Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients.

PURPOSE: Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. METHODS: Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. RESULTS: We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. CONCLUSION: The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.

Proton pump inhibitors may hinder hypophosphatemic effect of lanthanum carbonate, but not of ferric citrate hydrate or sucroferric oxyhydroxide, in hemodialysis patients.

Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by -18% in the absence of a PPI (n = 9), while a dosage of 700 ± 230 mg/day only decreased it by -3% in the presence of a PPI (n = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by -18% in the absence of a PPI (n = 7, FCH: 571 ± 189 mg/day) and by -17% in the presence of a PPI (n = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was -7% in the absence of a PPI (n = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by -13% in the presence of a PPI (n = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

Association of (pro)renin receptor mRNA expression with angiotensin-converting enzyme mRNA expression in human artery.

BACKGROUND/AIMS: A significant role of (pro)renin receptor in the pathogenesis of end-organ damage has been suggested only in animal studies. This study was conducted to examine the mRNA expression of (pro)renin receptor in human artery. METHODS: In 141 kidney failure patients, the mRNA was harvested from arterial fragments obtained during surgery constructing an arteriovenous access for hemodialysis therapy, and expression levels of (pro)renin receptor and other components of the renin-angiotensin system were determined. RESULTS: Arterial (pro)renin receptor expression was similar in diabetic and non-diabetic patients, although plasma prorenin levels were significantly higher in the diabetic patients than in the non-diabetic patients. The arterial (pro)renin receptor mRNA levels of the hypertensive patients, who had not been treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers, were significantly lower than those of the patients who had been treated with either drug. Multiple regression analyses showed a significant association with a large coefficient between the arterial mRNA level of the (pro)renin receptor and the arterial mRNA level of ACE; this significant association disappeared in patients who had been treated with either drug. CONCLUSION: (Pro)renin receptor may contribute to the generation of arterial angiotensin II in kidney failure patients.

Proliferating potential and apoptosis in the development of secondary hyperparathyroidism: a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay.

Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis (HD) patients. SHPT progresses from initial diffuse hyperplasia (diffuse) to early nodularity (early), then to multinodular hyperplasia (nodular), and finally to a single nodule (single) consisting of uniform parenchymal cells. We analyzed the roles of proliferation and apoptosis in SHPT progression. Seventy-four parathyroid glands from 36 HD patients with SHPT, and 10 parathyroid glands from 10 non-HD patients without SHPT were used for analysis. The former were classified as diffuse (N = 17), early (N = 22), nodular (N = 20), and single (N = 15); the latter were classified as normal (N = 10). To analyze proliferating cells we used Ki-67, and to detect apoptotic cells, we used the terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling (TUNEL) assay. Concerning the Ki-67 labeling index (LI), the incremental order was single, nodular, early, diffuse, and normal. Oxyphilic cells and around the central portion of each lesion were distinctly stained by Ki-67. Concerning the TUNEL LI, the incremental order was early, diffuse, nodular, single, and normal. Chief cells and around the peripheral portion of each lesion were distinctly stained by TUNEL. In the progression from early to nodular, for oxyphilic cells, the Ki-67 LI increased and the TUNEL LI decreased; for chief cells, the Ki-67 LI decreased and the TUNEL LI showed no significant change. We considered that proliferative activity increases and that the apoptosis rate decreases as SHPT progresses from diffuse to single. Moreover, the specific differences in the rate of proliferation and apoptosis between oxyphilic and chief cells might be associated with SHPT progression.

Cardio-ankle vascular index and ankle pulse wave velocity as a marker of arterial fibrosis in kidney failure treated by hemodialysis.

BACKGROUND: Patients with kidney failure treated with hemodialysis have a high incidence of cardiovascular diseases caused by accelerated arteriosclerosis. However, accurate evaluation of the extent of arteriosclerosis is difficult. This study sought to compare the strength of predictions of arterial fibrosis by using a new parameter, the cardio-ankle vascular index (CAVI), versus pulse wave velocity (PWV) in patients with kidney failure treated with hemodialysis. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 103 patients with kidney failure undergoing surgical construction of an arteriovenous access for hemodialysis therapy. INDEX TEST: CAVI and PWV. REFERENCE TEST: Arterial fibrosis, evaluated by using Masson trichrome stain on part of the brachial artery obtained during surgery, expressed as percentage of fibrosis of the layer of vascular smooth muscle cells. RESULTS: Median percentage of arterial stiffness was 52.85%. Mean PWV and CAVI were 18.3 +/- 5.6 (SD) m/s and 9.9 +/- 2.6, respectively. Multivariate regression analysis showed that arterial fibrosis was significantly associated with older age (0.247%/y; 95% confidence interval, 0.013 to 0.482) and CAVI (6.117%/unit; 95% confidence interval, 4.764 to 4.740), but not with systolic blood pressure (0.039%/mm Hg; 95% confidence interval, -0.076 to 0.153) or PWV (-0.044%/m/s; 95% confidence interval, -0.646 to 0.558). The area under the receiver operating characteristic curve to predict greater than median percentage of arterial stiffness was 0.892 for CAVI and 0.779 for PWV (P = 0.006). LIMITATION: It is unclear whether arterial fibrosis of the brachial artery evaluated by using CAVI is applicable for arteriosclerosis of other arterial districts, and clinical outcomes were not evaluated in this study. CONCLUSION: CAVI reflects the histological arterial fibrosis of hemodialysis patients and is a useful clinical marker for evaluating arterial stiffness in these patients.