Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer

BACKGROUND: High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. METHODS: CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. RESULTS: Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P < 0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P < 0.01). CONCLUSIONS: Higher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.

[Polymorphisms of vitamin D receptor gene [Apa I and Fok I] and its association with serum vitamin D and parathyroid hormone levels in hemodialysis patients]

Background and Objectives: Vitamin-D recptor [VDR], plays a key role in the development of cardiovascular diseases in hemodialysis patients via the modulation of the serum levels of calcium and parathyroid hormone. In this study, we aimed to determine the genetic association of VDR gene polymorphisms with serum levels of vitamin D, parathyroid hormone and fetuin-A in hemodialysis patients

Material and Methods: Forty six hemodialysis patients and 43 control cases were studied. VDR Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of iPTH, Fetuin-A and Vit D were measured by enzyme-linked immunosorbent assay

Results: There was no significant difference in the genotype frequencies between two study groups in both Fok I and Apa I polymorphisms [p=0.2]. There was significant difference in serum iPTH levels in Fok I polymorphism [p=0.02] and Vit D levels in Apa I polymorphism [p=0.04]. Although a significant positive correlation between iPTH and Vitamin D levels in aa genotype of patients [p=0.02, r=0.4] and Vit D and Fetuin-A levels in FF genotype of control group [p=0.001, r=1] was seen

Conclusion: Polymorphisms of VDR gene Fok I and Apa I play a key role in the development of cardiovascular diseases in hemodialysis patients

Effect of fish oil supplements on serum paraoxonase activity in female patients with rheumatoid arthritis: a double-blind randomized controlled trial

This study was conducted to determine the effect of fish oil [FO] supplements on high density lipoprotein cholesterol [HDL-C], apolipoprotein-Al [Apo-Al], malondialdehyde [MDA], arylesterase [Aryl], and paraoxonase-1 [PON1] activity in female patients with rheumatoid arthritis [RA]. A total of 90 RA patients were randomly allocated into two groups that were treated with one FO pearl [1 gr] daily or placebo for three months in addition to conventional treatment. HDL-C, Apo-Al, and MDA levels as well as POW and Aryl activities were measured before and after treatment. Independent t-test was used to match basal parameters of case and control groups. Paired t-test was used to assess significance of the differences. Correlation was evaluated by Pearson's test and the statistical significance was set at P < 0.05. No significant differences were noted between FO and placebo patients with regards to age, disease duration, post-menopausal status, conventional therapy, body mass index [BMI], and numbers of swollen and tender joints at the beginning of the study. There were 83 patients who completed the three-month follow up. Serum levels of HDL-C [P = 0.018], Apo-Al [P = 0.165], Aryl [P = 0.026], and POW [P = 0.049] activity increased, whereas MDA levels decreased significantly with FO supplementation [P= 0.077]. Significant correlations between increased POW activity and both HDL-C [P = 0.007, r = 0.419] and Apo-Al [P < 0.001, r = 0.742] concentrations as well as between HDL-C and Apo Al levels [P= 0.01, r = 0.403] were found. According to the results of this study, EQ could increase serum HDL-C and PQN1 levels and Aryl activity in female patients with RA

Arterial atherosclerosis in patients with chronic kidney disease and its relationship with serum and tissue

We investigated the correlation between atherosclerosis and tissue and serum levels of endothelin-1 in patients with chronic kidney disease [CKD]. Arterial samples were obtained from 35 patients with CKD during arteriovenous fistula placement. Thirty-one patients with cardiovascular disease who underwent coronary artery bypass graft [CABG] were selected as the atherosclerotic group, and a piece of their aorta punched during CABG was obtained. Also, a small piece of the renal artery was dissected during donation in 24 kidney donors [control group]. Tissue endothelin-1 level was measured and atherosclerosis grading was determined by pathologic examination. Serum levels of endothelin-1 were also measured in the three groups. The mean tissue endothelin-1 levels were 10.73 +/- 7.57 pg/ mL, 12.16 +/- 3.95 pg/mL, and 0.93 +/- 1.06 pg/mL in the patients with CKD, those with CABG, and donors, respectively [P < .001]. The mean serum endothelin-1 level was 25.23 +/- 15.15 pg/mL in the patients with CKD, 21.13 +/- 17.22 pg/mL in the patients with CABG, and 2.66 +/- 1.51 pg/mL in the donors [P < .001]. Atherosclerosis grades correlated with tissue endothelin-1 level [r = 0.823, P < .001] and serum endothelin-1 level [r = 0.608, P < .001] in the patients with CKD. Multiple regression analysis showed tissue endothelin-1 level as the main predicting factor of atherosclerosis [P < .001]. Tissue endothelin-1 concentration is more important than serum endothelin-1 or lipids levels in prediction of atherosclerosis. Thus, blockade of tissue endothelin-1 receptors with its antagonists may prevent atherosclerosis progression

C-reactive protein level following treatment and withdrawal of lovastatin in diabetic nephropathy

We aimed to evaluate the high-sensitivity C-reactive protein [HS-CRP] level changes at the beginning and after withdrawal of lovastatin therapy in patients with diabetic nephropathy. Thirty male patients with type 2 diabetes mellitus and diabetic nephropathy were enrolled in the study. Lovastatin, 20 mg/d, was administered for 90 days. Afterwards, Lovastatin was withdrawn for the next 30 days. Blood samples were obtained before the intervention, on the 90th day, and days 1, 7, and 30 after withdrawal of Lovastatin. Serum level of HS-CRP was determined by enzyme-linked immunosorbent assay. Alterations in lipid profile was assessed, as well, and compared with that of HS-CRP. Serum level of HS-CRP was significantly reduced after 90 days of lovastatin therapy [P < .001]. Then, the HS-CRP reached the pretreatment baseline level on the 7th day after lovastatin withdrawal and maintained until the 30th day [P < .001]. Serum HS-CRP changes showed no significant association with lipid profile except for serum total cholesterol level [r = 0.9, P = .006] after 3 months of lovastatin therapy. Their association was re-evaluated after 7 days and 1 month of treatment withdrawal and no significant correlations were found. Our findings suggest that lovastatin decreases serum CRP level in patients with diabetic nephropathy, and 7 days after lovastatin cessation, CRP level increases again

PDpoietin in comparison with eprex in treatment of anemic patients on hemodialysis

PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis. This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex [Janssen Cilag] or PDpoietin [Pooyesh Darou] for 3 months. Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively [P = .002; P = .01]. The mean hemoglobin per cumulative of drug dose index [hemoglobin/[erythropoietin dose/1000 x injections per month]] was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported. Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PDpoietin can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price

Doppler ultrasonographic indeces in kidney transplant recipients its relationship with kidney function

Doppler ultrasonography [DU] is mostly used for assessment of both graft and native kidneys' vascular status. In this study, correlation between the DU indexes and kidney allograft function was evaluated. Hospital records of 273 kidney transplant patients [154 men and 119 women] were reviewed. In all cases, DU had been performed 1 month after kidney transplantation. We evaluated the data on the resistive index [RI] and pulsatility index [PI] in the interlobar arteries and renal artery stenosis [RAS], and renal vessels thrombosis were determined. Concurrent serum creatinine and cyclosporine values were assessed in relation to the DU findings. The RI and PI had significant linear correlations with serum creatinine [P = .03 and P = .002, respectively]. Also, there were direct linear correlations between the age of the patients and the RI and PI values. The frequency of RAS was 10.3%. In patients with RAS, the mean creatinine level [2.08 +/- 1.70 mg/dL] was significantly higher than that in patients without RAS [1.48 +/- 0.97 mg/dL; P = .004]. Despite this finding, RI and PI were significantly lower in patients with RAS than in the patients with patent renovascular tributary [0.59 +/- 0.15 versus 0.65 +/- 0.11; P = .03 and 1.02 +/- 0.40 versus 1.18 +/- 0.46; P = .049, respectively]. There were no associations between serum cyclosporine level or panel reactive antibodies and the RI or PI. The RI and PI are valuable DU markers for determining the kidney allograft function and the related vascular complications