Corresponding author:
Hamid Nasri, MD
Shahrekord University of Medical Sciences
Hajar Medical, Educational
and Therapeutic Center
Department of Internal Medicine
Shahrekord, Iran
Phone: (00) 98 381 222 00 16
Fax: (00) 98 381 224 37 15
E-mail: hamidnasri@yahoo.com, hamidnasri@skums.ac.ir
Introduction
25-hydroxyvitamin D (25-OH vitamin D) is the major circulating metabolite of vitamin D. Although the biological active form of vitamin D is 1,25(OH)2 vitamin D, synthesised in the kidney, it is widely accepted that the measurement of circulating 25-OH vitamin D provides better information with respect to the patients vitamin D status and is used for diagnosis of hypovitaminosis [1, 2]. The concentration of 25-OH vitamin D decreases with age and deficiency is common among the elderly [3, 4]. Recently, some authors have emphasized the role of plasma 25(OH) vitamin D levels in mineral metabolism dysregulation in chronic kidney diseases [5, 6]. It has been demonstrated that a moderate reduction in plasma 25-OHD levels plays a role in the development of secondary hyperparathyroidism (SHPTH) in hemodialysis patients [7], whereas a greater reduction in plasma 25-OHD levels is associated with osteomalacia and with the risk of developing osteoporosis [7]. Furthermore, K-DOQI clinical practice guidelines emphasize the importance of monitoring plasma levels of the hormone and suggest, even though as "an opinion", vitamin D administration when plasma 25-OHD levels are <30 ng/mL [8]. Furthermore, to date little attention has been paid to 25-OHD metabolism abnormalities as a marker of nutritional status in maintenance hemodialysis patients (MHPs). This cross-sectional study was aimed to better understand the role of 25-OHD as a marker of nutrition as well as its association with mineral metabolism and serum parathormone secretion in end-stage renal failure patients undergoing regular hemodialysis.
Material and methods
Patients
This cross-sectional study was conducted on patients with end-stage renal disease (ESRD), who were undergoing maintenance hemodialysis treatment with acetate basis dialysate and polysulfone membranes. According to the severity of secondary hyperparathyroidism, each patient being treated for secondary hyperparathyroidism was given oral active vitamin D3 (Calcitriol; Rocaltrol) (Roche Hexagon; Roche Laboratories Inc, New Jersey, USA), calcium carbonate capsule , and Rena-Gel (sevelamer; Genzyme Europe B.V.; United Kingdom/Ireland) tablet at various doses.
According to the severity of anemia, the patients were prescribed intravenous iron therapy with
Iron Sucrose (Venofer; International Inc. St. Gallen/ Switzerland) at various doses after each dialysis session. All patients received treatments of 6 mg folic acid daily, 500 mg Acetyl-L-Carnitine (Jarrow Formulas, Inc™ Los Angeles, CA) daily, oral vitamin B-complex tablets daily, and 2,000 U intravenous Eprex (recombinant human erythropoietin (Janssen-Cilag; CILAG- AG International 6300 Zug/Switzerland) after each dialysis session. Exclusion criteria were active or chronic infection and using NSAID or ACE inhibitor drugs. The study was done in the hemodialysis section of Hajar Medical Educational & Therapeutic Center of Shahrekord University of Medical Sciences in Shahrekord of Iran.
Laboratory methods
Serum 25-hydroxy (25-OH vitamin D) level (normal range of values is 25 to 125 nmol/L) and intact serum PTH (iPTH) were measured as follows. Blood samples were drawn after an overnight fast, blood samples were centrifuged within 15 min of venepuncture, and were measured by enzyme-linked immunosorbent assay (ELISA) method using DRG kits from Germany. Intact serum PTH (iPTH) was measured by the radioimmunoassay (RIA) method using DSL-8000 kits from the USA (normal range of values is 10-65 pg/ml). Also peripheral venous blood samples were collected after an overnight fast, for biochemical analysis including serum predialysis creatinine (Creat), post and predialysis blood urea nitrogen (BUN), albumin (Alb) as well as serum C-reactive protein (CRP), serum calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were measured using standard methods. Body mass index (BMI) calculated using the standard formula (postdialyzed weight in kilograms/height in square meters; kg/m2). For the efficacy of hemodialysis the urea reduction rate (URR) was calculated from pre- and post-blood urea nitrogen (BUN) data. Duration and the amount of sessions of hemodialysis treatment were calculated from the patients' records. The duration of each hemodialysis session was 4 hours.
Statistical analysis
Results are expressed as the mean ±SD and median values. The comparison between the groups was done using the Student's t-test. Statistical correlations were assessed using a partial correlation test. The statistical analysis was performed on total hemodialysis (HD), females, males, diabetics and non diabetics populations separately. All statistical analyses were performed using SPSS (version 11.5.00). The statistical significance was determined at a p-value below 0.05.
Results
The total number of patients was 36 (F 15, M 21), consisting of 25 (F 11, M 14) non-diabetic HD patients and 11 (F 4, M 7) diabetic HD patients. Tables I, II and III show the Mean ±SD, minimum and maximum and median of age, duration and sessions of hemodialysis and also laboratory results of total hemodialysis (HD) patients. The mean patient's age was 47 (±17) years. The value of serum predialysis creatinine in total patients was 9.5±3.6 mg/dl. The value of serum 25-OH vitamin D of total HD patients was 10.5±18.7 (median: 3.5) nmol/L, the value of serum 25-OH vitamin D of diabetic and nondiabetic dialysis patients were 5.8±10 (median: 2.8) and 12.6±21 (median: 6) nmol/L, respectively. The value of serum iPTH of total HD patients was 434±455 (median: 309) pg/ml, the value of serum iPTH of diabetic and nondiabetic-dialysis patients were 201±277 (median: 41) and 537±483 (median: 340) pg/ml, respectively. There were no significant differences of serum 25-OH vitamin D between diabetic and non-diabetics or male and females of total HD patients was seen (p NS), however a significant differences of serum 25-OH vitamin D between diabetic and non-diabetics of male dialysis patients was found (r=0.014; Figure 1). In non diabetic HD patients, there was a significant positive correlation of serum 25-OH vitamin D with BMI (r=0.51, p=0.011; Figure 2) was seen (adjusted for age). In this group also there was a near significant inverse correlation of serum 25-OH vitamin D with serum phosphorus (r=- 0.39, p=0.057) and also a significant inverse correlation of serum 25-OH vitamin D with serum calcium (r=-0.42, p=0.040; Figure 3) was found, too (adjusted for dialysis sessions for two above correlations). In male HD patients a near significant inverse correlation of serum 25-OH vitamin D with serum iPTH (r=-0.43, p=0.057) (adjusted for duration dialysis) was seen. In this study no significant association between serum 25-OH vitamin D with serum albumin, CRP, ALP, URR and age, duration and sessions of dialysis were found (p=ns).
Discussion
In this study we found a significant difference of serum 25-OH vitamin D between diabetic and non-diabetics of male dialysis patients with more values in nondiabetic HD patients and a significant positive correlation of serum 25-OH vitamin D with BMI and also a near significant inverse correlation of serum 25-OH vitamin D with serum phosphorus were seen, also a significant inverse correlation of serum 25-OH vitamin D with serum calcium were found, too. Moreover, a near significant inverse correlation of serum 25-OH vitamin D with serum iPTH was seen, too. In a study conducted by Gonzalez et al. on 103 patients undergoing hemodialysis, it was found that 97% of the patients had vitamin D levels in the suboptimal range, and there was no correlation of 25(OH)D levels with either PTH or serum albumin values [9]. In agreement with this study we also could not show the correlation of 25(OH)D with serum albumin. Interestingly, we showed a positive correlation of 25(OH)D with BMI, implies that serum 25(OH)D have an association with nutritional status in MHPs. In contrast to the mentioned study we showed a near significant inverse correlation of serum 25-OH vitamin D[25(OH)D] with serum iPTH also negative association of serum 25(OH)D with Ca and P, showed that low levels of serum 25(OH)D clearly aggravate the secondary hyperparathyroidism of regular HD patients. In this regard Ghazali et al. in a study to evaluate the plasma 25(OH)D levels as a risk factor for parathyroid hormone hypersecretion and radiological bone disease, on 113 patients who were not taking supplements of alphacalcidol or calcitriol, found that plasma PTH was correlated negatively with plasma 25-OHD. They concluded that low plasma 25-OH vitamin D is a major risk factor for hyperparathyroidism and Looser's zones [10]. Therefore, our study strengthens the suggestion that low serum 25-OH vitamin D levels could be a risk factor for secondary hyperparathyroidism in hemodialysis patients as well as serum 25-OH vitamin D could show the nutritional status of HD patients. In summary, we think that our results are of interest for two reasons: first, because there is limited previous data concerning this topic and, secondly, because our results indicate the importance of monitoring plasma 25-OH vitamin D levels in HD patients. In dialysis patients, we suggest that the plasma levels of 25-OH vitamin D are maintained around the upper limit of the reference range of sunny countries.
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