of insulin-like growth factor.[10]

The reported prevalence of ABD in dialysis patients is 15 to 60%. [2] It is more common in diabetic patients and patients on peritoneal dialysis. In some patients, the cause of ABD may be over suppression of the parathyroid gland with high calcium intake and/or admini­stration of active vitamin D.[2] Although this is an asymptomatic condition, it is asso­ciated with a higher incidence of metastatic calcification. [2],[3],[4],[5]

Earlier studies have emphasized the need for vigorous control of hyperphosphatemia to improve the survival of ESRD patients. How­ever, the use of calcium-containing phosphate binders in addition to long-term medication with high doses of active vitamin D analogues may lead to hypercalcemia and metastatic calcification, increasing the risk of cardio­vascular deaths. Vascular and other abnormal tissue calcification are major causes of mortality in dialysis patients; they are associated with almost 50% of cardiovascular deaths.[11]

Thus, serum levels of calcium, phosphate, and iPTH must be monitored regularly during vitamin D therapy and the dose of the medication should be adjusted accordingly. [9] According to the National Kidney Disease Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines published in 2003, serum levels of calcium, phosphorus, calcium- phosphate product and iPTH levels should be tightly controlled in patients with CKD. Regular monitoring should be under­taken. Serum calcium should be maintained between 8.4 and 9.5 mg/dl, serum phosphorus between 3.5 and 5.5 mg/dl and iPTH in the range of 150 to 300 pg/ml.[9]

In our study, the target serum level of iPTH was achieved in only 17.4% of the patients. Only 30% of the patients had serum calcium levels within the target range (8.4-9.5 mg/dl) and 34.5% had calcium-phosphate products higher than 55.

The study also showed that control of anemia, the other major problem of CKD, was not satisfactory as 50% of study patients had hemo­globin levels below 10 g/dl. Hyperpara­thyroidism is thought to contribute to renal anemia and serves as a possible cause for the impaired response to recombinant erythro­poietin in patients with renal disease. [12] In our study, we did not find any statistically significant correlation between serum iPTH and blood hemoglobin levels.

Routine bone radiography is not indicated in the assessment of bone disease in CKD; standard bone radiography can reliably detect bone disease but has a sensitivity of approxi­mately 60% and specificity of 75%. Thus, its use is limited to the detection of vascular calcification. [2] In our study, the most common finding on radiographic examination was changes of hyper parathyroidism (47%), while seven of the 30 patients screened (23%) had significant vascular calcifications.

Lastly, our study had two major limitations. First, we depended completely on plasma PTH levels in our diagnosis of renal bone disease, which although is a good predictor of bone histology, is not as accurate as bone biopsy. The second limitation is that we were not able to measure serum levels of 25-OH vitamin D and aluminum to exclude the possibility of osteomalacia due to vitamin D deficiency or aluminum toxicity.

In conclusion, this cross sectional study, in a limited collection of patients, clearly showed that the prevalence of ROD in our institution was high, possibly because of inadequate patient monitoring and lack of insight into the problem by patients and physicians.

Physicians should be more sensitized and educated in dealing with the problem of CKD. Patients need to be taught about their disease similar to patients with other chronic illnesses like hypertension and diabetes. Also, caretakers must be aware of the importance of making the facilities necessary for the diagnosis and management of CKD easily available.


   Acknowledgments Top


The authors thank the director of 2nd March dialysis center for his cooperation and the director of the laboratory at Tripoli organ transplantation center for performing the blood tests.

 
   References Top

1.Massry S, Glassock R. Textbook of Nephrology. Vol. 2 .3rd edition. Williams& Wilkins. page 1457.  Back to cited text no. 1    
2.Eknoyan G, Levin A, Levin NW. Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42 Suppl: 1130-3.  Back to cited text no. 2    
3.Stevens L A, Djurdjev O, Cardew S, et al. Calcium, phosphate and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality. J Am Soc Nephrol 2004;15:770-9.  Back to cited text no. 3    
4.Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-18.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Black GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus, and calcium x phosphate product with mortality risk in chronic hemodialysis patients.( a national study). Am J Kidney Dis 1998;31:607-17.  Back to cited text no. 5    
6.Qi Q, Monier-Faugere MC, Geng Z, Malluche H. Predictive value of serum parathyroid hormone levels for bone turnover in patients on chronic maintenance dialysis. Am J Kidney Dis 1995;26(4):622-31.  Back to cited text no. 6    
7.Bevoets J, Spasovski GB, Behets GJ, et al. Useful biochemical markers for diagnosing renal osteodystrophy in pre-dialysis end­stage renal failure patients. Am J Kidney Dis 2003;41(5):997-1007.  Back to cited text no. 7    
8.Gerakis A, Hutchison AJ, Apostolou T, Freemont A, Billis A. Biochemical markers for non-invasive diagnosis of hyper parathyroid bone disease and adynamic bone in patients on hemodialysis. Nephrol Dial Transplant 1996;11(12):2430-8.  Back to cited text no. 8    
9.National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2004;42(4 suppl 3):S1-202.  Back to cited text no. 9    
10.Daugirdas JT, Blake PG, Ing TS. Handbook of Dialysis. 3rd Edition. Lippincott. Williams & Wilkins.  Back to cited text no. 10    
11.Razzaque MS, St-Arnaud R, Taguchi T, Lanske B. FGF-23, vitamin D, and calcification: the unholy triad. Nephrol Dial Tranplant 2005;20(10):2032-5.  Back to cited text no. 11    
12.Drueke T. Hyporesonsiveness to recombinant human erythropoietin. Nephrol Dial Transplant 2001;16 [Suppl]: 25-8.  Back to cited text no. 12    

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Correspondence Address:
Mahdia A Buargub
P. O. Box 83478, Tripoli
Libya
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    Figures

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    Tables

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    Abstract
    Introduction
    Patients and Methods
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    Results
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