Background-The novel phosphate binder sevelamer has been shown to prevent the progression of aortic and coronary calcification in uremic patients. Whether it also decreases the progression of atheromatous plaques is unknown. The aim of our study was to examine the effect of sevelamer administration on the development of atherosclerosis and aortic calcification in the uremic apolipoprotein E-deficient mouse as an established model of accelerated atherosclerosis. Methods and Results-Female mice were randomly assigned to 4 groups: 2 groups of nonuremic mice (sevelamer versus control) and 2 groups of uremic mice (sevelamer versus control). Sevelamer was given at 3% with chow. The increases in serum phosphorus concentration and calcium-phosphorus product observed in uremic control mice were prevented by sevelamer. Serum total cholesterol was increased in the 2 uremic mouse groups and remained unchanged in response to sevelamer. After 8 weeks of sevelamer treatment, uremic mice exhibited a significantly lower degree of atherosclerosis (PϽ0.001) and vascular calcification than uremic control mice. Of interest, sevelamer exerted an effect on both intima and media calcification (Pϭ0.005) in uremic mice. Among possible mechanisms involved, we found no evidence for the modulation by sevelamer of inflammation or selected uremic toxins. In contrast, nitrotyrosine staining as a measure of oxidative damage was significantly decreased in response to sevelamer treatment in control and uremic mice (PϽ0.005). Conclusions-Sevelamer delays not only vascular calcification but also atherosclerotic lesion progression in uremic apolipoprotein E-deficient mice. It opens the possibility of a cholesterol-independent action of sevelamer on atheroma formation via effects on mineral metabolism, oxidative stress, or both.

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The number of chronic kidney disease (CKD) patients and related adverse outcomes has dramatically increased worldwide in the past decade. Therefore, numerous experimental and clinical studies have recently addressed the underlying mechanisms, in particular the marked increase in cardiovascular mortality. Hyperphosphatemia is a major problem in these patients with advanced stage of CKD. Its control by calcium-containing phosphate binders is effective, but at the price of potentially noxious calcium overload. Sevelamer hydrochloride is a phosphate binder that offers an effective control of hyperphosphatemia as calcium-rich binders but without increase of calcium load. Beyond the control of phosphate, sevelamer seems to exert pleiotropic effects which include the correction of lipid abnormalities and the clearance of some uremic toxins.

Background. In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF). Methods. Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods. Results. Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p < 0.05) and non-plaque-associated calcification surface (p < 0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions.

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients’ age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951–0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.

Chronic kidney disease (CKD) is frequently complicated by arterial calcification. The latter is part of the associated mineral and bone disorder (CKD-MBD). Hypercalcemia and hyperphosphatemia have long been known to play a major role in the occurrence of vascular and other soft tissue calcification in patients with CKD, together with endocrine disturbances including vitamin D, parathyroid hormone, fibroblast growth factor-23, and klotho. In addition, many other systemic and local promoters, including inflammation and uremic toxins, contribute to the occurrence of vascular calcification, despite a powerful defense system made up of systemic and local inhibitors, as demonstrated in elegant experimental studies done in vitro and in vivo. Most importantly, several reports have shown that both hyperphosphatemia and hypophosphatemia, and to a lesser degree hypercalcemia and hypocalcemia, are associated with an increased relative risk of mortality in patients with CKD. However, all these reports were observational in nature and must therefore be considered as hypothesis generating. It remains to be demonstrated in prospective randomized trials whether normalization of serum phosphorus and/or calcium leads to better patient outcome. In order to improve outcome in patients with CKD-MBD, early medical intervention is of utmost importance.