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Sample records for calcific uremic arteriolopathy

  1. Calcific Uremic Arteriolopathy: An Underrecognized Entity

    PubMed Central

    Kumar, Victoria Ann

    2011-01-01

    Calcific uremic arteriolopathy (CUA), or calciphylaxis, is an uncommon and underrecognized disease that often occurs in the setting of chronic kidney disease or end-stage renal disease. It is characterized by small-vessel calcification, although many times it is associated with normal serum levels of calcium, phosphorus, and parathyroid hormone. The lesions appear as necrotic eschars, ulcerations, indurated nodules, and dry gangrene and are usually very painful. Diagnosis is based on clinical judgment and recognition of characteristic skin lesions. Biopsy can be performed but may be complicated by poor wound healing. Treatment of CUA involves rigorous wound care, strict control of mineral metabolism with avoidance of calcium and vitamin D analogs, and pain control. Other treatment options include sodium thiosulfate, hyperbaric oxygen therapy, daily hemodialysis using low-calcium dialysate, and bisphosphonates. Even with treatment, CUA is associated with significant morbidity and mortality. The patient in the case reported here had characteristic skin lesions and several risk factors for CUA, but diagnosis was delayed. PMID:21841931

  2. Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy

    PubMed Central

    Brunelli, Steven M.; Meade, Debra; Wang, Weiling; Hymes, Jeffrey; Lacson, Eduardo

    2013-01-01

    Summary Background and objective Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. Design, setting, participants, & measurements This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. Results Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. Conclusions Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study. PMID:23520041

  3. Sodium thiosulfate therapy for calcific uremic arteriolopathy.

    PubMed

    Nigwekar, Sagar U; Brunelli, Steven M; Meade, Debra; Wang, Weiling; Hymes, Jeffrey; Lacson, Eduardo

    2013-07-01

    Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study.

  4. A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors.

    PubMed

    Nigwekar, Sagar U; Zhao, Sophia; Wenger, Julia; Hymes, Jeffrey L; Maddux, Franklin W; Thadhani, Ravi I; Chan, Kevin E

    2016-11-01

    Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology. Copyright © 2016 by the American Society of Nephrology.

  5. [Calcific uremic arteriolopathy (Calcyphilaxis): a rare disease? Report of three cases].

    PubMed

    Napolitano, Paola; Capuano, Alfredo; D'Apice, Ludovica; Mosella, Francesca; Pota, Andrea; Saviano, Caterina; Russo, Domenico

    2015-01-01

    Calcific uremic arteriolopathy (CUA; CALCYPHILAXIS) is a syndrome that occurs prevalently in patients with chronic kidney disease on dialysis. It is characterized by the medial calcification of skin small arteries leading to necrotic lesions. Several risk factors have been identified: obesity, female gender, diabetes mellitus, hyperphosphatemia, inflammation, treatment with vitamin D, calcium-based phosphate binders and warfarin. We report three cases of CUA observed from October 2011 to September 2014. The mean age at diagnosis was 56 years (range 33-68). Biochemistry showed: mean levels of PTH=1277 pg/ml (range 1000-1696), serum calcium =10.2 mg/dl (range 9.4-11.1), phosphorus=4.5 mg/dl (range 3.4-5.5). All patients were taking vitamin D, two patients were on warfarin therapy. Following actions were undertaken: interruption of calcium-based phosphate binders, vitamin D and warfarin therapy, initiation of cinacalcet and sodium thiosulfate therapy, use of dialysate with lowest available calcium concentration (1.25 mmol/l), Hyperbaric Oxygen Therapy, surgical dressings of skin lesions three times a week. Significant improvement was observed in mean levels of PTH (331 pg/ml, range 200-465), serum calcium (8.3 mg/dl, range 7.4-9.6) and phosphorus (3.4 mg/dl, range 2.6-3.8). In two out of three patients complete healing of ulcerative lesions was obtained. These cases underline the importance of early diagnosis of CUA especially in patients with concomitant risk factors and careful clinical monitoring, being CUA characterized by a rapid evolution and high mortality.

  6. The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial

    PubMed Central

    Kubo, Yumi; Floege, Anna; Chertow, Glenn M.; Parfrey, Patrick S.

    2015-01-01

    Background and objectives Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis). Design, setting, participants, & measurements Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug. Results Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%–7% at any one time point in patients in whom CUA was not reported. Conclusion Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT. PMID:25887067

  7. Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

    PubMed Central

    Hayden, Melvin R; Tyagi, Suresh C; Kolb, Lisa; Sowers, James R; Khanna, Ramesh

    2005-01-01

    Background Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling). The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. Results The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare) is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. Conclusion A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications. PMID:15777477

  8. Ecto-5' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients – Data from the German Calciphylaxis Registry

    PubMed Central

    Brandenburg, Vincent; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Ketteler, Markus; Wanner, Christoph

    2017-01-01

    Introduction Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. Methods We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD). 144 dialysis patients from the German calciphylaxis registry were compared with 370 dialysis patients without history of CUA. Genotyping was performed using iPLEX Gold MassARRAY(Sequenom, San Diego, USA), KASP genotyping chemistry (LGC, Teddington, Middlesex, UK) or sequencing. Statistical analysis comprised logistic regression analysis with adjustment for age and sex. Results 165 SNPs were finally analyzed and 6 SNPs were associated with higher probability for calciphylaxis (OR>1) in our cohort. Nine SNPs of three genes (CD73, FGF23 and Vitamin D receptor) reached nominal significance (p< 0.05), but did not reach statistical significance after correction for multiple testing. Of the CD73 gene, rs4431401 (OR = 1.71, 95%CI 1.08–2.17, p = 0.023) and rs9444348 (OR = 1.48, 95% CI 1.11–1.97, p = 0.008) were associated with a higher probability for CUA. Of the FGF23 and VDR genes, rs7310492, rs11063118, rs13312747 and rs17882106 were associated with a higher probability for CUA. Conclusion Polymorphisms in the genes encoding CD73, vitamin D receptor and FGF23 may play a role in calciphylaxis development. Although our study is the largest genetic study on calciphylaxis, it is limited by the low sample sizes. It therefore requires replication in other cohorts if available. PMID:28212442

  9. Treatment with pyrophosphate inhibits uremic vascular calcification.

    PubMed

    O'Neill, W Charles; Lomashvili, Koba A; Malluche, Hartmut H; Faugere, Marie-Claude; Riser, Bruce L

    2011-03-01

    Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone.

  10. Treatment with pyrophosphate inhibits uremic vascular calcification

    PubMed Central

    O’Neill, W. Charles; Lomashvili, Koba A.; Malluche, Hartmut H.; Faugere, Marie-Claude; Riser, Bruce L.

    2011-01-01

    Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone. PMID:21124302

  11. Role of Vitamin D in Uremic Vascular Calcification

    PubMed Central

    Zheng, Jing-Quan

    2017-01-01

    The risk of cardiovascular death is 10 times higher in patients with CKD (chronic kidney disease) than in those without CKD. Vascular calcification, common in patients with CKD, is a predictor of cardiovascular mortality. Vitamin D deficiency, another complication of CKD, is associated with vascular calcification in patients with CKD. GFR decline, proteinuria, tubulointerstitial injury, and the therapeutic dose of active form vitamin D aggravate vitamin D deficiency and reduce its pleiotropic effect on the cardiovascular system. Vitamin D supplement for CKD patients provides a protective role in vascular calcification on the endothelium by (1) renin-angiotensin-aldosterone system inactivation, (2) alleviating insulin resistance, (3) reduction of cholesterol and inhibition of foam cell and cholesterol efflux in macrophages, and (4) modulating vascular regeneration. For the arterial calcification, vitamin D supplement provides adjunctive role in regressing proteinuria, reverse renal osteodystrophy, and restoring calcification inhibitors. Recently, adventitial progenitor cell has been linked to be involved in the vascular calcification. Vitamin D may provide a role in modulating adventitial progenitor cells. In summary, vitamin D supplement may provide an ancillary role for ameliorating uremic vascular calcification. PMID:28286758

  12. Acid-Base Balance in Uremic Rats with Vascular Calcification

    PubMed Central

    Peralta-Ramírez, Alan; Raya, Ana Isabel; Pineda, Carmen; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; López, Ignacio

    2014-01-01

    Background/Aims Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied. Results The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected. Conclusions In an experimental model of uremic rats, VC showed high positive correlation with AG and SID. PMID:25177336

  13. Acid-base balance in uremic rats with vascular calcification.

    PubMed

    Peralta-Ramírez, Alan; Raya, Ana Isabel; Pineda, Carmen; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; López, Ignacio

    2014-01-01

    Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied. The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected. In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

  14. Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats.

    PubMed

    Diaz-Tocados, Juan M; Peralta-Ramirez, Alan; Rodríguez-Ortiz, María E; Raya, Ana I; Lopez, Ignacio; Pineda, Carmen; Herencia, Carmen; Montes de Oca, Addy; Vergara, Noemi; Steppan, Sonja; Pendon-Ruiz de Mier, M Victoria; Buendía, Paula; Carmona, Andrés; Carracedo, Julia; Alcalá-Díaz, Juan F; Frazao, Joao; Martínez-Moreno, Julio M; Canalejo, Antonio; Felsenfeld, Arnold; Rodriguez, Mariano; Aguilera-Tejero, Escolástico; Almadén, Yolanda; Muñoz-Castañeda, Juan R

    2017-07-28

    Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65-NF-κB in TNF-α-treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. Cinacalcet ameliorates aortic calcification in uremic rats via suppression of endothelial-to-mesenchymal transition

    PubMed Central

    wu, Min; Tang, Ri-ning; Liu, Hong; Pan, Ming-ming; Liu, Bi-cheng

    2016-01-01

    Aim: Experimental studies found that cinacalcet (CINA) markedly attenuated vascular calcification in uremic rats, but its underlying mechanisms are still largely unknown. Recent evidence have demonstrated that endothelial cells (ECs) participate in ectopic calcification in part by mediating endothelial-to-mesenchymal transition (EndMT). In this study, we investigated whether CINA ameliorated aortic calcification in uremic rats via suppression of EndMT. Methods: Uremia was induced in rats by feeding rats a 0.75% adenine diet for 4 weeks. After adenine withdrawal, the rats were maintained on a 1.03% phosphorus diet for next 8 weeks. At initiation of the adenine diet, rats were orally administered CINA (10mg/kg one day) for 12 weeks. The aortic expression of EndMT- and chondrocyte- markers was examined. The effect of elevated PTH on EndMT was also studied in aortic ECs. Results: In uremic rats, CINA treatment significantly decreased the serum PTH concentrations, but did not affect the elevated levels of serum calcium (Ca), phosphorus (P) and Ca×P product. Besides, CINA significantly attenuated aortic calcification, and inhibited the expression of chondrocyte markers (SOX9 and COL2A1) and chondrocyte proteoglycan in uremic aortas. Moreover, CINA treatment largely abolished the up-regulation of mesenchymal markers (FSP1 and α-SMA) and down-regulation of the endothelial marker (CD31), which accompanied aortic calcification in uremic aorta samples. In vitro, PTH increased the expression of EndMT-markers in a concentration- and time-dependent manner. Conclusion: These findings suggest that strategies aiming at reducing serum PTH might prevent uremic aortic calcification by abrogating EndMT. PMID:27593220

  16. Phosphate restriction significantly reduces mortality in uremic rats with established vascular calcification.

    PubMed

    Finch, Jane L; Lee, Duk H; Liapis, Helen; Ritter, Cindy; Zhang, Sarah; Suarez, Edu; Ferder, Leon; Slatopolsky, Eduardo

    2013-12-01

    The role of hyperphosphatemia in the pathogenesis of secondary hyperparathyroidism, cardiovascular disease, and progression of renal failure is widely known. Here we studied effects of dietary phosphate restriction on mortality and vascular calcification in uremic rats. Control and uremic rats were fed a high-phosphate diet and at 3 months a portion of rats of each group were killed. Serum phosphate and the calcium phosphate product increased in uremic rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were continued on diets containing high phosphate without and with sevelamer, or low phosphate, and after 3 more months they were killed. Serum phosphate was highest in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation than those of uremic rats on high phosphate. Importantly, kidneys from rats on low phosphate showed improvement over kidneys from high-phosphate rats at 3 months. Left ventricles from rats on low phosphate had less perivascular fibrosis and smaller cardiomyocyte size compared to rats on high phosphate. Thus, intensive phosphate restriction significantly reduces mortality in uremic rats with severe vascular calcification.

  17. Very low protein diet enhances inflammation, malnutrition, and vascular calcification in uremic rats.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Tatsumoto, Narihito; Tsuruya, Kazuhiko; Kitazono, Takanari; Ooboshi, Hiroaki

    2016-02-01

    Clinical studies have shown that very low protein diet (VLPD) has negative effects on long-term survival. It remains unclear why VLPD induces premature death. The present study determined the underlying mechanism whereby VLPD exerts its harmful effects on uremic rats. Rats were divided into four groups and fed a normal diet or diets containing 0.3% adenine and low/normal protein with high/low phosphate. After 6 weeks, body weight, urinary biochemistry (creatinine and phosphate), serum biochemical parameters (urea, creatinine, fibroblast growth factor 23, albumin, and fetuin-A), systemic inflammatory markers (serum tumor necrosis factor-alpha and urinary 8-hydroxy-2'-deoxyguanosine), calcium content in the aorta, and serum calcium-phosphate precipitates were evaluated. Hepatic mRNA levels were also determined. Rats fed the diet containing 0.3% adenine developed severe azotemia. Rats fed VLPD developed malnutrition (decreases in body weight, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary 8-hydroxy-2'-deoxyguanosine) independent of phosphate status. VLPD decreased the serum fetuin-A level and hepatic fetuin-A synthesis and increased serum calcium-phosphate precipitates, a marker of calciprotein particle. A high-phosphate diet induced arterial medial calcification, which was enhanced by VLPD. Serum calcium-phosphate precipitate levels were correlated with the degree of inflammation, malnutrition, and aortic calcium content. Dietary phosphate restriction prevented VLPD-enhanced vascular calcification, but could not halt inflammation and malnutrition induced by VLPD. VLPD enhances inflammation, malnutrition, and vascular calcification in uremic rats, among which only vascular calcification is prevented by dietary phosphate restriction. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats.

    PubMed

    Cozzolino, Mario; Dusso, Adriana S; Liapis, Helen; Finch, Jane; Lu, Yan; Burke, Steven K; Slatopolsky, Eduardo

    2002-09-01

    The control of serum phosphorus (P) and calcium-phosphate (Ca x P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO(3)) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic + high-P diet (U-HP); UHP + 3% CaCO(3) (U-HP+C); UHP + 3% sevelamer (U-HP+S). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca x P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO(3) in the control of high-P-induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 +/- 8.6 micro g/g wet tissue) compared with both U-HP (175.5 +/- 45.7 micro g/g wet tissue, P < 0.01) and the U-HP+C (58.9 +/- 13.7 micro g/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 +/- 25) was reduced to 33.0 +/- 11.3 by CaCO(3) and decreased even further with sevelamer (16.4 +/- 8.9, P < 0.02 versus CaCO(3)). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with either U-HP+C (30%) or U-HP (50

  19. Fetuin-A decrease induced by a low-protein diet enhances vascular calcification in uremic rats with hyperphosphatemia.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Tsuruya, Kazuhiko; Tatsumoto, Narihito; Noguchi, Hideko; Kitazono, Takanari; Ooboshi, Hiroaki

    2015-10-15

    Although dietary phosphate restriction is important for treating hyperphosphatemia in patients with chronic kidney disease, it remains unclear whether a low-protein diet (LPD), which contains low phosphate, has beneficial effects on malnutrition, inflammation, and vascular calcification. The effects of LPD on inflammation, malnutrition, and vascular calcification were therefore assessed in rats. Rats were fed a normal diet or diets containing 0.3% adenine and low/normal protein and low/high phosphate. After 6 wk, serum and urinary biochemical parameters, systemic inflammation, and vascular calcification were examined. The protective effect of fetuin-A and albumin were assessed in cultured vascular smooth muscle cells. Rats fed the diet containing 0.3% adenine developed severe azotemia. LPD in rats fed high phosphate induced malnutrition (decreases in body weight, food intake, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary oxidative stress marker). LPD decreased the serum fetuin-A level and fetuin-A synthesis in the liver and increased serum calcium-phosphate precipitates. A high-phosphate diet increased aortic calcium content, which was enhanced by LPD. Reduced fetal calf serum in the medium of cultured vascular smooth muscle cells enhanced phosphate-induced formation of calcium-phosphate precipitates in the media and calcification of vascular smooth muscle cells, both of which were prevented by fetuin-A administration. Our results suggest that phosphate restriction by restricting dietary protein promotes vascular calcification by lowering the systemic fetuin-A level and increasing serum calcium-phosphate precipitates and induces inflammation and malnutrition in uremic rats fed a high-phosphate diet. Copyright © 2015 the American Physiological Society.

  20. Phosphate binders prevent phosphate-induced cellular senescence of vascular smooth muscle cells and vascular calcification in a modified, adenine-based uremic rat model.

    PubMed

    Yamada, S; Tatsumoto, N; Tokumoto, M; Noguchi, H; Ooboshi, H; Kitazono, T; Tsuruya, K

    2015-04-01

    Clinical and experimental studies have reported that phosphate overload plays a central role in the pathogenesis of vascular calcification in chronic kidney disease. However, it remains undetermined whether phosphate induces cellular senescence during vascular calcification. We established a modified uremic rat model induced by a diet containing 0.3% adenine that showed more slowly progressive kidney failure, more robust vascular calcification, and longer survival than the conventional model (0.75% adenine). To determine the effect of phosphate on senescence of vascular smooth muscle cells (VSMCs) and the protective effect of phosphate binders, rats were divided into four groups: (1) normal control rats; (2) rats fed with the modified adenine-based diet (CKD); (3) CKD rats treated with 6% lanthanum carbonate (CKD-LaC); and (4) CKD rats treated with 6% calcium carbonate (CKD-CaC). After 8 weeks, CKD rats showed circumferential arterial medial calcification, which was inhibited in CKD-LaC and CKD-CaC rats. CKD rats showed increased protein expression of senescence-associated β-galactosidase, bone-related proteins, p16 and p21, and increased oxidative stress levels in the calcified area, which were inhibited by both phosphate binders. However, serum levels of oxidative stress and inflammatory markers, serum fibroblast growth factor 23, and aortic calcium content in CKD-CaC rats were higher than those in CKD-LaC rats. In conclusion, phosphate induces cellular senescence of VSMCs in the modified uremic rat model, and phosphate binders can prevent both cellular senescence and calcification of VSMCs via phosphate unloading. Our modified adenine-based uremic rat model is useful for evaluating uremia-related complications, including vascular calcification.

  1. Effect of water fluoridation on the development of medial vascular calcification in uremic rats.

    PubMed

    Martín-Pardillos, Ana; Sosa, Cecilia; Millán, Ángel; Sorribas, Víctor

    2014-04-06

    Public water fluoridation is a common policy for improving dental health. Fluoride replaces the hydroxyls of hydroxyapatite, thereby improving the strength of tooth enamel, but this process can also occur in other active calcifications. This paper studies the effects of water fluoridation during the course of vascular calcification in renal disease. The effect of fluoride was studied in vitro and in vivo. Rat aortic smooth muscle cells were calcified with 2mM Pi for 5 days. Fluoride concentrations of 5-10 μM--similar to those found in people who drink fluoridated water--partially prevented calcification, death, and osteogene expression in vitro. The anticalcifying mechanism was independent of cell activity, matrix Gla protein, and fetuin A expressions, and it exhibited an IC50 of 8.7 μM fluoride. In vivo, however, fluoridation of drinking water at 1.5mg/L (concentration recommended by the WHO) and 15 mg/L dramatically increased the incipient aortic calcification observed in rats with experimental chronic kidney disease (CKD, 5/6-nephrectomy), fed a Pi-rich fodder (1.2% Pi). Fluoride further declined the remaining renal function of the CKD animals, an effect that most likely overwhelmed the positive effect of fluoride on calcification in vitro. Ultrastructural analysis revealed that fluoride did not modify the Ca/P atomic ratio, but it was incorporated into the lattice of in vivo deposits. Fluoride also converted the crystallization pattern from plate to rode-like structures. In conclusion, while fluoride prevents calcification in vitro, the WHO's recommended concentrations in drinking water become nephrotoxic to CKD rats, thereby aggravating renal disease and making media vascular calcification significant. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Lanthanum carbonate prevents accelerated medial calcification in uremic rats: role of osteoclast-like activity

    PubMed Central

    2013-01-01

    Background Arterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing. Methods Detailed time-course studies were conducted of Sprague–Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa’s and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit. Results Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 ± 0.73 mmol/L vs CRF Group 3.48 ± 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found. Conclusions Abnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased

  3. Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

    PubMed

    de Oliveira, Rodrigo B; Louvet, Loïc; Riser, Bruce L; Barreto, Fellype C; Benchitrit, Joyce; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Massy, Ziad A

    2015-08-01

    Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n = 18-19/group). Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65 mg/kg or low dose, 0.33 mg/kg per day), oral sevelamer (3 % in diet), or placebo treatment for 8 weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16 weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

  4. Elastin Degradation and Vascular Smooth Muscle Cell Phenotype Change Precede Cell Loss and Arterial Medial Calcification in a Uremic Mouse Model of Chronic Kidney Disease

    PubMed Central

    Pai, Ashwini; Leaf, Elizabeth M.; El-Abbadi, Mohga; Giachelli, Cecilia M.

    2011-01-01

    Arterial medial calcification (AMC), a hallmark of vascular disease in uremic patients, is highly correlated with serum phosphate levels and cardiovascular mortality. To determine the mechanisms of AMC, mice were made uremic by partial right-side renal ablation (week 0), followed by left-side nephrectomy at week 2. At 3 weeks, mice were switched to a high-phosphate diet, and various parameters of disease progression were examined over time. Serum phosphate, calcium, and fibroblast growth factor 23 (FGF-23) were up-regulated as early as week 4. Whereas serum phosphate and calcium levels declined to normal by 10 weeks, FGF-23 levels remained elevated through 16 weeks, consistent with an increased phosphate load. Elastin turnover and vascular smooth muscle cell (VSMC) phenotype change were early events, detected by week 4 and before AMC. Both AMC and VSMC loss were significantly elevated by week 8. Matrix metalloprotease 2 (MMP-2) and cathepsin S were present at baseline and were significantly elevated at weeks 8 and 12. In contrast, MMP-9 was not up-regulated until week 12. These findings over time suggest that VSMC phenotype change and VSMC loss (early phosphate-dependent events) may be necessary and sufficient to promote AMC in uremic mice fed a high-phosphate diet, whereas elastin degradation might be necessary but is not sufficient to induce AMC (because elastin degradation occurred also in uremic mice on a normal-phosphate diet, but they did not develop AMC). PMID:21281809

  5. Restoration of bone mineralization by cinacalcet is associated with a significant reduction in calcitriol-induced vascular calcification in uremic rats.

    PubMed

    De Schutter, Tineke M; Behets, Geert J; Jung, Susanne; Neven, Ellen; D'Haese, Patrick C; Querfeld, Uwe

    2012-11-01

    The present study investigated to what extent normalization of bone turnover goes along with a reduction of high-dose calcitriol-induced vascular calcifications in uremic rats. Five groups of male Sprague-Dawley rats were studied: sham-operated controls (n = 7), subtotally nephrectomized (SNX) uremic (CRF) animals (n = 12), CRF + calcitriol (vitD) (0.25 μg/kg/day) (n = 12), CRF + vitD + cinacalcet (CIN) (10 mg/kg/day) (n = 12), and CRF + vitD + parathyroidectomy (PTX) (n = 12). Treatment started 2 weeks after SNX and continued for the next 14 weeks. High-dose calcitriol treatment in hyperparathyroid rats went along with the development of distinct vascular calcification, which was significantly reduced by >50 %, in both CIN-treated and PTX animals. Compared to control animals and those of the CRF group, calcitriol treatment either in combination with CIN or PTX or not was associated with a significant increase in bone area comprising ±50 % of the total tissue area. However, whereas excessive woven bone accompanied by a dramatically increased osteoid width/area was seen in the CRF + vitD group, CIN treatment and PTX resulted in significantly reduced serum PTH level, which was accompanied by a distinct reduction of both the bone formation rate and the amount of osteoid. These data indicate that less efficient calcium and phosphorus incorporation in bone inherent to the severe hyperparathyroidism in vitamin D-treated uremic rats goes along with excessive vascular calcification, a process which is partially reversed by CIN treatment in combination with a more efficacious bone mineralization, thus restricting the availability of calcium and phosphate for being deposited in the vessel wall.

  6. Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats.

    PubMed

    Shimomura, Akihiro; Matsui, Isao; Hamano, Takayuki; Ishimoto, Takuya; Katou, Yumiko; Takehana, Kenji; Inoue, Kazunori; Kusunoki, Yasuo; Mori, Daisuke; Nakano, Chikako; Obi, Yoshitsugu; Fujii, Naohiko; Takabatake, Yoshitsugu; Nakano, Takayoshi; Tsubakihara, Yoshiharu; Isaka, Yoshitaka; Rakugi, Hiromi

    2014-09-01

    Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.

  7. Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

    PubMed Central

    Shimomura, Akihiro; Matsui, Isao; Hamano, Takayuki; Ishimoto, Takuya; Katou, Yumiko; Takehana, Kenji; Inoue, Kazunori; Kusunoki, Yasuo; Mori, Daisuke; Nakano, Chikako; Obi, Yoshitsugu; Fujii, Naohiko; Takabatake, Yoshitsugu; Nakano, Takayoshi; Tsubakihara, Yoshiharu; Rakugi, Hiromi

    2014-01-01

    Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC. PMID:24652795

  8. Uremic pruritus.

    PubMed

    Robertson, K E; Mueller, B A

    1996-09-15

    Uremic pruritus and its treatment are reviewed. Pruritus affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis; symptoms usually begin about six months after the start of dialysis and range from localized and mild to generalized and severe. The mechanism underlying uremic pruritus is poorly understood; possibilities include secondary hyperparathyroidism and divalent-ion abnormalities; histamine, allergic sensitization, and proliferation of skin mast cells; hypervitaminosis A; iron-deficiency anemia; neuropathy and neurologic changes; or some combination of these. The cornerstone of therapy for uremic pruritus is regular, intensive, efficient dialysis. Other nonpharmacologic measures consist of the use of non-complement-activating dialysis membranes, compliance with dietary restrictions, electric-needle (acupuncture) therapy, and ultraviolet light therapy. Pharmacologic treatments that have been used include activated charcoal, antihistamines, capsaicin, cholestyramine, emollients and topical corticosteroids, epoetin, pizotyline, ketotifen, and nicergoline. Treatment results have been highly variable, and many of the clinical trials have been flawed. Phosphate-binding agents appear to be the most effective. Although enough is known to determine a reasonable set of steps in approaching a patient's uremic pruritus, more research is needed to understand the pathophysiology of this condition and to establish more reliable treatments. Pruritus is a common and sometimes severe complication of chronic renal failure. Efficient dialysis, dietary restrictions, phosphate-binding therapy, and phototherapy are the most effective treatments currently available.

  9. [Uremic pruritus].

    PubMed

    Corić-Martinović, Valentina; Basić-Jukić, Nikolina

    2008-01-01

    Uremic pruritus is a common and sometimes severe complication of chronic renal failure. Itch affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis and 25% of patients with preterminal chronic renal failure. The mechanism underlying uremic pruritus is poorly understood; possibilities include histamin, proteases, interleukin-2 and TNF- produced by skin mast-cells, substance P, neuropathy and neurological changes, high level of Ca, P, PTH, Al, Mg, divalent ion abnormalities, hypervitaminosis A, inflammation, or some combination of these. Therapeutic measures include regular efficient dialysis, transplantation, topical measures as an emollients, topical steroids, systemic measures as diet, opioids and physical treatment with phototherapy, acupuncture etc. Treatment results are highly variable and more research is needed to understand the patophysiology of this condition and to establish more reliable treatments. Most effective treatments in this moment are efficient dialysis, dietary restrictions, phosphate-binding therapy and phototherapy.

  10. Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells.

    PubMed

    Liu, Yaorong; Zhang, Lin; Ni, Zhaohui; Qian, Jiaqi; Fang, Wei

    2016-11-01

    Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals' inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day <0.001 for all). Compared to cells incubated in control serum, uremic serum significantly induced the mRNA expression of bone morphogenetic factor-2, osteopontin and RUNX2, and increased their protein levels as well (P < 0.05 for all). Inhibition of CaP crystals with pyrophosphate incubation prevented calcium deposition and bone-calcifying gene over-expression increased by uremic serum. CaP crystals, rather than the rest of uremic serum, were responsible for these effects. Uremic serum accelerates arterial calcification by mediating osteogenic differentiation. This effect might be mainly attributed to the CaP crystal content.

  11. Uremic pruritus.

    PubMed

    Mettang, Thomas; Kremer, Andreas E

    2015-04-01

    Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP.

  12. [Ectopic calcification].

    PubMed

    Fukumoto, Seiji

    2014-02-01

    Calcium deposition can be observed in many tissues in addition to bones and teeth which physiologically calcify. This unphysiological calcification can damage several organs. It has been shown that vascular calcification which is a risk factor for cardiovascular events develops through similar mechanisms to physiological calcification. Further studies to clarify detailed mechanisms of calcification are necessary to develop measures that inhibit unphysiological ectopic calcification without affecting physiological calcification in bones and teeth.

  13. Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure

    PubMed Central

    Lomashvili, Koba A.; Monier-Faugere, Marie-Claude; Wang, Xiaonan; Malluche, Hartmut H.; O’Neill, W. Charles

    2010-01-01

    Although it is known that bisphosphonates prevent medial vascular calcification in vivo, their mechanism of action remains unknown and, in particular, whether they act directly on the blood vessels or indirectly through inhibition of bone resorption. To determine this, we studied the effects of two bisphosphonates on calcification of rat aortas in vitro and on in vivo aortic calcification and bone metabolism in rats with renal failure. We produced vascular calcification in rats with adenine-induced renal failure fed a high-phosphate diet. Daily treatment with either etidronate or pamidronate prevented aortic calcification, with the latter being 100-fold more potent. Both aortic calcification and bone formation were reduced in parallel; however, bone resorption was not significantly affected. In all uremic rats, aortic calcium content correlated with bone formation but not with bone resorption. Bisphosphonates also inhibited calcification of rat aortas in culture and arrested further calcification of precalcified vessels but did not reverse their calcification. Expression of osteogenic factors or calcification inhibitors was not altered by etidronate in vitro. Hence, these studies show that bisphosphonates can directly inhibit uremic vascular calcification independent of bone resorption. The correlation between inhibition of aortic calcification and bone mineralization is consistent with a common mechanism such as the prevention of hydroxyapatite formation and suggests that bisphosphonates may not be able to prevent vascular calcification without inhibiting bone formation in uremic rats. PMID:19129793

  14. Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure.

    PubMed

    Lomashvili, Koba A; Monier-Faugere, Marie-Claude; Wang, Xiaonan; Malluche, Hartmut H; O'Neill, W Charles

    2009-03-01

    Although it is known that bisphosphonates prevent medial vascular calcification in vivo, their mechanism of action remains unknown and, in particular, whether they act directly on the blood vessels or indirectly through inhibition of bone resorption. To determine this, we studied the effects of two bisphosphonates on calcification of rat aortas in vitro and on in vivo aortic calcification and bone metabolism in rats with renal failure. We produced vascular calcification in rats with adenine-induced renal failure fed a high-phosphate diet. Daily treatment with either etidronate or pamidronate prevented aortic calcification, with the latter being 100-fold more potent. Both aortic calcification and bone formation were reduced in parallel; however, bone resorption was not significantly affected. In all uremic rats, aortic calcium content correlated with bone formation but not with bone resorption. Bisphosphonates also inhibited calcification of rat aortas in culture and arrested further calcification of precalcified vessels but did not reverse their calcification. Expression of osteogenic factors or calcification inhibitors was not altered by etidronate in vitro. Hence, these studies show that bisphosphonates can directly inhibit uremic vascular calcification independent of bone resorption. The correlation between inhibition of aortic calcification and bone mineralization is consistent with a common mechanism such as the prevention of hydroxyapatite formation and suggests that bisphosphonates may not be able to prevent vascular calcification without inhibiting bone formation in uremic rats.

  15. Prevention of vascular calcification with bisphosphonates without affecting bone mineralization: a new challenge?

    PubMed

    Neven, Ellen G; De Broe, Marc E; D'Haese, Patrick C

    2009-03-01

    Arterial calcification has been found to coexist with bone loss. Bisphosphonates, used as standard therapy for osteoporosis, inhibit experimentally induced vascular calcification, offering perspectives for the treatment of vascular calcification in renal failure patients. However, Lomashvili et al. report that the doses of etidronate and pamidronate that are effective in attenuating aortic calcification also decrease bone formation and mineralization in uremic rats, limiting their therapeutic use as anticalcifying agents.

  16. Ultrastructural Analysis of Vascular Calcifications in Uremia

    PubMed Central

    Aretz, Anke; Verberckmoes, Steven C.; Krüger, Thilo; Behets, Geert J.; Ghadimi, Reza; Weirich, Thomas E.; Rohrmann, Dorothea; Langer, Stephan; Tordoir, Jan H.; Amann, Kerstin; Westenfeld, Ralf; Brandenburg, Vincent M.; D'Haese, Patrick C.; Mayer, Joachim; Ketteler, Markus; McKee, Marc D.; Floege, Jürgen

    2010-01-01

    Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2- to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus. PMID:20203159

  17. The vascular biology of calcification.

    PubMed

    Shroff, Rukshana C; Shanahan, Catherine M

    2007-01-01

    Vascular calcification is an active, cell-mediated process that results from an imbalance between the promoters and inhibitors of mineralization. The process of vascular calcification shares many similarities with that of skeletal mineralization. However, while skeletal mineralization is a regulated process induced by complex, well-timed developmental cues, vascular calcification is a pathological process, occurring in response to dysregulated/inappropriate environmental cues. Damage inducing agents present in the uremic milieu such as a mineral imbalance, induce vascular smooth muscle cell (VSMC) apoptosis, and vesicle release resulting in mineral nucleation and the deposition of hydroxyapatite. Under normal conditions, inhibitors of soft-tissue mineralization such as matrix gamma-carboxyglutamic acid protein are expressed locally within the vessel wall while others such as fetuin-A are present in the circulation. Down-regulation or perturbation of these proteins leads to a phenotypic transformation of VSMC into osteo/chondrocytic-like cells that have the capacity to modulate the mineralization process. Many aspects of the mechanisms underlying vascular calcification have been defined through in vitro studies and molecular biological techniques; however, there are still unanswered questions, particularly with respect to the relationship between bone and vascular calcification, processes that appear to be inversely related. A better understanding of the complex mechanisms regulating tissue calcification may have therapeutic potential in reducing the cardiovascular disease-associated morbidity and mortality in patients with renal disease.

  18. Pineal calcification.

    PubMed

    Bhatti, I H; Khan, A

    1977-04-01

    The incidence of pineal calcification was studied by reviewing skull radiographs of 1400 patients admitted to a major neurosurgical centre at Karachi over an eight year period. The total frequency as well as age and sex distribution of pineal calcification were worked out and compared with frequency and age distribution of calcification reported in Western and Eastern races by different workers.

  19. Vascular calcification in chronic kidney disease.

    PubMed

    Jono, Shuichi; Shioi, Atsushi; Ikari, Yuji; Nishizawa, Yoshiki

    2006-01-01

    Vascular calcification is often encountered in advanced atherosclerotic lesions and is a common consequence of aging. Calcification of the coronary arteries has been positively correlated with coronary atherosclerotic plaque burden, increased risk of myocardial infarction, and plaque instability. Chronic kidney disease (CKD) patients have two to five times more coronary artery calcification than healthy age-matched individuals. Vascular calcification is a strong prognostic marker of cardiovascular disease mortality in CKD patients. Vascular calcification has long been considered to be a passive, degenerative, and end-stage process of atherosclerosis and inflammation. However, recent evidence indicates that bone matrix proteins such as osteopontin, matrix Gla protein (MGP), and osteocalcin are expressed in calcified atherosclerotic lesions, and that calcium-regulating hormones such as vitamin D3 and parathyroid hormone-related protein regulate vascular calcification in in vitro vascular calcification models based on cultured aortic smooth muscle cells. These findings suggest that vascular calcification is an actively regulated process similar to osteogenesis, and that bone-associated proteins may be involved in the development of vascular calcification. The pathogenesis of vascular calcification in CKD is not well understood and is almost multifactorial. In CKD patients, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidemia, and diabetes, and uremic-specific risk factors with vascular calcification. Most patients with progressive CKD develop hyperphosphatemia. An elevated phosphate level is an important risk factor for the development of calcification and cardiovascular mortality in CKD patients. Thus, it is hypothesized that an important regulator of vascular calcification is the level of inorganic phosphate. In order to test this hypothesis, we characterized the response of human smooth muscle cell (HSMC

  20. Arterial calcifications

    PubMed Central

    Rennenberg, Roger J M W; Schurgers, Leon J; Kroon, Abraham A; Stehouwer, Coen D A

    2010-01-01

    Abstract Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk. The prevalence of arterial calcification increases with age and is stimulated by several common cardiovascular risk factors. In this review, the clinical importance of arterial calcification and the currently known proteins involved are discussed. Arterial calcification is the result of a complex interplay between stimulating (bone morphogenetic protein type 2 [BMP-2], RANKL) and inhibitory (matrix Gla protein, BMP-7, osteoprotegerin, fetuin-A, osteopontin) proteins. Vascular calcification is especially prevalent and related to adverse outcome in patients with renal insufficiency and diabetes mellitus. We address the special circumstances and mechanisms in these patient groups. Treatment and prevention of arterial calcification is possible by the use of specific drugs. However, it remains to be proven that reduction of vascular calcification in itself leads to a reduced cardiovascular risk. PMID:20716128

  1. Bone pyrophosphate in uremia and its association with extraosseous calcification.

    PubMed Central

    Alfrey, A C; Solomons, C C

    1976-01-01

    The mean bone pyrophosphate was 0.360 +/- 0.15 mg/g in 8 controls and 1.22 +/- 1.39 mg/g bone in 27 uremic patients (P less than 0.0025). 13 of the 27 uremic patients had bone pyrophosphate levels greater than 2 SD above control values. The ash content of uremic bones with increased pyrophosphate levels (group II) was 56 +/- 9% as compared to 64 +/- 2% in control bones (P less than 0.01) and 60 +/- 7% in uremic bones having normal pyrophosphate levels (P less than 0.1) (group I). The magnesium content of bones in group II was 338 +/- 47 as compared to 211 +/- 13 (P less than 0.0005) in the controls and 294 +/- 73 mmol/kg ash (P less than 0.05) in group I. In group II, but not group I, there was a significant inverse correlation between duration of dialysis and percent bone ash (r = -0.59) (P less than 0.05). A definite relationship existed between elevated bone pyrophosphate levels and soft tissue calcification. In group II the mean pulmonary calcium content was 530 +/- 459 as compared to 32 +/- 26 mmol/kg/ash in group I (P less than 0.0025). All patients with a bone pyrophosphate level greater than 1.4 mg/g bone had extensive pulmonary calcification. It is concluded that the excess bone pyrophosphate present in some uremic patients is either deposited in the apatite crystal in the transphosphorylated form or else as the magnesium salt since the pyrophosphate is resistant to pyrophosphatase and surface adsorption of pyrophosphate is not altered by the increased bone pyrophosphate levels. The excess bone pyrophosphate could disturb bone calcification mechanisms in uremic patients. The association between increased bone pyrophosphate and soft tissue calcification suggests that the disordered pyrophosphate metabolism may be important in the pathogenesis of extraosseous calcification. PMID:175092

  2. Uremic toxins and oral adsorbents.

    PubMed

    Goto, Shunsuke; Yoshiya, Kunihiko; Kita, Tomoyuki; Fujii, Hideki; Fukagawa, Masafumi

    2011-04-01

    Uremic toxins are associated with various disorders in patients with end-stage renal disease and it is difficult to remove some of these toxins by dialysis. Since some uremic toxins are generated by bacterial metabolites in the colon, oral adsorbents that interfere with the absorption of uremic toxins or their precursors are believed to prevent their accumulation in the body. AST-120 adsorbs various uremic retention solutes in the gastrointestinal system and has potential for providing clinical benefit. Sevelamer hydrochloride binds some harmful compounds in addition to phosphate and seems to have pleiotropic effects that include lowering serum LDL cholesterol levels and reduction of inflammation. The effect of sevelamer hydrochloride on indoxyl sulfate and p-cresol has been shown in an in vitro study; however, in vivo studies in mice or humans did not demonstrate this effect on protein-binding uremic toxins. Oral adsorbents are thus one of the important modalities in the treatment of uremic syndrome.

  3. Hemolytic uremic syndrome

    PubMed Central

    Canpolat, Nur

    2015-01-01

    Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management and outcome. In recent years, better understanding of the HUS, especially those due to genetic mutations in the alternative complement pathway have provided an update on the terminology, classification, and treatment of the disease. This review will provide the updated classification of the disease and the current diagnostic and therapeutic approaches on the complement-mediated HUS in addition to STEC-HUS which is the most common cause of the HUS in childhood. PMID:26265890

  4. Mechanisms underlying uremic encephalopathy.

    PubMed

    Scaini, Giselli; Ferreira, Gabriela Kozuchovski; Streck, Emilio Luiz

    2010-06-01

    In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.

  5. Atypical Hemolytic Uremic Syndrome

    PubMed Central

    Kavanagh, David; Goodship, Tim H.; Richards, Anna

    2013-01-01

    Summary Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease management. PMID:24161037

  6. Breast Calcifications

    MedlinePlus

    ... remain unchanged. References What mammograms show: Calcifications, cysts, fibroadenomas. Breastcancer.org. http://www.breastcancer.org/symptoms/testing/types/mammograms/mamm_show. Accessed Dec. 9, 2015. Mammograms and other breast imaging tests. American Cancer Society. http://www.cancer. ...

  7. Guanidino compounds as uremic (neuro)toxins.

    PubMed

    De Deyn, Peter Paul; Vanholder, Raymond; Eloot, Sunny; Glorieux, Griet

    2009-01-01

    Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, "uremic" GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N-methyl-d-aspartate receptors by GSA, concomitant inhibition of gamma-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins.

  8. An association between uric acid levels and renal arteriolopathy in chronic kidney disease: a biopsy-based study.

    PubMed

    Kohagura, Kentaro; Kochi, Masako; Miyagi, Tsuyoshi; Kinjyo, Takanori; Maehara, Yuichi; Nagahama, Kazufumi; Sakima, Atsushi; Iseki, Kunitoshi; Ohya, Yusuke

    2013-01-01

    Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is an association between UA and renal arteriolopathy in patients with chronic kidney disease (CKD) is unknown. Here, we examined the cross-sectional association of serum UA levels with renal arteriolar hyalinosis and wall thickening. Arteriolar parameters were assessed by semiquantitative grading (max: grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and 81 women) who underwent renal biopsy. The mean serum UA level was 6.4 mg dl(-1). We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2 and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age ≥40 years, sex, hypertension status, diabetes mellitus status and estimated glomerular filtration rate <60 ml min(-1) per 1.73 m(2) showed that hyperuricemia (UA ≥7 mg dl(-1)) was significantly associated with a higher risk of hyalinosis (adjusted odds ratio: 3.13; 95% confidence interval: 1.23-7.94; P=0.02) and higher-grade (equal to or higher than the mean value) wall thickening (adjusted odds ratio: 2.66; 95% confidence interval: 1.11-6.38; P=0.03). Hence, these results suggest that hyperuricemia may be related to renal arteriolar damage in patients with CKD.

  9. Brain activation in uremic anorexia.

    PubMed

    Aguilera, Abelardo; Sánchez-Tomero, José Antonio; Selgas, Rafael

    2007-01-01

    This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.

  10. The dualistic role of vitamin D in vascular calcifications

    PubMed Central

    Razzaque, M. Shawkat

    2011-01-01

    Vitamin D is a multifunctional hormone that can affect many essential biological functions, ranging from the immune regulation to mineral ion metabolism. A close association between altered activity of vitamin D and vascular calcification has been reported in various human diseases, including in patients with atherosclerosis, osteoporosis, and chronic kidney disease (CKD). Vascular calcification is a progressive disorder and is a major determinant of morbidity and mortality of the affected patients. Experimental studies have shown that excessive vitamin D activities can induce vascular calcification, and such vascular pathology can be reversed by reducing vitamin D activities. The human relevance of these experimental studies is not clear, as vitamin D toxicity is relatively rare in the general population. Contrary to the relationship between vitamin D and vascular calcification, in experimental uremic models, low levels of vitamin D were shown to be associated with extensive vascular calcification, a phenomenon that is very similar to the vascular pathology seen in patients with CKD. The current treatment approach of providing vitamin D analogs to patients with CKD often poses a dilemma, as studies linked vitamin D treatment to subsequent vascular calcification. Recent genetic studies, however, have shown that vascular calcification can be prevented by reducing serum phosphate levels, even in the presence of extremely high serum 1,25-dihydroxyvitamin D and calcium levels. This article will briefly summarize the dual effects of vitamin D in vascular calcification and will provide evidence of vitamin D-dependent and -independent vascular calcification. PMID:20962746

  11. Uremic pruritus: a review.

    PubMed

    Lugon, Jocemir R

    2005-04-01

    Pruritus is a major disorder among the skin derangements in advanced renal failure. Its prevalence seems to be diminishing perhaps because of improvements in dialysis treatment. Recent information suggests that interactions between dermal mast cells and distal ends of nonmyelinated C fibers may be important in the precipitation and regulation of the sensory stimuli. The knowledge as to the control of pruritus transmission to cortex areas is still incomplete but endogenous opioid and opioid receptors may have a role in this regard. A recent classification was proposed for pruritus based on the level of its origin. Uremic pruritus, however, seems to be too complex to fit perfectly in any of the suggested modalities. Inflammation and malnutrition are recognized risk factors for cardiovascular death in end-stage renal disease patients, which may be related to the genesis of pruritus. Consistent with this concept, lower serum levels of albumin and higher serum levels of ferritin were found in pruritic patients when compared to nonpruritic ones. Newer treatments for this difficult clinical problem are being developed and tested.

  12. [Atypical hemolytic uremic syndrome].

    PubMed

    Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

    2015-11-20

    The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Hemolytic uremic syndrome.

    PubMed

    Webster, Kathleen; Schnitzler, Eugene

    2014-01-01

    The thrombotic microangiopathies include both hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Although debate exists as to whether these are separate entities or a spectrum of disease, both result in the clinical picture of thrombocytopenia, hemolytic anemia, and varying degrees of renal and neurologic involvement. Etiology of HUS includes diarrheal infection due to Shiga toxin-producing bacteria, complement deficiency, pneumococcal infection, and cobalamin deficiency. In disease ascribed to TTP, the main etiologic factor is deficiency of an enzyme known as a disintegrin-like and metalloprotease with thrombospondin type 1 repeats, number 13 (ADAMTS-13). The clinical manifestations may vary, but neurologic involvement can be significant, with reports of hypertensive encephalopathy, seizures, thrombosis and infarct. In nondiarrheal forms of disease, recurrence may occur and clinical diagnosis is essential in order to provide a targeted therapy for the suspected etiology. Therapies include supportive care, cobalamin supplementation, as well as plasma infusion and exchange. End stage renal disease may result and transplantation is curative for some forms of the disease. More recent research focuses on targeted immunotherapy to prevent autoantibody prevention. As of yet, there is no one cure for these potentially devastating diseases, and diagnosis and treatment selection presents a challenge to the clinician. © 2014 Elsevier B.V. All rights reserved.

  14. Uremic toxins and peritoneal dialysis.

    PubMed

    Lameire, N; Vanholder, R; De Smet, R

    2001-02-01

    Uremic toxicity is related in part to the accumulation of toxic substances, the nature of which has only partly been characterized. Because of the use of a highly permeable membrane and better preservation of the residual renal function, it could be anticipated that some of these uremic toxins are more efficiently cleared across the peritoneal membrane, and that the plasma and tissue levels of these compounds are lower than in hemodialysis patients. This article analyzes the generation and removal of several uremic toxins in peritoneal dialysis patients. The following uremic toxins are discussed: beta2-microglobulin, advanced glycation end products, advanced oxidation protein products, granulocyte inhibitory proteins, p-Cresol, and hyperhomocysteinemia. Some recent studies are reviewed suggesting that uremic toxins are involved in the progression of renal failure and are at least partially removed by peritoneal dialysis. We conclude that, although the plasma levels of some of these compounds are lower in peritoneal dialysis versus hemodialysis patients, it does not mean that the peritoneal dialysis patient is "better" protected against the numerous disturbances caused by these toxins.

  15. Management of hemolytic uremic syndrome.

    PubMed

    Loirat, Chantal; Saland, Jeffrey; Bitzan, Martin

    2012-03-01

    2011 has been a special year for hemolytic uremic syndrome (HUS): on the one hand, the dramatic epidemic of Shiga toxin producing E. coli -associated HUS in Germany brought the disease to the attention of the general population, on the other hand it has been the year when eculizumab, the first complement blocker available for clinical practice, was demonstrated as the potential new standard of care for atypical HUS. Here we review the therapeutic options presently available for the various forms of hemolytic uremic syndrome and show how recent knowledge has changed the therapeutic approach and prognosis of atypical HUS. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. [Uremic encephalopathy in regular dialysis treatment: uremic stroke?].

    PubMed

    Prencipe, Michele Antonio; Del Giudice, Antonio; Di Giorgio, Giuseppe; Aucella, Filippo

    2014-01-01

    This case report a 59 years-old male in regular dialysis treatment with neurologic emergency characterized by neurologic signs as deep sopor the cause of which was uremic encephalopathy. At presentation, laboratory investigations revealed creatinine 12,75 mg/dl, BUN 174 mg/% and hyperkalemia 7,5 mq/L. The most common abnormal test results were EEG and ECG. CT brain showed no evidence of hemorrhagic areas or hematoma subdural. The patient was treated with hemodialysis and after the first hour of hemodialysis, laboratory control revealed hypokaliemia with metabolic acidosis due to arteiovenous fistula recirculation. After placement of jugular venous hemodialysis catheter and intensive treatment, the patient showed gradual improvement of uremic stroke due to arteriovenous fistula recirculation for high grade venous stenoses. Arteriovenous fistula dysfunction remains a major contributor to the morbidity and mortality of hemodialysis patients. The failure of a newly created AVF to mature and to develop stenosis in an estabilished AVF are two common clinical predicaments. The goal is to identify a dysfunctional AVF early enough to intervene in a timely manner, either to assist the maturation process or to prevent thrombosis. Most clinical features of neurologic complications in uremics are nonspecific and do not reliable, but it is important to identify specific causes such as vascular access recirculation for adequate treatment and regression of uremic stroke.

  17. Endogenous guanidino compounds as uremic neurotoxins.

    PubMed

    De Deyn, P P; D'Hooge, R; Van Bogaert, P P; Marescau, B

    2001-02-01

    Epileptic and cognitive symptomatologies are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be highly increased as well in serum, cerebrospinal fluid, and brain of uremic patients, whereas the levels of other metabolically relevant GCs were not or only moderately increased and others were even decreased. These highly increased compounds or "uremic" GCs are creatinine (CTN), guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine (MG). All four compounds were shown to be experimental convulsants in brain concentrations similar to those found in uremic brain. We have described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. The excitatory effects of uremic GCs on the central nervous system may be explained by the activation of N-methyl-D-aspartate (NMDA) receptors by GSA, concomitant inhibition of GABA(A) receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy.

  18. Atypical hemolytic uremic syndrome

    PubMed Central

    2011-01-01

    Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently

  19. Normal and Pathologic Concentrations of Uremic Toxins

    PubMed Central

    Duranton, Flore; Cohen, Gerald; De Smet, Rita; Rodriguez, Mariano; Jankowski, Joachim; Vanholder, Raymond

    2012-01-01

    An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD. PMID:22626821

  20. [Uremic pruritus: an unresolved challenge].

    PubMed

    Aucella, F; Gesuete, A

    2009-01-01

    Pruritus is a common and unpleasant symptom in the dialysis setting, affecting about half of all hemodialysis and peritoneal dialysis patients. It has a great impact on patients' quality of life and is also associated with increased mortality. The pathogenesis of uremic pruritus (UP) is clearly multifactorial and still poorly understood. At least four main hypotheses have been put forward: dermatological abnormalities, an immune-system derangement that results in a proinflammatory state, an imbalance of the endogenous opioidergic system, and a neuropathic mechanism. The neurophysiology of itch has been shown to be quite similar to that of pain, supporting the hypothesis that the two phenomena may be closely related in dialysis patients, who often also experience uremic neuropathy. Moreover, an array of other triggering factors may include uremic toxins, systemic inflammation, cutaneous xerosis, and common comorbidities such as diabetes mellitus, endocrinopathies and viral hepatitis. The first step in the treatment of UP focuses on some general strategies that include the optimization of the dialysis schedule using biocompatible membranes such as polymethyl methacrylate, and the control of the divalent ion metabolism. The second step may be local therapy with skin emollients and capsaicin creams. More specific treatments that appear promising but have not been proven to be definitively efficacious include UVB light, gabapentin and the novel k-opioid-agonist nalfurafine. Nephrologists, who still tend to neglect this disabling symptom, need to be aware that UP is associated with poorer patient outcomes and that a stepwise therapeutic approach is now available.

  1. Diffuse uremic tumoral calcinosis in a patient on long-term hemodialysis.

    PubMed

    Akasbi, Nessrine; Houssaini, Tarik Sqalli; Rabhi, Samira; Lahlou, Mariam; Boukhrissa, Amal; Tahiri, Latifa; El Maaroufi, Chakib; Berrady, Rhizlane; Harzy, Taoufik; Bono, Wafaa

    2011-08-01

    Tumoral calcinosis is an uncommon and severe complication of hemodialysis therapy. The most important pathogenic factor involved in uremic tumoral calcinosis is an increase in calcium-phosphorus product, not necessarily related to hyperparathyroidism. We report here a patient on hemodialysis who presented with increasing multifocal and uncommon sites of massive calcifications. The patient was examined, and a diagnosis of uremic tumor calcinosis was made. The patient was treated with the noncalcemic phosphate binder sevelamer, a strict diet, multiple hemodialysis sessions per week, and a low calcium dialysate, with improvement on biological findings a decrease in the volume of some tumors on his fingers and a global stable disease. Some nodes in hands and feet disappeared; in other sites, their diameter was reduced, and the largest nodule decreased from 5- to 2-cm diameter.

  2. An update on uremic toxins.

    PubMed

    Neirynck, N; Vanholder, R; Schepers, E; Eloot, S; Pletinck, A; Glorieux, G

    2013-02-01

    In the last decade, uremic toxicity as a potential cause for the excess of cardiovascular disease and mortality observed in chronic kidney disease gained more and more interest. This review focuses on uremic toxins with known cardiovascular effects and their removal. For protein-bound solutes, for example, indoxylsulfate and the conjugates of p-cresol, and for small water-soluble solutes, for example, guanidines, such as ADMA and SDMA, there is a growing evidence for a role in cardiovascular toxicity in vitro (e.g., affecting leukocyte, endothelial, vascular smooth muscle cell function) and/or in vivo. Several middle molecules (e.g., beta-2-microglobulin, interleukin-6, TNF-alpha and FGF-23) were shown to be predictors for cardiovascular disease and/or mortality. Most of these solutes, however, are difficult to remove during dialysis, which is traditionally assessed by studying the removal of urea, which can be considered as a relatively inert uremic retention solute. However, even the effective removal of other small water-soluble toxins than urea can be hampered by their larger distribution volumes. Middle molecules (beta-2-microglobulin as prototype, but not necessarily representative for others) are cleared more efficiently when the pore size of the dialyzer membrane increases, convection is applied and dialysis time is prolonged. Only adding convection to diffusion improves the removal of protein-bound toxins. Therefore, alternative removal strategies, such as intestinal adsorption, drugs interfering with toxic biochemical pathways or decreasing toxin concentration, and extracorporeal plasma adsorption, as well as kinetic behavior during dialysis need further investigation. Even more importantly, randomized clinical studies are required to demonstrate a survival advantage through these strategies.

  3. Familial calcific periarthritis.

    PubMed Central

    Hajiroussou, V J; Webley, M

    1983-01-01

    A family of 4 is described in which both children had calcific periarthritis affecting the shoulders, and the mother had radiological evidence of periarticular calcification near the left greater trochanter. PMID:6882045

  4. Penile calciphylaxis in end stage renal disease.

    PubMed

    Barbera, Vincenzo; Di Lullo, Luca; Gorini, Antonio; Otranto, Giovanni; Floccari, Fulvio; Malaguti, Moreno; Santoboni, Alberto

    2013-01-01

    Calciphylaxis, better described as "Calcific uremic arteriolopathy" (CUA), involves about 1-4% of hemodialysis patients all around the world with high mortality rates. We describe a rare clinical case of CUA in peritoneal dialysis patient associated with urological disease. Penile calciphylaxis represents rare clinical complication, and an early diagnosis and multidisciplinary approach are requested. Pathogenesis is still unclear, and therapeutic approaches need more long-term clinical trials to test their efficacy and safety.

  5. Pancreatic ectasia in uremic macaques.

    PubMed Central

    Bronson, R. T.; Strauss, W.; Wheeler, W.

    1982-01-01

    Pancreatic ectasia (PE) is a common incidental finding in people dying from uremia. It has been described as dilatation of acini, inspissation of secretions, and proliferation of ductal cells. PE occurred in 17 macaques, 11 of which were known to have been uremic. The lesion was studied by light and electronmicroscopy and histochemistry and by construction of a three-dimensional model of a dilated acinar ductal system from serial semithick Epon sections. Atrophic acinar cells interspersed with clumps of centroacinar cells lined all portions of the system. There was no evidence of ductular proliferation. Fibrillar material was present in the dilated acinar lumens and associated with epithelial cells and leukocytes, but no blockage of the system was demonstrated. The lesion is similar to those induced by a variety of experimental procedures and to the pancreatic lesions of cystic fibrosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:6175218

  6. Uremic pleuritis in chronic hemodialysis patients.

    PubMed

    Rashid-Farokhi, Farin; Pourdowlat, Guitti; Nikoonia, Mohammad-Reza; Behzadnia, Neda; Kahkouee, Shahram; Nassiri, Amir-Ahmad; Masjedi, Mohammad-Reza

    2013-01-01

    Chronic hemodialysis (HD) patients are predisposed to several complications associated with pleural effusion. In addition, uremia can directly cause pleuritis. However, there are inadequate data about pathogenesis and natural course of uremic pleuritis. In this study, 76 chronic HD patients with pleural effusion admitted to the Respiratory Center of Masih Daneshvari Hospital, in Tehran, Iran between June 2005 and May 2011 were evaluated to figure out the etiology of their pleural disease. Among these patients, patients with uremic pleuritis were identified and studied. The rate of uremic pleuritis was 23.7%. Other frequent etiologies of pleural effusion were parapneumonic effusion (23.7%), cardiac failure (19.7%), tuberculosis (6.6%), volume overload, malignancy, and unknown. In patients with uremic pleuritis, dyspnea was the most common symptom, followed by cough, weight loss, anorexia, chest pain, and fever. Compared to patients with parapneumonic effusion, patients with uremic effusion had a significantly higher rate of dyspnea and lower rate of cough and fever. Pleural fluid analysis showed that these patients had a significantly lower pleural to serum lactic dehydrogenase ratio, total pleural leukocytes, and polymorphonuclear count compared to patients with parapneumonic effusion. Improvement was achieved in 94.1% of patients with uremic pleuritis by continuation of HD, chest tube insertion or pleural decortication; an outcome better than the previous reports. Despite the association with an exudative effusion, inflammatory pleural reactions in patients with uremic pleuritis may not be as severe as infection-induced effusions. Owing to the advancement in HD technology and other interventions, outcome of uremic pleuritis may be improved.

  7. An Enlarged Profile of Uremic Solutes

    PubMed Central

    Tanaka, Hisae; Sirich, Tammy L.; Plummer, Natalie S.; Weaver, Daniel S.; Meyer, Timothy W.

    2015-01-01

    Better knowledge of the uremic solutes that accumulate when the kidneys fail could lead to improved renal replacement therapy. This study employed the largest widely available metabolomic platform to identify such solutes. Plasma and plasma ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls were first compared using a platform combining gas and liquid chromatography with mass spectrometry. Further studies compared plasma from 6 HD patients who had undergone total colectomy and 9 with intact colons. We identified 120 solutes as uremic including 48 that had not been previously reported to accumulate in renal failure. Combination of the 48 newly identified solutes with those identified in previous reports yielded an extended list of more than 270 uremic solutes. Among the solutes identified as uremic in the current study, 9 were shown to be colon-derived, including 6 not previously identified as such. Literature search revealed that many uremic phenyl and indole solutes, including most of those shown to be colon-derived, come from plant foods. Some of these compounds can be absorbed directly from plant foods and others are produced by colon microbial metabolism of plant polyphenols that escape digestion in the small intestine. A limitation of the metabolomic method was that it underestimated the elevation in concentration of uremic solutes which were measured using more quantitative assays. PMID:26317986

  8. MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus.

    PubMed

    Panizo, Sara; Naves-Díaz, Manuel; Carrillo-López, Natalia; Martínez-Arias, Laura; Fernández-Martín, José Luis; Ruiz-Torres, María Piedad; Cannata-Andía, Jorge B; Rodríguez, Isabel

    2016-03-01

    Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or high-phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high-calcium and -phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.

  9. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients.

    PubMed

    Ito, Shunsuke; Yoshida, Masayuki

    2014-02-20

    Chronic kidney disease (CKD) has been considered a major risk factor for cardiovascular diseases. Although great advances have recently been made in the pathophysiology and treatment of cardiovascular diseases, CKD remains a major global health problem. Moreover, the occurrence rates of cardiovascular events among CKD patients increase even in cases in which patients undergo hemodialysis, and the mechanisms underlying the so-called "cardiorenal syndrome" are not clearly understood. Recently, small-molecule uremic toxins have been associated with cardiovascular mortality in CKD and/or dialysis patients. These toxins range from small uncharged solutes to large protein-bound structures. In this review, we focused on protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which are poorly removed by current dialysis techniques. Several studies have demonstrated that protein-bound uremic toxins, especially indoxyl sulfate, induce vascular inflammation, endothelial dysfunction, and vascular calcification, which may explain the relatively poor prognosis of CKD and dialysis patients. The aim of this review is to provide novel insights into the effects of indoxyl sulfate and p-cresyl sulfate on the pathogenesis of atherosclerosis.

  10. Functional Profile of the Isolated Uremic Nephron

    PubMed Central

    Fine, Leon G.; Schlondorff, Detlef; Trizna, Walter; Gilbert, Richard M.; Bricker, Neal S.

    1978-01-01

    Resistance of the chronically diseased kidney to vasopressin has been proposed as a possible explanation for the urinary concentrating defect of uremia. The present studies examined the water permeability and adenylate cyclase responsiveness of isolated cortical collecting tubules (CCT) from remnant kidneys of uremic rabbits to vasopressin. In the absence of vasopressin the CCTs of both normal and uremic rabbits were impermeable to water. At the same osmotic gradient, addition of a supramaximal concentration of vasopressin to the peritubular bathing medium led to a significantly lower net water flux per unit length (and per unit luminal surface area) in uremic CCTs than in normal CCTs. Transepithelial osmotic water permeability coefficient, Pf, was 0.0232 ±0.0043 cm/s in normal CCTs and 0.0059±0.001 cm/s in uremic CCTs (P < 0.001). The impaired vasopressin responsiveness of the uremic CCTs was observed whether normal or uremic serum was present in the bath. Basal adenylate cyclase activity per microgram protein was comparable in normal and uremic CCTs. Stimulation by NaF led to equivalent levels of activity in both, whereas vasopressin-stimulated activity was 50% lower in the uremic than in the normal CCTs (P < 0.025). The cyclic AMP analogue, 8-bromo cyclic AMP, produced an increase in the Pf of normal CCTs closely comparable to that observed with vasopressin. In contrast, the Pf of uremic CCTs was only minimally increased by this analogue and was not further stimulated by theophylline. These studies demonstrate an impaired responsiveness of the uremic CCT to vasopressin. This functional defect appears to be a result, at least in part, of a blunted responsiveness of adenylate cyclase to vasopressin. The data further suggest that an additional defect in the cellular response to vasopressin may exist, involving a step (or steps) subsequent to the formation of cyclic AMP. A unifying concept of the urinary concentrating defect of uremia is proposed which

  11. Genetics in Arterial Calcification

    PubMed Central

    Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

    2011-01-01

    Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

  12. [Bisphosphonates for vascular calcification].

    PubMed

    Tanaka, Yoshiya; Okada, Yosuke

    2007-03-01

    Recent progress in basic research has revealed certain similarities between processes of bone calcification and calcifications of vascular tissues which contribute to several cardiovascular diseases. Bisphosphonates, which are inhibitors of bone resorption that are widely used to treat osteoporosis, also inhibit cholesterol biosynthesis, differentiation of macrophage to foam cell, differentiation of smooth muscle cells to osteoblast-like cells in certain stimuli during calcification processes of vessels. These findings extend the link between bone remodeling and vascular calcification, opening perspectives toward novel therapeutic strategies, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.

  13. [Mechanisms of bone calcification].

    PubMed

    Hoshi, Kazuto

    2007-10-01

    In bone calcification, hydroxyapatite is crystallized on the type I collagen-based organic matrices. It occurs in the extracellular spaces. Osteoblasts trigger and promote the crystallization by the biological control to the secretion of various matrix proteins or enzymes. The author overviews the mineral and organic environments in calcification areas and the roles of osteoblasts in mineral/organic interaction.

  14. Hemolytic Uremic Syndrome Causing Multicystic Leukoencephalomalacia

    PubMed Central

    Batur, Abdussamet; Alpaslan, Muhammed; Yavuz, Alpaslan; Bora, Aydın; Bulut, Mehmet Deniz

    2016-01-01

    Summary Backgrund Hemolytic uremic syndrome is a disease characterized by hemolytic anemia, thrombocytopenia and acute renal failure with multiple organ involvement. Central nervous system involvement is detected in 20–50% of the patients and this leads to increased morbidity and mortality. Case Report We report the neuroimaging findings in a four-month-old male with hemolytic uremic syndrome. The cerebral cortex and white matter showed mild signal intensity on T2-weighted images. The diffusion weighted imaging demonstrated restricted diffusion in the cerebral cortex and white matter with corresponding low signal intensity on the apparent diffusion coefficient maps representing cytotoxic edema. These findings ended in multicystic leukoencephalomalacia. Conclusions In hemolytic uremic syndrome with brain involvement symptoms develop due to the different level of actions of factors and thus MRI protocol towards cerebral parenchyma should include DWI, especially in pediatric patients. PMID:27354878

  15. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  16. Calcific neurocysticercosis and epileptogenesis

    PubMed Central

    Nash, T.E.; Del Brutto, O.H.; Butman, J.A.; Corona, T.; Delgado-Escueta, A.; Duron, R.M.; Evans, C.A.W.; Gilman, R.H.; Gonzalez, A.E.; Loeb, J.A.; Medina, M.T.; Pietsch-Escueta, S.; Pretell, E.J.; Takayanagui, O.M.; Theodore, W.; Tsang, V.C.W.; Garcia, H.H.

    2010-01-01

    Neurocysticercosis is responsible for increased rates of seizures and epilepsy in endemic regions. The most common form of the disease, chronic calcific neurocysticercosis, is the end result of the host’s inflammatory response to the larval cysticercus of Taenia solium. There is increasing evidence indicating that calcific cysticercosis is not clinically inactive but a cause of seizures or focal symptoms in this population. Perilesional edema is at times also present around implicated calcified foci. A better understanding of the natural history, frequency, epidemiology, and pathophysiology of calcific cysticercosis and associated disease manifestations is needed to define its importance, treatment, and prevention. PMID:15184592

  17. [Pathology of coronary arterial calcification].

    PubMed

    Yutani, Chikao

    2007-03-01

    Calcification is an invariable component of advanced coronary artery atherosclerosis. Recent study showed that genetic variations such as matrix inhibitory proteins, polymorphisms for tumor necrosis factor, and inflammatory cytokines may influence coronary artery calcification. And also there have been numerous studies on screening patients for coronary artery disease using electron beam computed tomography, but details of mechanism on calcification have still been unclear. An example of coronary calcification in diabetic patients disclosed that its diffuse distribution might be metabolic on calcification mechanism.

  18. Hemolytic uremic syndrome in children.

    PubMed

    Talarico, Valentina; Aloe, Monica; Monzani, Alice; Miniero, Roberto; Bona, Gianni

    2016-12-01

    Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption. Moreover, new studies have shown that the complement system is an important factor also in the typical HUS, in which the infection could highlight an underlying dysregulation of complement factors. Clinical signs and symptoms may overlap among the different forms of HUS. Shiga toxin-producing Escherichia Coli (STEC) infection cause a spectrum of clinical sings ranging from asymptomatic carriage to non-bloody diarrhea, hemorrhagic colitis, HUS and death. The average interval between ingestion of STEC and illness manifestation is approximately 3 days, although this can vary between 2 and 12 days. Patients with pneumococcal HUS usually have a severe clinical picture with microangiopathic hemolytic anemia, respiratory distress, neurological involvement. The atypical HUS, in contrast to STEC-HUS which tends to occur as a single event, is a chronic condition and involves a poorer prognosis. Early diagnosis and identification of underlying pathogenic mechanism allow instating specific support measures and therapies. Typical management of STEC-HUS patients relies on supportive care of electrolyte and water imbalance, anemia, hypertension and renal failure. For the aHUS the initial management is supportive and similar to the approach for STEC

  19. Targeting the Opioid Pathway for Uremic Pruritus

    PubMed Central

    Jaiswal, Deep; Uzans, Drea; Hayden, Jill; Kiberd, Bryce A.; Tennankore, Karthik K.

    2016-01-01

    Background: Patients undergoing hemodialysis or peritoneal dialysis often experience pruritus which is associated with morbidity and mortality. One proposed treatment approach is to target the opioid pathway using either µ-opioid antagonists or κ-opioid agonists. Objective: To review the efficacy of targeting the opioid pathway for pruritus among dialysis patients (uremic pruritus). Design: Systematic review and meta-analysis. Setting/Methods: The systematic review included randomized controlled and randomized crossover trials identified in the MEDLINE, EMBASE, and Cochrane databases (1990 to June 2014) evaluating the efficacy of µ-opioid antagonists or κ-opioid agonists in the treatment of uremic pruritus. Patients: Adult (≥18 years) chronic dialysis patients. Measurements: The primary outcome being evaluated was reduction in itch severity measured on a patient-reported visual analog scale (VAS). Results: Five studies out of 3587 screened articles met the inclusion criteria. Three studies evaluated the efficacy of naltrexone, a µ-opioid antagonist, and 2 studies evaluated the efficacy of nalfurafine, a κ-opioid agonist. Duration of included studies was short, ranging from 2 to 9 weeks. Limitations: Due to the heterogeneity in reporting of outcomes, data from the studies evaluating naltrexone could not be pooled. Pooled analysis, using a random effects model, found that use of nalfurafine resulted in a 9.50 mm (95% confidence interval [CI], 6.27-12.74, P < .001) greater reduction of itch severity (measured on a 100-mm VAS) than placebo in the treatment of uremic pruritus. Conclusions: Nalfurafine holds some promise with respect to the treatment of uremic pruritus among dialysis patients. However, more long-term randomized controlled trials evaluating the efficacy of therapies targeting the opioid pathway for uremic pruritus are required. PMID:28270926

  20. The effects of rhBMP-2 and Treg/Th17 functional disequilibrium in uremic patients with cardiovascular complication after maintenance hemodialysis.

    PubMed

    Danyan, Chen; Xiaolong, Huang; Song, Lu; Hua, Gan; Weixue, Tang; Ke, Liu

    2013-07-01

    We compared the correlation of regulatory T cell (Treg) and Th17 cell function disequilibrium with calcification in uremic patients on maintenance hemodialysis (MHD) with healthy controls, and investigated if their influence possibly increased the development and outcome of cardiovascular complications in uremic patients after MHD. The extent of coronary artery calcification was assessed by coronary artery calcification scoring (CACS) in uremic patients with and without adverse cardiovascular events after MHD (MHD group 1 vs. MHD group 2, respectively). Peripheral blood mononuclear cells were incubated with rhBMP-2 as positive control. The Treg/Th17 cell frequencies, Foxp3 ROR-gt mRNA expressions, and MIP 3α/CCL20 concentrations were measured. The CACS score was significantly higher in MHD group 1 as compared group 2. In comparison with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremic patients, displayed higher Treg and Th17 frequencies, Foxp3 and ROR-gt expressions, and MIP3α/CCL20 concentrations. However, the up-regulations of Treg frequencies and Foxp3 expressions were significant in controls but not in MHD patients. It was also observed that Treg/Th17 functional disequilibrium was not only correlated with rhBMP-2 state but also consistent with the cardiovascular complications. Moreover, the CACS was negatively correlated with Treg cell frequencies but positively correlated with Th17 cell frequencies and MIP3a/CCL20 concentrations. Function disequilibrium of Treg/Th17 was related to the degree of the rhBMP-2 state. Function disequilibrium of the Treg/Th17 might act synergistically with rhBMP-2 in the high incidence of immune-mediated cardiovascular complications after MHD.

  1. Heart in An Eggshell Calcification: Idiopathic Calcific Constrictive Pericarditis

    PubMed Central

    Song, Bong Gun; Kang, Gu Hyun; Park, Yong Hwan; Chun, Woo Jung; Oh, Ju Hyeon

    2011-01-01

    Constrictive pericarditis is caused by fibrosis and calcification of the pericardium, which inhibits diastolic filling of the heart. Chest roentgenogram can show the calcification as a mass or sheet over the heart and computed tomography scan allows anatomic delineation of the pericardium and determines the extent of calcification. We reported a case of eggshell calcification of idiopathic chronic constrictive pericarditis diagnosed by echocardiography and multi-detector computed tomography.

  2. Electrical needle therapy of uremic pruritus.

    PubMed

    Duo, L J

    1987-01-01

    Six patients with intractable uremic pruritus were treated with a modified acupuncture technique, the electrical needle stimulation (ENS). Results were followed with a pruritic score scale based on severity, frequency and distribution of itching, together with sleeping hours and waking up at night. The results were encouraging: pruritus was drastically improved during or after ENS in several patients. A control treatment with superficial electrical stimulation was ineffective.

  3. Pathological role of aminolevulinate in uremic patients.

    PubMed

    Hasuike, Yukiko; Nonoguchi, Hiroshi; Tokuyama, Masanori; Hata, Reiko; Kitamura, Rie; Hori, Kahori; Nanami, Masayoshi; Otaki, Yoshinaga; Kuragano, Takahiro; Nakanishi, Takeshi

    2011-02-01

    Previous reports have demonstrated that δ-aminolevulinate (ALA) can promote iron release from horse spleen ferritin under conditions of high serum ALA levels in uremia; therefore, we speculated that the accumulated ALA in uremic patients would stimulate iron release from ferritin, resulting in accelerated oxidative stress and uremic complications. We measured the plasma ALA of uremic patients and examined the ALA-induced iron release from human ferritin. The participants consisted of 30 hemodialysis patients and 14 healthy subjects. Plasma malondialdehyde was measured as a surrogate marker of lipid peroxidation. The plasma exchange effluent from two patients who had undergone plasma exchange (for the treatment of systemic lupus erythematosus and acute myeloblastic leukemia) was collected and treated to obtain the human ferritin-rich fraction. Iron release from ferritin was examined using bathophenanthroline sulfate. The influence of antioxidants and different pH levels on iron release were investigated. Plasma ALA and malondialdehyde concentration in the hemodialysis patient was significantly higher than that in healthy subjects. ALA was positively correlated with malondialdehyde. The abundance of iron release was dependent on the ALA concentration and incubation time. Iron release at the high pH of 7.6 was decreased compared with that at pH 7.4. Citrate increased iron release at pH 7.4, but citrate-stimulated iron release was totally abolished at pH 7.6. Our study suggests that ALA accumulation may have a role to play in certain complications in uremic patients, such as oxidative stress, by releasing iron from ferritin.

  4. Bioengineered kidney tubules efficiently excrete uremic toxins

    PubMed Central

    Jansen, J.; Fedecostante, M.; Wilmer, M. J.; Peters, J. G.; Kreuser, U. M.; van den Broek, P. H.; Mensink, R. A.; Boltje, T. J.; Stamatialis, D.; Wetzels, J. F.; van den Heuvel, L. P.; Hoenderop, J. G.; Masereeuw, R.

    2016-01-01

    The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs. PMID:27242131

  5. Protein-bound uremic retention solutes.

    PubMed

    Brunet, Philippe; Dou, Laetitia; Cerini, Claire; Berland, Yvon

    2003-10-01

    Protein-bound uremic retention solutes are molecules with low molecular weight (MW) but should be considered middle or high MW substances. This article describes the best known substances of this group, which include p-cresol, indoxyl sulfate, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furan-propionic acid (CMPF), and homocysteine. At concentrations encountered during uremia, p-cresol inhibits phagocyte function and decreases leukocyte adhesion to cytokine-stimulated endothelial cells. CMPF has been implicated in anemia and neurologic abnormalities of uremia. CMPF could alter the metabolism of drugs of inhibiting their binding to albumin and their tubular excretion. Indoxyl sulfate administrated to uremic rats increases the rate of progression of renal failure. Hippuric acid inhibits glucose utilization in the muscle, and its serum concentration is correlated with neurologic symptoms of uremia. Homocysteine predisposes uremic patients to cardiovascular disease through impairment of endothelial and smooth muscle cell functions. The removal of protein-bound compounds by conventional hemodialysis is low. Other strategies to decrease their concentrations include increase in dialyze pore size, daily hemodialysis, peritoneal dialysis, reduction of production or acceleration of degradation, and preservation of residual renal function.

  6. Acute Prevertebral Calcific Tendinitis.

    PubMed

    Tamm, Alexander; Jeffery, Caroline C; Ansari, Khalid; Naik, Sandeep

    2015-11-01

    We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below.

  7. Calcific Metamorphosis: A Review

    PubMed Central

    Siddiqui, Shoaib Haider; Mohamed, Ahmed Nabil

    2016-01-01

    Dental trauma to the permanent dentition can lead to clinical complications and its management may considerably challenge a practitioner. The incidence of pulp canal obliteration following dental trauma has been reported to be approximately 4 – 24%. Attempting to locate canals following calcific metamorphosis and negotiating it to full working length may lead to iatrogenic errors such as fractured instrument and perforation. This review article describes the possible etiology of Calcific Metamorphosis, its clinical and radiographic features as well as its management. PMID:27610067

  8. [Oxalic acid--important uremic toxin].

    PubMed

    Mydlík, M; Derzsiová, K

    2010-07-01

    Oxalic acid is thought to be a significant uremic toxin that participates in the pathogenesis of uremic syndrome. AIM OF THE STUDY was to summarise results which we obtained during the study ofoxalic acid in biological fluids (plasma, saliva, urine and dialysate) in patients suffering from chronic kidney diseases (CKD), stage 3-5 and after renal transplantation. In the retrospective study were investigated 28 healthy subjects, 112 CKD stage 1-4 patients, 39 haemodialysis patients and 27 CAPD patients. Besides 21 patients were investigated after renal transplantation. We used the following therapeutic methods: maximal water diuresis, diet with low (2g/day) and high (15g/day) sodium chloride intake, administration intravenous furosemide (20mg) and renal replacement therapy [CAPD, haemodialysis (HD), haemofiltration (HF) and postdilution haemodiafiltration (HDF)] and renal transplantation. Oxalic acid was determined by spectrophotometric method using oxalate oxidase which is free from vitamin C interference. Vitamin C was determined by spectrophotometric method. In CKD patients and those after renal transplantation direct relationships between plasma oxalic acid and serum creatinine were found (r = 0.904 and 0.943, respectively, P < 0.001). Despite of high plasma oxalic acid in uremic patients (23.1 +/- 10 micromol/l), there was no significant difference in salivary oxalic acid between control subjects (126.5 +/- 18 micromol/l) and CKD stage 3-4 patients (133.9 +/- 23.7 micromol/I). The urinary excretion of oxalic acid during maximal water diuresis in healthy subjects (n = 15) (from 37.5 +/- 17.4 to 110.2 +/- 49.3 micromol/4 hours) and after intravenous furosemide (CKD stage 3-4, n = 15) (from 34.5 +/- 5.5 to 66.7 +/- 8.1 micromol/3 hours) increased significantly, but was not affected by high intake of NaCI in diet (CKD stage 3-4, n = 12). One tablet of Sorbifer Durules containing 100 mg Fe2+ and 60 mg vitamin C did not lead to further increase of uremic hyperoxalemia

  9. Hemolytic Uremic Syndrome Incidence in New York1

    PubMed Central

    Tserenpuntsag, Boldtsetseg; Kacica, Marilyn; Smith, Perry F.; Morse, Dale L.

    2004-01-01

    A comparison of New York’s traditional communicable disease surveillance system for diarrhea-associated hemolytic uremic syndrome with hospital discharge data showed a sensitivity of 65%. Escherichia coli O157:H7 was found in 63% of samples cultured from hemolytic uremic syndrome patients, and samples were more likely to be positive when collected early in illness. PMID:15200834

  10. Genetic Pathways of Vascular Calcification

    PubMed Central

    Bowman, Marion A. Hofmann; McNally, Elizabeth M.

    2012-01-01

    Vascular calcification is an independent risk factor for cardiovascular disease. Arterial calcification of the aorta, coronary, carotid and peripheral arteries becomes more prevalent with age. Genomewide association studies have identified regions of the genome linked to vascular calcification, and these same regions are linked to myocardial infarction risk. The 9p21 region linked to vascular disease and inflammation also associates with vascular calcification. In addition to these common variants, rare genetic defects can serve as primary triggers of accelerated and premature calcification. Infancy-associated calcific disorders are caused by loss of function mutations in ENPP1 an enzyme that produces extracellular pyrophosphate. Adult onset vascular calcification is linked to mutations NTE5, another enzyme that regulates extracellular phosphate metabolism. Common conditions that secondarily enhance vascular calcification include atherosclerosis, metabolic dysfunction, diabetes, and impaired renal clearance. Oxidative stress and vascular inflammation, along with biophysical properties, converge with these predisposing factors to promote soft tissue mineralization. Vascular calcification is accompanied by an osteogenic profile, and this osteogenic conversion is seen within the vascular smooth muscle itself as well as the matrix. Herein we will review the genetic causes of medial calcification in the smooth muscle layer, focusing on recent discoveries of gene mutations that regulate extracellular matrix phosphate production and the role of S100 proteins as promoters of vascular calcification. PMID:23040839

  11. Pineal Calcification Among Black Patients

    PubMed Central

    Fan, Kuang-Jaw

    1983-01-01

    A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

  12. Renal (uremic) encephalopathy in a goat.

    PubMed

    Radi, Z A; Thomsen, B V; Summers, B A

    2005-10-01

    Renal encephalopathy was diagnosed in a 2-year-old male boar goat with a history of chronic weight loss and ataxia. Histopathological examination of the brain revealed a striking myelin vacuolation distributed mainly in two patterns: (i) along the junction of the neocortex and corona radiata, and (ii) in the bundles of the internal capsule as it dissects through the basal nuclei. The kidneys had diffuse severe tubular and glomerular necrosis and degeneration. The neural lesions are consistent with renal (uremic) encephalopathy. To the authors' knowledge, this is the first report of renal encephalopathy in a goat.

  13. Rectus Femoris Tendon Calcification

    PubMed Central

    Zini, Raul; Panascì, Manlio; Papalia, Rocco; Franceschi, Francesco; Vasta, Sebastiano; Denaro, Vincenzo

    2014-01-01

    Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. Study Design: Case series; Level of evidence, 4. Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). Conclusion: Arthroscopic excision of

  14. Placental calcification: a metastatic process?

    PubMed

    Poggi, S H; Bostrom, K I; Demer, L L; Skinner, H C; Koos, B J

    2001-07-01

    Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

  15. Uremic toxins originating from colonic microbial metabolism.

    PubMed

    Evenepoel, Pieter; Meijers, Bjorn K I; Bammens, Bert R M; Verbeke, Kristin

    2009-12-01

    Numerous molecules, which are either excreted or metabolized by the kidney, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules (URMs), contributing to the syndrome of uremia, may be classified according to their site of origin, that is, endogenous metabolism, microbial metabolism, or exogenous intake. It is increasingly recognized that bacterial metabolites, such as phenols, indoles, and amines, may contribute to uremic toxicity. In vitro studies have implicated bacterial URMs in CKD progression, cardiovascular disease, and bone and mineral disorders. Furthermore, several observational studies have demonstrated a link between serum levels of bacterial URMs and clinical outcomes. Bacterial metabolism may therefore be an important therapeutic target in CKD. There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD. Factors promoting URM generation and absorption include an increased ratio of dietary protein to carbohydrate due to insufficient intake of fiber and/or reduced intestinal protein assimilation, as well as prolonged colonic transit time. Two main strategies exist to reduce bacterial URM levels: interventions that modulate intestinal bacterial growth (e.g., probiotics, prebiotics, dietary modification) and adsorbent therapies that bind bacterial URMs in the intestines to reduce their absorption (e.g., AST-120, sevelamer). The efficacy and clinical benefit of these strategies are currently an active area of interest.

  16. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure

    PubMed Central

    Phan, Olivier; Maillard, Marc; Malluche, Hartmut H.; Stehle, Jean-Christophe; Funk, Felix; Burnier, Michel

    2015-01-01

    Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed. PMID:26221597

  17. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

    PubMed

    Phan, Olivier; Maillard, Marc; Malluche, Hartmut H; Stehle, Jean-Christophe; Funk, Felix; Burnier, Michel

    2015-01-01

    Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

  18. PA21, a new iron-based noncalcium phosphate binder, prevents vascular calcification in chronic renal failure rats.

    PubMed

    Phan, Olivier; Maillard, Marc; Peregaux, Christine; Mordasini, David; Stehle, Jean-Christophe; Funk, Felix; Burnier, Michel

    2013-08-01

    Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

  19. Abnormal cytoskeletal assembly in platelets from uremic patients.

    PubMed Central

    Escolar, G.; Díaz-Ricart, M.; Cases, A.; Castillo, R.; Ordinas, A.; White, J. G.

    1993-01-01

    The mechanisms involved in the hemostatic abnormality of uremic patients remain obscure. We have explored the response of normal and uremic platelets to surface activation at the ultrastructural level and analyzed changes in the composition of proteins associated with normal and uremic platelet cytoskeletons after stimulation with thrombin (0.01 and 0.1 U/ml). Cytoskeletons were obtained by extraction with Triton X-100, processed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of cytoskeletal proteins analyzed by densitometry. Under static conditions, uremic platelets spread with difficulty on formvar-coated grids. The percentage of platelets that spread fully on this polymer surface was statistically reduced compared with that of control platelets (11 +/- 1.4 vs. 21 +/- 1.6; P < 0.05). An impairment of cytoskeletal organization was observed in resting uremic platelets but abnormalities were more evident after thrombin activation. The incorporation of actin into the cytoskeletons of thrombin-stimulated uremic platelets was significantly reduced with respect to controls (6 +/- 3% vs. 29 +/- 5%; P < 0.01 after 0.01 U/ml and 28 +/- 9% vs. 59 +/- 10%; P < 0.05 after 0.1 U/ml). Decreased associations of actin-binding protein (P < 0.01), alpha-actinin (P < 0.05), and tropomyosin (P < 0.05) with the cytoskeletons of uremic platelets were also noted. No difference was observed for the incorporation of myosin into the cytoskeletons of activated uremic platelets. These results suggest functional and biochemical alterations of the platelet cytoskeleton in uremia, which may contribute to the impairment of platelet function observed in uremic patients. Images Figure 2 Figure 3 Figure 4 PMID:8362980

  20. Intervertebral disc calcifications in children.

    PubMed

    Beluffi, G; Fiori, P; Sileo, C

    2009-03-01

    This study was done to assess the presence of both asymptomatic and symptomatic intervertebral disc calcifications in a large paediatric population. We retrospectively reviewed the radiographs taken during the past 26 years in children (age 0-18 years) undergoing imaging of the spine or of other body segments in which the spine was adequately depicted, to determine possible intervertebral disc calcifications. The following clinical evaluation was extrapolated from the patients' charts: presence of spinal symptoms, history of trauma, suspected or clinically evident scoliosis, suspected or clinically evident syndromes, bone dysplasias, and pre- or postoperative chest or abdominal X-rays. We detected intervertebral disc calcifications in six patients only. Five calcifications were asymptomatic (one newborn baby with Patau syndrome; three patients studied to rule out scoliosis, hypochondroplasia and syndromic traits; one for dyspnoea due to sunflower seeds inhalation). Only one was symptomatic, with acute neck pain. Calcifications varied in number from one in one patient to two to five in the others. Apart from the calcification in the patient with cervical pain, all calcifications were asymptomatic and constituted an incidental finding (particularly those detected at the thoracic level in the patient studied for sunflower-seed inhalation). Calcification shapes were either linear or round. Our series confirms that intervertebral disc calcifications are a rare finding in childhood and should not be a source of concern: symptomatic calcifications tend to regress spontaneously within a short time with or without therapy and immobilisation, whereas asymptomatic calcifications may last for years but disappear before the age of 20 years. Only very few cases, such as those of medullary compression or severe dysphagia due to anterior herniation of cervical discs, may require surgical procedures.

  1. Vascular Calcification: Mechanisms of Vascular Smooth Muscle Cell Calcification

    PubMed Central

    Leopold, Jane A.

    2014-01-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk. PMID:25435520

  2. Uremic frost: a harbinger of impending renal failure.

    PubMed

    Saardi, Karl M; Schwartz, Robert A

    2016-01-01

    Uremic frost is a striking cutaneous finding seen in patients with severe kidney disease. Familiarity with this condition can be a life-saving signal to initiate urgent dialysis. Uremic frost generally occurs at blood urea nitrogen levels of approximately 200 mg/dl, although it may arise with less severe uremia. Recently confirmed urea transporters in the skin may play a role in the development of uremic frost. Alternatively, damage to the cutaneous microvasculature and pilosebaceous units, as seen in chronic kidney disease, could account for the high levels of urea deposited outside the skin. The treatment of uremic frost is largely aimed at correcting the underlying cause of uremia and the other life-threatening conditions associated with renal failure.

  3. Clinical grand rounds: atypical hemolytic uremic syndrome.

    PubMed

    Hodgkins, Kavita S; Bobrowski, Amy E; Lane, Jerome C; Langman, Craig B

    2012-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

  4. Hemolytic uremic syndrome associated with Acinetobacter hemolyticus.

    PubMed

    da Silva, Paulo Sérgio Lucas; Lipinski, Rubens Wolfe

    2014-08-01

    Shiga toxin-producing Escherichia coli and Shigella dysenteriae have been associated with bloody diarrhea and hemolytic uremic syndrome (HUS) in humans. However, there have been only a couple of reports describing bloody diarrhea associated with Acinetobacter spp. and there are no reports of these bacteria causing HUS in children. Here, we report the case of a nine-month-old boy with bloody diarrhea who developed non-oliguric renal failure. The clinical and laboratory findings supported the diagnosis of Acinetobacter hemolyticus infection associated with HUS. The patient responded favorably to antibiotic therapy plus conservative treatment. In conclusion, Acinetobacter infection should be considered as a plausible cause of HUS in cases where E. coli infection is not involved. The rapid transformation ability of Acinetobacter is a matter of concern.

  5. Arterial calcification: A new perspective?

    PubMed

    Nicoll, R; Henein, M

    2017-02-01

    Arterial calcification is commonly seen in atherosclerosis, chronic kidney disease (CKD) and diabetes and has long been considered a natural progression of atherosclerosis. Yet it is a systemic condition, occurring in a wide and diverse range of disease states and no medical treatment for cardiovascular disease has yet found a way to regress it; on the contrary, lipid-lowering therapy may worsen its progression. Although numerous studies have found associations between calcification and biomarkers, none has yet found a unifying mechanism that explains the calcification found in atherosclerosis, CKD or diabetes and many of the biomarkers are equally associated with atheroma development and cardiovascular events. Furthermore, both presence and absence of coronary artery calcification appear predictive of plaque rupture and cardiovascular events, indicating that the association is not causal. This suggests that we are no further forward in understanding the true nature of arterial calcification or its pathogenesis, other than noting that it is 'multifactorial'. This is because most researchers view arterial calcification as a progressive pathological condition which must be treated. Instead, we hypothesise that calcification develops as an immune response to endothelial injury, such as shear stress or oxidative stress in diabetics, and is consequently part of the body's natural defences. This would explain why it has been found to be protective of plaque rupture and why it is unresponsive to lipid-lowering agents. We propose that instead of attempting to treat arterial calcification, we should instead be attempting to prevent or treat all causes of endothelial injury.

  6. Common variable immunodeficiency complicated with hemolytic uremic syndrome

    PubMed Central

    2012-01-01

    Common variable immunodeficiency is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. Recurrent pyogenic infections of upper and lower respiratory tracts are the main clinical manifestations of common variable immunodeficiency. Hemolytic uremic syndrome is a multisystemic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia due to platelet aggregation in the arterial microvasculature. This is one of the rare cases of patients diagnosed with common variable immunodeficiency, which was complicated by hemolytic uremic syndrome. PMID:22059898

  7. Renal osteodystrophy and vascular calcification.

    PubMed

    Arcidiacono, T; Paloschi, V; Rainone, F; Terranegra, A; Dogliotti, E; Aloia, A; Soldati, L; Vezzoli, G

    2009-01-01

    Chronic kidney disease (CKD) is characterized by phosphate retention and reduced synthesis of 1.25(OH)2-vitamin D stimulating parathyroid hyperplasia. These changes cause a complex osteopathy, defined as renal osteodystrophy, and vascular calcification. Renal osteodystrophy increases the risk of fracture and causes deformities and disability. Vascular calcification occurs in a large proportion of hemodialysis patients and is a marker of arteriopathy. Calcifying arteriopathy induces arterial stiffness and contributes to the high cardiovascular mortality and morbidity among CKD patients. Vascular calcification results from a process of local bone formation induced by osteoblast-like cells developing in the vascular wall from resident cells. Osteoblast differentiation of resident vascular cells may be mediated by metabolic factors and may be induced by high concentrations of phosphate. Therefore, phosphate retention appears as the most detrimental factor affecting arteries in CKD patients. There is no specific therapy to revert soft tissue calcification, but calcification must be prevented in the early stages of CKD.

  8. [Calcification in nonfunctioning transplanted kidneys].

    PubMed

    Peces, R; Sánchez, R J; Fernández, E J; Peces, C

    2007-01-01

    Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These organs may be the site of massive calcification despite their lack of physiological function. Calcification of an endstage renal allograft is sometimes found incidentally. We report here two patients who developed extensive calcification of the renal graft, one was on chronic hemodialysis and the other had a second renal transplantation with normal renal function. The precise pathogenesis of calcification and the factors which determine its tissue localization are unclear. Factors postulated to promote the development of metastatic calcification include an elevated calcium phosphate product, severe secondary hyperparathyroidism, aluminium toxicity and duration of dialytic therapy. In some cases local factors related with the chronic inflammatory rejection process are probably involved as well. However, the exact relative contribution of these factors remains unresolved. Unless specific clinical indications are present, transplant nephrectomy is not necessary for calcified end-stage renal allografts.

  9. Effects of Sevelamer Hydrochloride on Uremic Toxins Serum Indoxyl Sulfate and P-Cresyl Sulfate in Hemodialysis Patients.

    PubMed

    Lin, Cheng-Jui; Pan, Chi-Feng; Chuang, Chih-Kuang; Liu, Hsuan-Liang; Huang, Sung-Fa; Chen, Han-Hsiang; Wu, Chih-Jen

    2017-09-01

    Beside the phosphate binding effect, non-calcium non-aluminum phosphate binder, namely sevelamer hydrochloride (SH), has many other effects in dialysis patients. It can absorb many other compounds, decrease low-density lipoprotein cholesterol (LDL-C) level, and attenuate the progression of vascular calcification; it has been reported to have anti-inflammatory effect. However, it is not clear whether it has any effect on uremic toxins, i.e. serum indoxyl sulfate (IS) and p-cresyl sulfate, (PCS) in hemodialysis (HD) patients. This study was carried out to appraise the effect of sevelamer on serum IS and PCS in HD patients. Five adult HD patients from a single medical center were enrolled in this study; these patients were treated with 800 mg of sevelamer thrice per day for 3 months; a series of biochemical parameters, serum IS and PCS were monitored concurrently. There was a significant reduction in the mean level of phosphate from 7.20 ± 0.70 mg/dL (mean ± SD) before treatment to 5.40 ± 0.50 mg/dL (mean ± SD) after treatment, total cholesterol from 151.00 ± 37.40 mg/dL (mean ± SD) before treatment to 119.20 ± 29.40 mg/dL (mean ± SD) after treatment, and PCS from 31.30 ± 10.60 mg/L (mean ± SD) before treatment to 19.70 ± 10.50 mg/L (mean ± SD) after treatment. On the contrary, this treatment had no effect on IS. A statistically significant reduction of serum phosphate and PCS in HD patients treated with SH suggests that beside the action of lowering serum phosphate, sevelamer may have an important role in the treatment of uremic syndrome by decreasing the uremic toxin.

  10. Disposition and clinical implications of protein-bound uremic toxins.

    PubMed

    Jansen, Jitske; Jankowski, Joachim; Gajjala, Prathibha R; Wetzels, Jack F M; Masereeuw, Rosalinde

    2017-07-15

    In patients with chronic kidney disease (CKD), adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds with intrinsic biological activities, many of which are too large to be filtered and/or are protein bound. The renal excretion of protein-bound toxins depends largely on active tubular secretion, which shifts the binding and allows for active secretion of the free fraction. To facilitate this process, renal proximal tubule cells are equipped with a range of transporters that co-operate in basolateral uptake and luminal excretion. Many of these transporters have been characterized as mediators of drug disposition, but have recently been recognized for their importance in the proximal renal tubular transport of uremic toxins as well. This also indicates that during uremia, drug disposition may be severely affected as a result of drug-uremic toxin interaction. In addition, CKD patients receive various drugs to treat their complications potentially resulting in drug-drug interactions (DDIs), also for drugs that are non-renally excreted. This review discusses the current knowledge on formation, disposition and removal of protein-bound uremic toxins. Furthermore, implications associated with drug treatment in kidney failure, as well as innovative renal replacement therapies targetting the protein-bound uremic toxins are being discussed. It will become clear that the complex problems associated with uremia warrant a transdisciplinary approach that unites research experts in the area of fundamental biomedical research with their colleagues in clinical nephrology. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. [Animal models for vascular calcification].

    PubMed

    Ikeda, Koji; Nakagawa, Yusuke; Matsubara, Hiroaki

    2010-11-01

    Analysis of animal models is indispensable to elucidate the molecular mechanism in vascular calcification (VC) as well as to develop new therapies for VC. Various gene-modified mice that show VC have been reported, and considerable progress has been made through the analyses of these animals. Mice of which bone-calcification regulatory factors were modified are the representative animal models for VC, indicating that these factors certainly regulate VC as well as bone-calcification. Inducible VC in wild-type animals is also an important research tool for developing preventive and therapeutic approach for VC.

  12. [Eight cases of calcific retropharyngeal tendinitis/retropharyngeal calcific tendinitis].

    PubMed

    Ohtsuka, Yuichiro; Chazono, Hideaki; Suzuki, Homare; Ohkuma, Yusuke; Sakurai, Toshioki; Hanazawa, Toyoyuki; Okamoto, Yoshitaka

    2013-11-01

    Calcific retropharyngeal tendinitis/retropharyngeal calcific tendinitis is an inflammation of the longus colli muscle caused by calcium hydroxyapatite crystal depositon in the longus colli muscle tendon. The three major symptoms are neck pain, limitations of neck movement, and swallowing pain. We treated 8 cases of calcific retropharyngeal tendinitis/ retropharyngeal calcific tendinitis. Each patient complained of neck pain, limitations of neck movement, and swallowing pain. The only local finding was the smooth swelling of the posterior pharyngeal wall. CT imaging showed calcification of the tendon of the longus colli muscle and a low density area in the retropharyngeal space without ring enhancement, suggesting a retropharyngeal abscess. MR imaging showed the smooth swelling of the retropharyngeal space and an increased signal intensity on T2-weighted MR imaging. Calcific retropharyngeal tendinitis heals spontaneously, and treatment is not usually required. However, the clinical outcomes are similar and can be confused with retropharyngeal abscess and pyogenic spondylitis, so antibiotics are administrated in many cases. In our report, 7 patients were hospitalized and were treated with the intravenous administration of antibiotics, while 1 patient who refused hospitalization was treated with an oral antibiotic. Steroids were administrated in 2 cases. The 7 patients who were hospitalized were cured within 6 to 10 days.

  13. Hemolytic-uremic syndrome in a dog.

    PubMed

    Dell'Orco, Marta; Bertazzolo, Walter; Pagliaro, Luigi; Roccabianca, Paola; Comazzi, Stefano

    2005-09-01

    A 3-year-old, spayed, female Boxer was presented because of acute onset of anorexia, vomiting, and hemorrhagic diarrhea. Microangiopathic hemolytic anemia with intravascular hemolysis, thrombocytopenia, and acute renal failure were detected. The dog was treated with fluids, antiemetics, antibiotics, and diuretics. Despite supportive therapy, the dog's condition worsened, and the owners elected euthanasia. Necropsy revealed disseminated petechiae on the parietal peritoneum and serosal surfaces of the intestinal tract. The histologic lesions were consistent with severe arteritis and microvascular thrombosis involving only the renal and intestinal arterioles. The final diagnosis was hemolytic-uremic syndrome (HUS), a rarely described disorder in dogs. The clinical presentation of primarily gastrointestinal clinical signs was similar to that of typical or diarrhea-associated HUS (D+ HUS) in humans (mainly children), which is caused by gastrointestinal proliferation of verocytotoxin-producing Escherichia coli. Bacterial toxins can be adsorbed and cause endothelial injury, activation of hemostasis, and thrombosis, with lesions confined primarily to the kidneys. Although rare, HUS should be considered in the differential diagnosis of dogs with microangiopathic hemolytic anemia.

  14. Hemolytic uremic syndrome associated with paraquat intoxication.

    PubMed

    Jang, Ha Nee; Bae, Eun Jin; Hwang, Kyungo; Kang, Yeojin; Yun, Seongeun; Cho, Hyun Seop; Chang, Se-Ho; Park, Dong Jun

    2014-06-01

    We report a case of a 66-year-old patient with paraquat intoxication resulting in the requirement for hemoperfusion, hemodialysis, and plasma exchange. His initial serum paraquat level was 0.24 µg/mL (0.0-0.1 µg/mL). Activated charcoal (50 g) was administered orally, and high-dose N-acetylcysteine (150 mg/kg) was administered intravenously. In addition, immediate 4 h hemoperfusion was also performed for three consecutive days after admission. Hemodialysis was started on the 4th day after admission because of uremia. On the 9th day after admission, laboratory findings demonstrated hemolytic uremic syndrome (HUS): microangiopathic hemolytic anemia (MAHA), thrombocytopenia, elevated reticulocyte count, and lactate dehydrogenase (LDH). Plasma exchange was performed three times consecutively. Anemia and thrombocytopenia were improved, and LDH was normalized after plasma exchange. Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. We should suspect paraquat-associated HUS when thrombocytopenia and anemia are maintained for a long time after paraquat intoxication.

  15. Hemolytic Uremic Syndrome: Toxins, Vessels, and Inflammation

    PubMed Central

    Cheung, Victoria; Trachtman, Howard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy of the glomerular microcirculation and other vascular beds. Its defining clinical phenotype is acute kidney injury (AKI), microangiopathic anemia, and thrombocytopenia. There are many etiologies of HUS including infection by Shiga toxin-producing bacterial strains, medications, viral infections, malignancy, and mutations of genes coding for proteins involved in the alternative pathway of complement. In the aggregate, although HUS is a rare disease, it is one of the most common causes of AKI in previously healthy children and accounts for a sizable number of pediatric and adult patients who progress to end stage kidney disease. There has been great progress over the past 20 years in understanding the pathophysiology of HUS and its related disorders. There has been intense focus on vascular injury in HUS as the major mechanism of disease and target for effective therapies for this acute illness. In all forms of HUS, there is evidence of both systemic and intra-glomerular inflammation and perturbations in the immune system. Renewed investigation into these aspects of HUS may prove helpful in developing new interventions that can attenuate glomerular and tubular injury and improve clinical outcomes in patients with HUS. PMID:25593915

  16. Extracorporeal removal of uremic toxins: can we still do better?

    PubMed

    Eloot, Sunny; Ledebo, Ingrid; Ward, Richard A

    2014-03-01

    Improving outcomes by manipulating the prescription of renal replacement therapy to increase the removal of uremic toxins has had limited success. Failure to achieve better outcomes can be attributed to the heterogenic nature of uremic toxins, the complex distribution of some toxins in the body, and the predominant regimen of thee times weekly, in-center hemodialysis. This review summarizes the various mechanisms and kinetics of removal for the three major classes of uremic toxin-small water-soluble solutes, middle molecules, and protein-bound solutes-from both a theoretical and an experimental perspective. Taken together, the available data suggest that contemporary dialyzers are not a significant impediment to the removal of water-soluble uremic toxins, particularly when combined with commonly used blood and dialysis fluid flow rates and in online convective therapies. Enhancing the removal of those solutes will require a change in paradigm to longer and more frequent treatment sessions. Whether or not such a strategy also would improve the removal of protein-bound uremic toxins is less clear; that goal might require the development of different, more complex devices than those currently used for renal replacement therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Does P-Cresylglucuronide Have the Same Impact on Mortality as Other Protein-Bound Uremic Toxins?

    PubMed Central

    Liabeuf, Sophie; Glorieux, Griet; Lenglet, Aurelie; Diouf, Momar; Schepers, Eva; Desjardins, Lucie; Choukroun, Gabriel; Vanholder, Raymond; Massy, Ziad A.

    2013-01-01

    Background Uremic toxins are emerging as important, non-traditional cardiovascular risk factors in chronic kidney disease (CKD). P-cresol has been defined as a prototype protein-bound uremic toxin. Conjugation of p-cresol creates p-cresylsulfate (PCS) as the main metabolite and p-cresylglucuronide (PCG), at a markedly lower concentration. The objective of the present study was to evaluate serum PCG levels, determine the latter’s association with mortality and establish whether the various protein-bound uremic toxins (i.e. PCS, PCG and indoxylsulfate (IS)) differed in their ability to predict mortality. Methodology/Principal Findings We studied 139 patients (mean ± SD age: 67±12; males: 60%) at different CKD stages (34.5% at CKD stages 2–3, 33.5% at stage 4–5 and 32% at stage 5D). A recently developed high-performance liquid chromatography method was used to assay PCG concentrations. Total and free PCG levels increased with the severity of CKD. During the study period (mean duration: 779±185 days), 38 patients died. High free and total PCG levels were correlated with overall and cardiovascular mortality independently of well-known predictors of survival, such as age, vascular calcification, anemia, inflammation and (in predialysis patients) the estimated glomerular filtration rate. In the same cohort, free PCS levels and free IS levels were both correlated with mortality. Furthermore, the respective predictive powers of three Cox multivariate models (free PCS+other risk factors, free IS+other risk factors and free PCS+other risk factors) were quite similar - suggesting that an elevated PCG concentration has much the same impact on mortality as other uremic toxins (such as PCS or IS) do. Conclusions Although PCG is the minor metabolite of p-cresol, our study is the first to reveal its association with mortality. Furthermore, the free fraction of PCG appears to have much the same predictive power for mortality as PCS and IS do. PMID:23826225

  18. Uremic toxins: some thoughts on acrolein and spermine.

    PubMed

    Sindhu, Kunal K

    2016-11-01

    Chronic kidney disease (CKD) is characterized by the progressive reduction of glomerular filtration rate and subsequent retention of organic waste compounds called uremic toxins. While patients with CKD are at a higher risk of premature death due to cardiovascular complications, this increased risk cannot be completely explained by classical cardiovascular risk factors such as hypertension, diabetes mellitus, and obesity. Instead, recent research suggests that uremic toxins may play a key role in explaining this marked increase in cardiovascular mortality in patients with CKD. While spermine, a tetra-amine, has previously been hypothesized to act as an uremic toxin, the following review presents a summary of recent literature that casts doubt on this assertion. Instead, acrolein, an oxidative product of spermine and the triamine spermidine, is likely responsible for the toxic effects previously attributed to spermine.

  19. [Compression of the sciatic nerve in uremic tumor calcinosis].

    PubMed

    García, S; Cofán, F; Combalia, A; Casas, A; Campistol, J M; Oppenheimer, F

    1999-02-01

    Tumoral calcinosis is an uncommon and benign condition characterized by the presence of slow-growing calcified periarticular soft tissue masses of varying size. They are usually asymptomatic and nerve compression is rare. We describe the case of a 54-year-old female patient on long-term hemodialysis for chronic renal failure presenting sciatica in the left lower limb secondary to an extensive uremic tumoral calcinosis that affected the hip and thigh. The pathogenesis of uremic tumoral calcinosis as well as the treatment and clinical outcome are analyzed. The uncommon nerve compression due to tumoral calcinosis are reviewed. In conclusion, uremic tumoral calcinosis is a not previously reported infrequent cause of sciatic nerve compression.

  20. Identification of beta-aminoisobutyric acid in uremic serum.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1976-08-02

    An unidentified ninhydrin-positive substance found in uremic sera but not found in normal sera was isolated by gel-filtration through Sephadex G-75 followed by high voltage paper electrophoresis (pH 3.5), and identified as beta-aminoisobutyric acid using paper chromatography and automated amino acid analyzer. The quantitative determination of beta-aminoisobutyric acid in serum revealed that the level of beta-aminoisobutyric acid in uremic sera was much higher than that of normal sera. Gas chromatographic determination of the enantiomorphs of beta-aminoisobutyric acid showed that uremic sera contain R- and S-isomers of the amino acid, but with the R-isomer as the dominating form.

  1. Calcification prevention tablets

    NASA Technical Reports Server (NTRS)

    Lindsay, Geoffrey A.; Hasting, Michael A.; Gustavson, Michael A.

    1991-01-01

    Citric acid tablets, which slowly release citric acid when flushed with water, are under development by the Navy for calcification prevention. The citric acid dissolves calcium carbonate deposits and chelates the calcium. For use in urinals, a dispenser is not required because the tablets are non-toxic and safe to handle. The tablets are placed in the bottom of the urinal, and are consumed in several hundred flushes (the release rate can be tailored by adjusting the formulation). All of the ingredients are environmentally biodegradable. Mass production of the tablets on commercial tableting machines was demonstrated. The tablets are inexpensive (about 75 cents apiece). Incidences of clogged pipes and urinals were greatly decreased in long term shipboard tests. The corrosion rate of sewage collection pipe (90/10 Cu/Ni) in citric acid solution in the laboratory is several mils per year at conditions typically found in traps under the urinals. The only shipboard corrosion seen to date is of the yellow brass urinal tail pieces. While this is acceptable, the search for a nontoxic corrosion inhibitor is underway. The shelf life of the tablets is at least one year if stored at 50 percent relative humidity, and longer if stored in sealed plastic buckets.

  2. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome.

    PubMed

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

  3. Uremic parkinsonism with atypical phenotypes and radiologic features.

    PubMed

    Yoon, Jee-Eun; Kim, Ji Sun; Park, Jeong-Ho; Lee, Kyung-Bok; Roh, Hakjae; Park, Sung Tae; Cho, Jin Whan; Ahn, Moo-young

    2016-04-01

    Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy.

  4. Genetic predisposition to calcific aortic stenosis and mitral annular calcification.

    PubMed

    Kutikhin, Anton G; Yuzhalin, Arseniy E; Brusina, Elena B; Ponasenko, Anastasia V; Golovkin, Alexey S; Barbarash, Olga L

    2014-09-01

    Valvular calcification precedes the development of valvular stenosis and may represent an important early phenotype for valvular heart disease. It is known that development of valvular calcification is likely to occur among members of a family. However, the knowledge about the role of genomic predictive markers in valvular calcification is still elusive. Aims of this review are to assess the impact of gene polymorphisms on risk and severity of aortic stenosis and mitral annular calcification. According to the results of the investigations carried out, all polymorphisms may be divided into the three groups conferring the level of evidence of their association with valvular stenosis. It is possible to conclude that apoB (XbaI, rs1042031, and rs6725189), ACE (rs4340), IL10 (rs1800896 and rs1800872), and LPA (rs10455872) gene polymorphisms may be associated with valvular calcific stenosis with a relatively high level of evidence. A number of other polymorphisms, such as PvuII polymorphism within the ORα gene, rs1042636 polymorphism within the CaSR gene, rs3024491, rs3021094, rs1554286, and rs3024498 polymorphisms within the IL10 gene, rs662 polymorphism within the PON1 gene, rs2276288 polymorphism within the MYO7A gene, rs5194 polymorphism within the AGTR1 gene, rs2071307 polymorphism within the ELN gene, rs17659543 and rs13415097 polymorphisms within the IL1F9 gene may correlate with a risk of calcific valve stenosis with moderate level of evidence. Finally, rs1544410 polymorphism within the VDR gene, E2 and E4 alleles within the apoE gene, rs6254 polymorphism within the PTH gene, and rs1800871 polymorphism within the IL10 gene may be associated with aortic stenosis with low level of evidence.

  5. Calcification Transformation of Diasporic Bauxite

    NASA Astrophysics Data System (ADS)

    Zhao, Qiuyue; Zhu, Xiaofeng; Lv, Guozhi; Zhang, Zimu; Yin, Zhengnan; Zhang, Tingan

    2016-06-01

    The disposal of red mud, which is a solid waste that is generated during the extraction of alumina from bauxite, is one of major problems faced by the aluminum industry. Alkali in red mud seeping under the soil may pollute land and water. The Northeastern University, China, has proposed a calcification-carbonation method to deal with low-grade bauxite or red mud. Its main purpose is to change the equilibrium phase of red mud to 2CaO·SiO2 and CaCO3 hydrometallurgically, so that recomposed alkali-free red mud can be widely used. We conducted calcification transformation experiments using diasporic bauxite sampled from Wenshan, and investigated the effects of parameters such as diasporic bauxite grain size, temperature and treatment time on the calcification transformation digestion rate, which is also termed the calcification transformation rate (CTR). The main phase in the calcification transformation slag (CTS) is hydrogarnet with different grain sizes. The CTR increases with decrease in diasporic bauxite grain size, or increase in temperature or reaction time. The CTR reaches a maximum of 87% after 120 min reaction at 240°C. The Na2O/Al2O3 ratio decreases with increase in temperature and reaches 1.5. The sodium content in the CTS decreases with increasing reaction time and is lower than that in the red mud treated using the Bayer process (4-12%).

  6. Pontine calcification following radiotherapy: CT demonstration.

    PubMed

    Price, D B; Hotson, G C; Loh, J P

    1988-01-01

    Development of pontine calcifications following radiation therapy for suprasellar tumors is described in two patients, 5 and 9 years old. Post-radiotherapy brain calcifications are rare in the brain stem.

  7. [Calcific tendinitis of the shoulder].

    PubMed

    Diehl, P; Gerdesmeyer, L; Gollwitzer, H; Sauer, W; Tischer, T

    2011-08-01

    Calcific tendinitis of the shoulder is a process involving crystal calcium deposition in the rotator cuff tendons, which mainly affects patients between 30 and 50 years of age. The etiology is still a matter of dispute. The diagnosis is made by history and physical examination with specific attention to radiologic and sonographic evidence of calcific deposits. Patients usually describe specific radiation of the pain to the lateral proximal forearm, with tenderness even at rest and during the night. Nonoperative management including rest, nonsteroidal anti-inflammatory drugs, subacromial corticosteroid injections, and shock wave therapy is still the treatment of choice. Nonoperative treatment is successful in up to 90% of patients. When nonsurgical measures fail, surgical removal of the calcific deposit may be indicated. Arthroscopic treatment provides excellent results in more than 90% of patients. The recovery process is very time consuming and may take up to several months in some cases.

  8. Should dialysis modalities be designed to remove specific uremic toxins?

    PubMed

    Baurmeister, Ulrich; Vienken, Joerg; Ward, Richard A

    2009-01-01

    The definition of optimal dialysis therapy remains elusive. Randomized clinical trials have neither supported using urea as a surrogate marker for uremic toxicity nor provided clear cut evidence in favor of larger solutes. Thus, where to focus resources in the development of new membranes, and therapies remains unclear. Three basic questions remain unanswered: (i) what solute(s) should be used as a marker for optimal dialysis; (ii) should dialytic therapies be designed to remove a specific solute; and (iii) how can current therapies be modified to provide better control of uremic toxicity? Identification of a single, well-defined uremic toxin appears to be unlikely as new analytical tools reveal an increasingly complex uremic milieu. As a result, it is probable that membranes and therapies should be designed for the nonspecific removal of a wide variety of solutes retained in uremia. Removal of the widest range of solutes can best be achieved using existing therapies that incorporate convection in conjunction with longer treatment times and more frequent treatments. Membranes capable of removing solutes over an expanded effective molecular size range can already be fabricated; however, their use will require novel approaches to conserve proteins, such as albumin.

  9. Putative uremic encephalopathy in horses: five cases (1978-1998).

    PubMed

    Frye, M A; Johnson, J S; Traub-Dargatz, J L; Savage, C J; Fettman, M J; Gould, D H

    2001-02-15

    To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

  10. Protein-bound uremic toxins: new insight from clinical studies.

    PubMed

    Liabeuf, Sophie; Drüeke, Tilman B; Massy, Ziad A

    2011-07-01

    The uremic syndrome is attributed to the progressive retention of a large number of compounds which, under normal conditions, are excreted by healthy kidneys. The compounds are called uremic toxins when they interact negatively with biological functions. The present review focuses on a specific class of molecules, namely the family of protein-bound uremic toxins. Recent experimental studies have shown that protein-bound toxins are involved not only in the progression of chronic kidney disease (CKD), but also in the generation and aggravation of cardiovascular disease. Two protein-bound uremic retention solutes, namely indoxyl sulfate and p-cresyl sulfate, have been shown to play a prominent role. However, although these two molecules belong to the same class of molecules, exert toxic effects on the cardiovascular system in experimental animals, and accumulate in the serum of patients with CKD they may have different clinical impacts in terms of cardiovascular disease and other complications. The principal aim of this review is to evaluate the effect of p-cresyl sulfate and indoxyl sulfate retention on CKD patient outcomes, based on recent clinical studies.

  11. [Uremic toxins: the case of protein-bound compounds].

    PubMed

    Basile, Carlo; Libutti, Pasquale; Teutonico, Annalisa; Lomonte, Carlo

    2010-01-01

    Uremic retention solutes, if biologically or biochemically active, are called ''uremic toxins''. The retention of these solutes has a negative impact on many functions of the organism, particularly the cardiovascular system. The classification which is applied today is based on the kinetic behavior of the uremic retention solutes during dialysis: 1) small water-soluble molecules (< 500 Daltons); 2) middle molecules (> 500 Daltons); 3) protein-bound compounds. The latter are the object of the present review. The most important among them are p-cresol, p-cresyl sulfate, homocysteine, phenols, and indoles. No interventional studies are currently available that show the effect of an improvement in the removal of protein-bound compounds on patient outcomes, simply because most of the alternative dialysis strategies proposed so far are not superior to standard dialysis in removing protein-bound compounds. The question as to how to improve the removal of these solutes therefore remains unanswered. Alternative strategies might include adsorption therapies, either administered orally or during the extracorporeal treatment. In conclusion, the uremic syndrome is a complex clinical entity which involves a large number of retention solutes, many more than the small water-soluble molecules. Dialysis strategies should therefore aim to remove not only urea but also retention solutes, mainly because middle and protein-bound molecules appear to be correlated more frequently with deleterious biological, biochemical and clinical effects.

  12. Hemolytic-uremic syndrome in adolescents.

    PubMed

    Siegler, R L; Pavia, A T; Cook, J B

    1997-02-01

    To compare the epidemiological characteristics, clinical features, and outcome of adolescents with hemolytic-uremic syndrome (HUS) with those of children with HUS. A retrospective descriptive study using data stored in the computerized Utah HUS registry. The HUS registry contains data on postdiarrheal and nondiarrheal HUS cases since 1970 in which the patients were younger than 18 years of age at the time of diagnosis and includes virtually all Utah cases as well as those referred from surrounding states. Seventeen adolescents (age, 12-17 years) and 276 younger patients from September 30, 1970, through December 5, 1993, who met the diagnostic criteria for HUS. Age, sex, seasonality, prodromal features (eg, antecedent diarrhea), laboratory values, hospital course, outcome, and chronic sequelae. The 17 adolescent patients, who composed 5.8% of the study population, experienced a course of the disease that was similar to that of the younger patients. Diarrhea preceded HUS in approximately 90% of the patients in both groups. Laboratory values were similar in teenagers and younger patients. The hospital courses were also similar; seizures occurred in almost 20%, and hypertension and oligoanuric renal failure occurred in most. Two (12%) of the teenagers and 7 (2.4%) of the younger patients died during the acute phase of the syndrome (P = .09); almost 50% of both groups experienced 1 or more chronic renal sequelae. End-stage renal disease has occurred in 1 (5.8%) of the teenagers and 6 (2.2%) of the children. At follow-up, 1 or more years (median, 5 years) after the onset of HUS, hypertension was present in 22% of the teenagers and 6.7% of the preteens (P = .14). A below-normal glomerular filtration rate was seen in approximately 30% of both groups; proteinuria was noted in approximately 25% of both groups. Approximately 10% of both groups had a combination of proteinuria and a low glomerular filtration rate and are, therefore, at risk for eventual end-stage renal disease

  13. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Mechanisms of vascular calcification].

    PubMed

    Shioi, Atsushi

    2015-05-01

    Vascular calcification is an independent risk factor for the development of cardiovascular disease and is classified into two types based on the site of calcification : intimal atherosclerotic calcification and Mönckeberg's medial calcification. Matrix vesicles released from macrophages and vascular smooth muscle cells (VSMC) during apoptosis play a pivotal role in formation of fine granular calcification, while osteogenic differentiation of VSMC contributes to progression of advanced calcification. Recent noninvasive imaging studies of atherosclerotic calcification provide robust evidence that inflammation precedes active calcification, leading to establish the inflammation-dependent calcification paradigm. On the other hand, elastin degradation by increased elastolytic activities and disturbance of regulatory systems of extracellular pyrophosphate metabolism play an important role in development of Mönckeberg's medial calcification.

  14. CT of schistosomal calcification of the intestine

    SciTech Connect

    Fataar, S.; Bassiony, H.; Satyanath, S.; Rudwan, M.; Hebbar, G.; Khalifa, A.; Cherian, M.J.

    1985-01-01

    The spectrum of schistosomal colonic calcification on abdominal radiographs has been described. The appearance on computed tomography (CT) is equally distinctive and occurs with varying degrees of genitourinary calcification. The authors have experience in three cases with the appearance on CT of intestinal calcification due to schistosomiasis.

  15. Intracranial calcification in central diabetes insipidus.

    PubMed

    Al-Kandari, Salwa Ramadan; Pandey, Tarun; Badawi, Mona H

    2008-01-01

    Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification.

  16. Chronic calcific tendinitis of the neck

    SciTech Connect

    Newmark, H.; Zee, C.S.; Frankel, P.; Robinson, A.; Blau, L.; Gans, D.C.

    1981-12-01

    The authors present the first three cases of chronic calcific tendinits of the neck. This condition is diagnosed radiologically by the presence of calcification located just inferior to the anterior tubercle of C1. The calcification is at the insertion of the longus colli muscle. No soft tissue swelling is present and the patients are asymptomatic.

  17. MR appearance of pulmonary metastatic calcification

    SciTech Connect

    Taguchi, Yasushi; Fuyuno, Gentaro; Shioya, Sumie; Yanagimachi, Noriharu; Katoh, Hirokazu; Matsuyama, Seiya; Ohta, Yasuyo

    1996-01-01

    We report a case of metastatic pulmonary calcification that showed hyperintense signal on T1-weighted MRI. This uncommon MR appearance of calcification is similar to the MR characteristics of calcification in the brain due to abnormal calcium metabolism. 11 refs., 5 figs.

  18. Calcification of intraocular hydrogel lens: evidence of dystrophic calcification.

    PubMed

    Yong, Jim L C; Lertsumitkul, Somsak; Killingsworth, Murray C; Filipic, Marijan

    2004-10-01

    To report and describe the surface calcification of three cases of implanted intraocular hydrogel lens. Three surgically extracted hydrogel intraocular lenses were studied by light and transmission electron microscopy as well as by energy dispersion X-ray microanalysis. The lens surfaces were covered by granular deposits of calcium phosphate, clearly delineated by von Kossa and alizarin stains for calcium. Transmission electron microscopy showed the deposits to be located within the superficial lens material to a depth of 7 microm and to be associated with what appear to be traces of cellular material including basement membrane and plasmalemma. To the authors' knowledge there has been only one other transmission electron microscopic study. Energy dispersion X-ray microanalysis showed the deposits to contain calcium and phosphorous in all cases. This study confirms and extends the previous reports of five cases of calcification of hydrogel intraocular lenses. The exact mechanism of calcification remains obscure but evidence suggesting cell-mediated dystrophic calcification of the lens surface is presented. Further study is required to monitor the incidence and development of this phenomenon.

  19. Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

    PubMed

    Kim, D M; Lee, I H; Song, C J

    2016-09-01

    Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy. This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging. MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions. The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy. © 2016 by American Journal of Neuroradiology.

  20. Genetics and molecular biology of brain calcification.

    PubMed

    Deng, Hao; Zheng, Wen; Jankovic, Joseph

    2015-07-01

    Brain calcification is a common neuroimaging finding in patients with neurological, metabolic, or developmental disorders, mitochondrial diseases, infectious diseases, traumatic or toxic history, as well as in otherwise normal older people. Patients with brain calcification may exhibit movement disorders, seizures, cognitive impairment, and a variety of other neurologic and psychiatric symptoms. Brain calcification may also present as a single, isolated neuroimaging finding. When no specific cause is evident, a genetic etiology should be considered. The aim of the review is to highlight clinical disorders associated with brain calcification and provide summary of current knowledge of diagnosis, genetics, and pathogenesis of brain calcification.

  1. [Molecular mechanisms of bone calcification].

    PubMed

    Hoshi, Kazuto; Ozawa, Hidehiro

    2003-04-01

    Bone matrix consists mainly of hydroxyapatite and organics. The latter include various substances which interact with minerals. Osteoblasts secrete these organic substances and control crystal formation and growth of hydroxyapatite. The authors discuss the molecular mechanisms of calcification by focusing on the mineral/organic interaction.

  2. Vascular calcification in maintenance hemodialysis patients.

    PubMed

    Wang, Mi; Wang, Mei; Gan, Liang-Ying; Li, Si-Jun; Hong, Nan; Zhang, Meng

    2009-01-01

    The objective was to investigate the status of vascular calcification, and to explore factors influencing vascular calcification in maintenance hemodialysis patients. Vascular calcification was quantitatively evaluated using radiographic films of the abdomen, pelvis and hands. Plasma fetuin-A and other parameters related to calcification were examined. 33/50 cases of vascular calcification were identified by radiographic film. Calcifications of the abdominal aorta and peripheral muscular arteries were seen in 90.9 and 36.4%. Patients with moderate to severe calcification were older, more likely to be male, had lower diastolic blood pressure and fetuin-A levels, and a higher incidence of diabetes than those with mild calcification. Logistic regression analysis showed that diabetes and plasma fetuin-A were independent risk factors for vascular calcification. Vascular calcification was present in a large proportion of maintenance hemodialysis patients, most frequently in the abdominal aorta. Diabetes and plasma fetuin-A levels were independent risk factors for vascular calcification in maintenance hemodialysis patients. (c) 2009 S. Karger AG, Basel.

  3. Visualizing novel concepts of cardiovascular calcification.

    PubMed

    Hjortnaes, Jesper; New, Sophie E P; Aikawa, Elena

    2013-04-01

    Cardiovascular calcification is currently viewed as an active disease process similar to embryonic bone formation. Cardiovascular calcification mainly affects the aortic valve and arteries and is associated with increased mortality risk. Aortic valve and arterial calcification share similar risk factors, including age, gender, diabetes, chronic renal disease, and smoking. However, the exact cellular and molecular mechanism of cardiovascular calcification is unknown. Late-stage cardiovascular calcification can be visualized with conventional imaging modalities such as echocardiography and computed tomography. However, these modalities are limited in their ability to detect the development of early calcification and the progression of calcification until advanced tissue mineralization is apparent. Due to the subsequent late diagnosis of cardiovascular calcification, treatment is usually comprised of invasive interventions such as surgery. The need to understand the process of calcification is therefore warranted and requires new imaging modalities which are able to visualize early cardiovascular calcification. This review focuses on the use of new imaging techniques to visualize novel concepts of cardiovascular calcification. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Recent progress in the analysis of uremic toxins by mass spectrometry.

    PubMed

    Niwa, Toshimitsu

    2009-09-01

    Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on recent progress in the analysis of uremic toxins by using MS. Uremic toxins include low-molecular-weight compounds (e.g., indoxyl sulfate, p-cresol sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, asymmetric dimethylarginine), middle-molecular-weight peptides, and proteins modified with advanced glycation and oxidation. These uremic toxins are considered to be involved in a variety of symptoms which may appear in patients with stage 5 chronic kidney disease. Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms.

  5. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

    PubMed Central

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach. PMID:27110144

  6. Uremic encephalopathy and other brain disorders associated with renal failure.

    PubMed

    Seifter, Julian Lawrence; Samuels, Martin A

    2011-04-01

    Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed. © Thieme Medical Publishers.

  7. Nanoporous biomaterials for uremic toxin adsorption in artificial kidney systems: A review.

    PubMed

    Cheah, Wee-Keat; Ishikawa, Kunio; Othman, Radzali; Yeoh, Fei-Yee

    2017-07-01

    Hemodialysis, one of the earliest artificial kidney systems, removes uremic toxins via diffusion through a semipermeable porous membrane into the dialysate fluid. Miniaturization of the present hemodialysis system into a portable and wearable device to maintain continuous removal of uremic toxins would require that the amount of dialysate used within a closed-system is greatly reduced. Diffused uremic toxins within a closed-system dialysate need to be removed to maintain the optimum concentration gradient for continuous uremic toxin removal by the dialyzer. In this dialysate regenerative system, adsorption of uremic toxins by nanoporous biomaterials is essential. Throughout the years of artificial kidney development, activated carbon has been identified as a potential adsorbent for uremic toxins. Adsorption of uremic toxins necessitates nanoporous biomaterials, especially activated carbon. Nanoporous biomaterials are also utilized in hemoperfusion for uremic toxin removal. Further miniaturization of artificial kidney system and improvements on uremic toxin adsorption capacity would require high performance nanoporous biomaterials which possess not only higher surface area, controlled pore size, but also designed architecture or structure and surface functional groups. This article reviews on various nanoporous biomaterials used in current artificial kidney systems and several emerging nanoporous biomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1232-1240, 2017. © 2016 Wiley Periodicals, Inc.

  8. Uremic encephalopathy with atypical magnetic resonance features on diffusion-weighted images.

    PubMed

    Kang, Eugene; Jeon, Se Jeong; Choi, See-Sung

    2012-01-01

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

  9. Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

    PubMed Central

    Kang, Eugene; Choi, See-Sung

    2012-01-01

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings. PMID:23118581

  10. Lipoprotein(a) accelerates atherosclerosis in uremic mice[S

    PubMed Central

    Pedersen, Tanja X.; McCormick, Sally P.; Tsimikas, Sotirios; Bro, Susanne; Nielsen, Lars B.

    2010-01-01

    Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo(a)-Tg and WT mice. Uremia did not result in increased plasma apo(a) or Lp(a). Mean atherosclerotic plaque area in the aortic root was increased 1.8-fold in apo(a)-Tg (P = 0.025) and 3.3-fold (P = 0.0001) in Lp(a)-Tg mice compared with WT mice. Plasma OxPL, as detected with the E06 antibody, was associated with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia. PMID:20584868

  11. Cardiomyopathy: a late complication of hemolytic uremic syndrome.

    PubMed

    Walker, A M; Benson, L N; Wilson, G J; Arbus, G S

    1997-04-01

    This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS.

  12. Reversible MRI changes in a patient with uremic encephalopathy.

    PubMed

    Schmidt, M; Sitter, T; Lederer, S R; Held, E; Schiffl, H

    2001-01-01

    A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.

  13. [Clinical approach to hydatid disease in uremic patients].

    PubMed

    Vaccaro, F; Pagano, A; Romano, G; Romano, G

    1996-03-01

    Uremic patients in hemodialytic treatment have the same opportunity to be affected with hydatid disease as healthy people. However, because these patients usually have an immunodeficiency syndrome, it is always necessary to evaluate correctly the most common immune diagnostic procedures; furthermore the clinical approach and successive surgical treatment must evaluate carefully electrolyte and acid-base balances, the cardiovascular system, hemostasis and energy intake. Authors, in this paper, report 8 cases of hydatid disease in as many patients during a period of 27 years. At the beginning they describe diagnostic and therapeutic management; later they emphasize the necessity of a careful immunological diagnostic evaluation (which is often falsely negative), and of radiological, ultrasonographic and scintigraphic diagnosis. They conclude by emphasizing that uremic patients with hemodialytic treatment survive with disease and although a surgical approach of hydatid disease is not really different from others it could be insidious not to consider the peculiar immunological and clinical metabolic state of uremic patients also to perform a correct treatment.

  14. Effect of Sertraline on Uremic Pruritus Improvement in ESRD Patients

    PubMed Central

    Shakiba, Mansor; Sanadgol, Hoshang; Azmoude, Hamid Reza; Mashhadi, Mohamad Ali; Sharifi, Hassan

    2012-01-01

    Background. Although uremic pruritus is a common and upsetting problem of chronic kidney disease, there is no approved treatment for it. This study was undertaken to find the efficiency of sertraline as a possible treatment for uremic pruritus. Methods. 19 ESRD patients under hemodialysis with severe chronic pruritus were randomly selected to participate in this before-after clinical trial. Before and after starting treatment with sertraline, a detailed pruritus history was obtained and pruritus graded by the 30-item inventory of pruritus that patients based on priorities grade allocated to 3 classes. Subjects were treated with sertraline 50 mg oral daily for four months, with monthly assessments of pruritus symptoms. Results. Before treatment with sertraline, the grade of pruritus in 9 (47.4%) patients was moderate and severe in 10 (52.6%) patients. After treatment, grade of pruritus in 11 (57.8%) patients was weak, 6 (31.5%) have moderate and only 2 (10.7%) patients have severe pruritus. Of 10 patients with severe pruritus, 5 (50%) patients experiencing weak pruritus, and 4 (40%) patients have moderate pruritus after treatment. Based on Wilcoxon signed-rank test, the difference between the grade of pruritus before and after treatment with sertraline was significant (P = 0.001). Conclusions. Although no definitive recommendation can be made regarding treatment of uremic pruritus, we found an increased antipruritic effect of sertraline in ESRD patients. PMID:22973512

  15. Gabapentin: a promising drug for the treatment of uremic pruritus.

    PubMed

    Naini, Afsoon Emami; Harandi, Ali Amini; Khanbabapour, Saeid; Shahidi, Shahrzad; Seirafiyan, Shiva; Mohseni, Masood

    2007-09-01

    Despite advances made in treatment, uremic pruritus remains a common and distressing symptom in patients on hemodialysis (HD). Gabapentin is an effective drug in the management of neuropathic pain. Considering that neuropathic pain and pruritus share similar pathogenic mechanisms, we conducted this study to evaluate the efficacy of gabapentin in controlling uremic itch. In a double blind, placebo-controlled trial, 34 adult patients on maintenance HD were enrolled. The patients were assigned to receive four weeks of treatment with either gabapentin (400 mg) or placebo administered twice weekly after HD sessions. Pruritus scores were measured using a visual analogue scale and compared between the two groups.After four weeks of treatment, the mean decrease in pruritus score in gabapentin and placebo groups was 6.7 +/- 2.6 and 1.5 +/- 1.8, respectively (p< 0.001). None of the patients was forced to drop out of the study due to side effects of the treatment. Our study suggests that gabapentin is a safe and effective treatment for uremic itch.

  16. Cromolyn sodium: a potential therapy for uremic pruritus?

    PubMed

    Rosner, Mitchell H

    2006-04-01

    Uremic pruritus occurs in up to 50% of patients undergoing chronic hemodialysis. The pathogenesis of this disabling condition is unknown but likely involves multiple pathways involving the peripheral and central nervous system as well as local chemical and inflammatory mediators. Therapy has involved modification of the dialysis procedure, topical medications such as emollients, physical treatments such as ultraviolet light, and several oral medications such as antihistamines, activated charcoal, and gabapentin. Unfortunately, most of these therapies have not been subjected to rigorous clinical trials and clinical success has been variable. Two patients with disabling uremic pruritus refractory to multiple interventions are reported, who showed significant improvement in pruritus severity as assessed by a visual analog scale when they were treated with the mast cell stabilizer cromolyn sodium. Cessation of cromolyn resulted in return of pruritus, which improved with rechallenge with the medication. Cromolyn sodium may offer an alternative therapy for patients with refractory uremic pruritus, and should be subjected to a randomized placebo-controlled trial.

  17. Gases as uremic toxins: is there something in the air?

    PubMed

    Jankowski, Joachim; Westhof, Timm; Vaziri, Nosratola D; Ingrosso, Diego; Perna, Alessandra F

    2014-03-01

    The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example, protein-binding, dimensions, and so forth. The endogenous compounds of a gaseous nature have received much attention lately from the scientific community because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds are phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid and phenyl acetic acid, trimethylamine, and dimethylamine; among the inorganic solutes are ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this article, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools, and the gastrointestinal tract. In addition, the effect of the dialysis procedure on exhaled gases are described.

  18. Calcific retropharyngeal tendinitis. [Radiological findings

    SciTech Connect

    Karasick, D.; Karasick, S.

    1981-12-01

    Calcific retropharyngeal tendinitis is an imflammation of the longus colli muscle tendon which is located on the anterior surface of the verterbral column extending from the atlas to the third thoracic vertebra. The acute inflammatory condition is selflimiting with symptoms consisting of a gradually increasing neck pain often associated with throat pain and difficulty swallowing. The pain is aggravated by head and neck movement. Clinically the condition can be confused with retropharyngeal absecess, meningitis, infectious spondylitis, and post-traumatic muscle spasm. The radiographic features of this condition consist of pre-vertebral soft tissue swelling from C1 to C4 and amorphous calcific density in the longus colli tendon anterior to the body of C2 and inferior to the anterior arch of C1.

  19. Coral calcification and ocean acidification

    USGS Publications Warehouse

    Jokiel, Paul L.; Jury, Christopher P.; Kuffner, Ilsa B.

    2016-01-01

    Over 60 years ago, the discovery that light increased calcification in the coral plant-animal symbiosis triggered interest in explaining the phenomenon and understanding the mechanisms involved. Major findings along the way include the observation that carbon fixed by photosynthesis in the zooxanthellae is translocated to animal cells throughout the colony and that corals can therefore live as autotrophs in many situations. Recent research has focused on explaining the observed reduction in calcification rate with increasing ocean acidification (OA). Experiments have shown a direct correlation between declining ocean pH, declining aragonite saturation state (Ωarag), declining [CO32_] and coral calcification. Nearly all previous reports on OA identify Ωarag or its surrogate [CO32] as the factor driving coral calcification. However, the alternate “Proton Flux Hypothesis” stated that coral calcification is controlled by diffusion limitation of net H+ transport through the boundary layer in relation to availability of dissolved inorganic carbon (DIC). The “Two Compartment Proton Flux Model” expanded this explanation and synthesized diverse observations into a universal model that explains many paradoxes of coral metabolism, morphology and plasticity of growth form in addition to observed coral skeletal growth response to OA. It is now clear that irradiance is the main driver of net photosynthesis (Pnet), which in turn drives net calcification (Gnet), and alters pH in the bulk water surrounding the coral. Pnet controls [CO32] and thus Ωarag of the bulk water over the diel cycle. Changes in Ωarag and pH lag behind Gnet throughout the daily cycle by two or more hours. The flux rate Pnet, rather than concentration-based parameters (e.g., Ωarag, [CO3 2], pH and [DIC]:[H+] ratio) is the primary driver of Gnet. Daytime coral metabolism rapidly removes DIC from the bulk seawater. Photosynthesis increases the bulk seawater pH while providing the energy that drives

  20. Deficiencies of physiologic calcification inhibitors and low-grade inflammation in arterial calcification: lessons for cartilage calcification.

    PubMed

    Rutsch, Frank; Terkeltaub, Robert

    2005-03-01

    Apart from clinical parallels, similarities in the pathogenesis of arterial and articular cartilage calcification have come to light in recent years. These include the roles of aging, of chronic low-grade inflammation and of genetic and acquired dysregulation of inorganic pyrophosphate (PP(i)) metabolism. This review focuses on recent developments in understanding the pathogenesis of artery calcification pertinent to interpretation of the mechanistic basis for articular cartilage calcification in aging and osteoarthritis.

  1. Atypical Steatocystoma Multiplex with Calcification

    PubMed Central

    Rahman, Muhammad Hasibur; Islam, Muhammad Saiful; Ansari, Nazma Parvin

    2011-01-01

    A 60-year-old male reported to us with an atypical case of giant steatocystoma multiplex in the scrotum with calcification. There was no family history of similar lesions. Yellowish, creamy material was expressed from a nodule during punch biopsy. The diagnosis was based on clinical as well as histological findings. Successful surgical excision was done to cure the case without any complications. PMID:22363850

  2. Arterial calcification: friend or foe?

    PubMed

    Nicoll, Rachel; Henein, Michael Y

    2013-07-31

    There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. [Differential diagnosis of intrasinusal calcifications].

    PubMed

    Hernández Montero, E; Martínez Berganza, R; Carmen Sampériz, L

    2004-01-01

    We present a case of a patient with a sinusitis of three months evolution. The CT scan showed an occupation of the middle meatus of the left nasal fossa with alergic polyps and a total opacification of the left maxillary sinus with calcifications, that makes to discard the metalic on dental nature of an intrasinusal body, and other chronic granulomatous processes. The correct surgical restauration of the osteomeotal complex obtained the complete resolution of the process.

  4. Pleural calcification in northwest Greece

    SciTech Connect

    Bazas, T.; Oakes, D.; Gilson, J.C.; Bazas, B.; McDonald, J.C.

    1985-12-01

    Mass miniature radiography in 1969 detected a high prevalence of pleural calcification in three villages in northwest Greece. In 1980 a survey of a 15% sample of the population over the age of 10 was carried out with a 80% response rate. Full-size radiographs, ventilatory capacity measurements, and a detailed questionnaire on respiratory symptoms, type of work, and residence were used. Independent classification of the 408 films by two readers using the ILO/UC scheme showed very few small opacities but a very high prevalence of pleural calcification first evident in young adults and rising to 70% in the elderly. The overall prevalence was 34.7% in men and 21.5% in women. A comparison with the 1969 survey showed a progression rate of 5% per annum. In neither sex was there a significant relation of pleural calcification to smoking, ventilatory capacity, nor type of work, though those classified as field croppers had a slightly higher prevalence. There was no obvious evidence of increased lung cancer or mesothelioma in the village. The agent responsible for this apparently benign condition was not identified.

  5. Review on uremic toxins: classification, concentration, and interindividual variability.

    PubMed

    Vanholder, Raymond; De Smet, Rita; Glorieux, Griet; Argilés, Angel; Baurmeister, Ulrich; Brunet, Philippe; Clark, William; Cohen, Gerald; De Deyn, Peter Paul; Deppisch, Reinhold; Descamps-Latscha, Beatrice; Henle, Thomas; Jörres, Achim; Lemke, Horst Dieter; Massy, Ziad A; Passlick-Deetjen, Jutta; Rodriguez, Mariano; Stegmayr, Bernd; Stenvinkel, Peter; Tetta, Ciro; Wanner, Christoph; Zidek, Walter

    2003-05-01

    The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications. An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002. For all compounds, CU and/or CMAX exceeded CN. Molecular weight was lower than 500 D for 68 compounds; of the remaining 22 middle molecules, 12 exceeded 12,000 D. CU ranged from 32.0 ng/L (methionine-enkephalin) up to 2.3 g/L (urea). CU in the ng/L range was found especially for the middle molecules (10/22; 45.5%), compared with 2/68 (2.9%) for a molecular weight <500 D (P < 0.002). Twenty-five solutes (27.8%) were protein bound. Most of them had a molecular weight <500 D except for leptin and retinol-binding protein. The ratio CU/CN, an index of the concentration range over which toxicity is exerted, exceeded 15 in the case of 20 compounds. The highest values were registered for several guanidines, protein-bound compounds, and middle molecules, to a large extent compounds with known toxicity. A ratio of CMAX/CU <4, pointing to a Gaussian distribution, was found for the majority of the compounds (74/90; 82%). For some compounds, however, this ratio largely exceeded 4 [e.g., for leptin (6.81) or indole-3-acetic acid (10.37)], pointing to other influencing factors than renal function, such as gender, genetic predisposition, proteolytic breakdown, posttranslation modification, general condition, or nutritional status. Concentrations of retention solutes in uremia vary over a

  6. Senile Cardiac Calcification Syndrome: A Rare Case of Extensive Calcification of Left Ventricular Papillary Muscle

    PubMed Central

    Kim, Eun Jin; Song, Bong Gun; Sohn, Hyung Rae; Hong, Su-Min; Park, Dong Won; Heo, Seung Hye; Kim, Kye Yeon; Cho, Wook-Hyun; Choi, Suk-Koo

    2011-01-01

    Extensive papillary muscle calcification is uncommon and only scarce literature about causes and the clinical significance is available, whereas small calcific deposits are common findings in elderly people and are located most commonly at the apex. Papillary muscle calcification has been associated with coronary artery disease, dilated cardiomyopathy, mitral valve disease, hypercalcemia, and increased calcium phosphate product in end stage renal disease. We reported a rare case of extensive calcification of anterolateral papillary muscle diagnosed by echocardiography and multidetector computed tomography.

  7. Incidental Anterior Cruciate Ligament Calcification: Case Report.

    PubMed

    Hayashi, Hisami; Fischer, Hans

    2016-03-01

    The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding.

  8. [Positioning of bisphosphonates for vascular calcification].

    PubMed

    Okada, Yosuke; Mori, Hiroko; Tanaka, Yoshiya; Hashimoto, Osamu

    2010-11-01

    High-frequency severe atherosclerosis/calcinosis is observed in aging, diabetes mellitus and chronic dialysis, which leads to cardiovascular events. Recent progress in basic research has revealed certain similarities between processes of bone calcification and calcifications of vascular tissues which contribute to several cardiovascular diseases. These findings extend the link between bone remodeling and vascular calcification, opening perspectives toward novel therapeutic strategies, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.

  9. Calcification of thoracic aorta - solar eclipse sign.

    PubMed

    Dhoble, Abhijeet; Puttarajappa, Chethan

    2008-08-29

    Calcification of thoracic aorta is very common in old people, especially ones with hypertension. This can sometime be visible on plain chest radiograph. We present a case of a male patient who had extensive deposition of calcium in the thoracic aorta. The relationship between aortic calcification and coronary atherosclerosis remains contentious. Computed tomography of the thorax can display this calcification which appears like 'solar eclipse'.

  10. Incidental Anterior Cruciate Ligament Calcification: Case Report

    PubMed Central

    Hayashi, Hisami; Fischer, Hans

    2016-01-01

    The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding. PMID:27200163

  11. New concept of vascular calcification and metabolism.

    PubMed

    Nakagami, Hironori; Osako, Mariana K; Morishita, Ryuichi

    2011-01-01

    Vascular calcification is recently considered as one of the major complications and an independent risk factor of cardiovascular diseases. Although vascular calcification was commonly regarded as a passive process of mineral adsorption or precipitation, it tends to be an active process associated with the expression of growth factors, matrix proteins, and other bone-related proteins. There are 2 main types of vascular calcification. Intimal calcification is found in atherosclerotic plaques and is associated with the vascular events such as myocardial infarction. Medial calcification is usually associated with age and chronic kidney disease patients, which leads to increased vascular stiffness and reduced vascular compliance. Interestingly, our vascular calcification model using ApoE deficient mice showed intima calcification at sites of atherosclerotic plaques under high fat diet with ovariectomy. Thus, lipid metabolism is one of the therapeutic targets to prevent intima calcification of aorta. Previously we reported that ezetimibe significantly prevented atherosclerosis through lipid-lowering effects in ApoE-deficient mice. Based on these findings, we speculate that ezetimibe might prevent aortic intima calcification, which may give us the benefits to decrease vascular events.

  12. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    PubMed Central

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-01-01

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

  13. Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

    PubMed

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-09-03

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

  14. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in klotho deficient environment].

    PubMed

    Hasegawa, Tomoka; Yamamoto, Tomomaya; Hongo, Hiromi; Tsuboi, Kanako; Amizuka, Norio

    2015-05-01

    Klotho deficient (kl/kl) mice exhibit Möncheberg's vascular calcification in the tunica media due to hyperphosphatemia and hypercalcemia by mediating the disrupted signaling of FGF23/klotho axis. Recent studies have hypothesized the mechanism of medial vascular calcification : Vascular smooth muscle cells acquired excessive intake of phosphate ions undergo a phenotypic differentiation into osteoblasts and induce biological calcification in the tunica media. It is useful to clarify the underlying cellular mechanism of vascular calcification for the development of the treatment and preventive medicine. This review will introduce the histological and ultrastructual findings on medial vascular calcification in kl/kl mice.

  15. Isolated posterior cruciate ligament calcification

    PubMed Central

    Koukoulias, Nikolaos E; Papastergiou, Stergios G

    2011-01-01

    The authors present a case of calcified posterior cruciate ligament (PCL). A 61-year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra-articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID:22669889

  16. Silicon: a possible factor in bone calcification.

    PubMed

    Carlisle, E M

    1970-01-16

    Silicon, a relatively unknown trace element in nutritional research, has been uniquely localized in active calcification sites in young bone. Silicon increases directly with calcium at relatively low calcium concentrations and falls below the detection limit at compositions approaching hydroxyapatite. It is suggested that silicon is associated with calcium in an early stage of calcification.

  17. Aortic Valve Calcification in Mild Primary Hyperparathyroidism

    PubMed Central

    Iwata, Shinichi; Walker, Marcella Donovan; Di Tullio, Marco R.; Hyodo, Eiichi; Jin, Zhezhen; Liu, Rui; Sacco, Ralph L.; Homma, Shunichi

    2012-01-01

    Context: It is unclear whether cardiovascular disease is present in primary hyperparathyroidism (PHPT). Objective: Aortic valve structure and function were compared in PHPT patients and population-based controls. Design: This is a case-control study. Setting: The study was conducted in a university hospital metabolic bone disease unit. Participants: We studied 51 patients with PHPT and 49 controls. Outcome Measures: We measured the aortic valve calcification area and the transaortic pressure gradient. Results: Aortic valve calcification area was significantly higher in PHPT (0.24 ± 0.02 vs. 0.17 ± 0.02 cm2, p<0.01), although there was no difference in the peak transaortic pressure gradient, a functional measure of valvular calcification (5.6 ± 0.3 vs. 6.0 ± 0.3 mm Hg, P = 0.39). Aortic valve calcification area was positively associated with PTH (r = 0.34; P < 0.05) but not with serum calcium, phosphorus, or 25-hydroxyvitamin D levels or with calcium-phosphate product. Serum PTH level remained an independent predictor of aortic valve calcification area after adjustment for age, sex, body mass index, smoking status, history of hypercholesterolemia and hypertension, and estimated glomerular filtration rate. Conclusions: Mild PHPT is associated with subclinical aortic valve calcification. PTH, but not serum calcium concentration, predicted aortic valve calcification. PTH was a more important predictor of aortic valve calcification than well-accepted cardiovascular risk factors. PMID:22031523

  18. Vascular calcification: pathobiological mechanisms and clinical implications.

    PubMed

    Johnson, Rebecca C; Leopold, Jane A; Loscalzo, Joseph

    2006-11-10

    Once thought to result from passive precipitation of calcium and phosphate, it now appears that vascular calcification is a consequence of tightly regulated processes that culminate in organized extracellular matrix deposition by osteoblast-like cells. These cells may be derived from stem cells (circulating or within the vessel wall) or differentiation of existing cells, such as smooth muscle cells (SMCs) or pericytes. Several factors induce this transition, including bone morphogenetic proteins, oxidant stress, high phosphate levels, parathyroid hormone fragments, and vitamin D. Once the osteogenic phenotype is induced, cells gain a distinctive molecular fingerprint, marked by the transcription factor core binding factor alpha1. Alternatively, loss of inhibitors of mineralization, such as matrix gamma-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to vascular calcification. The normal balance between promotion and inhibition of calcification becomes dysregulated in chronic kidney disease, diabetes mellitus, atherosclerosis, and as a consequence of aging. Once the physiological determinants of calcification are perturbed, calcification may occur at several sites in the cardiovascular system, including the intima and media of vessels and cardiac valves. Here, calcification may occur through overlapping yet distinct molecular mechanisms, each with different clinical ramifications. A variety of imaging techniques are available to visualize vascular calcification, including fluoroscopy, echocardiography, intravascular ultrasound, and electron beam computed tomography. These imaging modalities vary in sensitivity and specificity, as well as clinical application. Through greater understanding of both the mechanism and clinical consequences of vascular calcification, future therapeutic strategies may be more effectively designed and applied.

  19. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome.

    PubMed

    Groves, Andrew P; Reich, Patrick; Sigdel, Binayak; Davis, T Keefe

    2016-08-01

    Pneumococcal-associated hemolytic uremic syndrome (pHUS) is a rare but severe complication of invasive Streptococcus pneumoniae infection. We report the case of a 12-year-old female with steroid-resistant nephrotic syndrome treated with adrenocorticotrophic hormone (H.P. Acthar(®) Gel), who developed pneumococcal pneumonia and subsequent pHUS. While nephrotic syndrome is a well-known risk factor for invasive pneumococcal disease, this is the first reported case of pHUS in an adolescent patient with nephrotic syndrome, and reveals novel challenges in the diagnosis, treatment and potential prevention of this complication.

  20. [Hemolytic uremic syndrome caused by enterohaemorrhagic Escherichia coli].

    PubMed

    Ibarra, Cristina; Goldstein, Jorge; Silberstein, Claudia; Zotta, Elsa; Belardo, Marcela; Repetto, Horacio A

    2008-10-01

    Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, plaquetopenia and kidney damage. It is the leading cause of acute renal failure in pediatric age and the second for chronic renal failure. Shiga toxin-producing Escherichia coli (STEC) is the first etiologic agent of HUS being its main reservoir cattle and transmitted via contaminated food. At present, there is no specific treatment to reduce the progression of HUS. The study of the mechanisms by which STEC infects and Shiga toxin induces HUS can help to find new strategies to prevent this disease.

  1. Recurrent Hemolytic and Uremic Syndrome Induced by Escherichia Coli

    PubMed Central

    Commereuc, Morgane; Weill, Francois-Xavier; Loukiadis, Estelle; Gouali, Malika; Gleizal, Audrey; Kormann, Raphaël; Ridel, Christophe; Frémeaux-Bacchi, Véronique; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    Abstract A widespread belief is that typical hemolytic and uremic syndrome (HUS) does not recur. We report the case of a patient infected twice with raw milk taken from his own cow and containing a Shiga toxin–producing Escherichia coli O174:H21 that induced recurrent HUS causing severe renal and cerebral disorders. A genomic comparison of the human and bovine Shiga toxin–producing Escherichia coli O174:H21 isolates revealed that they were identical. Typical HUS may recur. Since milk from this animal was occasionally distributed locally, thereby posing a serious threat for the whole village, this particular cow was destroyed. PMID:26735524

  2. Mechanisms and Clinical Consequences of Vascular Calcification

    PubMed Central

    Zhu, Dongxing; Mackenzie, Neil C. W.; Farquharson, Colin; MacRae, Vicky E.

    2012-01-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health. PMID:22888324

  3. Mechanisms of vascular calcification and associated diseases.

    PubMed

    Marulanda, Juliana; Alqarni, Saleh; Murshed, Monzur

    2014-01-01

    Mineralization of bone and tooth extracellular matrix (ECM) is a physiologic process, while soft tissue mineralization, also known as ectopic mineralization (calcification), is a pathologic condition. Vascular calcification is common in aging and also in a number of genetic and metabolic disorders. The calcific deposits in arteries complicate the prognosis and increase the morbidity in diseases such as atherosclerosis, diabetes and chronic kidney disease (CKD). To completely understand the pathophysiology of these lifethreatening diseases, it is critical to elucidate the molecular mechanisms underlying vascular calcification. Unveiling these mechanisms will eventually identify new therapeutic targets and also improve the management of the associated complications. In the current review, we discussed the common determinants of ECM mineralization, the mechanism of vascular calcification associated with several human diseases and outlined the most common therapeutic approaches to prevent its progression.

  4. Physiopathology of intratendinous calcific deposition

    PubMed Central

    2012-01-01

    In calcific tendinopathy (CT), calcium deposits in the substance of the tendon, with chronic activity-related pain, tenderness, localized edema and various degrees of decreased range of motion. CT is particularly common in the rotator cuff, and supraspinatus, Achilles and patellar tendons. The presence of calcific deposits may worsen the clinical manifestations of tendinopathy with an increase in rupture rate, slower recovery times and a higher frequency of post-operative complications. The aetiopathogenesis of CT is still controversial, but seems to be the result of an active cell-mediated process and a localized attempt of the tendon to compensate the original decreased stiffness. Tendon healing includes many sequential processes, and disturbances at different stages of healing may lead to different combinations of histopathological changes, diverting the normal healing processes to an abnormal pathway. In this review, we discuss the theories of pathogenesis behind CT. Better understanding of the pathogenesis is essential for development of effective treatment modalities and for improvement of clinical outcomes. PMID:22917025

  5. Calcification of the ligamentum arteriosum in adults: CT features

    SciTech Connect

    Wimpfheimer, O.; Haramati, L.B.; Haramati, N.

    1996-01-01

    The present study describes the frequency and pattern of ligamentum arteriosum calcification seen on chest CT in adults. We retrospectively reviewed 402 sequential unenhanced chest CT studies for ligamentum arteriosum calcification, atherosclerotic cardiac or aortic calcification, and granulomatous calcification. The pattern of calcification was characterized as curvilinear, punctate, or clumped. Mean patient age was 60 ({+-}18, range 18-97) years with 214 women (53%) and 188 men (47%). Of these patients 194 (48%) had calcification in the ligamentum arteriosum including 26 (6%) with calcification in the ligamentum arteriosum alone, 108 (27%) with atherosclerotic calcification, 11 (3%) with granulomatous calcification, and 49 (12%) with both. A total of 100 patients (25%) had no calcifications. In the study population 169 patients (42%) had atherosclerotic calcification, 32 (8%) had granulomatous calcification, and 75 (19%) had both. The patterns of calcification for the 26 patients with calcification of the ligamentum arteriosum alone were curvilinear (7 patients, 27%), punctate (17 patients, 65%), and clumped (2 patients, 8%). The pattern of ligamentum arteriosum calcification for the 108 patients with only atherosclerotic and ligamentum arteriosum calcification was curvilinear (28 patients, 26%), punctate (32 patients, 30%), and clumped (48 patients, 44%). The patients without any calcifications and the patients with ligamentum arteriosum calcification formed one group (based on their similarity in age, mean 47 years) with a prevalence of ligamentum arteriosum calcification of 21%. The patients with atherosclerotic and ligamentum arteriosum calcification formed a second group (mean age 71 years) with a prevalence of ligamentum arteriosum calcification of 65%. On unenhanced chest CT calcification of the ligamentum arteriosum is a common finding in adults and increases in prevalence with increasing age and atherosclerosis. 6 refs., 4 figs., 1 tab.

  6. Calcification

    MedlinePlus

    ... joints, and soft tissue tumors. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic ... PA: Elsevier Saunders; 2015:chap 26. Kumar V, Abbas AK, Aster JC. Cellular responses to stress and ...

  7. Serum Amyloid A in Uremic HDL Promotes Inflammation

    PubMed Central

    Kopecky, Chantal; Kubicek, Markus; Haidinger, Michael; Döller, Dominik; Katholnig, Karl; Suarna, Cacang; Eller, Philipp; Tölle, Markus; Gerner, Christopher; Zlabinger, Gerhard J.; van der Giet, Markus; Hörl, Walter H.; Stocker, Roland

    2012-01-01

    Uremia impairs the atheroprotective properties of HDL, but the mechanisms underlying why this occurs are unknown. Here, we observed that HDL isolated from healthy individuals inhibited the production of inflammatory cytokines by peripheral monocytes stimulated with a Toll-like receptor 2 agonist. In contrast, HDL isolated from the majority of patients with ESRD did not show this anti-inflammatory property; many HDL samples even promoted the production of inflammatory cytokines. To investigate this difference, we used shotgun proteomics to identify 49 HDL-associated proteins in a uremia-specific pattern. Proteins enriched in HDL from patients with ESRD (ESRD-HDL) included surfactant protein B (SP-B), apolipoprotein C-II, serum amyloid A (SAA), and α-1-microglobulin/bikunin precursor. In addition, we detected some ESRD-enriched proteins in earlier stages of CKD. We did not detect a difference in oxidation status between HDL isolated from uremic and healthy patients. Regarding function of these uremia-specific proteins, only SAA mimicked ESRD-HDL by promoting inflammatory cytokine production. Furthermore, SAA levels in ESRD-HDL inversely correlated with its anti-inflammatory potency. In conclusion, HDL has anti-inflammatory activities that are defective in uremic patients as a result of specific changes in its molecular composition. These data suggest a potential link between the high levels of inflammation and cardiovascular mortality in uremia. PMID:22282592

  8. FGF23 fails to inhibit uremic parathyroid glands.

    PubMed

    Canalejo, Rocío; Canalejo, Antonio; Martinez-Moreno, Julio Manuel; Rodriguez-Ortiz, M Encarnacion; Estepa, Jose C; Mendoza, Francisco Javier; Munoz-Castaneda, Juan Rafael; Shalhoub, Victoria; Almaden, Yolanda; Rodriguez, Mariano

    2010-07-01

    Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition.

  9. FGF23 Fails to Inhibit Uremic Parathyroid Glands

    PubMed Central

    Canalejo, Rocío; Canalejo, Antonio; Martinez-Moreno, Julio Manuel; Rodriguez-Ortiz, M. Encarnacion; Estepa, Jose C.; Mendoza, Francisco Javier; Munoz-Castaneda, Juan Rafael; Shalhoub, Victoria; Rodriguez, Mariano

    2010-01-01

    Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D3. FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal–regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal–regulated kinase 1/2–mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition. PMID:20431039

  10. An update on protein-bound uremic retention solutes.

    PubMed

    Vanholder, Raymond; Schepers, Eva; Pletinck, Anneleen; Neirynck, Nathalie; Glorieux, Griet

    2012-01-01

    Although protein-bound uremic retention solutes are recognized as 1 of the 3 main categories of uremic retention solutes, they only recently have been submitted to thorough analysis. In vitro and ex vivo data link both p-cresyl sulfate and indoxyl sulfate, two of the main compounds of this solute group, to negative impact on the cardiovascular system and progression of kidney failure. Recent in vivo observational data also relate concentration of these compounds to survival outcome, inflammation, and vascular disease in different, even moderate, stages of chronic kidney disease. Removal by different dialysis strategies, even high-flux hemodialysis, is difficult, and only by applying convection, some improvement of removal has been obtained. The other strategy with the potential to decrease concentration is by influencing intestinal generation and/or absorption. The sorbent Kremezin (AST-120) has been shown in controlled studies to decrease protein-bound solute concentration. In pilot controlled studies, AST-120 has been shown to be superior on outcome parameters to placebo. Results from large randomized trials are awaited, before these data can be considered as solid enough to warrant the recommendation to use these compounds for overall therapeutic purposes.

  11. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    PubMed

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-10-28

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process.

  12. Factor I Autoantibodies in Patients with Atypical Hemolytic Uremic Syndrome: Disease-Associated or an Epiphenomenon?

    PubMed Central

    Kavanagh, David; Pappworth, Isabel Y.; Anderson, Holly; Hayes, Christine M.; Moore, Iain; Hunze, Eva-Maria; Bennaceur, Karim; Roversi, Pietro; Lea, Susan; Strain, Lisa; Ward, Roy; Plant, Nick; Nailescu, Corina; Goodship, Timothy H. J.

    2012-01-01

    Summary Background and objectives Atypical hemolytic uremic syndrome is a disease associated with mutations in the genes encoding the complement regulators factors H and I. In addition, factor H autoantibodies have been reported in ∼10% of patients with atypical hemolytic uremic syndrome. This study searched for the presence of factor I autoantibodies in atypical hemolytic uremic syndrome. Design, setting, participants, & measurements This study screened 175 atypical hemolytic uremic syndrome patients for factor I autoantibodies using ELISA with confirmatory Western blotting. Functional studies using purified immunoglobulin from one patient were subsequently undertaken. Results Factor I autoantibodies were detected in three patients. In one patient with a high titer of autoantibody, the titer was tracked over time and was found to have no association with disease activity. This study found evidence of an immune complex of antibody and factor I in this patient, but purified IgG, isolated from current serum samples, had only a minor effect on fluid phase and cell surface complement regulation. Genetic analysis of the three patients with factor I autoantibodies revealed that they had two copies of the genes encoding factor H–related proteins 1 and 3 and therefore, did not have a deletion commonly associated with factor H autoantibodies in atypical hemolytic uremic syndrome. Two patients, however, had functionally significant mutations in complement factor H. Conclusions These findings reinforce the concept of multiple concurrent risk factors being associated with atypical hemolytic uremic syndrome but question whether autoantibodies per se predispose to atypical hemolytic uremic syndrome. PMID:22223611

  13. Plasmin Prevents Dystrophic Calcification After Muscle Injury.

    PubMed

    Mignemi, Nicholas A; Yuasa, Masato; Baker, Courtney E; Moore, Stephanie N; Ihejirika, Rivka C; Oelsner, William K; Wallace, Christopher S; Yoshii, Toshitaka; Okawa, Atsushi; Revenko, Alexey S; MacLeod, A Robert; Bhattacharjee, Gourab; Barnett, Joey V; Schwartz, Herbert S; Degen, Jay L; Flick, Matthew J; Cates, Justin M; Schoenecker, Jonathan G

    2017-02-01

    Extensive or persistent calcium phosphate deposition within soft tissues after severe traumatic injury or major orthopedic surgery can result in pain and loss of joint function. The pathophysiology of soft tissue calcification, including dystrophic calcification and heterotopic ossification (HO), is poorly understood; consequently, current treatments are suboptimal. Here, we show that plasmin protease activity prevents dystrophic calcification within injured skeletal muscle independent of its canonical fibrinolytic function. After muscle injury, dystrophic calcifications either can be resorbed during the process of tissue healing, persist, or become organized into mature bone (HO). Without sufficient plasmin activity, dystrophic calcifications persist after muscle injury and are sufficient to induce HO. Downregulating the primary inhibitor of plasmin (α2-antiplasmin) or treating with pyrophosphate analogues prevents dystrophic calcification and subsequent HO in vivo. Because plasmin also supports bone homeostasis and fracture repair, increasing plasmin activity represents the first pharmacologic strategy to prevent soft tissue calcification without adversely affecting systemic bone physiology or concurrent muscle and bone regeneration. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  14. Corneal calcification after amniotic membrane transplantation

    PubMed Central

    Anderson, S B; de Souza, R Ferreira; Hofmann-Rummelt, C; Seitz, B

    2003-01-01

    Background/aims: Amniotic membrane transplantation (AMT) has become well established as a treatment for chronic epithelial defects, conjunctival reconstruction, and partial limbal cell deficiency. The aim of this study was to describe cases of corneal calcification following AMT and to search for risk factors that might predispose to this unusual finding. Methods: Details of 117 AMTs on 93 corneas of 91 patients with a follow up period of at least 1 month performed since 1999 were collected prospectively. In those with calcification clinical photographs were studied and the medical records retrospectively examined. Results: 15 calcifications in 117 AMTs (12.8%) were identified, occurring 3–17 (median 6.1) weeks after AMT, during a follow up period of 4–151 (median 25) weeks. Overall epithelial healing rate was 83%. Calcification covered a surface area between 0.7–40.5 mm2 maximum size with varied morphology. The primary diagnosis was diverse. Risk factors included the use of phosphate eye drops and pre-existing calcification in the operative or other eye. No patient with a “patch” AMT developed calcification. Conclusions: Corneal calcification occurs after some cases of AMT. A common risk factor was the postoperative use of phosphate containing eye drops. PMID:12714401

  15. Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

    PubMed Central

    van den Brand, Jan A. J. G.; Mutsaers, Henricus A. M.; van Zuilen, Arjan D.; Blankestijn, Peter J.; van den Broek, Petra H.; Russel, Frans G. M.; Masereeuw, Rosalinde; Wetzels, Jack F. M.

    2016-01-01

    Background To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Methods Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. Results In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Conclusions Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated. PMID:28033375

  16. A Zebrafish Model for Uremic Toxicity: Role of the Complement Pathway

    PubMed Central

    Thurman, Josh; Reinecke, James; Raff, Amanda C.; Melamed, Michal L.; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W.; Hostetter, Thomas H

    2016-01-01

    Many organic solutes accumulate in ESRD and some are poorly removed removed with urea based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients pre-dialysis or from normal subjects. Zebrafish embryos 24 hours post fertilization were exposed to experimental media at a ratio of 3:1 water:human serum. Those exposed to serum from uremic subjects had significantly reduced survival at 8 hours (19% +/− 18% vs. 94% +/− 6%; p < 0.05, uremic serum vs control, respectively). Embryos exposed to serum from ESRD subjects fractionated at 50kD showed significantly greater toxicity with the larger molecular weight fraction (83% +/− 11% vs 7% +/−17% survival, p < 0.05, <50kD vs >50 kD, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96%+/− 5% vs 28%+/− 20% survival, p < 0.016, chelated vs non chelated serum respectively). Anti- factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98% +/− 6% vs. 3% +/− 9% survival, p < 0.016, anti- factor B treated vs non treated, respectively).Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and non-specific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. PMID:23689420

  17. A zebrafish model for uremic toxicity: role of the complement pathway.

    PubMed

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p < 0.05, uremic serum vs. control, respectively). Embryos exposed to serum from ESRD subjects fractionated at 50 kDa showed significantly greater toxicity with the larger molecular weight fraction (83 ± 11 vs. 7 ± 17% survival, p < 0.05, <50 vs. >50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement.

  18. Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

    PubMed

    van den Brand, Jan A J G; Mutsaers, Henricus A M; van Zuilen, Arjan D; Blankestijn, Peter J; van den Broek, Petra H; Russel, Frans G M; Masereeuw, Rosalinde; Wetzels, Jack F M

    2016-01-01

    To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

  19. Application of shape analysis to mammographic calcifications

    SciTech Connect

    Shen, L.; Rangayyan, R.M. . Dept. of Electrical and Computer Engineering); Desautels, J.E.L. . Dept. of Radiology)

    1994-06-01

    The authors have developed a set of shape factors to measure the roughness of contours of calcifications in mammograms and for use in their classification as malignant or benign. The analysis of mammograms is performed in three stages. First, a region growing technique is used to obtain the contours of calcifications. Then, three measures of shape features, including compactness, moments, and Fourier descriptors are computed for each region. Finally, their applicability for classification is studied by using the three shape measures to form feature vectors. Classification of 143 calcifications from 18 biopsy-proven cases as benign or malignant using the three measures with the nearest-neighbor method was 100% accurate.

  20. Distribution of calcification within the pineal gland.

    PubMed

    Pilling, J R; Hawkins, T D

    1977-11-01

    The distribution of calcification in the normal pineal gland was investigated by a macroradiographic in vitro technique. The centre of calcification in 72 out of 73 glands studied was within 2 mm of the mid-line of the gland. In one gland it lay 2.6 mm from the mid-line. These findings explain the accepted normal limits for pineal calcification on the standard semi-axial projection of the skull of up to 2 mm to either side of the mid-line and the occasional measurement in excess of this in normal subjects.

  1. Diffuse soft tissue calcification in tumoral calcinosis

    SciTech Connect

    Feldman, E.S.; Schumacher, H.R.; Dalinka, M.K.

    1981-10-01

    Tumoral calcinosis is a rare disease characterized biochemically by hyperphosphatemia, normocalcemia, and reduced fractional excretion of phosphate. Radiographically, it has been defined by the presence of large, amorphous juxtaarticular calcific deposits. A 53-year-old woman with tumoral calcinosis was found to have unusual diffuse soft tissue calcification indistinguishable from that usually seen in collagen vascular disease and previously referred to as calcinosis universalis. It is suggested that tumoral calcinosis is a misnomer as the calcification seen in patients with this disease may be 'tumoral' or diffuse.

  2. Cardiovascular calcification: current controversies and novel concepts.

    PubMed

    Ruiz, Jessica L; Hutcheson, Joshua D; Aikawa, Elena

    2015-01-01

    Cardiovascular calcification is a commonly observed but incompletely understood mechanism of increased atherosclerotic plaque instability and accelerated aortic valve stenosis. Traditional histological staining and imaging techniques are nonspecific for the type of mineral present in calcified tissues, information that is critical for proper validation of in vitro and in vivo models. This review highlights current gaps in our understanding of the biophysical implications and the cellular mechanisms of valvular and vascular calcification and how they may differ between the two tissue types. We also address the hindrances of current cell culture systems, discussing novel platforms and important considerations for future studies of cardiovascular calcification. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Uremic Toxins – Novel Arrhythmogenic Factor in Chronic Kidney Disease – Related Atrial Fibrillation

    PubMed Central

    Huang, Shih-Yu; Chen, Yi-Ann; Chen, Shih-Ann; Chen, Yi-Jen; Lin, Yung-Kuo

    2016-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. Chronic kidney disease (CKD) is associated with a high prevalence of AF, and uremic toxins are an important risk factor for cardiovascular diseases associated with CKD. Uremic toxins can produce pro-fibrotic, pro-hypertrophic, and pro-inflammatory effects on cardiac tissues and enhance oxidative stress or neurohormonal phenomena of cardiovascular injury, which are recognized as arrhythmogenic factors of AF. This article reviews the clinical, molecular, and electrophysiological data of uremic toxins in CKD considered to induce AF through multiple mechanisms on structural and electrical remodeling of the cardiovascular system. PMID:27274165

  4. Coral calcification in a changing ocean

    USGS Publications Warehouse

    Kuffner, Ilsa B.

    2010-01-01

    One of the goals of the Coral Reef Ecosystem Studies (CREST) project is to examine how calcification rates in reef-building corals and encrusting coralline algae are changing in response to changes in the ocean environment.

  5. Proton pumping accompanies calcification in foraminifera

    NASA Astrophysics Data System (ADS)

    Toyofuku, Takashi; Matsuo, Miki Y.; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

    2017-01-01

    Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

  6. Proton pumping accompanies calcification in foraminifera

    PubMed Central

    Toyofuku, Takashi; Matsuo, Miki Y.; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

    2017-01-01

    Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production. PMID:28128216

  7. Treating calcific aortic stenosis: an evolving science.

    PubMed

    Hull, Christine L

    2012-01-01

    Calcific aortic stenosis is a common valvular disease, but its pathophysiology remains undetermined and important considerations exist for treatment. Pathophysiology, treatment by the advanced practice nurse, and literature review are discussed in the context of a case study.

  8. Alendronate conjugated nanoparticles for calcification targeting.

    PubMed

    Li, Nanying; Song, Juqing; Zhu, Guanglin; Shi, Xuetao; Wang, Yingjun

    2016-06-01

    In this article, the synthesis of a novel calcification-targeting nanoparticle (NP) is reported, which is realized through dopamine self-polymerization on the poly(lactic-co-glycolic acid) (PLGA) particle surface and subsequent alendronate conjugation. Cell viability and proliferation tests confirmed that such particle has low cytotoxicity and good biocompatibility. Experiments were designed to observe whether the synthesized NPs can pass through an obstructive hydrogel and directly bind themselves to hydroxyapatite (HA) NPs (mimicking calcified spots) and HA porous scaffolds (mimicking calcified tissues); and the result was positive, indicating ingenious targeting of NPs on calcifications. The calcification-targeting NPs are expected to be with promising applications on calcification-related disease diagnoses and therapies. Copyright © 2016. Published by Elsevier B.V.

  9. Middle-Molecule Uremic Toxins and Outcomes in Chronic Kidney Disease.

    PubMed

    Massy, Ziad A; Liabeuf, Sophie

    2017-01-01

    In patients with chronic kidney disease (CKD), uremic toxins constitute a specific nontraditional risk factor. Research in this field started in the early 1990s, and a growing body of preclinical and epidemiological evidence suggests that elevated levels of uremic toxins are associated with poor outcomes in a CKD setting. The present review focuses on a specific class of uremic toxins (the "middle molecules"), which includes well-known candidates like beta-2 microglobulin and fibroblast growth factor 23. Here, we summarize the epidemiological evidence linking the middle-molecule uremic toxin (and especially the larger ones) with hard clinical end points. Our findings highlight the urgent need for clinical trials of interventions designed to decrease levels of these middle molecules in CKD patients. © 2017 S. Karger AG, Basel.

  10. Regulating in vivo calcification of alginate microbeads

    PubMed Central

    Lee, Christopher S.D.; Moyer, Hunter R.; Gittens, Rolando A.; Williams, Joseph K.; Boskey, Adele L.; Boyan, Barbara D.; Schwartz, Zvi

    2012-01-01

    Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium-crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1–6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mM bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification. PMID:20363022

  11. The Role of Epigenetics in Arterial Calcification

    PubMed Central

    Wu, Shan-Shan; Lin, Xiao; Yuan, Ling-Qing; Liao, Er-Yuan

    2015-01-01

    Arterial calcification is highly prevalent and correlated with cardiovascular mortality, especially in patients with ESRD or diabetes. The pathogenesis of arterial calcification is multifactorial, with both genetic and environmental factors being implicated. In recent years, several mechanisms contributing to arterial calcification have been proposed. However, these can only explain a small proportion of the variability in arterial calcification, which is a major obstacle for its prevention and management. Epigenetics has emerged as one of the most promising areas that may fill in some of the gaps in our current knowledge of the interaction between the environmental insults with gene regulation in the development of diseases. Epigenetics refers to heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Well-known components of epigenetic regulation include DNA methylation, histone modifications, and microRNAs. Epigenetics research in the regulation of arterial calcification has only recently been elucidated. In this review, we will summarise recent progress in epigenetic pathways involved in arterial calcification and discuss potential therapeutic interventions based on epigenetic mechanisms. PMID:26221588

  12. A comparative study of physiologic intracranial calcifications.

    PubMed

    Abbassioun, K; Aarabi, B; Zarabi, M

    1978-04-01

    It has been the impression of clinicians that pineal calcification is infrequent in Shiraz, Iran. In order to evaluate this clinical impression 2000 consecutive skul X-rays taken at Saadi Hospital, Shiraz, Iran, were reviewed for the presence of physiologic intracranial calcifications. The incidence of these clasifications in male and female in consecutive age groups of 10 years from 0 to over 70 years of age were assessed and compared with previous reports from other countries. The average incidence of pineal calcification for those over 20 years of age was 18.29% in this study compared with 55% in the U.S.A. The incidence of calcification in the choroid plexus and the falx cerebri was also considerably less than previously reported. The literature is reviewed and the possible causes for the geographical differences in the reported frequency of physiologic intracranial calcifications is discussed. It is possible that racial and dietary factors may be significant in the variation in the incidence of pineal and other cranial calcifications noted in different countries. Within a population group, age and sex are additional factors.

  13. Cellular Mechanisms of Aortic Valve Calcification

    PubMed Central

    Leopold, Jane A.

    2012-01-01

    Acquired aortic valve disease and valvular calcification is highly prevalent in adult populations worldwide and is associated with significant cardiovascular morbidity and mortality. At present, there are no medical therapies that will prevent or regress aortic valve calcification or stenosis and surgical or transcatheter aortic valve replacement remain the only effective therapies for treating this disease. In the setting of valve injury as a result of exposure to biochemical mediators or hemodynamic forces, normal homeostatic processes are disrupted resulting in extracellular matrix degradation, aberrant matrix deposition and fibrosis, inflammatory cell infiltration, lipid accumulation, and neoangiogenesis of the valve tissue and, ultimately, calcification of the valve. Calcification of the aortic valve is now understood to be an active process that involves the coordinated actions of resident valve endothelial and interstitial cells, circulating inflammatory and immune cells, and bone marrow-derived cells. These cells may undergo a phenotype transition to become osteoblast-like cells and elaborate bone matrix, endothelial-to-mesenchymal transition, and form matrix vesicles that serve as a nidus for microcalcifications. Each of these mechanisms has been shown to contribute to aortic valve calcification suggesting that strategies that target these cellular events may lead to novel therapeutic interventions to halt the progression or reverse aortic valve calcification. PMID:22896576

  14. Three-dimensional imaging of breast calcifications

    NASA Astrophysics Data System (ADS)

    Maidment, Andrew D. A.; Albert, Michael; Conant, Emily F.

    1998-03-01

    Approximately 50 percent of breast cancers are detected on the basis of calcifications alone. Regrettably, the presence of such calcifications is non-specific; only 30 percent of biopsies based on suspicious calcifications are malignant. We have investigated three methods (LVR) for 3D imaging and analysis of microcalcifications. Our aim is to increase specificity by more accurately distinguishing between calcifications indicative of benign and malignant breast lesions. We have demonstrated that 3D imaging of calcifications is possible using an LVR technique that includes semi-automated segmentation, correlation, and reconstruction of the calcifications. A clinical study of he LVR method is ongoing in which 2D film and digital images are compared to 3D images. The images are evaluated using a rating of 1 to 5, where 1 equals definitely benign, 5 equals definitely malignant, and a score of 3 or higher requires biopsy. To date, 3 radiologists have evaluated the images of 44 patients for which biopsy results were available. The use of 2D and 3D digital images resulted in doubling the diagnostic accuracy from 36 percent to 77 percent. Comparison to other techniques is ongoing. Additionally, a high resolution CT scanner for breast tissue specimens is under construction for comparison of the reconstructed images to a 'gold standard'.

  15. Regulating in vivo calcification of alginate microbeads.

    PubMed

    Lee, Christopher S D; Moyer, Hunter R; Gittens, Rolando A I; Williams, Joseph K; Boskey, Adele L; Boyan, Barbara D; Schwartz, Zvi

    2010-06-01

    Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium-crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1-6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mm bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification. (c) 2010 Elsevier Ltd. All rights reserved.

  16. Complements Spurned: Our Experience with Atypical Hemolytic Uremic Syndrome

    PubMed Central

    Nagar, Vidya S.; Chaterjee, Rudrarpan; Sood, Ankita; Sajjan, Basavaraj; Kaushik, Aniruddha; Vyahalkar, Sameer V.

    2017-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disorder resulting from a dysregulated activation of the alternative pathway of the complement system. It results in significant morbidity and mortality if not diagnosed and treated promptly. It lends itself to myriad renal and extrarenal manifestations, all potentially disabling. Eculizumab, a monoclonal antibody to complement C5 is now the widely accepted norm for treatment. However, in resource-limited settings, plasma exchange if instituted early may be as beneficial. We report a case of aHUS treated with extended plasma exchange with excellent results. Critical care monitoring is essential for the management of the disease in view of a tendency to develop multiple complications. Long-term immunosuppression may be successful in maintaining remission. PMID:28250608

  17. Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

    PubMed

    Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

    2017-09-25

    The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

  18. [Vitrectomy for retinal proliferation in childhood following hemolytic uremic syndrome].

    PubMed

    Wirths, G; Alnawaiseh, M; Eter, N

    2016-07-01

    The formation of retinal membranes can occur due to a variety of reasons but they are most commonly idiopathic due to the aging process. In addition, epiretinal and subretinal membranes can be formed after severe infections. The present case description shows the appearance of a retinal membrane after hemolytic uremic syndrome caused by Shiga toxin positive E. coli. The question arose whether the patient would benefit from vitrectomy with membrane peeling because of the presence of both epiretinal and subretinal gliotic changes. After the operation on the more severely affected right eye a morphological improvement could be achieved so that an operation on the left eye was also recommended. Judging by the course of this case vitrectomy with membrane peeling seems to be a useful instrument even for the simultaneous presence of subretinal and epiretinal membranes.

  19. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  20. Inhibition of microtubule formation by uremic toxins: action mechanism and hypothesis about the active component.

    PubMed

    Braguer, D; Gallice, P; Monti, J P; Murisasco, A; Crevat, A

    1986-04-01

    We show in vitro inhibitory effect of a mixture of uremic toxins on tubulin 6S polymerization. It proves the existence of a direct interaction protein-toxin where micro-tubule associated proteins are not involved. A similar phenomenom could occur in uremic neuropathy. The action mechanism of this interaction is quite different from that of classical tubulin inhibitors: Vinca alcaloïdes and colchicine. Finally we hypothesize about the active molecule.

  1. Bilateral basal ganglia and unilateral cortical involvement in a diabetic uremic patient.

    PubMed

    Yoon, Chang Hyo; Seok, Jung Im; Lee, Dong Kuck; An, Gee Sung

    2009-06-01

    We report a 57-year-old woman with uremic encephalopathy who presented with dysarthria, dysphagia, hypophonia, and drowsiness. The patient's radiologic findings were rather unusual in that magnetic resonance imaging (MRI) showed abnormal findings involving the basal ganglia bilaterally and frontal cortex unilaterally. After intensified hemodialysis, her symptoms and follow-up brain MRI showed marked improvement. We postulated that the underlying mechanism of uremic encephalopathy based on diffusion-weighted imaging and apparent diffusion coefficient maps.

  2. An oral adsorbent, AST-120, suppresses oxidative stress in uremic rats.

    PubMed

    Nakagawa, Naoki; Hasebe, Naoyuki; Sumitomo, Kazuhiro; Fujino, Takayuki; Fukuzawa, Jun; Hirayama, Tomoya; Kikuchi, Kenjiro

    2006-01-01

    The production of reactive oxygen species (ROS) has been suggested to play an important role in the progression of chronic kidney disease (CKD). An oral adsorbent, AST-120, removes uremic toxins such as indoxyl sulfate (IS) and delays the progression of CKD, but the effect on ROS production is unknown. The present study aimed to determine whether AST-120 reduces oxidative stress in uremic rat kidneys using markers of ROS production such as acrolein and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Daily administration of AST-120 was started 6 weeks after 5/6 nephrectomy and continued for 18 weeks. The changes in metabolic data, serum and urine IS levels, urinary excretion of markers of oxidative stress, and renal histological findings were investigated in uremic rats with or without AST-120 treatment. In parallel with the increase in serum and urine IS, the serum creatinine, urinary protein and acrolein levels started to increase at 6 weeks, but urinary 8-OHdG remained unchanged and significantly increased at 18 weeks in uremic rats. AST-120 markedly and significantly attenuated increases in uremic toxins and oxidative stress levels as well as the histological changes in glomerular sclerosis, interstitial fibrosis, and the tubular staining of 8-OHdG. AST-120 suppressed the progression of CKD, at least in part, via attenuation of oxidative stress induced by uremic toxin. Copyright (c) 2006 S. Karger AG, Basel.

  3. Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy.

    PubMed

    Wang, Xiaoliang; Liu, Jiang; Drummond, Christopher A; Shapiro, Joseph I

    2017-05-01

    Clinically, patients with significant reductions in renal function present with cardiovascular dysfunction typically termed, uremic cardiomyopathy. It is a progressive series of cardiac pathophysiological changes, including left ventricular diastolic dysfunction and hypertrophy (LVH) which sometimes progress to left ventricular dilation (LVD) and systolic dysfunction in the setting of chronic kidney disease (CKD). Uremic cardiomyopathy is almost ubiquitous in patients afflicted with end stage renal disease (ESRD). Areas covered: This article reviews recent epidemiology, pathophysiology of uremic cardiomyopathy and provide a board overview of Na/K-ATPase research with detailed discussion on the mechanisms of Na/K-ATPase/Src/ROS amplification loop. We also present clinical and preclinical evidences as well as molecular mechanism of this amplification loop in the development of uremic cardiomyopathy. A potential therapeutic peptide that targets on this loop is discussed. Expert opinion: Current clinical treatment for uremic cardiomyopathy remains disappointing. Targeting the ROS amplification loop mediated by the Na/K-ATPase signaling function may provide a novel therapeutic target for uremic cardiomyopathy and related diseases. Additional studies of Na/K-ATPase and other strategies that regulate this loop will lead to new therapeutics.

  4. Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy

    PubMed Central

    Wang, Xiaoliang; Liu, Jiang; Drummond, Christopher A

    2017-01-01

    Introduction Clinically, patients with significant reductions in renal function present with cardiovascular dysfunction typically termed, uremic cardiomyopathy. It is a progressive series of cardiac pathophysiological changes, including left ventricular diastolic dysfunction and hypertrophy (LVH) which sometimes progress to left ventricular dilation (LVD) and systolic dysfunction in the setting of chronic kidney disease (CKD). Uremic cardiomyopathy is almost ubiquitous in patients afflicted with end stage renal disease (ESRD). Areas covered This article reviews recent epidemiology, pathophysiology of uremic cardiomyopathy and provide a board overview of Na/K-ATPase research with detailed discussion on the mechanisms of Na/K-ATPase/Src/ROS amplification loop. We also present clinical and preclinical evidences as well as molecular mechanism of this amplification loop in the development of uremic cardiomyopathy. A potential therapeutic peptide that targets on this loop is discussed. Expert opinion Current clinical treatment for uremic cardiomyopathy remains disappointing. Targeting the ROS amplification loop mediated by the Na/K-ATPase signaling function may provide a novel therapeutic target for uremic cardiomyopathy and related diseases. Additional studies of Na/K-ATPase and other strategies that regulate this loop will lead to new therapeutics. PMID:28338377

  5. Acute Renal Infarction Secondary to Calcific Embolus from Mitral Annular Calcification

    SciTech Connect

    Bande, Dinesh; Abbara, Suhny; Kalva, Sanjeeva P.

    2011-06-15

    We report a case of a 62-year-old man who presented with right groin pain who subsequently was found to have a renal infarct secondary to calcific embolus from mitral annular calcification on CT and angiography. We briefly review the literature and discuss the importance of this entity in clinical practice.

  6. Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

    PubMed Central

    Hutcheson, Joshua D.; Burke, Megan F.; Martyn, Trejeeve; Thayer, Timothy E.; Shakartzi, Hannah R.; Buswell, Mary D.; Tainsh, Robert E.; Yu, Binglan; Bagchi, Aranya; Rhee, David K.; Wu, Connie; Derwall, Matthias; Buys, Emmanuel S.; Yu, Paul B.; Bloch, Kenneth D.; Aikawa, Elena; Bloch, Donald B.; Malhotra, Rajeev

    2016-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy. PMID:27284788

  7. Pseudohypoparathyroidism with basal ganglia calcification

    PubMed Central

    Song, Cheng-Yuan; Zhao, Zhen-Xiang; Li, Wei; Sun, Cong-Cong; Liu, Yi-Ming

    2017-01-01

    Abstract Rationale: Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. Patient concerns and diagnoses: A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection. The son of the patient was also examined and was diagnosed as pseudohypoparathyroidism, who had ever complained of the history of epilepsy. The clinical manifestations of parkinsonism of the patient was reevaluated after the supplement of serum calcium according to the diagnosis. Interventions and outcomes: The brain computed tomography revealed the basal ganglia calcification of the patient, accompanying by serum hypocalcemia and hyperphosphatemia. Loss of function mutation also confirmed the diagnosis. Five days after the therapy targeting at correction of serum hypocalcemia, the patient improved greatly in dyskinesia. Lessons: This study reported a patient presenting as acute reversible parkinsonism, who was finally diagnosed as pseudohypoparathyroidism. It indicated us that secondary parkinsonism should be carefully differentiated for its dramatic treatment effect. And the family history of seizures might be an indicator for the consideration of pseudohypoparathyroidism. PMID:28296742

  8. Imaging Patterns of Intratumoral Calcification in the Abdominopelvic Cavity

    PubMed Central

    Yu, Mi Hye; Park, Hee Sun; Jung, Sung Il; Jeon, Hae Jeong

    2017-01-01

    Intratumoral calcification is one of the most noticeable of radiologic findings. It facilitates detection and provides information important for correctly diagnosing tumors. In the abdominopelvic cavity, a wide variety of tumors have calcifications with various imaging features, though the majority of such calcifications are dystrophic in nature. In this article, we classify the imaging patterns of intratumoral calcification according to number, location, and morphology. Then, we describe commonly-encountered abdominopelvic tumors containing typical calcification patterns, focusing on their differentiable characteristics using the imaging patterns of intratumoral calcification. PMID:28246512

  9. Pandemic H1N1 influenza A viral infection complicated by atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage.

    PubMed

    Rhee, Harin; Song, Sang Heon; Lee, Yong Jae; Choi, Hyun Ju; Ahn, Jin Hee; Seong, Eun Young; Lee, Soo Bong; Kwak, Ihm Soo

    2011-12-01

    We report here on a case of a 27-year-old man with atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage associated with influenza A H1N1 infection. Treatment with oseltamivir, plasma exchange and hemodiafiltration for the hemolytic uremic syndrome and meticulous supportive care with steroid pulse therapy for the pulmonary alveolar hemorrhage was successful in this case. We discuss the relationship between hemolytic uremic syndrome and influenza A and the underlying immunologic factors that should be tested in a patient with atypical hemolytic uremic syndrome. We also discuss using steroid therapy for patients with H1N1-related diffuse alveolar hemorrhage.

  10. Idiopathic Arterial Calcification of Infancy: Case Report.

    PubMed

    Attia, Tarek Hamed; Abd Alhamed, Mohamed Maisara; Selim, Mohamed Fouad; Haggag, Mohamed Salah; Fathalla, Diaa

    2015-11-01

    Idiopathic arterial calcification of infancy is a rare autosomal recessive disease, characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima which causes luminal narrowing. Here we are reporting a case of idiopathic arterial calcification of infancy in a Saudi female newborn of non-consanguineous pregnant woman who had polyhydramnios. The newborn baby had severe respiratory distress, systemic hypertension and persistent pulmonary hypertension of newborn. She was admitted to Neonatal Intensive Care Unit, where she was ventilated and proper treatment was provided. Molecular genetic testing was positive for mutations of ectonucleotide pyrophosphatase/phosphodiesterase1 gene which is reported in 80% of cases of Idiopathic arterial calcification of infancy. The baby died at about 5 month of age because of myocardial ischemia and cardiorespiratory arrest. Idiopathic Arterial Calcification of Infancy should be considered in any newborn who presented with persistent pulmonary hypertension of newborn, severe systemic hypertension and echogenic vessels on any radiological study. Calcifications of large and medium-sized arteries are important diagnostic finding.

  11. Idiopathic Arterial Calcification of Infancy: Case Report

    PubMed Central

    Attia, Tarek Hamed; Abd Alhamed, Mohamed Maisara; Selim, Mohamed Fouad; Haggag, Mohamed Salah; Fathalla, Diaa

    2015-01-01

    Idiopathic arterial calcification of infancy is a rare autosomal recessive disease, characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima which causes luminal narrowing. Here we are reporting a case of idiopathic arterial calcification of infancy in a Saudi female newborn of non-consanguineous pregnant woman who had polyhydramnios. The newborn baby had severe respiratory distress, systemic hypertension and persistent pulmonary hypertension of newborn. She was admitted to Neonatal Intensive Care Unit, where she was ventilated and proper treatment was provided. Molecular genetic testing was positive for mutations of ectonucleotide pyrophosphatase/phosphodiesterase1 gene which is reported in 80% of cases of Idiopathic arterial calcification of infancy. The baby died at about 5 month of age because of myocardial ischemia and cardiorespiratory arrest. Idiopathic Arterial Calcification of Infancy should be considered in any newborn who presented with persistent pulmonary hypertension of newborn, severe systemic hypertension and echogenic vessels on any radiological study. Calcifications of large and medium-sized arteries are important diagnostic finding. PMID:27252793

  12. [Sturge-Weber syndrome with atypical calcifications].

    PubMed

    Prieto, M L; de Juan, J; Antón, M; Roiz, C; Crespo, M

    1997-09-01

    The syndrome, or disease, or Sturge Weber (SSW) is a neuro-ectodermic disorder of unknown incidence, sporadic presentation and specific sex incidence. It is characterized by the presence of a flat, facial angioma which affects at least the first branch of the trigeminal nerve, association with ipsilateral leptomeningeal vascular anomalies, one or more symptoms (epilepsy, hemiparesia, hemiplegia or mental retardation) and ipsilateral vascular lesions of the choroid which lead to glaucoma. As a consequence of lepto-meningeal involvement, homolateral cerebral hemi-atrophy develops together with cortico-subcortical calcifications with a characteristic "railway line" appearance. We present the case of a six month old girl with a flat port wine angioma on the left half of her face, including three branches of the trigeminal nerve and the left half of her body. She had partial motor crises of the right leg. On the cranial CT there were left periventricular calcifications and calcifications of the choroid plexus. Gadolinium-MR showed signs of left cerebral hemi-atrophy, which was confirmed on the cerebral SPECT (left temporal hypoperfusion). This case is interesting on account of the presence of atypical calcifications, both with regard to the sites and age of presentation. We emphasize the need for cranial CT to rule out the presence of calcifications, (as in this case) not seen on Xray of the skull or on MR. We favour the use of cerebral SPECT as a complementary diagnostic technique.

  13. Gallium-67 uptake in the lung associated with metastatic calcification

    SciTech Connect

    Auerbach, J.M.; Ho, J.

    1981-03-01

    The case of a patient in whom pulmonary calcification appeared rapidly, accompanied by diffuse gallium-67 uptake in the lungs is reported. This finding, associated with metastatic calcification in the absence of inflammation or neoplasm, has not been previously reported.

  14. Vascular Calcification: an Update on Mechanisms and Challenges in Treatment

    PubMed Central

    Wu, Meiting; Rementer, Cameron; Giachelli, Cecilia M.

    2013-01-01

    Vascular calcification is highly associated with cardiovascular disease mortality, particularly in high risk patients with diabetes and chronic kidney diseases (CKD). In blood vessels, intimal calcification is associated with atherosclerosis, whereas medial calcification is a non-occlusive process which leads to increased vascular stiffness and reduced vascular compliance. In the valves, calcification of the leaflets can change the mechanical properties of the tissue and result in stenosis. For many decades, vascular calcification has been noted as a consequence of aging. Studies now confirm that vascular calcification is an actively regulated process and shares many features with bone development and metabolism. This review provides an update on the mechanisms of vascular calcification including the emerging roles of the RANK/RANKL/OPG triad, osteoclasts and microRNAs. Potential treatments adapted from osteoporosis and CKD treatments that are under investigation for preventing and/or regressing vascular calcification will also be reviewed. PMID:23456027

  15. Dark calcification and the daily rhythm of calcification in the scleractinian coral, Galaxea fascicularis

    NASA Astrophysics Data System (ADS)

    Al-Horani, F. A.; Tambutté, É.; Allemand, D.

    2007-09-01

    The rate of calcification in the scleractinian coral Galaxea fascicularis was followed during the daytime using 45Ca tracer. The coral began the day with a low calcification rate, which increased over time to a maximum in the afternoon. Since the experiments were carried out under a fixed light intensity, these results suggest that an intrinsic rhythm exists in the coral such that the calcification rate is regulated during the daytime. When corals were incubated for an extended period in the dark, the calcification rate was constant for the first 4 h of incubation and then declined, until after one day of dark incubation, calcification ceased, possibly as a result of the depletion of coral energy reserves. The addition of glucose and Artemia reduced the dark calcification rate for the short duration of the experiment, indicating an expenditure of oxygen in respiration. Artificial hypoxia reduced the rate of dark calcification to about 25% compared to aerated coral samples. It is suggested that G. fascicularis obtains its oxygen needs from the surrounding seawater during the nighttime, whereas during the day time the coral exports oxygen to the seawater.

  16. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies.

    PubMed

    Proudfoot, D; Skepper, J N; Hegyi, L; Bennett, M R; Shanahan, C M; Weissberg, P L

    2000-11-24

    The mechanisms involved in the initiation of vascular calcification are not known, but matrix vesicles, the nucleation sites for calcium crystal formation in bone, are likely candidates, because similar structures have been found in calcified arteries. The regulation of matrix vesicle production is poorly understood but is thought to be associated with apoptotic cell death. In the present study, we investigated the role of apoptosis in vascular calcification. We report that apoptosis occurs in a human vascular calcification model in which postconfluent vascular smooth muscle cell (VSMC) cultures form nodules spontaneously and calcify after approximately 28 days. Apoptosis occurred before the onset of calcification in VSMC nodules and was detected by several methods, including nuclear morphology, the TUNEL technique, and external display of phosphatidyl serine. Inhibition of apoptosis with the caspase inhibitor ZVAD.fmk reduced calcification in nodules by approximately 40%, as measured by the cresolphthalein method and alizarin red staining. In addition, when apoptosis was stimulated in nodular cultures with anti-Fas IgM, there was a 10-fold increase in calcification. Furthermore, incubation of VSMC-derived apoptotic bodies with (45)Ca demonstrated that, like matrix vesicles, they can concentrate calcium. These observations provide evidence that apoptosis precedes VSMC calcification and that apoptotic bodies derived from VSMCs may act as nucleating structures for calcium crystal formation.

  17. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

    PubMed

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-18

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

  18. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Bisphosphonates for vascular calcification].

    PubMed

    Kurozumi, Akira; Okada, Yosuke; Nakano, Kazuhisa; Tanaka, Yoshiya

    2015-05-01

    In Japan, the number of diabetes mellitus and chronic kidney disease patients is increasing yearly. Vascular calcification is prevailing in patients suffering from diabetes mellitus and/or chronic kidney disease, and carries a poor prognosis. However, the effective treatment for suppressing the progression of vascular calcification has not been established. On the other hand, treatment of osteoporosis has advanced dramatically as the details of the mechanism become clearer. Bisphosphonates, which are inhibitors of bone resorption that are widely used to treat osteoporosis, also inhibit cholesterol biosynthesis, differentiation of macrophage to foam cell, differentiation of smooth muscle cells to osteoblast-like cells in certain stimuli during calcification processes of vessels. These findings extend the link between bone remodeling and vascular calcification, opening perspectives toward novel therapeutic strategies. We herein review recent findings about effectiveness of bisphosphonates for vascular calcification with our data. Here we will review recent advances in the researches of treatment of vascular calcification and present our findings that the bisphosphonate is useful in prevention of vascular calcification.

  19. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  20. Regulatory Circuits Controlling Vascular Cell Calcification

    PubMed Central

    Sallam, Tamer; Cheng, Henry; Demer, Linda L.; Tintut, Yin

    2013-01-01

    Vascular calcification is a common feature of chronic kidney disease, cardiovascular disease, and aging. Such abnormal calcium deposition occurs in medial and/or intimal layers of blood vessels as well as in cardiac valves. Once considered a passive and inconsequential finding, the presence of calcium deposits in the vasculature is widely accepted as a predictor of increased morbidity and mortality. Recognition of the importance of vascular calcification in health is driving research into mechanisms that govern its development, progression, and regression. Diverse, but highly interconnected factors, have been implicated, including disturbances in lipid metabolism, oxidative stress, inflammatory cytokines, and mineral and hormonal balances, which can lead to formation of osteoblast-like cells in the artery wall. A tight balance of procalcific and anticalcific regulators dictates the extent of disease. In this review, we focus on the main regulatory circuits modulating vascular cell calcification. PMID:23269436

  1. Fibroblast involvement in soft connective tissue calcification

    PubMed Central

    Ronchetti, Ivonne; Boraldi, Federica; Annovi, Giulia; Cianciulli, Paolo; Quaglino, Daniela

    2013-01-01

    Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of pseudoxanthoma elasticum (PXE) patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibers and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization. PMID:23467434

  2. [Sclerochoroidal calcification associated with hypovitaminosis D].

    PubMed

    Sierra-Rodríguez, M A; Bailez Fidalgo, C; Sáenz-Francés, F; Gonzalez Romero, J C; Muñoz Bellido, L

    2014-07-01

    A 69 year-old woman was referred for a routine visit, during which funduscopy revealed white-yellow subretinal lesions in the superotemporal mid-periphery of both eyes. A and B scan ultrasound showed hyperechogenic lesions located at scleral and choroidal level. Computed tomography revealed posterolateral sclerochoroidal calcifications. Metabolic studies showed a severe vitamin D deficiency with no other remarkable findings. Sclerochoroidal calcifications are an infrequent finding that occur as a result of calcium deposit at scleral and choroidal level. They have a characteristic clinical picture and are idiopathic in most cases, but may be associated with some systemic diseases, such as calcium and phosphorous metabolic disorders; this fact warrants a thorough metabolic study. We report a case of bilateral sclerochoroidal calcifications associated with severe vitamin D deficiency with no other significant metabolic findings. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  3. [Arterial calcification and risk of cardiovascular events in diabetes mellitus].

    PubMed

    Iwai, Kunimitu; Morimoto, Shigeto

    2010-11-01

    The cohort studies reported the subclinical vascular calcification including atheroslerosis starts during prediabetic state characterized by impaired fasting glucose. In the cardiovascular systems of diabetes mellitus there is an original mechanism to induce the medial calcification other than intimal calcification observed in the classical atherosclerosis. This is characterized as the ectipic osteogenesis induced by paracrine signals from inflammatory lesions in the adventitia. On the other hand, many internal systems have been discovered to inhibit vascular calcification.

  4. Extensive pelvic calcification in association with ovarian serous cystadenofibroma.

    PubMed

    Hayes, Stephen J; Misfar, Nasira; Slade, Richard; Mamtora, Hari; Wilson, Godfrey

    2008-08-01

    We describe the first reported case of extensive calcification seen in association with serous cystadenofibroma of the ovary, illustrating that calcification in the female genital tract may be extensive in nature, presenting in a fashion that is not entirely typical of dystrophic or metastatic calcification. This case demonstrates that extensive calcification within the pelvis should be interpreted with caution, as it may not represent disseminated malignancy.

  5. Calcific band keratopathy in an alpaca.

    PubMed

    Pucket, Jonathan D; Boileau, Melanie J; Sula, Mee Ja M

    2014-07-01

    A 4-year-old female Suri alpaca was presented for evaluation of acute onset weakness, lethargy, and recent development of opacities in both eyes. On ophthalmic examination, bilaterally symmetrical corneal opacities were noted along the interpalpebral fissures with a few corneal blood vessels intermingled. A presumed diagnosis of calcific band keratopathy was made based on location and appearance. The patient was euthanized a short while after diagnosis due to reasons unrelated to the eyes and histologic examination of the corneas revealed subepithelial calcium and vascularization, consistent with calcific band keratopathy. This case report is the first to document this ocular condition in an alpaca.

  6. Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients

    PubMed Central

    2013-01-01

    Background Process of accelerated atherosclerosis specific for uremia increases cardiovascular risk in patients with chronic kidney disease (CKD) and may be influenced by the different structure of arteries. The study assesses the influence of traditional and novel risk factors on calcification of coronary arteries (CAC) and abdominal aorta (AAC) in hemodialysis patients (HD). Methods CAC and AAC were assessed by CT in 104 prevalent adult HD and 14 apparently healthy subjects with normal kidney function (control group). Mineral metabolism parameters, plasma levels of FGF-23, MGP, osteoprotegerin, osteopontin, fetuin-A, CRP, IL-6 and TNF-α were measured. Results CAC and AAC (calcification score ≥ 1) were found in 76 (73.1%) and 83 (79.8%) HD respectively, more frequent than in the control group. In 7 HD with AAC no CAC were detected. The frequency and severity of calcifications increased with age. Both CAC and AAC were more frequently detected in diabetics (OR = 17.37 and 13.00, respectively). CAC score was significantly greater in males. CAC and AAC scores were correlated significantly with pack-years of smoking and plasma osteoprotegrin levels. However the independent contribution of plasma osteoprotegerin levels was not confirmed in multiple regression analysis. Age (OR = 1.13) and hemodialysis vintage (OR = 1.14) were the independent risk factor favoring the occurrence of CAC; while age (OR = 1.20) was the only predictor of AAC occurrence in HD. Conclusions 1. AAC precedes the occurrence of CAC in HD patients. 2. The exposition to uremic milieu and systemic chronic microinflammation has more deteriorative effect on the CAC than the AAC. PMID:23317172

  7. A Comparison of Uremic Pruritus in Patients Receiving Peritoneal Dialysis and Hemodialysis

    PubMed Central

    Wu, Hon-Yen; Peng, Yu-Sen; Chen, Hung-Yuan; Tsai, Wan-Chuan; Yang, Ju-Yeh; Hsu, Shih-Ping; Pai, Mei-Fen; Lu, Hui-Min; Chiang, Ju-Fen; Ko, Mei-Ju; Wen, Su-Ying; Chiu, Hsien-Ching

    2016-01-01

    Abstract Uremic pruritus is common and bothersome in patients receiving either peritoneal dialysis (PD) or hemodialysis (HD). To date, the preferred dialysis modality regarding the alleviation of uremic pruritus remains controversial. We conducted this cross-sectional study to compare the prevalence, intensity, and characteristics of uremic pruritus between PD and HD patients. Patients receiving maintenance dialysis at a referral medical center in Taiwan were recruited. Dialysis modality, patient demographic, clinical characteristics, and laboratory data were recorded. The intensity of uremic pruritus was measured using visual analogue scale (VAS) scores. Multivariate linear regression analysis was conducted to compare the severity of uremic pruritus between PD and HD patients. Generalized additive models were applied to detect nonlinear effects between pruritus intensity and continuous covariates. A total of 380 patients completed this study, with a mean age of 60.3 years and 49.2% being female. Uremic pruritus was presented in 24 (28.6%) of the 84 PD patients and 113 (38.2%) of the 296 HD patients (P = .12). The VAS score of pruritus intensity was significantly lower among the PD patients than the HD patients (1.32 ± 2.46 vs 2.26 ± 3.30, P = .04). Multivariate linear regression analysis showed that PD was an independent predictor for lower VAS scores of pruritus intensity compared with HD (β-value −0.88, 95% confidence interval −1.62 to −0.13). The use of active vitamin D was also an independent predictor for a lower intensity of uremic pruritus, whereas hyperphosphatemia and higher serum levels of triglyceride and aspartate transaminase were significantly associated with higher pruritus intensity. There was a trend toward a less affected body surface area of uremic pruritus in the PD patients than in the HD patients, but the difference did not reach statistical significance (P = .13). In conclusion, the severity of uremic pruritus

  8. [Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome].

    PubMed

    Cubillos C, María Paz; Del Salas, Paulina; Zambrano, Pedro O

    2015-01-01

    Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  9. [Enterohemorrhagic Escherichia coli and hemolytic-uremic syndrome in Argentina].

    PubMed

    Rivero, Mariana A; Padola, Nora L; Etcheverría, Analía I; Parma, Alberto E

    2004-01-01

    The hemolytic-uremic syndrome (HUS) is a multisystemic disorder that is characterized by the onset of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. It is the most common cause of acute renal failure and the second cause of chronic renal failure and renal transplantation in children in Argentina. Our country has the highest incidence of HUS in the world, with approximately 420 new cases observed each year with an incidence of 12.2 cases per 100,000 children in the age group 0-5 years. Numerous etiologic factors have been associated with HUS but the infection with enterohemorrhagic Escherichia coli (EHEC) is considered the most common cause. The majority of outbreaks and sporadic cases in humans have been associated with serotype O157:H7, although other O:H serotypes have been isolated, and they are a subgroup of Verocytotoxin-producing Escherichia coli (VTEC). Cattle are the principal reservoir of VTEC. Infections in humans are a consequence of consumption of undercooked meat, raw milk and other contaminated food or water. Direct contact with animals or people infected is another source of infection.

  10. Acute Neurological Involvement in Diarrhea-Associated Hemolytic Uremic Syndrome

    PubMed Central

    Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-01-01

    Background and objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). Design, setting, participants, & measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability. PMID:20498239

  11. [Incomplete hemolytic uremic syndrome associated with partial factor H deficiency].

    PubMed

    Olaciregui Echenique, I; Areses Trapote, R; Ubetagoyena Arrieta, M; Sota Busselo, I; García Pardos, C; Echaniz Aizpuru, P

    2007-02-01

    Hemolytic uremic syndrome (HUS) consists of the association of hemolytic anemia, thrombocytopenia and renal failure. Most cases are related to toxins (verotoxins) produced by Escherichia coli 0157:H7 and generally have good renal prognosis. Atypical forms can occur, with a less favorable prognosis, and can be due to mutations in the gene codifying factor H, a protein that regulates activation of the alternative complement pathway, among other causes. Factor H deficiency produces continuous complement activation, causing injury to capillary endothelial cells. We report a case of incomplete (absence of thrombocytopenia and uremia), atypical HUS in which hypocomplementemia secondary to partial factor H deficiency was detected, with favorable outcome. Prior to symptom onset, the patient had a Campylobacter infection, precipitating the symptoms. Genetic analysis showed a heterozygous mutation (C846T) located in the SCR4 domain, generating an amino acid change in the factor H molecule (Pro240Leu). This mutation may have been the cause of the partial factor H deficiency and the patient's symptoms on admission.

  12. Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats.

    PubMed

    Yamazaki-Nakazawa, Ai; Mizobuchi, Masahide; Ogata, Hiroaki; Kumata, Chiaki; Kondo, Fumiko; Ono, Naoko; Koiwa, Fumihiko; Uda, Susumu; Kinugasa, Eriko; Akizawa, Tadao

    2014-02-01

    Hyperphosphatemia is associated with cardiovascular disease in patients with chronic kidney disease. To examine the effects of correction of hyperphosphatemia, we investigated the association between phosphate metabolism and cardiac remodeling in uremic rats. Four groups were studied for 8 weeks: (1) control (sham), (2) 5/6 nephrectomized (Nx) rats fed a normal phosphate regular diet (Nx + NP), (3) Nx rats fed a high phosphate (1.2 %) diet (Nx + HP), and (4) Nx rats fed a high phosphate diet containing 2 % lanthanum carbonate (Nx + HP + La). The relationship between phosphate metabolism and cardiac remodeling was analyzed. Nx + HP rats showed a significant increase in serum phosphate and PTH compared with Nx + NP rats, while Nx + HP + La rats showed slight decreases in these levels. Both Nx + HP and Nx + HP + La rats showed a significant increase in fibroblast growth factor-23 (FGF23) compared with Nx + NP rats. Urinary phosphate excretion showed a similar trend to that of FGF23. Nx + HP rats showed a significant increase in LV weight and matrix deposition compared with Nx + NP rats, and this increase was also significantly suppressed in Nx + HP + La rats. Serum phosphate levels and PTH were significantly correlated with LV weight and matrix deposition, but FGF23 levels did not show the correlation. FGF23 had a high correlation with urinary phosphate excretion. These results suggest that correction of hyperphosphatemia by lanthanum carbonate could suppress cardiac remodeling independently of changes in FGF23.

  13. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome

    PubMed Central

    Lemaire, Mathieu; Frémeaux-Bacchi, Véronique; Schaefer, Franz; Choi, Murim; Tang, Wai Ho; Le Quintrec, Moglie; Fakhouri, Fadi; Taque, Sophie; Nobili, François; Martinez, Frank; Ji, Weizhen; Overton, John D.; Mane, Shrikant M.; Nürnberg, Gudrun; Altmüller, Janine; Thiele, Holger; Morin, Denis; Deschenes, Georges; Baudouin, Véronique; Llanas, Brigitte; Collard, Laure; Majid, Mohammed A.; Simkova, Eva; Nürnberg, Peter; Rioux-Leclerc, Nathalie; Moeckel, Gilbert W.; Gubler, Marie Claire; Hwa, John; Loirat, Chantal; Lifton, Richard P.

    2013-01-01

    Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure1. Atypical HUS (aHUS) can result from genetic or autoimmune factors2 that lead to pathologic complement cascade activation3. By exome sequencing we identify recessive mutations in DGKE (diacylglycerol kinase epsilon) that co-segregate with aHUS in 9 unrelated kindreds, defining a distinctive Mendelian disease. Affected patients present with aHUS before age 1, have persistent hypertension, hematuria and proteinuria (sometimes nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets, and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C, which promotes thrombosis. DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a pro-thrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treatment of aHUS patients. PMID:23542698

  14. Urea, a true uremic toxin: the empire strikes back.

    PubMed

    Lau, Wei Ling; Vaziri, Nosratola D

    2017-01-01

    Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8-10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation. Urea induces apoptosis of vascular smooth muscle cells as well as endothelial dysfunction, thus directly promoting cardiovascular disease. Further, urea stimulates oxidative stress and dysfunction in adipocytes, leading to insulin resistance. Finally, there are widespread indirect effects of elevated urea as a result of the carbamylation reaction, where isocyanic acid (a product of urea catabolism) alters the structure and function of proteins in the body. Carbamylation has been linked with renal fibrosis, atherosclerosis and anaemia. In summary, urea is a re-emerging Dark Force in CKD pathophysiology. Trials examining low protein diet to minimize accumulation of urea and other toxins suggest a clinical benefit in terms of slowing progression of CKD. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  15. Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome.

    PubMed

    Nathanson, Sylvie; Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-07-01

    Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability.

  16. Extrarenal Manifestations in Shigatoxin-associated Haemolytic Uremic Syndrome.

    PubMed

    Matthies, J; Hünseler, C; Ehren, R; Volland, R; Körber, F; Hoppe, B; Weber, L T; Habbig, S

    2016-07-01

    Shigatoxin-associated haemolytic uremic syndrome (STEC-HUS) is the most frequent cause of acute kidney injury in children worldwide. Extrarenal manifestations are the main determinants for both, short- and long-term prognosis of patients with STEC-HUS. 46 patients treated over the last 10 years for STEC-HUS in a single center. This retrospective study analysed the incidence and outcome of extrarenal manifestations in our cohort of children with STEC-HUS. Risk factors for extrarenal involvement and adverse outcome were assessed by detailed chart review. Eleven extrarenal manifestations occurred in 9/46 patients comprising 8 neurological, 2 gastro-intestinal, and 1 cardiovascular complication. One patient died from cerebral bleeding. Liver transplantation was required in a girl 18 months after HUS due to secondary sclerosing cholangitis. PATIENTS with extrarenal manifestations were significantly younger and presented with higher leucocyte counts and higher alanine aminotransferase levels at admission. Renal replacement therapy was necessary for a longer period than in patients without extrarenal complications. Extrarenal manifestations occurred in about 20% of our patients with STEC-HUS. The identification of risk-factors will help to provide a better management of these patients which might also include novel treatment strategies like complement inhibition. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Long-term outcomes of Shiga toxin hemolytic uremic syndrome.

    PubMed

    Spinale, Joann M; Ruebner, Rebecca L; Copelovitch, Lawrence; Kaplan, Bernard S

    2013-11-01

    Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI). The outcomes of STEC HUS have improved, and the acute mortality rate in children is 1-4%. About 70% of patients recover completely from the acute episode and the remainder have varying degrees of sequelae. Only a few retrospective studies have reviewed these patients over long periods. Methodological flaws include a lack of strict definitions, changing modes of treatment, ascertainment bias and loss of subjects to follow-up. The kidneys bear the brunt of the long-term damage: proteinuria (15-30% of cases); hypertension (5-15%); chronic kidney disease (CKD; 9-18%); and end-stage kidney disease (ESKD; 3%). A smaller number have extra-renal sequelae: colonic strictures, cholelithiasis, diabetes mellitus or brain injury. Most renal sequelae are minor abnormalities, such as treatable hypertension and/or variable proteinuria. Most of the patients who progress to ESKD do not recover normal renal function after the acute episode. Length of anuria (more than 10 days) and prolonged dialysis are the most important risk factors for a poor acute and long-term renal outcome. After the acute episode all patients must be followed for at least 5 years, and severely affected patients should be followed indefinitely if there is proteinuria, hypertension or a reduced glomerular filtration rate (GFR).

  18. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2013-01-01

    Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both “traditional therapy” (including plasma therapy, kidney and kidney-liver transplantation) and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy. PMID:24255888

  19. Microbiota and prebiotics modulation of uremic toxin generation.

    PubMed

    Koppe, Laetitia; Fouque, Denis

    2017-06-01

    Recent data have shown that the host-intestinal microbiota interaction is intrinsically linked with overall health. Chronic kidney disease (CKD) could influence intestinal microbiota and gut dysbiosis is also considered as a cause of progression of kidney disease. An increasing body of evidence indicates that dysbiosis is a key contributor of uremic retention solutes (URS) accumulating in patients with CKD. The discovery of the kidney-gut axis has created new therapeutic opportunities for nutritional intervention in order to prevent adverse outcomes. One of these strategies is prebiotics, which refers to nondigestible food ingredients or substances that beneficial affect growth and/or activity of limited health-promoting bacteria in the gastrointestinal tract. The influence of prebiotics on the production and concentration of URS have been investigated in various animal and human CKD studies. However, to date, there is still paucity of high-quality intervention trials. Randomized controlled trials and adequately powered intervention studies are needed before recommending prebiotics in clinical practice. This review will outline the interconnection between CKD progression, dysbiosis and URS production and will discuss mechanisms of action and efficacy of prebiotics as a new CKD management tool, with a particular emphasis on URS generation.

  20. [Role of the Shiga toxin in the hemolytic uremic syndrome].

    PubMed

    Creydt, Virginia Pistone; Nuñez, Pablo; Boccoli, Javier; Silberstein, Claudia; Zotta, Elsa; Goldstein, Jorge; Ibarra, Cristina

    2006-01-01

    In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed.

  1. Protein-bound uremic solutes: the forgotten toxins.

    PubMed

    Vanholder, R; De Smet, R; Lameire, N

    2001-02-01

    The present concept of dialysis focuses mainly on the removal of small water-soluble compounds, and also, the currently applied kinetic parameters of dialysis adequacy are based on the behavior of water-soluble compounds. Nevertheless, many of the currently known biological effects in uremia are attributable to compounds with different physicochemical characteristics, and among these, protein-bound solutes play an important role. In this article, we review the characteristics and consequences of changes in protein binding in uremia, as well as the toxicity of the protein-bound uremic solutes 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indoxyl sulfate, hippuric acid, homocysteine, and p-cresol. Starting from the example of p-cresol, we then summarize the impact of protein-binding on dialytic removal, whereby it is concluded that this removal is largely hampered by this protein-binding compared with that of classic markers such as urea and creatinine. Alternative removal strategies, such as strategies to modify intestinal generation or absorption, are considered.

  2. Pleural effusion complicating acute peritoneal dialysis in hemolytic uremic syndrome.

    PubMed

    Butani, L; Polinsky, M S; Kaiser, B A; Baluarte, H J

    1998-11-01

    Hemolytic uremic syndrome (HUS) is a leading cause of acute renal failure (ARF) in children, and one for which treatment with peritoneal dialysis (PD) is often necessary. Between January 1982 and December 1996, 176 children received PD for ARF at St. Christopher's Hospital for Children; 34 (19%) of whom had HUS. Of these 34, 7 (20%) developed pleural effusions (PE) while receiving PD, whereas none of the remaining 142 children with other causes of ARF did so. The mean age of the 7 affected children was 5.2 (range 0.4-17) years; none had heart failure or nephrotic syndrome, nor had any of them undergone thoracic surgery. PE were diagnosed by chest radiograph at an interval of 2 (range 1-3) days after starting PD. Thereafter, 4 (57%) patients were successfully maintained on a modified PD prescription; 2 others were converted to hemodialysis and 1 to continuous venovenous hemodiafiltration. Although PE are a known complication of PD, none of the patients so treated for non-HUS related ARF developed them. Whether they represent a purely mechanical complication of PD, or are in some way attributable to HUS itself, is not entirely clear. Regardless, when children with HUS require PD, physicians should monitor for the development of this potential complication to minimize the risk of serious respiratory compromise.

  3. Adsorption capacity of poly(ether imide) microparticles to uremic toxins.

    PubMed

    Tetali, Sarada D; Jankowski, Vera; Luetzow, Karola; Kratz, Karl; Lendlein, Andreas; Jankowski, Joachim

    2016-01-01

    Uremia is a phenomenon caused by retention of uremic toxins in the plasma due to functional impairment of kidneys in the elimination of urinary waste products. Uremia is presently treated by dialysis techniques like hemofiltration, dialysis or hemodiafiltration. However, these techniques in use are more favorable towards removing hydrophilic than hydrophobic uremic toxins. Hydrophobic uremic toxins, such as hydroxy hipuric acid (OH-HPA), phenylacetic acid (PAA), indoxyl sulfate (IDS) and p-cresylsulfate (pCRS), contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease. Therefore, objective of the present study is to test adsorption capacity of highly porous microparticles prepared from poly(ether imide) (PEI) as an alternative technique for the removal of uremic toxins. Two types of nanoporous, spherically shaped microparticles were prepared from PEI by a spraying/coagulation process.PEI particles were packed into a preparative HPLC column to which a mixture of the four types of uremic toxins was injected and eluted with ethanol. Eluted toxins were quantified by analytical HPLC. PEI particles were able to adsorb all four toxins, with the highest affinity for PAA and pCR. IDS and OH-HPA showed a partially non-reversible binding. In summary, PEI particles are interesting candidates to be explored for future application in CKD.

  4. Vascular incompetence in dialysis patients--protein-bound uremic toxins and endothelial dysfunction.

    PubMed

    Jourde-Chiche, Noémie; Dou, Laetitia; Cerini, Claire; Dignat-George, Françoise; Brunet, Philippe

    2011-01-01

    Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium-dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia-specific factors. Several uremic toxins, mostly protein-bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p-cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro-oxidant and pro-inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein-bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.

  5. Estrogen inhibits vascular calcification via vascular RANKL system: common mechanism of osteoporosis and vascular calcification.

    PubMed

    Osako, Mariana Kiomy; Nakagami, Hironori; Koibuchi, Nobutaka; Shimizu, Hideo; Nakagami, Futoshi; Koriyama, Hiroshi; Shimamura, Munehisa; Miyake, Takashi; Rakugi, Hiromi; Morishita, Ryuichi

    2010-08-20

    Arterial calcification and osteoporosis are associated in postmenopausal women. RANK (the receptor activator of nuclear factor kappaB), RANKL (RANK ligand), and osteoprotegerin are key proteins in bone metabolism and have been found at the site of aortic calcification. The role of these proteins in vasculature, as well as the contribution of estrogen to vascular calcification, is poorly understood. To clarify the mechanism of RANKL system to vascular calcification in the context of estrogen deficiency. RANKL induced the calcification inducer bone morphogenetic protein-2 by human aortic endothelial cells (HAECs) and decreased the calcification inhibitor matrix Gla protein (MGP) in human aortic smooth muscle cells (HASMCs), as quantified by real-time PCR and Western blot analysis. RANKL also induced bone-related gene mRNA expression and calcium deposition (Alizarin red staining) followed by the osteogenic differentiation of HASMCs. Estrogen inhibited RANKL signaling in HAECs and HASMCs mainly through estrogen receptor alpha. Apolipoprotein E-deficient mice fed with Western high-fat diet for 3 months presented atherosclerotic calcification (Oil red and Alizarin red staining) and osteoporosis (microcomputed tomographic analysis) after ovariectomy and increased expression of RANKL, RANK, and osteopontin in atherosclerotic lesion, as detected by in situ hybridization. Estrogen replacement inhibited osteoporosis and the bone morphogenetic protein osteogenic pathway in aorta by decreasing phosphorylation of smad-1/5/8 and increasing MGP mRNA expression. RANKL contributes to vascular calcification by regulating bone morphogenetic protein-2 and MGP expression, as well as bone-related proteins, and is counteracted by estrogen in a receptor-dependent manner.

  6. Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease

    PubMed Central

    Meuwese, Christiaan Lucas; Olauson, Hannes; Qureshi, Abdul Rashid; Ripsweden, Jonaz; Barany, Peter; Vermeer, Cees; Drummen, Nadja; Stenvinkel, Peter

    2015-01-01

    Introduction Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho. Methods and Material In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively. Results fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness. Discussion The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail. PMID:26147960

  7. Reversible vascular calcifications associated with hypervitaminosis D.

    PubMed

    Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

    2016-02-01

    A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

  8. Acute calcific tendinitis of the wrist.

    PubMed

    Torbati, Sam S; Bral, Daniel; Geiderman, Joel M

    2013-02-01

    Acute calcific tendinitis, a benign and self-limiting inflammatory condition commonly seen in the shoulder, is also described in many other tendons, including those in the hand and wrist. When involving the wrist, acute calcific tendinitis is often misdiagnosed and mistaken for infection. We present this case to increase familiarity with this condition to avoid errors in diagnosis resulting in inappropriate treatment with antibiotics or even surgery. A 27-year-old man presented to the Emergency Department with a 2-week history of volar wrist pain, with sudden increase in pain associated with chills and new onset swelling and redness of the wrist. Plain radiographs showed characteristic soft-tissue calcification overlying the insertion of the flexor carpi ulnaris tendon into the wrist. Treatment with ibuprofen and splinting resulted in complete symptom resolution. Acute calcific tendinitis is an important consideration in the differential diagnosis of acute wrist pain. Radiographs are helpful in confirming the diagnosis when symptoms and examination findings are characteristic. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Does glutaraldehyde induce calcification of bioprosthetic tissues?

    PubMed

    Vincentelli, A; Latrémouille, C; Zegdi, R; Shen, M; Lajos, P S; Chachques, J C; Fabiani, J N

    1998-12-01

    Glutaraldehyde has been said to be responsible in part for the calcification of glutaraldehyde-treated tissues after implantation in animals or humans. We investigated whether the origin of the tissue, autologous or heterologous, could have a more prominent role in the process of calcification. Three-month-old sheep received sheep pericardial samples (n = 133) and human pericardial samples (n = 123) implanted subcutaneously. Samples were treated with 0.6% glutaraldehyde for 5, 10, or 20 minutes or 7 days and then rinsed thoroughly before implantation. Samples were then retrieved after 3 months. Calcium content was assessed by spectrophometry. The results show a low calcium content in the autologous group (mean 1.14+/-2.07) and a high calcium content in the heterologous group (mean 38.97+/-26). These results were the same regardless of the duration of the treatment. Glutaraldehyde treatment (0.6%) does not play a significant role in the calcification of glutaraldehyde-treated tissue regardless of the origin, autologous or heterologous, of the tissue. Glutaraldehyde-treated autologous tissues are associated with an incidence of calcification lower than heterologous tissues.

  10. NT5E mutations and arterial calcifications.

    PubMed

    St Hilaire, Cynthia; Ziegler, Shira G; Markello, Thomas C; Brusco, Alfredo; Groden, Catherine; Gill, Fred; Carlson-Donohoe, Hannah; Lederman, Robert J; Chen, Marcus Y; Yang, Dan; Siegenthaler, Michael P; Arduino, Carlo; Mancini, Cecilia; Freudenthal, Bernard; Stanescu, Horia C; Zdebik, Anselm A; Chaganti, R Krishna; Nussbaum, Robert L; Kleta, Robert; Gahl, William A; Boehm, Manfred

    2011-02-03

    Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G→A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C→A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients' cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification. We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. (Funded by the National Human Genome Research Institute and the National Heart, Lung

  11. NT5E Mutations and Arterial Calcifications

    PubMed Central

    St. Hilaire, Cynthia; Ziegler, Shira G.; Markello, Thomas C.; Brusco, Alfredo; Groden, Catherine; Gill, Fred; Carlson-Donohoe, Hannah; Lederman, Robert J.; Chen, Marcus Y.; Yang, Dan; Siegenthaler, Michael P.; Arduino, Carlo; Mancini, Cecilia; Freudenthal, Bernard; Stanescu, Horia C.; Zdebik, Anselm A.; Chaganti, R. Krishna; Nussbaum, Robert L.; Kleta, Robert; Gahl, William A.; Boehm, Manfred

    2011-01-01

    BACKGROUND Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. METHODS We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. RESULTS We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G→A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C→A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients’ cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification. CONCLUSIONS We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. (Funded by the National Human Genome Research

  12. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease

    PubMed Central

    Sato, Emiko; Mori, Takefumi; Mishima, Eikan; Suzuki, Arisa; Sugawara, Sanae; Kurasawa, Naho; Saigusa, Daisuke; Miura, Daisuke; Morikawa-Ichinose, Tomomi; Saito, Ritsumi; Oba-Yabana, Ikuko; Oe, Yuji; Kisu, Kiyomi; Naganuma, Eri; Koizumi, Kenji; Mokudai, Takayuki; Niwano, Yoshimi; Kudo, Tai; Suzuki, Chitose; Takahashi, Nobuyuki; Sato, Hiroshi; Abe, Takaaki; Niwa, Toshimitsu; Ito, Sadayoshi

    2016-01-01

    Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD. PMID:27830716

  13. Diffusion-weighted imaging findings in hemolytic uremic syndrome with central nervous system involvement.

    PubMed

    Toldo, Irene; Manara, Renzo; Cogo, Paola; Sartori, Stefano; Murer, Luisa; Battistella, Pier Antonio; Laverda, Anna Maria

    2009-02-01

    Hemolytic uremic syndrome is a multisystem disease that can affect central nervous system in up to 50% of cases. Central nervous system involvement can be clinically severe and its pathogenesis is not yet fully understood. Various magnetic resonance imaging findings, on conventional sequences, documenting the involvement of deep gray-matter structures, have been described. Diffusion-weighted imaging features of brain lesions have been reported only in 2 cases, but the potential role of this technique has not been considered yet. We describe a 19-month-old child affected by hemolytic uremic syndrome with basal ganglia lesions documented by diffusion-weighted imaging, with a 42-day neuroradiological follow-up and a 6-month clinical follow-up. In our case, diffusion-weighted imaging was more sensible in detecting the affected brain areas compared to T1, suggesting that reduced apparent diffusion coefficient values in the acute phase could reliably identify irreversible brain lesions in hemolytic uremic syndrome patients.

  14. Recombinant factor VIIa use in refractory ulcer bleeding in uremic patient.

    PubMed

    Wang, An-Yi; Yuan, Ang; Huang, Chien-Hua; Chang, Wei-Tien; Liang, Po-Chin; Lin, Tzu-Hsin; Chen, Shyr-Chyr

    2012-09-01

    Peptic ulcer bleeding is thought to be a major cause of bleeding in patients with end-stage renal disease and is more complicated in uremic patients. We described a 41-year-old man with end-stage renal disease who underwent hemodialysis with refractory ulcer bleeding, failure to all traditional peptic ulcer treatments, and correction of uremic component, who has been successfully treated by using recombinant factor VIIa. There have been few case reports in dealing refractory upper gastrointestinal bleeding in uremic patients in the literature; and in this case report, we demonstrates that recombinant factor VIIa could be used as a rescue therapy in these high–surgical risk patients when medical therapy fails.

  15. Preexisting venous calcification prior to dialysis vascular access surgery.

    PubMed

    Lee, Timmy; Safdar, Nida; Mistry, Meenakshi J; Wang, Yang; Chauhan, Vibha; Campos, Begoña; Munda, Rino; Cornea, Virgilius; Roy-Chaudhury, Prabir

    2012-01-01

    Vascular calcification is present in arterial vessels used for dialysis vascular access creation prior to surgical creation. Calcification in the veins used to create a new vascular access has not previously been documented. The objective of this study was to describe the prevalence of venous calcification in samples collected at the time of vascular access creation. Sixty-seven vein samples were studied. A von Kossa stain was performed to quantify calcification. A semi-quantitative scoring system from 0 to 4+ was used to quantify the percentage positive area for calcification as a fraction of total area (0: 0; 1+: 1-10%; 2+: 11-25%; 3+: 26-50%; 4+: >50% positive). Twenty-two of 67 (33%) samples showed evidence of venous calcification. Histologic examination showed varying degrees of calcification within each cell layer. Among the subset of patients with calcification, 4/22 (18%), 19/22 (86%), 22/22 (100%), and 7/22 (32%) had calcification present within the endothelium, intima, media, and adventitia, respectively. The mean semi-quantitative scores of the 22 samples with calcification were 0.18 ± 0.08, 1.2 ± 0.14, 1.6 ± 0.13, and 0.36 ± 0.12 for the endothelium, intima, media, and adventitia, respectively. Our results demonstrate that vascular calcification is present within veins used to create new dialysis vascular access, and located predominately within the neointimal and medial layers. © 2012 Wiley Periodicals, Inc.

  16. Vascular calcification in Mexican hemodialysis patients.

    PubMed

    Rojas-Campos, Enrique; Herrera-Llamas, Rebeca; Montañez-Fernández, José L; Martínez-Martínez, Petra; Andrade-Sierra, Jorge; Avila-Baray, Angel A; Cueto-Manzano, Alfonso M

    2013-11-01

    Vascular calcification (VC) is a predictor of poor survival and cardiovascular outcome in end-stage renal disease (ESRD) patients; however, there is scarce information of VC in Latin America, and virtually no data in our setting. We undertook this study to evaluate the prevalence and characteristics of VC in a hemodialysis (HD) population from western Mexico and to determine possible associated factors. This was a cross-sectional study performed in 52 patients. VC was evaluated using plain X-ray films (Adragao's score) of hands and pelvis; clinical and biochemical variables were also collected. Statistical analysis was carried out with Student t and χ(2) tests performed as appropriate and logistic regression to determine predictors of VC. Mean age was 43 years, 48% were female, 23% had diabetes mellitus (DM), and median time on dialysis was 46 months. Percentage prevalence was 52% with a mean calcification score of 2.0 ± 2.6; 23% of patients had severe calcification. VC was present in about 23-37% among the different vascular territories evaluated (radial, digital, femoral and iliac). Patients with calcification were significantly older, had a higher frequency of DM, higher alkaline phosphatase and lower HDL lipoproteins than those without VC. In the multivariate analysis, VC in these patients was significantly predicted only by an older age (OR [95% CI]: 1.15 [1.01-1.31], p = 0.04); lower HDL-cholesterol and higher alkaline phosphatase were marginal predictors. Half of our HD patients had VC. Territories of radial, iliac, femoral and digital arteries were roughly equally affected, and 25% of patients had a calcification considered as severe. Older age was the only significant predicting variable for VC, with low HDL-cholesterol and high alkaline phosphatase as marginal predictors. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  17. Intracranial physiological calcifications evaluated with cone beam CT.

    PubMed

    Sedghizadeh, P P; Nguyen, M; Enciso, R

    2012-12-01

    The purpose of this study was to evaluate cone beam CT (CBCT) scans for the presence of physiological and pathological intracranial calcifications. CBCT scans from male and female patients that met our ascertainment criteria were evaluated retrospectively (n=500) for the presence of either physiological or pathological intracranial calcifications. Out of the 500 patients evaluated, 176 had evidence of intracranial physiological calcification (35.2% prevalence), and none had evidence of pathological calcification. There was a 3:2 male-to-female ratio and no ethnic predilection; the ages of affected patients ranged from 13 years to 82 years with a mean age of 52 years. The majority of calcifications appeared in the pineal/habenular region (80%), with some also appearing in the choroid plexus region bilaterally (12%), and a smaller subset appearing in the petroclinoid ligament region bilaterally (8%). Intracranial physiological calcifications can be a common finding on CBCT scans, whereas pathological intracranial calcifications are rare.

  18. The relationship between deiodinase activity and inflammatory responses under the stimulation of uremic toxins.

    PubMed

    Xu, Gaosi; Tu, Weiping; Qin, Shulan

    2014-08-31

    It is unclear to what extent uremic toxins participate in inflammatory responses and the activities of deiodinases, as well as the effects of deiodinases on inflammatory cytokines. Hepatocellular carcinoma cell lines (HepG2) were transfected with small interfering ribonucleic acid (siRNA) specific for deiodinase type 1 (DIO1) and cultured with or without uremic toxins. The mRNA expression of DIO1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was detected by quantitative real-time PCR. The presence of selenoprotein M (SelM) and DIO1 was assessed by western blotting. Sonicate deiodinase activities in HepG2 cells were measured by a dithiothreitol-stimulated assay. The NF-κB, AP-1 and CREB-1 inflammatory signal pathways were confirmed by EMSA. After culturing for 24 h, the mRNA expression of DIO1 was significantly decreased by the specific siRNA (reduced by 76%, P = 0.0002). Uremic toxins significantly increased the mRNA expression (P < 0.01) of IL-1β, IL-6 and TNF-α and inhibited DIO1 mRNA expression (P < 0.01) compared with controls. Suppression of DIO1 by siRNA significantly decreased the mRNA expression of IL-1β and IL-6 (P < 0.05) but not TNF-α (P = 0.093). Uremic toxins and specific siRNA synchronously reduced the protein expression of SelM and DIO1. Uremic toxins activate the expression of inflammatory cytokines. The major findings of this study indicate that the uremic toxins, more than inflammatory cytokines, play direct inhibitory roles in DIO1 enzyme activity, which then provides a negative feedback to the growing accumulation of inflammatory cytokines.

  19. Adipocyte induced arterial calcification is prevented with sodium thiosulfate

    SciTech Connect

    Chen, Neal X.; O’Neill, Kalisha; Akl, Nader Kassis; Moe, Sharon M.

    2014-06-20

    Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes, and

  20. Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies

    PubMed Central

    Keir, Lindsay S; Marks, Stephen D; Kim, Jon Jin

    2012-01-01

    Hemolytic uremic syndrome is the leading cause of acute kidney injury in childhood. Ninety percent of cases are secondary to gastrointestinal infection with shigatoxin-producing bacteria. In this review, we discuss the molecular mechanisms of shigatoxin leading to hemolytic uremic syndrome and the emerging role of the complement system and vascular endothelial growth factor in its pathogenesis. We also review the evidence for treatment options to date, in particular antibiotics, plasma exchange, and immunoadsorption, and link this to the molecular pathology. Finally, we discuss future avenues of treatment, including shigatoxin-binding agents and complement inhibitors, such as eculizumab. PMID:22888220

  1. A Longitudinal Study of Uremic Pruritus in Hemodialysis Patients

    PubMed Central

    Mathur, Vandana S.; Lindberg, Jill; Germain, Michael; Block, Geoffrey; Tumlin, James; Smith, Mark; Grewal, Mandeep

    2010-01-01

    Background and objectives: Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP. Design, setting, participants, & measurements: The intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months. Results: Itching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures. Conclusions: This first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients. PMID:20558560

  2. Physiologic calcification of the pineal gland in children on computed tomography: prevalence, observer reliability and association with choroid plexus calcification.

    PubMed

    Doyle, Anthony James; Anderson, Graeme D

    2006-07-01

    To evaluate the prevalence of physiologic pineal calcification, estimate observer variability, and examine the association with choroid plexus calcification. A retrospective review of hard copy head computed tomography films of 242 patients age younger than 16 years by two independent observers. Physiologic pineal calcification was present in 20% of the whole group, in 39% of those 8-14 years age, in 8% of those younger than 10 years age, and in 1% of those younger than age 6 years. Observer agreement was very good (kappa = 0.72). Choroid plexus calcification was present in 16% and was four times as common in those with pineal calcification (38% versus 10%, P = .005), with very good observer agreement (kappa = 0.74). Physiologic pineal calcification is more common in children than previously reported, mostly because of improving computed tomography technology. There is an association with choroid plexus calcification.

  3. Calcification by reef-building sclerobionts.

    PubMed

    Mallela, Jennie

    2013-01-01

    It is widely accepted that deteriorating water quality associated with increased sediment stress has reduced calcification rates on coral reefs. However, there is limited information regarding the growth and development of reef building organisms, aside from the corals themselves. This study investigated encruster calcification on five fore-reefs in Tobago subjected to a range of sedimentation rates (1.2 to 15.9 mg cm(-2) d(-1)). Experimental substrates were used to assess rates of calcification in sclerobionts (e.g. crustose coralline algae, bryozoans and barnacles) across key reef microhabitats: cryptic (low-light), exposed (open-horizontal) and vertical topographic settings. Sedimentation negatively impacted calcification by photosynthesising crustose coralline algae in exposed microhabitats and encrusting foram cover (%) in exposed and cryptic substrates. Heterotrophs were not affected by sedimentation. Fore-reef, turbid water encruster assemblages calcified at a mean rate of 757 (SD ±317) g m(-2) y(-1). Different microhabitats were characterised by distinct calcareous encruster assemblages with different rates of calcification. Taxa with rapid lateral growth dominated areal cover but were not responsible for the majority of CaCO3 production. Cryptobiont assemblages were composed of a suite of calcifying taxa which included sciaphilic cheilostome bryozoans and suspension feeding barnacles. These calcified at mean rates of 20.1 (SD ±27) and 4.0 (SD ±3.6) g m(-2) y(-1) respectively. Encruster cover (%) on exposed and vertical substrates was dominated by crustose coralline algae which calcified at rates of 105.3 (SD ±67.7) g m(-2) y(-1) and 56.3 (SD ±8.3) g m(-2) y(-1) respectively. Globally, encrusting organisms contribute significant amounts of carbonate to the reef framework. These results provide experimental evidence that calcification rates, and the importance of different encrusting organisms, vary significantly according to topography and sediment

  4. Calcification by Reef-Building Sclerobionts

    PubMed Central

    Mallela, Jennie

    2013-01-01

    It is widely accepted that deteriorating water quality associated with increased sediment stress has reduced calcification rates on coral reefs. However, there is limited information regarding the growth and development of reef building organisms, aside from the corals themselves. This study investigated encruster calcification on five fore-reefs in Tobago subjected to a range of sedimentation rates (1.2 to 15.9 mg cm−2 d−1). Experimental substrates were used to assess rates of calcification in sclerobionts (e.g. crustose coralline algae, bryozoans and barnacles) across key reef microhabitats: cryptic (low-light), exposed (open-horizontal) and vertical topographic settings. Sedimentation negatively impacted calcification by photosynthesising crustose coralline algae in exposed microhabitats and encrusting foram cover (%) in exposed and cryptic substrates. Heterotrophs were not affected by sedimentation. Fore-reef, turbid water encruster assemblages calcified at a mean rate of 757 (SD ±317) g m−2 y−1. Different microhabitats were characterised by distinct calcareous encruster assemblages with different rates of calcification. Taxa with rapid lateral growth dominated areal cover but were not responsible for the majority of CaCO3 production. Cryptobiont assemblages were composed of a suite of calcifying taxa which included sciaphilic cheilostome bryozoans and suspension feeding barnacles. These calcified at mean rates of 20.1 (SD ±27) and 4.0 (SD ±3.6) g m−2 y−1 respectively. Encruster cover (%) on exposed and vertical substrates was dominated by crustose coralline algae which calcified at rates of 105.3 (SD ±67.7) g m−2 y−1 and 56.3 (SD ±8.3) g m−2 y−1 respectively. Globally, encrusting organisms contribute significant amounts of carbonate to the reef framework. These results provide experimental evidence that calcification rates, and the importance of different encrusting organisms, vary significantly according to topography and sediment

  5. COX2 Inhibition Reduces Aortic Valve Calcification In Vivo

    PubMed Central

    Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E.

    2016-01-01

    Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432

  6. Intracellular precipitation of hydroxyapatite mineral and implications for pathologic calcification.

    PubMed

    Azari, Fereshteh; Vali, Hojatollah; Guerquin-Kern, Jean-Luc; Wu, Ting-Di; Croisy, Alain; Sears, S Kelly; Tabrizian, Maryam; McKee, Marc D

    2008-06-01

    In contrast to physiologic biomineralization occurring in bones, teeth and otoconia in vertebrates, calcification of soft tissues occurs in many pathologic conditions. Although similarities have been noted between the two processes, and despite the important clinical consequences of ectopic calcification, the molecular mechanisms regulating ectopic calcification are poorly understood. Although calcification is mainly extracellular, intracellular calcification has been reported and might indeed contribute to pathologic calcification of soft tissues. To better understand the process of intracellular calcification as a potential origin for pathologic calcification, and to examine the role of proteoglycans in this process, we investigated a pattern of intracellular nucleation and growth of hydroxyapatite in Madin-Darby Canine Kidney (MDCK) epithelial cells using electron microscopy, secondary ion mass spectroscopy (NanoSIMS), cytochemical staining, immunolabeling and biochemical analysis. We report here that under mineralizing cell culture conditions where beta-glycerophosphate (betaGP) was added as an exogenous organic source of phosphate, betaGP-cleaving alkaline phosphatase activity increased and hydroxyapatite crystals subsequently nucleated within intracellular, membrane-bounded compartments. The small, leucine-rich proteoglycan decorin was also upregulated and associated with mineral in these cultures. Such information provides insight into the mechanisms leading to pathologic calcification and describes a process whereby hydroxyapatite deposition in cells might lead to ectopic calcification.

  7. Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats.

    PubMed

    Raya, Ana I; Rios, Rafael; Pineda, Carmen; Rodriguez-Ortiz, Maria E; Diez, Elisa; Almaden, Yolanda; Muñoz-Castañeda, Juan R; Rodriguez, Mariano; Aguilera-Tejero, Escolastico; Lopez, Ignacio

    2016-11-14

    Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic VC.

  8. Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats

    PubMed Central

    Raya, Ana I.; Rios, Rafael; Pineda, Carmen; Rodriguez-Ortiz, Maria E.; Diez, Elisa; Almaden, Yolanda; Muñoz-Castañeda, Juan R.; Rodriguez, Mariano; Aguilera-Tejero, Escolastico; Lopez, Ignacio

    2016-01-01

    Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic VC. PMID:27841294

  9. Comparing different calcification scores to detect outcomes in chronic kidney disease patients with vascular calcification.

    PubMed

    NasrAllah, Mohamed M; Nassef, Amr; Elshaboni, Tarik H; Morise, Fadia; Osman, Noha A; Sharaf El Din, Usama A

    2016-10-01

    There is no consensus on the most appropriate technique to diagnose vascular calcification in chronic kidney disease. This is primarily because of the absence of direct comparisons of predictive values of the various calcification scores, especially outside the coronary vascular beds, to detect clinical outcomes. We included 93 haemodialysis patients and performed 6 vascular calcification scores: two scores utilised simple X-rays of abdominal aorta and peripheral vessels. CT scans of the thoracic, upper abdominal and lower abdominal aorta were performed to calculate the aortic calcification index and CT of the pelvis for calcification of iliac vessels. Patients were followed for 63months (mean 46.8months) for first major cardiovascular events and mortality. Nineteen cardiovascular events and 28 deaths occurred. Calcification was detected more sensitively in central and peripheral beds using CT scans compared to X-rays (p<0.001). CT scans detected calcification more frequently in distal than proximal vascular beds (p<0.001). Calcification of the pelvic vessels and lower abdominal aorta were most predictive of events including pre-existing cardiovascular disease O.R. 6.5 (95% C.I. 2-22; p=0.001) and O.R. 3 (95% C.I. 1.1-9; p=0.035); new major cardiovascular events H.R. 4.2 (95% C.I. 1.5-11; p=0.006) and H.R. 2 (95% C.I. 0.8-5.3; p=0.1) as well as mortality H.R. 2.8 (95% C.I. 1.3-6; p=0.01) and H.R. 2.2 (95% C.I. 1.04-5; p=0.04) respectively. CT based techniques are more sensitive than plain X-rays at detecting peripheral and aortic vascular calcifications. Distal CT scans of the aorta and pelvic vessels have the highest predictive value for cardiovascular events and mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Dystrophic Calcification of the Prostate after Cryotherapy

    PubMed Central

    2014-01-01

    We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP) and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses. PMID:25548712

  11. Hereditary folate malabsorption with extensive intracranial calcification.

    PubMed

    Ahmad, Ikhlas; Mukhtar, Gousia; Iqbal, Javed; Ali, Syed Wajid

    2015-01-01

    Anemia is a common accompaniment of cerebral palsy, mental retardation and neurodegenerative disorders. A 4-year-old boy with chronic megaloblastic anemia, global developmental delay, seizures, intracranial calcification and new onset neuro-regression. A diagnosis of hereditary folate malabsorption was made, and he was put on oral and injectable folinic acid. Marked improvement at 6 month follow up. Hereditary folate malabsorption should be suspected in any child having megaloblastic anemia and neuro degeneration disorder.

  12. [Massive hydrothorax in a ease of hemolytic uremic syndrome: conservative treatment without interruption of peritoneal dialysis].

    PubMed

    Marin, Gustavo R

    2016-12-01

    The hydrothorax is a known but rare complication of acute and chronic peritoneal dialysis. Patients with hemolytic uremic syndrome seem to be more prone to this complication. Usually discontinuation of treatment is necessary due to the lack of resolution or recurrence of hydrothorax and transfer to hemodialysis, but some patients can continue dialysis with modification of technique and with resolution of hydrothorax.

  13. The pharmacological treatment for uremic restless legs syndrome: evidence-based review.

    PubMed

    de Oliveira, Márcio Moysés; Conti, Cristiane Fiquene; Valbuza, Juliana Spelta; de Carvalho, Luciane Bizari Coin; do Prado, Gilmar Fernandes

    2010-07-30

    Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthesis of the evidence is needed in order to evaluate the effectiveness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double-blind trials on treatments for uremic RLS. The outcomes considered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life measured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg movement while asleep in the treatment group. No combined analysis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few therapeutic trials on patients with uremia with RLS have been published, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Therapy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed.

  14. Diarrhea, Urosepsis and Hemolytic Uremic Syndrome Caused by the Same Heteropathogenic Escherichia coli Strain.

    PubMed

    Ang, C Wim; Bouts, Antonia H M; Rossen, John W A; Van der Kuip, Martijn; Van Heerde, Marc; Bökenkamp, Arend

    2016-09-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains.

  15. Cerebro-renal interactions: impact of uremic toxins on cognitive function.

    PubMed

    Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-09-01

    Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Hemolytic Uremic Syndrome Risk and Escherichia coli O157:H7

    PubMed Central

    Tserenpuntsag, Boldtsetseg; Smith, Perry F.; Morse, Dale L.

    2005-01-01

    We reviewed medical records of 238 hospitalized patients with Escherichia coli O157:H7 diarrhea to identify risk factors for progression to diarrhea-associated hemolytic uremic syndrome (HUS). Data indicated that young age, long duration of diarrhea, elevated leukocyte count, and proteinuria were associated with HUS. PMID:16485489

  17. Recurrent hemolytic uremic syndrome in a renal transplant patient during pregnancy.

    PubMed

    Sølling, J; Paulsen, S M

    1995-12-01

    The recurrence of the hemolytic uremic syndrome (HUS) in a renal transplant patient during pregnancy and during treatment with cyclosporin is reported. After 4 1/2 months of treatment with hemodialysis the renal function partially recovered. A monozygote twin sister has not developed HUS in spite of 2 pregnancies.

  18. Retropharyngeal calcific tendonitis: report of two cases.

    PubMed

    Razon, Rhea Victoria B; Nasir, Asad; Wu, George S; Soliman, Manal; Trilling, Jeffrey

    2009-01-01

    Retropharyngeal calcific tendonitis is an inflammatory process of the superior oblique tendons of the longus colli muscle, a neck flexor in the upper cervical spine, caused by deposition of calcium hydroxyapatite crystals; the definitive diagnostic test is computed tomography (CT). Presented in this article are two cases seen at our institution. Patients typically present with acute onset of neck pain/spasm, odynophagia, dysphagia, and/or low grade fevers. Leukocytosis and elevated erythrocyte sedimentation rate may be noted. It is important to understand this entity because its signs and symptoms are mimickers of those of the more serious condition of retropharyngeal space abscess. Calcific tendonitis is managed conservatively whereas retropharyngeal abscess requires incision and drainage. Some may argue that this entity is a zebra because its reported incidence in the literature is low. However, most of these studies were done in an era when CT was not yet in vogue. With today's widespread use of CT and its superb ability to visualize the calcification, the true incidence of this condition is probably higher and, thus, it is important for the family practitioner to be aware of this entity. The astute clinician may save the patient from unnecessary diagnostic workup, undue anxiety, and delays in hospital discharge.

  19. Mammographically Detectable Breast Arterial Calcification and Atherosclerosis

    PubMed Central

    Shah, Neeraj; Chainani, Vinod; Delafontaine, Patrice; Abdo, Abir; Lafferty, James; Rafeh, Nidal Abi

    2014-01-01

    Breast arterial calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, with increasing age. The aim of this review is to discuss relevant literature examining relation between BAC and atherosclerosis. After a thorough literature search, in OVID and PubMed, 199 studies were identified, of which 25 were relevant to our review. Data were abstracted from each study and statistical analysis was done, including calculation of odds ratios and construction of forest plots. A total of 35,542 patients were enrolled across 25 studies looking at an association between BAC and coronary artery disease, cardiovascular disease, stroke, cerebral artery disease, carotid and peripheral artery diseases, and coronary artery calcification. A majority of the studies showed a statistically significant relation between BAC and presence of coronary artery disease cardiovascular disease and associated mortality. Sensitivity of BAC in predicting cardiovascular events was low, but specificity was high. BAC was predictive of incident and prevalent stroke but not mortality of stroke. Similarly, BAC was predictive of cerebral, carotid, and peripheral artery diseases. The role of BAC as a surrogate marker of coronary and systemic atherosclerosis is currently uncertain. Its role may be further elucidated by more large-scale prospective studies and clinical experience. PMID:23584424

  20. Calcium intake, vascular calcification, and vascular disease.

    PubMed

    Spence, Lisa A; Weaver, Connie M

    2013-01-01

    Recent research has reported a possible link between calcium supplementation and increased risk of cardiovascular disease and its endpoints in healthy, older adults. To evaluate the current evidence regarding the impact of calcium supplementation on cardiovascular disease risk and to address research gaps, the present review was conducted. Systematic reviews and meta-analyses were included, when available, along with original articles. The articles included in the review were obtained from PubMed using the following search terms: calcium intake, calcium supplementation, cardiovascular disease, myocardial infarction, mortality, and vascular calcification. The majority of the studies reviewed demonstrated no statistically significant adverse or beneficial effect of calcium supplementation on cardiovascular disease or its endpoints. While some studies indicate a possible increased risk, there is a lack of consensus on these findings and a need exists to further elucidate a mechanism. More experimental data are necessary to understand the impact of calcium intake, both levels and sources, on vascular calcification and vascular disease. The use of (41)C kinetic modeling in the Ossabaw swine provides an approach for assessing soft tissue calcification in an atherosclerotic and normal state to address research gaps.

  1. Aortic Stenosis and Vascular Calcifications in Alkaptonuria

    PubMed Central

    Hannoush, Hwaida; Introne, Wendy J.; Chen, Marcus Y.; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A.; Gahl, William A.; Sachdev, Vandana

    2011-01-01

    Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. PMID:22100375

  2. Chronic calcific pancreatitis and pancreatic cancer.

    PubMed

    Billah, M M; Chowdhury, M M; Das, B C; Shampa, N N; Khan, Z R

    2014-07-01

    An observational cross-sectional study of 50 cases of chronic calcific pancreatitis patients was conducted in Bangabandhu Sheikh Mujib Medical University (BSMMU) and some other tertiary level hospitals of Dhaka city from August 2008 to July 2010. Patients required laparotomy for different modalities of surgical treatment to manage chronic calcific pancreatitis were included in the study. Biopsy was taken from panceatic duct containing stone during laparotomy to determine the histopathological changes. Among 50 cases female predominance was observed. Male, female ratio was 2:3. Majority (62%) patients were in 20 to 40 years age group. Female presented earlier than male (20-30 years and 30-40 years respectively). All patients complained recurrent attack of epigastric pain. Other presentations were diabetes (74%), malnutrition and weight loss (56%), steatorrhoea (24%) and jaundice (12%). Adenocarcinoma was found in 3(6%) patients (2 male and 1 female) and rests were chronic pancreatitis. Several studies showed the association between chronic calcific pancreatitis and pancreatic cancer. Further large scale study is required to find out the national incidence level.

  3. A Case of Chronic Calcific Nonalcoholic Pancreatitis

    PubMed Central

    Kangas-Dick, Aaron; Khan, Umair; Awoniyi, Oluwafunbi; Waqar, Shanza; Tun, Nu Nwe; Wong, Cynthia

    2016-01-01

    Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP. PMID:27957355

  4. Corals concentrate dissolved inorganic carbon to facilitate calcification.

    PubMed

    Allison, Nicola; Cohen, Itay; Finch, Adrian A; Erez, Jonathan; Tudhope, Alexander W

    2014-12-22

    The sources of dissolved inorganic carbon (DIC) used to produce scleractinian coral skeletons are not understood. Yet this knowledge is essential for understanding coral biomineralization and assessing the potential impacts of ocean acidification on coral reefs. Here we use skeletal boron geochemistry to reconstruct the DIC chemistry of the fluid used for coral calcification. We show that corals concentrate DIC at the calcification site substantially above seawater values and that bicarbonate contributes a significant amount of the DIC pool used to build the skeleton. Corals actively increase the pH of the calcification fluid, decreasing the proportion of DIC present as CO2 and creating a diffusion gradient favouring the transport of molecular CO2 from the overlying coral tissue into the calcification site. Coupling the increases in calcification fluid pH and [DIC] yields high calcification fluid [CO3(2-)] and induces high aragonite saturation states, favourable to the precipitation of the skeleton.

  5. Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

    PubMed

    Ferreira, Carlos R; Ziegler, Shira G; Gupta, Ashutosh; Groden, Catherine; Hsu, Kevin S; Gahl, William A

    2016-05-01

    Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification.

  6. The uremic toxin indoxyl sulfate acts as a pro- or antioxidant on LDL oxidation.

    PubMed

    Praschberger, M; Hermann, M; Wanner, J; Jirovetz, L; Exner, M; Kapiotis, S; Gmeiner, B M K; Laggner, H

    2014-06-01

    Uremic toxins have been shown to play a role in chronic kidney disease (CKD) associated oxidative stress. Oxidative stress and inflammation have been associated with increased risk of cardiovascular disease in uraemia. The oxidative modification of LDL may play a role in early atherogenesis. Enhanced LDL oxidation has been found in uremic patients which may account for accelerated atherosclerosis observed in CKD. The uremic toxin indoxyl sulfate (IS) has been reported to exert oxidative and antioxidative activity. Thus, in the present study we have investigated the influence of IS on the atherogenic modifications of LDL exposed in vitro to different oxidising systems. The transition metal ion (Cu(2+)) and hemin/H2O2 induced lipid oxidation reactions monitored by conjugated diene formation, were inhibited by the presence of IS, which points to possible antioxidant effects by this uremic toxin. A protective effect of IS on LDL apoprotein modification by the exposure to the product of the myeloperoxidase/H2O2/Cl(-) system HOCl, was also observed as estimated by protein carbonyl formation. In contrast, a marked increase in conjugated dienes and lipid hydroperoxides was observed when lipid oxidation was initiated by the free radical generator AAPH in presence of IS. The GC-MS analysis revealed the formation of indole-2,3-dione and 6,12-dihydro-6,12-dioxo-indolo[2,1-b]quinazoline (tryptanthrin) in IS/AAPH reaction. A scheme for the generation of tryptanthrin from IS via indoxyl radicals is proposed, which may facilitate LDL lipid oxidation. Our observations add further insight in the Janus-faced properties of this important uremic toxin.

  7. Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol.

    PubMed

    Fujisaki, Kiichiro; Tsuruya, Kazuhiko; Yamato, Mayumi; Toyonaga, Jiro; Noguchi, Hideko; Nakano, Toshiaki; Taniguchi, Masatomo; Tokumoto, Masanori; Hirakata, Hideki; Kitazono, Takanari

    2014-03-01

    Chronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice. CKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain. Eight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2'-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice. The present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

  8. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    PubMed

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  9. Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD.

    PubMed

    Kramann, Rafael; Erpenbeck, Johanna; Schneider, Rebekka K; Röhl, Anna B; Hein, Marc; Brandenburg, Vincent M; van Diepen, Merel; Dekker, Friedo; Marx, Nicolaus; Floege, Jürgen; Becker, Michael; Schlieper, Georg

    2014-10-01

    Cardiovascular mortality is high in ESRD, partly driven by sudden cardiac death and recurrent heart failure due to uremic cardiomyopathy. We investigated whether speckle-tracking echocardiography is superior to routine echocardiography in early detection of uremic cardiomyopathy in animal models and whether it predicts cardiovascular mortality in patients undergoing dialysis. Using speckle-tracking echocardiography in two rat models of uremic cardiomyopathy soon (4-6 weeks) after induction of kidney disease, we observed that global radial and circumferential strain parameters decreased significantly in both models compared with controls, whereas standard echocardiographic readouts, including fractional shortening and cardiac output, remained unchanged. Furthermore, strain parameters showed better correlations with histologic hallmarks of uremic cardiomyopathy. We then assessed echocardiographic and clinical characteristics in 171 dialysis patients. During the 2.5-year follow-up period, ejection fraction and various strain parameters were significant risk factors for cardiovascular mortality (primary end point) in a multivariate Cox model (ejection fraction hazard ratio [HR], 0.97 [95% confidence interval (95% CI), 0.95 to 0.99; P=0.012]; peak global longitudinal strain HR, 1.17 [95% CI, 1.07 to 1.28; P<0.001]; peak systolic and late diastolic longitudinal strain rates HRs, 4.7 [95% CI, 1.23 to 17.64; P=0.023] and 0.25 [95% CI, 0.08 to 0.79; P=0.02], respectively). Multivariate Cox regression analysis revealed circumferential early diastolic strain rate, among others, as an independent risk factor for all-cause mortality (secondary end point; HR, 0.43; 95% CI, 0.25 to 0.74; P=0.002). Together, these data support speckle tracking as a postprocessing echocardiographic technique to detect uremic cardiomyopathy and predict cardiovascular mortality in ESRD.

  10. Dystrophic calcifications after autologous fat injection on face.

    PubMed

    Kim, Dai Hyun; Jang, Hee Won; Kim, Hee Joo; Son, Sang Wook

    2014-06-01

    Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection.

  11. Characteristics of calcification in tumors of the pineal gland.

    PubMed

    Lin, S R; Crane, M D; Lin, Z S; Bilaniuk, L; Plassche, W M; Marshall, L; Spataro, R F

    1978-03-01

    Thirty-two cases of proved pineal tumor were analyzed. Calcification was seen in 75%. The size, character, and position of the calcification were useful indicators of abnormality on plain-film evaluation. Fray's cranioangle method was more sensitive than Oon's method in determining abnormal position of the calcified pineal tumor on the lateral skull film. Most calcifications were displaced postero-inferiorly or inferiorly, which can be explained by obstructive hydrocephalus or direct tumor expansion.

  12. Calcifications of the palatine tonsillary region: CT demonstration.

    PubMed

    Aspestrand, F; Kolbenstvedt, A

    1987-11-01

    The scans of 100 consecutive patients referred for computed tomographic examinations that included the oropharynx were reviewed with regard to calcifications of the palatine tonsillary region. Calcifications were found in 20% of the female patients and 13% of the male patients. Ten patients had one calculus, and six had two or more. The sizes of the calculi ranged from 1 to 7 mm. Tonsillary calculi must be included among the diagnostic possibilities when survey radiographs of the neck show soft-tissue calcifications.

  13. Calcification of thoracic aorta – solar eclipse sign

    PubMed Central

    Dhoble, Abhijeet; Puttarajappa, Chethan

    2008-01-01

    Background Calcification of thoracic aorta is very common in old people, especially ones with hypertension. This can sometime be visible on plain chest radiograph. Case Presentation We present a case of a male patient who had extensive deposition of calcium in the thoracic aorta. Conclusion The relationship between aortic calcification and coronary atherosclerosis remains contentious. Computed tomography of the thorax can display this calcification which appears like 'solar eclipse'. PMID:18759981

  14. The matrix metalloproteinases 2 and 9 initiate uraemic vascular calcifications.

    PubMed

    Hecht, Eva; Freise, Christian; Websky, Karoline V; Nasser, Hamoud; Kretzschmar, Nadja; Stawowy, Philipp; Hocher, Berthold; Querfeld, Uwe

    2016-05-01

    The matrix metalloproteinases (MMP) MMP-2 and MMP-9 are physiological regulators of vascular remodelling. Their dysregulation could contribute to vascular calcification. We examined the role of the MMP-2 and MMP-9 in uraemic vascular calcification in vivo and in vitro. The impact of pharmacological MMP inhibition on the development of media calcifications was explored in an aggressive animal model of uraemic calcification. In addition, the selective effects of addition and inhibition, respectively, of MMP-2 and MMP-9 on calcium-/phosphate-induced calcifications were studied in a murine cell line of vascular smooth muscle cells (VSMCs). High-dose calcitriol treatment of uraemic rats given a high phosphate diet induced massive calcifications, apoptosis and increased gene expressions of MMP-2, MMP-9 and of osteogenic transcription factors and proteins in aortic VSMC. The MMP inhibitor doxycycline prevented the VSMC transdifferentiation to osteoblastic cells, suppressed transcription of mediators of matrix remodelling and almost completely blocked aortic calcifications while further increasing apoptosis. Similarly, specific inhibitors of either MMP-2 or -9, or of both gelatinases (Ro28-2653) and a selective knockdown of MMP-2/-9 mRNA expression blocked calcification of murine VSMC induced by calcification medium (CM). In contrast to MMP inhibition, recombinant MMP-2 or MMP-9 enhanced CM-induced calcifications and the secretion of gelatinases. These data indicate that both gelatinases provide essential signals for phenotypic VSMC conversion, matrix remodelling and the initiation of vascular calcification. Their inhibition seems a promising strategy in the prevention of vascular calcifications. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  15. Apoptosis and calcification of vascular endothelial cell under hyperhomocysteinemia.

    PubMed

    Fang, Kuaifa; Chen, Zhujun; Liu, Meng; Peng, Jian; Wu, Pingsheng

    2015-01-01

    In recent years, it is found that increase in Hcy level in blood can directly or indirectly cause vascular endothelial cell injury and induce vascular calcification. However, the mechanism of vascular endothelial cell injury and vascular calcification has not been studied thoroughly. This paper carried out experiment for research aiming at discussing the effect and action mechanism of Hhcy on endothelial cells and vascular calcification. Firstly, human umbilical vein endothelial cells (HUVECs) were cultured and then intervened by Hcy of different concentrations (0, 0.01, 0.1, 1.0, 3.0, 5.0 mmol/L) and at different action time (3, 6, 12, 24 h). Then apoptosis rate and reactive oxygen were detected by flow cytometry. At the same time, the model for the culture of rat vascular calcification was set up and induced into Hhcy so as to detect the total plasma Hcy level and judge vascular calcification degree. The results showed that with the increase in Hcy concentration and extension of action period, the apoptosis rate and generation of reactive oxygen of HUVECs all significantly increased, and the differences were all statistically significant (P < 0.01). In animal calcification model, mass of black particle deposition was seen after Von Kossa staining of rat vessels in calcification group. Compared with the control group, the vascular calcium content, alkaline phosphatase activity and osteocalcin content in calcification group all increased (P < 0.01). The content of plasma lipid conjugated olefine from highest to lowest wasas follows: calcification plus homoetheionin, homoetheionin, and calcification group. There was no significant difference between the calcification group and control group. All these findings suggested that Hcy could induce the apoptosis of endothelial cells and its effect degree depended on its concentration and action period; Hhcy could promote the calcification of blood vessels, and its mechanism might relate with the strengthening of

  16. Calcification Changes of Mesozoic Calcareous Nannofossils

    NASA Astrophysics Data System (ADS)

    Bornemann, A.; Mutterlose, J.

    2003-12-01

    Studies on plankton samples and cultures revealed a variety factors which presumably control calcification and the size of coccoliths. Among others temperature, nutrients and seawater pH are thought to influence nannoplankton calcification. Whereas these studies only provide information of very short time intervals from hours to years, global climatic and oceanographic changes occur, however, on geological timescales. Thus their impact on nannofossil calcification and carbonate production can only be studied from the fossil record. We investigated DSDP sites from the western Atlantic of late Jurassic to early Cretaceous age in order to better understand long-term variations of the size of common nannofossil taxa and the resulting carbonate accumulation. The studied interval is characterized by two events in the pelagic carbonate record: (1) the onset of pelagic carbonate accumulation in the Tithonian, and (2) the Valanginian 'nannoconid crisis'. The Tithonian event went along with high abundances of strongly calcified nannofossils which presumably have an affinity to more oligotrophic surface water conditions. The mid Valanginian is marked by a positive carbon isotope excursion (CIE). This coincides with a sea level rise, volcanic activity and elevated atmospheric pCO2 levels. Greenhouse climate and an accelerated hydrological cycle presumably intensified weathering processes causing enhanced nutrient transfer from the continents into the oceans. Increasing surface water fertility is indicated by high abundances of nannofossils which possibly indicate more eutrophic conditions. In the western Tethys the CIE is predated by a sharp decrease in the abundance of rockforming nannoconids. This event is less pronounced in the western Atlantic due to a general scarcity of nannoconids. Low nannofossil carbonate accumulation rates and a dominance of less calcified taxa were observed and may reflect a general marine biocalcification crisis. Possible factors, which may have

  17. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles

    PubMed Central

    Goettsch, Claudia; Hutcheson, Joshua D.; Aikawa, Masanori; Iwata, Hiroshi; Pham, Tan; Nykjaer, Anders; Kjolby, Mads; Rogers, Maximillian; Michel, Thomas; Shibasaki, Manabu; Hagita, Sumihiko; Kramann, Rafael; Singh, Sasha A.

    2016-01-01

    Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2–dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification. PMID:26950419

  18. Inhibitory role of Notch1 in calcific aortic valve disease.

    PubMed

    Acharya, Asha; Hans, Chetan P; Koenig, Sara N; Nichols, Haley A; Galindo, Cristi L; Garner, Harold R; Merrill, Walter H; Hinton, Robert B; Garg, Vidu

    2011-01-01

    Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  19. Vascular calcification in patients with chronic kidney disease.

    PubMed

    Nitta, Kosaku

    2011-12-01

    Vascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non-traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients. © 2011 The Author. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.

  20. Roles of High Mobility Group Box 1 in Cardiovascular Calcification.

    PubMed

    Chen, Qiang; Wang, Ze-Yang; Chen, Li-Yuan; Hu, Hou-Yuan

    2017-01-01

    Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development. © 2017 The Author(s). Published by S. Karger AG, Basel.

  1. Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

    PubMed

    Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

    2017-07-01

    To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

    NASA Technical Reports Server (NTRS)

    Rathfon, Megan; Brewer, Debbie

    1997-01-01

    Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

  3. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

    USDA-ARS?s Scientific Manuscript database

    OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

  4. Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

    NASA Technical Reports Server (NTRS)

    Rathfon, Megan; Brewer, Debbie

    1997-01-01

    Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

  5. Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease.

    PubMed

    Black, Ana Paula; Cardozo, Ludmila F M F; Mafra, Denise

    2015-10-01

    Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD-MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  6. Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy

    PubMed Central

    Liu, Jiang; Tian, Jiang; Chaudhry, Muhammad; Maxwell, Kyle; Yan, Yanling; Wang, Xiaoliang; Shah, Preeya T.; Khawaja, Asad A.; Martin, Rebecca; Robinette, Tylor J.; El-Hamdani, Adee; Dodrill, Michael W.; Sodhi, Komal; Drummond, Christopher A.; Haller, Steven T.; Kennedy, David J.; Abraham, Nader G.; Xie, Zijian; Shapiro, Joseph I.

    2016-01-01

    We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder. PMID:27698370

  7. Efficacy of epigallocatechin-3-gallate and Amla (Emblica officinalis) extract for the treatment of diabetic-uremic patients.

    PubMed

    Chen, Tung-Sheng; Liou, Show-Yih; Wu, Hsi-Chin; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang; Chang, Yen-Lin

    2011-01-01

    Uremic patients with diabetes suffer from high levels of oxidative stress due to regular hemodialysis therapy (neutrophil activation induced by hemo-incompatibility between the hemodialyser and blood) and complications associated with diabetes. Several plasma biomarkers were screened in 13 uremic diabetic patients after receiving the mixture of (-)-epigallocatechin gallate (EGCG), a major component of green tea extract, and Amla extract (AE), from Emblica officinalis, the Indian gooseberry, for 3 months. We found that oral administration of a 1:1 mixture of EGCG and AE for 3 months significantly improved antioxidant defense as well as diabetic and atherogenic indices in uremic patients with diabetes. Furthermore, no significant changes in hepatic function, renal function, or inflammatory responses were observed. These results suggest that a 1:1 combination of EGCG and AE is a safe and effective treatment for uremic patients with diabetes.

  8. Fibroblast Growth Factor-23—A Potential Uremic Toxin

    PubMed Central

    Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

    2016-01-01

    Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)2-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ–calcineurin–NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation. PMID:27941640

  9. Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

    PubMed Central

    Shi, Mingjun; Cho, Han Jun; Adams-Huet, Beverley; Paek, Jean; Hill, Kathy; Shelton, John; Amaral, Ansel P.; Faul, Christian; Taniguchi, Masatomo; Wolf, Myles; Brand, Markus; Takahashi, Masaya; Kuro-o, Makoto; Hill, Joseph A.

    2015-01-01

    Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency—genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor–23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1–, angiotensin II–, or high phosphate–induced fibrosis and abolished TGF-β1– or angiotensin II–induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor–23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging. PMID:25326585

  10. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling.

    PubMed

    Hu, Ming Chang; Shi, Mingjun; Cho, Han Jun; Adams-Huet, Beverley; Paek, Jean; Hill, Kathy; Shelton, John; Amaral, Ansel P; Faul, Christian; Taniguchi, Masatomo; Wolf, Myles; Brand, Markus; Takahashi, Masaya; Kuro-O, Makoto; Hill, Joseph A; Moe, Orson W

    2015-06-01

    Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-β1- or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging. Copyright © 2015 by the American Society of Nephrology.

  11. Substrate Properties Influence Calcification in Valvular Interstitial Cell Culture

    PubMed Central

    Benton, Julie A.; Kern, Hanna B.; Anseth, Kristi S.

    2009-01-01

    Background and aim of the study Valvular calcification is an active, cell-mediated process and results in significant morbidity and mortality. In standard culture, valvular interstitial cells (VICs) elicit significant calcification as a result of myofibroblast activation, and this limits the utility of these models to characterize VICs. In the work presented herein, we sought to investigate culturing substrates that suppress atypical VIC calcification and investigate culture substrates that represent a more physiological system. Methods Several culture platforms were selected to compare and contrast the influence of biochemical and mechanical properties on VIC calcification. Substrates investigated include: tissue culture polystyrene (TCPS), TCPS coated with either fibronectin or fibrin, and an elastic poly (ethylene glycol) (PEG) hydrogel with the same proteins coupled to the surface. Experiments were repeated with pro-fibrotic growth factor transforming growth factor- beta 1 (TGF-β1). VIC calcification was characterized by calcific nodule formation, alkaline phosphatase activity, and calcium accumulation. Gene and protein expression of alpha smooth muscle actin (αSMA) and core binding factor-1 (CBFa-1) were analyzed with qRT-PCR and immunostaining. Results Unmodified TCPS substrates had an innate ability to promote the markers of calcification studied. The addition of TGF-β1 enhanced all the levels of all osteoblastic markers studied. When TCPS surfaces were modified with fibronectin, all markers for calcification were repressed. However αSMA, a marker for myofibroblastic activity, was unchanged. Meanwhile fibrin modified TCPS surfaces enhanced calcification over unmodified TCPS substrates. On the soft PEG hydrogels, all markers for calcification were repressed regardless of the surface chemistry, while αSMA expression remained unaffected. Conclusions Collectively, VIC properties are highly linked to the culture microenvironment. Both the biochemical and

  12. Substrate properties influence calcification in valvular interstitial cell culture.

    PubMed

    Benton, Julie A; Kern, Hanna B; Anseth, Kristi S

    2008-11-01

    Valvular calcification is an active, cell-mediated process that results in significant morbidity and mortality. In standard culture, valvular interstitial cells (VICs) elicit significant calcification as a result of myofibroblast activation, and this limits their use in characterization studies. The study aim was to identify culturing substrates that would suppress atypical VIC calcification, and to investigate culture substrates representing a more physiological system. Several culture platforms were selected to compare and contrast the influence of biochemical and mechanical properties on VIC calcification. Substrates investigated included: tissue culture polystyrene (TCPS), TCPS coated with either fibronectin or fibrin, and an elastic poly(ethylene glycol) (PEG) hydrogel, also with fibronectin or fibrin coupled to the surface. Experiments were repeated with profibrotic growth factor transforming growth factor-beta 1 (TGF-beta1). VIC calcification was characterized by calcific nodule formation, alkaline phosphatase activity and calcium accumulation. Gene and protein expression of alpha smooth muscle actin (aSMA) and core binding factor-1 (CBFa-1) were analyzed with qRT-PCR and immunostaining. Unmodified TCPS substrates had an innate ability to promote the markers of calcification studied. The addition of TGF-beta1 enhanced levels of all osteoblastic markers studied. When TCPS surfaces were modified with fibronectin, all markers for calcification were repressed, but alphaSMA - a marker for myofibroblastic activity was unchanged. Meanwhile, fibrin-modified TCPS surfaces enhanced calcification over unmodified TCPS substrates. On soft PEG hydrogels, all markers for calcification were repressed, regardless of the surface chemistry, while alphaSMA expression remained unaffected. Collectively, VIC properties are highly linked to the culture microenvironment. Both, the biochemical and mechanical environment of tissue culture has an effect on the spontaneous calcification

  13. Biomarkers Associated with Vascular Calcification in Peritoneal Dialysis.

    PubMed

    Ramirez-Sandoval, Juan C; Casanova, Ivan; Villar, Alejandro; Gomez, F Enrique; Cruz, Cristino; Correa-Rotter, Ricardo

    2016-01-01

    ♦ Vascular calcification is strongly associated with cardiovascular disease and mortality. However, some factors related to vascular calcification in patients with end-stage renal disease receiving peritoneal dialysis (PD) remain unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23), magnesium, and phosphate clearance with vascular calcification in PD subjects, assessed by plain radiographs. ♦ Simple vascular calcification scores (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for ≥ 6 months (43 women, median age 39 years, median time on PD 1.4 years). Levels of OPG, OPN, OCN, and FGF-23 were determined by luminometry. ♦ Serum OPG levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3; n = 19 with KI > 7) compared with those with less calcification (p < 0.001). Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had significantly lower renal phosphate clearance. Multiple regression analysis showed that vascular calcification assessed by SVCS was associated with age (r = 0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r = 0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and magnesium were not associated with vascular calcification. ♦ Higher levels of OPG were consistently associated with vascular calcification in subjects on PD. Copyright © 2016 International Society for Peritoneal Dialysis.

  14. Secondary calcification and dissolution respond differently to future ocean conditions

    NASA Astrophysics Data System (ADS)

    Silbiger, N. J.; Donahue, M. J.

    2015-01-01

    Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP 8.5 to examine the combined effects of rising ocean acidity and sea surface temperature (SST) on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2 and temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest temperature-pCO2 condition. In contrast, dissolution increased linearly with temperature-pCO2 . The rubble community switched from net calcification to net dissolution at +271 μatm pCO2 and 0.75 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that (i) dissolution may be more sensitive to climate change than calcification and (ii) that calcification and dissolution have different functional responses to climate stressors; this highlights the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

  15. Secondary calcification and dissolution respond differently to future ocean conditions

    NASA Astrophysics Data System (ADS)

    Silbiger, N. J.; Donahue, M. J.

    2014-09-01

    Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP8.5 to examine the combined effects of rising ocean acidity and SST on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2-temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest pCO2-temperature condition. In contrast, dissolution increased linearly with pCO2-temperature. The rubble community switched from net calcification to net dissolution at +272 μatm pCO2 and 0.84 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that dissolution may be more sensitive to climate change than calcification, and that calcification and dissolution have different functional responses to climate stressors, highlighting the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

  16. Adipocyte induced arterial calcification is prevented with sodium thiosulfate.

    PubMed

    Chen, Neal X; O'Neill, Kalisha; Akl, Nader Kassis; Moe, Sharon M

    2014-06-20

    Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. High phosphorus induced calcification of mature adipocytes, and adipocytes exposed to elevated phosphorus can induce calcification of VSMC in a paracrine manner. Sodium thiosulfate inhibited this calcification and decreased the secretin of leptin and VEGF from adipocytes. These results suggest that adipocyte exposure to elevated phosphorus may be a

  17. Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier.

    PubMed

    Deguchi, Tsuneo; Isozaki, Kouya; Yousuke, Kouno; Terasaki, Tetsuya; Otagiri, Masaki

    2006-02-01

    Renal failure causes multiple physiological changes involving CNS dysfunction. In cases of uremia, there is close correlation between plasma levels of uremic toxins [e.g. 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), hippurate (HA) and indoleacetate (IA)] and the degree of uremic encephalopathy, suggesting that uremic toxins are involved in uremic encephalopathy. In order to evaluate the relevance of uremic toxins to CNS dysfunction, we investigated directional transport of uremic toxins across the blood-brain barrier (BBB) using in vivo integration plot analysis and the brain efflux index method. We observed saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA, which was inhibited by probenecid. For all uremic toxins evaluated, apparent efflux clearance across the BBB was greater than apparent influx clearance, suggesting that these toxins are predominantly transported from the brain to blood across the BBB. Saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA was completely inhibited by benzylpenicillin, which is a substrate of rat organic anion transporter 3 (rOat3). Taurocholate and digoxin, which are common substrates of rat organic anion transporting polypeptide (rOatp), partially inhibited the efflux of [(3)H]CMPF. Transport experiments using a Xenopus laevis oocyte expression system revealed that CMPF, HA and IA are substrates of rOat3, and that CMPF (but not HA or IA) is a substrate of rOap2. These results suggest that rOat3 mediates brain-to-blood transport of uremic toxins, and that rOatp2 is involved in efflux of CMPF. Thus, conditions typical of uremia can cause inhibition of brain-to-blood transport involving rOat3 and/or rOatp2, leading to accumulation of endogenous metabolites and drugs in the brain.

  18. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type.

    PubMed

    Tüysüz, Beyhan; Gazioğlu, Nurperi; Ungür, Savaş; Aji, Dolly Yafet; Türkmen, Seval

    2009-01-01

    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered.

  19. Mitral annular calcification and aortic valve calcification may help in predicting significant coronary artery disease.

    PubMed

    Acartürk, Esmeray; Bozkurt, Abdi; Cayli, Murat; Demir, Mesut

    2003-01-01

    Mitral annular calcification (MAC) and aortic valve calcification (AVC) are manifestations of atherosclerosis. To determine whether mitral annular calcification and aortic valve calcification detected by transthoracic echocardiography (TTE) might help in predicting significant coronary artery disease (CAD), 123 patients with significant CAD and 93 patients without CAD detected by coronary angiography were investigated. MAC and AVC identified CAD with a sensitivity and specificity of 60.2%, 55.9% and 74.8%, 52.7%, respectively, and with a negative and a positive predictive values of 51.5%, 64.3% and 61.3% and 67.6%, respectively. The positive predictive value of MAC was greater than gender, hypertension, and hypercholesterolemia. AVC showed a positive predictive value greater than gender, hypertension, family history, and hypercholesterolemia. The negative predictive values of MAC and AVC for CAD were greater than those of all risk factors except diabetes mellitus. In conclusion, presence of MAC and AVC on TTE may help in predicting CAD and should be added to conventional risk factors. Absence of MVC and AVC is a stronger predictor for absence of CAD than all conventional risk factors, except diabetes mellitus. Patients with MAC and AVC should be taken into consideration for the presence of significant CAD and thereby for diagnostic and therapeutic interventions in order to improve the prognosis.

  20. Association of conjunctival and corneal calcification with vascular calcification in dialysis patients.

    PubMed

    Seyahi, Nurhan; Altiparmak, Mehmet R; Kahveci, Arzu; Yetik, Huseyin; Kanberoglu, Kaya; Serdengecti, Kamil; Ataman, Rezzan; Erek, Ekrem

    2005-03-01

    Conjunctival and corneal calcification (CCC) is a well-known and easily detectable extraskeletal calcification, but its association with vascular calcification was not investigated previously. The aim of this study is to investigate the relationship of CCC with vascular calcification and bone metabolism parameters in dialysis patients. We evaluated 63 patients (30 men, 33 women; mean age, 43.5 +/- 13.4 years) who were on dialysis therapy for more than 6 months. Forty-four patients were on peritoneal dialysis and 19 patients were on hemodialysis therapy. The same observer evaluated the presence of CCC by using a slit-lamp microscope, and a total CCC score was recorded for each patient. Fifty-two age- and sex-matched healthy controls also were evaluated by using the same method. Biochemical data were collected from patient files. Bone mineral density (BMD) of the lumbar spine and femoral neck was measured, and the presence of vascular calcification was assessed by using x-ray examinations of the pelvis and hands. Mean CCC score in patients was significantly higher than that in controls (6.2 +/- 5.1 versus 1.3 +/- 1.8; P = 0.001). CCC score correlated significantly with duration of renal replacement therapy ( r s = 0.392; P = 0.002), serum phosphorus level ( r s = 0.259; P = 0.042), and calcium x phosphorus product ( r s = 0.337; P = 0.007). However, we did not find a significant correlation with calcium, parathyroid hormone, alkaline phosphatase, albumin, or C-reactive protein level or BMD. The frequency of vascular calcification was significantly greater in patients with a high CCC score (CCC score > or = 10) compared with a low CCC score (< or =3; 56.3% versus 5.6%; P = 0.002). Evaluation of CCC score is an easy, fast, and noninvasive method. It seems that CCC score can be used as an additional tool to assess the status of extraskeletal calcification in dialysis patients.

  1. Exploring binding characteristics and the related competition of different protein-bound uremic toxins.

    PubMed

    Deltombe, Olivier; de Loor, Henriette; Glorieux, Griet; Dhondt, Annemieke; Van Biesen, Wim; Meijers, Björn; Eloot, Sunny

    2017-08-01

    Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin. Copyright

  2. Acupressure and Transcutaneous Electrical Acupoint Stimulation for Improving Uremic Pruritus: A Randomized, Controlled Trial.

    PubMed

    Kılıç Akça, Nazan; Taşcı, Sultan

    2016-03-01

    Context • Uremic pruritus, a frequent and compromising symptom for patients with advanced or end-stage renal disease (ESRD), strongly reduces the patient's quality of life. Pruritus may be extremely difficult to control because therapeutic options are limited. Topical products are frequently used for easing pruritus, but their effects are generally temporary and marginal. Although acupressure and electrical-stimulation methods for the application of acupressure have been evaluated separately in terms of pruritus efficiency in different studies, the existence of any difference between the efficacies of the 2 methods has not been assessed yet. Objective • The study intended to test the effectiveness of acupressure and transcutaneous electrical acupoint stimulation (TEAS) on uremic pruritus in patients who were receiving the routine hemodialysis treatment. Design • The study was a randomized, controlled trial. Setting • The study took place in hemodialysis units located in hemodialysis centers in Turkey. Participants • Participants were patients in the hemodialysis units who were under hemodialysis treatment and had experienced uremic pruritus. Intervention • Participants were randomly assigned to the acupressure group (intervention group), the TEAS group (intervention group), or the control group. For the 2 intervention groups, the treatment was applied 3 ×/wk during the 4 wk of the study on the large intestine (LI-11) acupuncture points in the arm, for a total of 12 sessions. Outcome Measures • The study measured the severity of participants' pruritus using a patient information form and a visual analogue scale (VAS). The data were collected at baseline and posttreatment. Results • A total of 75 patients participated in the study. The results indicated that patients in the acupressure and TEAS groups had significant reductions from baseline to posttreatment in their levels of discomfort from uremic pruritus compared with patients in the control

  3. Intracranial Carotid Calcification on Cranial Computed Tomography

    PubMed Central

    Subedi, Deepak; Zishan, Umme Sara; Chappell, Francesca; Gregoriades, Maria-Lena; Sudlow, Cathie; Sellar, Robin

    2015-01-01

    Background and Purpose— Intracranial internal carotid artery calcification is associated with cerebrovascular risk factors and stroke, but few quantification methods are available. We tested the reliability of visual scoring, semiautomated Agatston score, and calcium volume measurement in patients with recent stroke. Methods— We used scans from a prospective hospital stroke registry and included patients with anterior circulation ischemic stroke or transient ischemic stroke whose noncontrast cranial computed tomographic scans were available electronically. Two raters measured semiautomatic quantitative Agatston score, and calcium volume, and performed qualitative visual scoring using the original 4-point Woodcock score and a modified Woodcock score, where each image on which the internal carotid arteries appeared was scored and the slice scores summed. Results— Intra- and interobserver coefficient of variations were 8.8% and 16.5% for Agatston, 8.8% and 15.5% for calcium volume, and 5.7% and 5.4% for the modified Woodcock visual score, respectively. The modified Woodcock visual score correlated strongly with both Agatston and calcium volume quantitative measures (both R2=0.84; P<0.0001); calcium volume increased by 0.47-mm/point increase in modified Woodcock visual score. Intracranial internal carotid artery calcification increased with age by all measures (eg, visual score, Spearman ρ=0.4; P=0.005). Conclusions— Visual scores correlate highly with quantitative intracranial internal carotid artery calcification measures, with excellent observer agreements. Visual intracranial internal carotid artery scores could be a rapid and practical method for epidemiological studies. PMID:26251250

  4. Calcific tendinitis of the rotator cuff

    PubMed Central

    ElShewy, Mohamed Taha

    2016-01-01

    Calcific tendinitis within the rotator cuff tendon is a common shoulder disorder that should be differentiated from dystrophic calcification as the pathogenesis and natural history of both is totally different. Calcific tendinitis usually occurs in the fifth and sixth decades of life among sedentary workers. It is classified into formative and resorptive phases. The chronic formative phase results from transient hypoxia that is commonly associated with repeated microtrauma causing calcium deposition into the matrix vesicles within the chondrocytes forming bone foci that later coalesce. This phase may extend from 1 to 6 years, and is usually asymptomatic. The resorptive phase extends from 3 wk up to 6 mo with vascularization at the periphery of the calcium deposits causing macrophage and mononuclear giant cell infiltration, together with fibroblast formation leading to an aggressive inflammatory reaction with inflammatory cell accumulation, excessive edema and rise of the intra-tendineous pressure. This results in a severely painful shoulder. Radiological investigations confirm the diagnosis and suggest the phase of the condition and are used to follow its progression. Although routine conventional X-ray allows detection of the deposits, magnetic resonance imaging studies allow better evaluation of any coexisting pathology. Various methods of treatment have been suggested. The appropriate method should be individualized for each patient. Conservative treatment includes pain killers and physiotherapy, or “minimally invasive” techniques as needling or puncture and aspiration. It is almost always successful since the natural history of the condition ends with resorption of the deposits and complete relief of pain. Due to the intolerable pain of the acute and severely painful resorptive stage, the patient often demands any sort of operative intervention. In such case arthroscopic removal is the best option as complete removal of the deposits is unnecessary. PMID

  5. N-acetylcysteine as a potential strategy to attenuate the oxidative stress induced by uremic serum in the vascular system.

    PubMed

    Rodrigues, Silvia D; França, Karime C; Dallin, Fernando T; Fujihara, Clarice K; Nascimento, Aguinaldo J; Pecoits-Filho, Roberto; Nakao, Lia S

    2015-01-15

    Chronic kidney disease (CKD) progression is accompanied by systemic oxidative stress, which contributes to an increase in the risk of cardiovascular diseases (CVDs). N-acetylcysteine (NAC) is among the most studied antioxidants, but its therapeutic benefits in CKD-associated CVDs remain controversial. Here, we investigated whether NAC could inhibit the oxidative stress induced by uremia in vitro and in vivo. Endothelial and smooth muscle cells were challenged with human uremic or non-uremic sera, and the effects of a pre-treatment with 2mM NAC were evaluated. Reactive oxygen species (ROS) production, protein oxidation and total glutathione/glutathione disulfide (tGSH/GSSG) ratios were measured. Five-sixths nephrectomized or sham-operated rats were orally treated (in the drinking water) with 60 mg/kg/day NAC or not treated for 53 days. Plasma cysteine/cystine reduction potential Eh(Cyss/2Cys) was determined as a novel marker of the systemic oxidative stress. NAC inhibited all the determined oxidative stress parameters, likely by increasing the tGSH/GSSG ratio, in both cell lines exposed to uremic serum. Orally administered NAC attenuated the systemic oxidative stress in uremic rats. The present results indicate that NAC, by preventing GSH depletion in vascular cells exposed to uremic serum and by attenuating the systemic oxidative stress during CKD progression, emerges as a potential strategy to prevent the oxidative stress induced by uremic toxicity in the vascular system. Copyright © 2014. Published by Elsevier Inc.

  6. Medial vascular calcification revisited: review and perspectives

    PubMed Central

    Lanzer, Peter; Boehm, Manfred; Sorribas, Victor; Thiriet, Marc; Janzen, Jan; Zeller, Thomas; St Hilaire, Cynthia; Shanahan, Catherine

    2014-01-01

    Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area. PMID:24740885

  7. [Celiac disease, cerebral calcifications and epilepsy syndrome].

    PubMed

    Cuvellier, J C; Vallée, L; Nuyts, J P

    1996-10-01

    The syndrome of coeliac disease, epilepsy and cerebral calcifications is a rare complication of coeliac disease. The pathological changes consist in a patchy pial angiomatosis and resemble those of Sturge-Weber syndrome, whose variant without port-wine angioma must be ruled out. Typical course includes three stages leading to a severe encephalopathy. However, the mental impairment is extremely variable. The pathogenetic process is so for unknown; main clues involve a chronic folic acid deficiency or a HLA-related autoimmune disorder. Treatment requires early gluten-free diet and anti-epileptic drug.

  8. Calcific tendinopathy of the rotator cuff tendons.

    PubMed

    Oliva, Francesco; Via, Alessio Giai; Maffulli, Nicola

    2011-09-01

    Calcific tendinopathy (CT) of the tendons of the rotator cuff is common in white populations, with a reported prevalence varying from 2.7% to 22%, mostly affecting women between 30 and 50 years. Although CT shows a strong tendency toward self-healing by spontaneous resorption of the deposits, it does not always follow this typical pattern. The etiopathogenesis of CT is still unknown. Many pathogenetic theories have been proposed, and clinical associations between CT and diabetes and thyroid disorders have been reported. The choice of therapeutic approach should depend on the evolution of the condition.

  9. Coronary artery calcification correlates with the presence and severity of valve calcification.

    PubMed

    Koulaouzidis, G; Nicoll, R; MacArthur, T; Jenkins, P J; Henein, M Y

    2013-10-15

    To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification. © 2013.

  10. Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease.

    PubMed

    Zucker, Inbar; Yosipovitch, Gil; David, Michael; Gafter, Uzi; Boner, Geoffrey

    2003-11-01

    Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch. The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis. A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch. Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002). This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.

  11. Expression of NPP1 is regulated during atheromatous plaque calcification

    PubMed Central

    Nitschke, Yvonne; Hartmann, Simone; Torsello, Giovanni; Horstmann, Rüdiger; Seifarth, Harald; Weissen-Plenz, Gabriele; Rutsch, Frank

    2011-01-01

    Abstract Mutations of the ENPP1 gene encoding ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) are associated with medial calcification in infancy. While the inhibitory role of matrix proteins such as osteopontin (OPN) with respect to atherosclerotic plaque calcification has been established, the role of NPP1 in plaque calcification is not known. We assessed the degree of plaque calcification (computed tomography), NPP1 and OPN localization (immunohistochemistry) and expression (RT-PCR) in a cohort of 45 patients undergoing carotid endatherectomy for significant stenosis of the internal carotid artery and in normal arteries (N= 50). We correlated NPP1 and OPN expression levels to the degree of plaque calcification, to pro-atherogenic factors and statin therapy. NPP1 was demonstrated in the base and in the shoulder of atherosclerotic plaques. Compared to normal arteries and non-calcified plaques, in calcified plaques NPP1 mRNA was decreased (P < 0.0001). OPN mRNA levels were up-regulated in carotid atheroma. NPP1 and OPN expression levels positively correlated with the degree of plaque calcification (R= 0.54, P= 0.00019 and R= 0.46, P= 0.017, respectively) and with risk factors of atherosclerosis. Expression of the calcification inhibitor NPP1 is down-regulated in calcified atherosclerotic plaques. Our correlation data point to a counter-active mechanism, which in the end turns out to be insufficient to prevent further progression of calcification. PMID:20015201

  12. Presternal soft tissue calcifications following mediastinal radiotherapy for Hodgkin's disease

    SciTech Connect

    Vainright, J.R.; Diaconis, J.N.; Haney, P.J.

    1987-01-01

    A patient is described in whom dense calcifications developed in the presternal soft tissues of the chest four years after mediastinal radiotherapy. This is believed to represent dystrophic calcification in previously normal but incidentally radiated tissues following standard dose radiotherapy to the mediastinum for stage IIA Hodgkin's disease.

  13. Pineal calcification is associated with pediatric primary brain tumor.

    PubMed

    Tuntapakul, Supinya; Kitkhuandee, Amnat; Kanpittaya, Jaturat; Johns, Jeffrey; Johns, Nutjaree Pratheepawanit

    2016-12-01

    Melatonin has been associated with various tumors, including brain tumor, and shown to inhibit growth of neuroblastoma cells and gliomas in animal models. Likewise, patients with glioblastoma receiving melatonin reported better survival than controls. Pineal calcification may lead to a decreased production of melatonin by calcified glands. This study assessed association between pineal calcification and primary brain tumor in pediatric/adolescent patients. Medical chart review was conducted in 181 patients <15 years old who had undergone brain computed tomography (CT) during 2008-2012. Pineal calcification was identified using brain CT scan by an experienced neurosurgeon. Primary brain tumor was confirmed by CT scan and histology, and association with pineal calcification was estimated using multiple logistic regression, adjusted for age and gender. Primary brain tumor was detected in 51 patients (mean age 9.0, standard deviation 4.0 years), with medulloblastoma being the most common (11 patients). Pineal calcification was detected in 12 patients (23.5%) with primary brain tumor, while only 11 patients (8.5%) without tumor had pineal calcification. Adjusted for patients' ages and genders, pineal calcification was associated with an increase in primary brain tumor of 2.82-fold (odds ratio 2.82; 95% confidence interval 1.12-7.08, P = 0.027). Pineal calcification appears to be associated with primary brain tumor. Further studies to explore this link are discussed and warranted. © 2016 John Wiley & Sons Australia, Ltd.

  14. Acromial morphology in patients with calcific tendinitis of the shoulder.

    PubMed

    Balke, Maurice; Banerjee, Marc; Vogler, Tim; Akoto, Ralph; Bouillon, Bertil; Liem, Dennis

    2014-02-01

    The purpose of this study was to evaluate whether the morphology of the acromion in calcific tendinitis differs from controls without subacromial pathology and matches subacromial impingement. Digital radiographs of 150 shoulders were evaluated with the open source DICOM-Viewer OsiriX. 50 patients had symptomatic calcific tendinitis of the shoulder, 50 had subacromial impingement without calcifications or rotator cuff tears, 50 with bruised shoulder that were previously asymptomatic served as controls. Acromial shape according to Bigliani et al. acromial tilt (AT) according to Kitay et al. and Aoki et al. acromion index (AI) according to Nyffeler et al. and lateral acromial angle (LAA) according to Banas et al. were measured. Both calcific (0.72; P = 0.001) and impingement groups (0.73; P = 0.008) were significantly different from controls (0.67) using AI measure, while only the calcific group (79.5°) was different from controls (84.1°) using LAA (P < 0.001), and only the impingement group (32.9°) was different from controls (29.2°) using AT (P < 0.001). An LAA <70° only occurred in two patients with calcific tendinitis. The hypothesis of this study was that the morphology of the acromion in calcific tendinitis differs from controls without subacromial pathology and matches subacromial impingement was only confirmed for the AI. The AI of shoulders with calcific tendinitis is comparable to that of shoulders with subacromial impingement.

  15. Evidence for a calcification process in the trabecular meshwork.

    PubMed

    Borrás, Teresa; Comes, Núria

    2009-04-01

    The human trabecular meshwork (TM) expresses many genes that have been associated with physiological (bone, cartilage, teeth) and pathological (vascular systems, kidney) calcification. In particular, the TM highly expresses the inhibitor of calcification Matrix Gla (MGP) gene, which encodes a vitamin K-dependent protein that requires post-translational activation to inhibit the formation of calcium precipitates. TM cells have high activity of the activating gamma-carboxylase enzyme and produce active MGP. Silencing MGP increases the activity of alkaline phosphatase (ALP), an enzyme of the matrix vesicles and marker of calcification. Overexpressing MGP reduces the ALP activity induced by bone morphogenetic 2 (BMP2), a potent inducer of calcification. In this review we gathered evidence for the existence of a mineralization process in the TM. We selected twenty regulatory calcification genes, reviewed their functions in their original tissues and looked at their relative abundance in the TM by heat maps derived from existing microarrays. Although results are not yet fully conclusive and more experiments are needed, examining TM expression in the light of the calcification literature brings up many similarities. One such parallel is the role of mechanical forces in bone induction and the high levels of mineralization inhibitors found in the constantly mechanically stressed TM. During the next few years, examination of other calcification-related regulatory genes and pathways, as well as morphological examination of knockout animals, would help to elucidate the relevance of a calcification process to TM's overall function.

  16. [Endomyocardial fibrosis with massive calcification of the left ventricle].

    PubMed

    Trigo, Joana; Camacho, Ana; Gago, Paula; Candeias, Rui; Santos, Walter; Marques, Nuno; Matos, Pedro; Brandão, Victor; Gomes, Veloso

    2010-03-01

    Endomyocardial fibrosis is a rare disease, endemic in tropical countries. It is characterized by fibrosis of the endocardium that can extend to myocardium. Important calcification of the endocardium is rare with only a few cases reported in the literature. We report a case of endomyocardial fibrosis in a european caucasian patient, associated with massive calcification of left ventricle.

  17. Matrix Gla Protein polymorphisms are associated with coronary artery calcification

    USDA-ARS?s Scientific Manuscript database

    Matrix Gla Protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). We examined the cross-sectional association between MGP SNPs [rs1800802 (T-138C), rs1800801 (G-7A),and rs4236 (Ala102Thr)...

  18. Left atrial calcification in a hemodialysis patient with cor triatriatum.

    PubMed

    Peces, R; Pobes, A; Rodriguez, M; Simarro, C; Iglesias, G; Simarro, E

    2000-05-01

    Myocardial calcification is a rare manifestation of abnormal calcium metabolism seen in some patients with chronic renal failure. This report describes the transesophageal echocardiographic and spiral computed tomography (CT) findings in a young hemodialysis female with severe secondary hyperparathyroidism. These findings included calcification of the multiperforated membrane of a cor triatriatum and the wall of the left atrium.

  19. Mechanisms of ectopic calcification: implications for diabetic vasculopathy

    PubMed Central

    Fadini, Gian Paolo

    2015-01-01

    Vascular calcification (VC) is the deposition of calcium/phosphate in the vasculature, which portends a worse clinical outcome and predicts major adverse cardiovascular events. VC is an active process initiated and regulated via a variety of molecular signalling pathways. There are mainly two types of calcifications: the media VC and the intima VC. All major risk factors for cardiovascular disease (CVD) have been linked to the presence/development of VC. Besides the risk factors, a genetic component is also operative to determine arterial calcification. Several events take place before VC is established, including inflammation, trans-differentiation of vascular cells and homing of circulating pro-calcific cells. Diabetes is an important predisposing factor for VC. Compared with non-diabetic subjects, patients with diabetes show increased VC and higher expression of bone-related proteins in the medial layer of the vessels. In this review we will highlight the mechanisms underlying vascular calcification in diabetic patients. PMID:26543821

  20. [Diabetic angiopathy and the progression of vascular calcification].

    PubMed

    Kotake, Hidetoshi; Oikawa, Shinichi

    2003-09-01

    The frequency of atherosclerotic diseases in diabetes is very high. In the occurrence of atherosclerosis the severity of diabetes is not so important. The mild diabetic condition with obesity will be a strong factor to relate with atherogenesis. As mentioned above the atherogenesis in diabetes is slightly complicated, because multiple risk factors accumulate in diabetes mellitus. These factors are hyperglycemia, hyperlipidemia, hypertension, smoking, and obesity, It has been clarified that the mechanism of arterial calcification will be same as in bone calcification process which is regulated by the various bone metabolic factors. In diabetes mellitus the characteristic vascular changes is that there is multiple calcification in the various arteries including aorta, coronary artery, and peripheral arterioles. It is considered that the necrosis and apoptosis of vascular smooth muscle cells and the transforming of vascular cells to bone cell or cartilage cell are induced and related to arterial calcification. The other factor of calcification would be inflammatory changes related to atheroma formation.

  1. Susceptibility weighted imaging: differentiating between calcification and hemosiderin*

    PubMed Central

    Barbosa, Jeam Haroldo Oliveira; Santos, Antonio Carlos; Salmon, Carlos Ernesto Garrido

    2015-01-01

    Objective To present a detailed explanation on the processing of magnetic susceptibility weighted imaging (SWI), demonstrating the effects of echo time and sensitive mask on the differentiation between calcification and hemosiderin. Materials and Methods Computed tomography and magnetic resonance (magnitude and phase) images of six patients (age range 41– 54 years; four men) were retrospectively selected. The SWI images processing was performed using the Matlab’s own routine. Results Four out of the six patients showed calcifications at computed tomography images and their SWI images demonstrated hyperintense signal at the calcification regions. The other patients did not show any calcifications at computed tomography, and SWI revealed the presence of hemosiderin deposits with hypointense signal. Conclusion The selection of echo time and of the mask may change all the information on SWI images, and compromise the diagnostic reliability. Amongst the possible masks, the authors highlight that the sigmoid mask allows for contrasting calcifications and hemosiderin on a single SWI image. PMID:25987750

  2. [Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

    PubMed

    García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

    2009-02-01

    Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

  3. Hydropic degeneration of the anterior pituitary gland (adenohypophysis) in uremic rats.

    PubMed

    Levine, Seymour; Saltzman, Arthur

    2004-03-01

    We observed hydropic degeneration of the anterior pituitary in rats made uremic by nephrotoxic chemicals, especially when the uremic rats were given a pure carbohydrate diet beforehand. The hydropic degeneration caused loss of nuclear and cytoplasmic content of many or most anterior pituitary cells. It was readily visible in paraffin sections by light microscopy. It was exaggerated when water was injected after the nephrotoxin and it was greatly reduced if saline was injected after the nephrotoxin. Low serum sodium levels in affected rats and the response to saline injection suggested that the mechanism for development of hydropic degeneration of the anterior pituitary gland involved hyponatremia. Depletion of total body sodium probably accounts for the enhancement of hydropic degeneration by the pure carbohydrate diet. Morphologic lesions of the anterior pituitary related to hyponatremia and uremia have not been described previously.

  4. Atypical hemolytic-uremic syndrome: a case report and literature review.

    PubMed

    Rafiq, Arsalan; Tariq, Hassan; Abbas, Naeem; Shenoy, Roopalekha

    2015-02-24

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal dysfunction. It is a disease related to genetic mutations in the alternative complement pathway and has a distinct pathophysiology but is difficult to differentiate from other thrombotic microangiopathies. We present a case of a 59-year-old female patient who presented with accelerated hypertension, acute renal failure, hemolysis, and encephalopathy. She was managed with antihypertensive medication, but her encephalopathy did not improve. Evaluation resulted in our impression of the disease being atypical hemolytic-uremic syndrome. The patient continued to be managed with good blood pressure control and later was started on eculizumab, but evaluation of response to therapy was hindered by the patient's non-compliance with therapy and follow-up appointments. We have a very limited understanding of the genetics and epidemiology of atypical HUS, and the overlapping clinical features sometimes delay diagnosis and initiation of appropriate treatment of this rare disease.

  5. Uremic pericarditis, pericardial effusion, and constrictive pericarditis in end-stage renal disease: Insights and pathophysiology.

    PubMed

    Rehman, Karim Abdur; Betancor, Jorge; Xu, Bo; Kumar, Arnav; Rivas, Carlos Godoy; Sato, Kimi; Wong, Leslie P; Asher, Craig R; Klein, Allan L

    2017-09-05

    A rising prevalence of end-stage renal disease (ESRD) has led to a rise in ESRD-related pericardial syndromes, calling for a better understanding of its pathophysiology, diagnoses, and management. Uremic pericarditis, the most common manifestation of uremic pericardial disease, is a contemporary problem that calls for intensive hemodialysis, anti-inflammatories, and often, drainage of large inflammatory pericardial effusions. Likewise, asymptomatic pericardial effusions can become large and impact the hemodynamics of patients on chronic hemodialysis. Constrictive pericarditis is also well documented in this population, ultimately resulting in pericardiectomy for definitive treatment. The management of pericardial diseases in ESRD patients involves internists, cardiologists, and nephrologists. Current guidelines lack clarity with respect to the management of pericardial processes in the ESRD population. Our review aims to describe the etiology, classification, clinical manifestations, diagnostic imaging tools, and treatment options of pericardial diseases in this population. © 2017 Wiley Periodicals, Inc.

  6. Vascular calcifications, vertebral fractures and mortality in haemodialysis patients

    PubMed Central

    Rodríguez-García, Minerva; Gómez-Alonso, Carlos; Naves-Díaz, Manuel; Diaz-Lopez, Jose Bernardino; Diaz-Corte, Carmen; Cannata-Andía, Jorge B.

    2009-01-01

    Background. Vascular calcifications and the bone fractures caused by abnormal bone fragility, also called osteoporotic fractures, are frequent complications associated with chronic kidney diseases (CKD). The aim of this study was to investigate the association between vascular calcifications, osteoporotic bone fractures and survival in haemodialysis (HD) patients. Methods. A total of 193 HD patients were followed up to 2 years. Vascular calcifications and osteoporotic vertebral fractures (quoted just as vertebral fractures in the text) were assessed by thoracic, lumbar spine, pelvic and hand X-rays and graded according to their severity. Clinical, biochemical and therapeutic data gathered during the total time spent on HD were collected. Results. The prevalence of aortic calcifications was higher in HD patients than in a random-based general population (79% versus 37.5%, P < 0.001). Total time on any renal replacement therapy (RRT) and diabetes were positively associated with a higher prevalence of vascular calcifications. In addition to these factors, time on HD was also positively associated with the severity of vascular calcifications, and higher haemoglobin levels were associated with a lower prevalence of severe vascular calcifications in large and medium calibre arteries. The prevalence of vertebral fractures in HD patients was similar to that of the general population (26.5% versus 24.1%). Age and time on HD showed a positive and statistically significant association with the prevalence of vertebral fractures. Vascular calcifications in the medium calibre arteries were associated with a higher rate of prevalent vertebral fractures. In women, severe vascular calcifications and vertebral fractures were positively associated with mortality [RR = 3.2 (1.0–10.0) and RR = 4.8 (1.7–13.4), respectively]. Conclusions. Positive associations between vascular calcifications, vertebral fractures and mortality have been found in patients on HD. PMID:18725376

  7. Fetuin-A Protects against Atherosclerotic Calcification in CKD

    PubMed Central

    Westenfeld, Ralf; Schäfer, Cora; Krüger, Thilo; Haarmann, Christian; Schurgers, Leon J.; Reutelingsperger, Chris; Ivanovski, Ognen; Drueke, Tilman; Massy, Ziad A.; Ketteler, Markus; Floege, Jürgen; Jahnen-Dechent, Willi

    2009-01-01

    Reduced serum levels of the calcification inhibitor fetuin-A associate with increased cardiovascular mortality in dialysis patients. Fetuin-A–deficient mice display calcification of various tissues but notably not of the vasculature. This absence of vascular calcification may result from the protection of an intact endothelium, which becomes severely compromised in the setting of atherosclerosis. To test this hypothesis, we generated fetuin-A/apolipoprotein E (ApoE)-deficient mice and compared them with ApoE-deficient and wild-type mice with regard to atheroma formation and extraosseous calcification. We assigned mice to three treatment groups for 9 wk: (1) Standard diet, (2) high-phosphate diet, or (3) unilateral nephrectomy (causing chronic kidney disease [CKD]) plus high-phosphate diet. Serum urea, phosphate, and parathyroid hormone levels were similar in all genotypes after the interventions. Fetuin-A deficiency did not affect the extent of aortic lipid deposition, neointima formation, and coronary sclerosis observed with ApoE deficiency, but the combination of fetuin-A deficiency, hyperphosphatemia, and CKD led to a 15-fold increase in vascular calcification in this model of atherosclerosis. Fetuin-A deficiency almost exclusively promoted intimal rather than medial calcification of atheromatous lesions. High-phosphate diet and CKD also led to an increase in valvular calcification and aorta-associated apoptosis, with wild-type mice having the least, ApoE-deficient mice intermediate, and fetuin-A/ApoE-deficient mice the most. In addition, the combination of fetuin-A deficiency, high-phosphate diet, and CKD in ApoE-deficient mice greatly enhanced myocardial calcification, whereas the absence of fetuin-A did not affect the incidence of renal calcification. In conclusion, fetuin-A inhibits pathologic calcification in both the soft tissue and vasculature, even in the setting of atherosclerosis. PMID:19389852

  8. Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation.

    PubMed

    Obafemi, Abimbola A; Bulas, Dorothy I; Troendle, James; Marini, Joan C

    2008-11-01

    Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Copyright 2008 Wiley-Liss, Inc.

  9. The Role of Inorganic Pyrophosphate in Aortic Valve Calcification

    PubMed Central

    Rathan, Swetha; Yoganathan, Ajit P.; O’Neill, W. Charles

    2017-01-01

    Background and aim of the study Aortic valve (AV) calcification is a major cause of morbidity and mortality, yet the molecular mechanisms involved are poorly understood. Hence, an ex vivo model of calcification in intact AVs was developed in order to test the role of orthophosphate and pyrophosphate (PPi), both of which factors are known to influence vascular calcification. Methods Porcine AV leaflets were cultured in serum-free medium under static conditions for eight days, over which time leaflet architecture and viability were preserved. Calcification was measured as the incorporation of 45Ca, with confirmation by Alizarin Red staining. Results Calcification required both a high phosphate concentration (3.8 mM) and removal of PPi with alkaline phosphatase or inorganic pyrophosphatase. Calcification occurred predominantly on the fibrosa and was arrested by the bisphosphonate etidronate, a non-hydrolyzable analog of PPi. Leaflets released PPi into the medium, and this was enhanced by MLS38949, a specific inhibitor of tissue non-specific alkaline phosphatase (TNAP). Furthermore, leaflets synthesized PPi from extracellular ATP, which was reduced by β, γ-methylene-ATP, an inhibitor of ectonucleotide pyrophosphorylase phosphodiesterase (NPP1). Conclusion The ex vivo AV calcification model developed in the present study showed that extracellular PPi, produced by valvular tissue, is a potent inhibitor of valvular calcification. In addition to synthesis, hydrolysis by TNAP also controls PPi levels and calcification. The results suggest that a decreased synthesis or increased hydrolysis of pyrophosphate may contribute to valvular calcification, and that bisphosphonates or inhibitors of TNAP are potential preventive strategies of the process. TNAP are potential preventive strategies. PMID:25803964

  10. Study of calcification during a daily cycle of the coral Stylophora pistillata: implications for 'light-enhanced calcification'.

    PubMed

    Moya, Aurélie; Tambutté, Sylvie; Tambutté, Eric; Zoccola, Didier; Caminiti, Natacha; Allemand, Denis

    2006-09-01

    This work, performed on the scleractinian coral Stylophora pistillata, aims at providing new information on the 'light-enhanced calcification' process. In a first step, in controlled conditions of culture and constant light supply, we studied the diurnal cycle of calcification. We determined that calcification rates are constant during the day and the night with a 2.6-fold difference between day and night calcification rates. We also showed that the photosynthetic rate is constant throughout the day when a constant light intensity is applied. Our results on free-running experiments in prolonged conditions of light or dark suggest that calcification is not regulated by an endogenous circadian rhythm. In a second step, using a kinetic isotopic approach with (45)Ca, we characterized the transition stages between day and night and vice versa. Under our experimental conditions, the lag-phase necessary to switch from the light to the dark calcification rate is the same as the lag-phase necessary to switch from the dark to the light calcification rate. We discuss our results in the context of two hypotheses of the light-enhanced calcification process: (1) the role of photosynthesis on the pH in the coelenteron and (2) the role of photosynthesis in supplying precursors of the organic matrix.

  11. A patient with Crohn's disease who presented with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.

    PubMed

    Unverdi, Selman; Ceri, Mevlut; Öztürk, Mehmet Akif; Akbal, Erdem; Ensari, Arzu; Yılmaz, Rahmi; Kocak, Erdem; Inal, Salih; Koklu, Seyfettin; Duranay, Murat

    2011-01-01

    Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is characterized with fever, purpura, anemia due to microangiopathic hemolysis, thrombocytopenia, kidney damage, and neurologic symptoms. The development of TTP/HUS during the course of inflammatory bowel diseases was rarely reported. However, coexistence of TTP/HUS and Crohn's disease in the same patient has not been reported previously. We herein present a case of TTP/HUS who presented with Crohn's disease. He responded to cyclosporine treatment.

  12. Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium.

    PubMed

    Vaziri, Nosratola D; Goshtasbi, Nisa; Yuan, Jun; Jellbauer, Stefan; Moradi, Hamid; Raffatellu, Manuela; Kalantar-Zadeh, Kamyar

    2012-01-01

    Chronic kidney disease (CKD) causes intestinal barrier dysfunction which by allowing influx of endotoxin and other noxious products contributes to the CKD-associated systemic inflammation and uremic toxicity. We have recently shown that intestinal barrier dysfunction in CKD animals is due to degradation of transcellular (claudin-1 and occludin) and intracellular (ZO1) constituents of epithelial tight junction (TJ). This study determined whether CKD-associated disruption of TJ is mediated by retained uremic toxins/metabolites and, if so, whether they are removed by hemodialysis. The TJ-forming human enterocytes (T84 cells) were seeded on the Transwell plates and utilized when transepithelial electrical resistance (TER) exceeded 1,000 mΩ/cm(2) to ensure full polarization and TJ formation. The cells were then incubated for 24 h in media containing 10% pre- or posthemodialysis plasma from end-stage renal disease (ESRD) patients or healthy individuals. TER was then measured and cells were processed for Western blot and immunohistological analyses. Compared with the control plasma, incubation in media containing predialysis plasma from ESRD patients resulted in a marked drop in TER pointing to increased epithelial permeability. This was accompanied by significant reductions in claudin-1 (85%), occludin (15%), and ZO1 (70%) abundance. The severity of TJ damage and dysfunction was significantly less in cells exposed to the postdialysis in comparison to predialysis plasma. These findings point to the presence of as-yet unidentified product(s) in the uremic plasma capable of depleting epithelial TJ. Exposure to uremic milieu damages the intestinal epithelial TJ and impairs its barrier function, events which are mediated by agents which are partially removed by hemodialysis. Copyright © 2012 S. Karger AG, Basel.

  13. Comparison of Gabapentin and Ketotifen in Treatment of Uremic Pruritus in Hemodialysis Patients

    PubMed Central

    Amirkhanlou, Saeid; Rashedi, Anna; Taherian, Jalal; Hafezi, Ali Akbar; Parsaei, Sahar

    2016-01-01

    Objectives: Uremic pruritus is a common problem in hemodialysis patients. Several treatments have been used for decreasing itching in these patients. Gabapentin and ketotifen are two drugs used for treating uremic patients. The aim of this study was to compare gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Methods: In this double-blind randomized clinical trial, 52 hemodialysis patients with uremic pruritus referred to 5azarTeaching Hospital in Gorgan in 2013 were studied. Patients were randomly assigned to two groups of 26 subjects (groups G and K). In group G, patients treated with gabapentin capsules 100 mg daily for 2 weeks, and in Group K, patients treated with ketotifen 1 mg twice daily for 2 weeks. Before and at the end of study, pruritus severity was determined based on Shiratori’s severity scores. Collected data were analyzed by SPSS-21 statistical software. Results: There was no significant different between two groups in the age and sex. After two weeks of treatment, severity of pruritus was significantly reduced in both groups (88.4% in group G vs. 76.9% in group K). Gabapentin compared with ketotifen had a better effect on improving itching in the age group of 30-60 years and in males. 5 patients (19.2%) in both groups suffered from drowsiness and dizziness, but no serious side effects were observed. Conclusions: The results showed that gabapentin and ketotifen significantly improved pruritus in hemodialysis patients, and no significant difference was observed between two groups. PMID:27022338

  14. Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis

    PubMed Central

    Balaskas, Elias; Szepietowski, Jacek C.; Bessis, Didier; Ioannides, Dimitrios; Ponticelli, Claudio; Ghienne, Corinne; Taberly, Alain

    2011-01-01

    Summary Background and objectives Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy. Design, setting, participants, & measurements A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7. Results Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P < 0.0001, intergroup analysis). This was associated with an objective reduction in the density and thickness of the scales on day 7 (P < 0.0001 compared with the comparator) and a substantial improvement of the uremic pruritus (75%) and quality of life of the patients at study end (P < 0.001, intragroup analysis). The test product was very well tolerated, with product-related local intolerance (exacerbated pruritus, local burning, or erythema) occurring in only five patients (5%). Conclusions Uremic xerosis can be managed successfully when an appropriate emollient therapy is used. PMID:21258039

  15. Uremic pleuritis: A case report and review of recurrent exudative pleural effusions in children.

    PubMed

    McGraw, Matthew D; Galambos, Csaba; Stillwell, Paul C

    2017-09-01

    Despite similar mechanisms driving pleural fluid accumulation, the causes of pleural effusions in children differ significantly from that of adults. When a pleural effusion re-occurs in an adult, literature recommends early thoracentesis, and consideration for pleuroscopy with biopsy to guide the diagnostic evaluation. In children, there is a paucity of literature for guiding management of recurrent exudative pleural effusion. We present an unusual pediatric case of uremic pleuritis with recurrent pericardial and exudative pleural effusions. © 2017 Wiley Periodicals, Inc.

  16. [Successful treatment of enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome and acute encephalopathy].

    PubMed

    Mizuno, Hideki; Minouchi, Keiji; Aoyama, Shou; Hinoue, Yoshinobu

    2015-07-01

    We report a case of a woman in her twenties with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome who developed acute encephalopathy on day 5 of admission. She recovered after treatment with steroid pulse therapy, plasmapheresis, and recombinant thrombomodulin, without any adverse sequelae. We report this interesting case and provide a summary of the recent outbreak of enterohemorrhagic Escherichia coli O111.

  17. Identification and management of atypical hemolytic uremic syndrome immediately post-heart transplantation.

    PubMed

    Vardas, Panos N; Hashmi, Zubair A; Hadi, M Azam

    2015-04-01

    Atypical hemolytic uremic syndrome (aHUS) is a serious hematologic disorder with high mortality if left untreated. A comprehensive literature review revealed only two cases of aHUS post-heart transplantation. In both cases the disease developed after induction of calcineurin inhibitor therapy. We report a case of immediate post-heart transplantation aHUS, manifested before the induction of, and therefore not associated with, calcineurin inhibitors.

  18. [Atypic hemolytic uremic syndrome taken for Goodpasture's syndrome: A case report].

    PubMed

    Bourgault, Marie; Sarret, Damien; Isnard, Pierre; Rabant, Marion; Labaye, Jacques

    2015-12-01

    We report the case of a patient suffering from atypical hemolytic uremic syndrome with inaugural intra-alveolar hemorrhage. Clinical features and detection of circulating anti-glomerular basal membrane antibodies first raise the possibility of a Goodpasture syndrome. Renal biopsy allows to correct the diagnosis. Partial remission is obtained thanks to specific care and eculizumab infusions. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  19. Recurrent Atypical Hemolytic Uremic Syndrome in Children With Acute Lymphoblastic Leukemia Undergoing Maintenance Chemotherapy.

    PubMed

    Cheng, Geoffrey; Ozgonenel, Bulent; Bhambhani, Kanta; Kapur, Gaurav; Smith, Richard J; Savaşan, Süreyya

    2017-10-04

    Chemotherapy-associated myelosuppression and renal dysfunction is not uncommon during childhood acute lymphoblastic leukemia (ALL) therapy. Here we report 2 cases of atypical hemolytic uremic syndrome (aHUS) presenting with pancytopenia and renal dysfunction that developed during maintenance chemotherapy characterized by hypocomplementemia. Both cases experienced recurrence after resolution of the initial aHUS episode upon resumption of chemotherapy, raising a possible contributory role for chemotherapy in the disease pathogenesis.

  20. Shiga toxin-producing Escherichia coli infections associated with hemolytic uremic syndrome, Italy, 1988-2000.

    PubMed

    Tozzi, Alberto E; Caprioli, Alfredo; Minelli, Fabio; Gianviti, Alessandra; De Petris, Laura; Edefonti, Alberto; Montini, Giovanni; Ferretti, Alfonso; De Palo, Tommaso; Gaido, Maurizio; Rizzoni, Gianfranco

    2003-01-01

    The mean annual incidence of hemolytic uremic syndrome in persons

  1. Shiga Toxin–Producing Escherichia coli Infections Associated with Hemolytic Uremic Syndrome, Italy, 1988–2000

    PubMed Central

    Caprioli, Alfredo; Minelli, Fabio; Gianviti, Alessandra; De Petris, Laura; Edefonti, Alberto; Montini, Giovanni; Ferretti, Alfonso; De Palo, Tommaso; Gaido, Maurizio; Rizzoni, Gianfranco

    2003-01-01

    The mean annual incidence of hemolytic uremic syndrome in persons <15 years of age in Italy from 1988 to 2000 was 0.28 per 100,000 population. Laboratory investigations showed that Shiga toxin–producing Escherichia coli (STEC) infection occurred in 73.1% of patients. STEC O157 was the most common serotype, but a considerable number of cases were from infections by non-O157 STEC. PMID:12533290

  2. The role of the gastrointestinal tract and microbiota on uremic toxins and chronic kidney disease development.

    PubMed

    Briskey, David; Tucker, Patrick; Johnson, David W; Coombes, Jeff S

    2017-02-01

    It is well-established that uremic toxins are positively correlated with the risk of developing chronic kidney disease and cardiovascular disease. In addition, emerging data suggest that gut bacteria exert an influence over both the production of uremic toxins and the development of chronic kidney disease. As such, modifying the gut microbiota may have the potential as a treatment for chronic kidney disease. This is supported by data that suggest that rescuing microbiota dysbiosis may: reduce uremic toxin production; prevent toxins and pathogens from crossing the intestinal barrier; and, reduce gastrointestinal tract transit time allowing nutrients to reach the microbiota in the distal portion of the gastrointestinal tract. Despite emerging literature, the gut-kidney axis has yet to be fully explored. A special focus should be placed on examining clinically translatable strategies that might encourage improvements to the microbiome, thereby potentially reducing the risk of the development of chronic kidney disease. This review aims to present an overview of literature linking changes to the gastrointestinal tract with microbiota dysbiosis and the development and progression of chronic kidney disease.

  3. Uremic toxins and lipases in haemodialysis: a process of repeated metabolic starvation.

    PubMed

    Stegmayr, Bernd

    2014-04-30

    Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL) and hepatic lipase (HL). For patients in haemodialysis (HD) and peritoneal dialysis (PD) the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3-4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.

  4. Uremic Toxins and Lipases in Haemodialysis: A Process of Repeated Metabolic Starvation

    PubMed Central

    Stegmayr, Bernd

    2014-01-01

    Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL) and hepatic lipase (HL). For patients in haemodialysis (HD) and peritoneal dialysis (PD) the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3–4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation. PMID:24784324

  5. Removal of the uremic retention solute p-cresol using fractionated plasma separation and adsorption.

    PubMed

    Meijers, Björn K; Weber, Viktoria; Bammens, Bert; Dehaen, Wim; Verbeke, Kristin; Falkenhagen, Dieter; Evenepoel, Pieter

    2008-03-01

    Removal of protein-bound uremic retention solutes, including p-cresol, by peritoneal dialysis and hemodialysis (HD) is limited. p-Cresol, mainly circulating as sulfate conjugate (p-cresyl sulfate [PCS]), is independently associated with mortality. Fractionated plasma separation and adsorption (FPSA) is a nonbiologic detoxification system for the treatment of liver failure. The FPSA clearance of uremic retention solutes is unknown. We studied PCS clearance by FPSA, using the Prometheus system. The neutral resin adsorbent and the anion exchange adsorbent bind PCS in vitro (reduction ratios [RRs] 37 and 70%). Ex vivo, the adsorbent mass removal (MR) (median 47.5 mg) contributes more than half to total MR (median 89.6 mg). In vivo, PCS RR during FPSA (50%) exceeded the RR during high flux HD (30%). We halted the study after four inclusions due to repeated thrombosis of the arterio-venous conduit. In conclusion, FPSA is a promising technique to improve clearance of protein-bound uremic retention solutes.

  6. Respiratory muscle weakness in uremic patients under continuous ambulatory peritoneal dialysis.

    PubMed

    Gómez-Fernández, P; Sánchez Agudo, L; Calatrava, J M; Escuin, F; Selgas, R; Martínez, M E; Montero, A; Sánchez-Sicilia, L

    1984-01-01

    The increasingly frequent use of continuous ambulatory peritoneal dialysis (CAPD) as substitutive therapy in terminal renal failure has induced the investigation of the advantages and disadvantages of this therapeutic modality. The effects of CAPD on pulmonary function are one of the aspects currently under study. Based on previous data suggesting the existence of extrapulmonary ventilatory restriction in uremic patients under CAPD, we have studied in these patients the respiratory muscle function as expressed in the maximal inspiratory pressure (MIP) and assessed the impact of the infusion of 2 liters of dialysis fluid into the peritoneal cavity on both MIP and the pulmonary volumes. Uremic patients evidenced significantly lower MIP values as compared with healthy controls. The filling of the peritoneal cavity induced, both in the supine and in the sitting position, a restrictive effect and an increase in the inspiratory capacity. We conclude that uremic patients under CAPD evidence a respiratory muscle dysfunction of as yet unclear cause. Our findings further suggest that the infusion of 2 liters of dialysis fluid into the peritoneal cavity induces not only a restrictive effect, but also an increase in the strength of the respiratory muscles, the latter effect being probably due to increased diaphragmatic contractility.

  7. Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats

    PubMed Central

    Inami, Yuko; Hamada, Chieko; Seto, Takuya; Hotta, Yoko; Aruga, Seiki; Inuma, Jiro; Azuma, Kosuke; Kaneko, Kayo; Watada, Hirotaka

    2014-01-01

    Aim. Chronic kidney disease (CKD) represents endothelial dysfunction. Monocyte adhesion is recognized as the initial step of arteriosclerosis. Indoxyl sulfate (IS) is considered to be a risk factor for arteriosclerosis in CKD. Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS. In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules. Methods. Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups. The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49. The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined. Results. Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase. The monocyte adhesion was related to serum creatinine and IS in sera. Overexpression of VCAM-1 and TGF-β1 mRNA in the arterial walls was observed in uremic rats. IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro. Conclusion. It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression. PMID:24829798

  8. Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

    PubMed Central

    Glorieux, Griet; Schepers, Eva; Cohen, Gerald; Gondouin, Bertrand; Van Landschoot, Maria; Eloot, Sunny; Rops, Angelique; Van de Voorde, Johan; De Vriese, An; van der Vlag, Johan; Brunet, Philippe; Van Biesen, Wim; Vanholder, Raymond

    2013-01-01

    Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels. PMID:24009240

  9. Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall.

    PubMed

    Pletinck, Anneleen; Glorieux, Griet; Schepers, Eva; Cohen, Gerald; Gondouin, Bertrand; Van Landschoot, Maria; Eloot, Sunny; Rops, Angelique; Van de Voorde, Johan; De Vriese, An; van der Vlag, Johan; Brunet, Philippe; Van Biesen, Wim; Vanholder, Raymond

    2013-12-01

    Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

  10. Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.

    PubMed

    Prokopienko, Alexander J; Nolin, Thomas D

    2017-09-20

    Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease. Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also discussed. Expert commentary: Large interindividual variability in toxin concentrations may explain some differences in nonrenal clearance of medications. Advances in human microbiome research provide unique opportunities to systematically evaluate the impact of individual and combined microbial toxins on drug metabolism and transport, and to explore microbiota-derived uremic toxins as potential therapeutic targets.

  11. Posterior reversible encephalopathy and cerebral vasoconstriction in a patient with hemolytic uremic syndrome.

    PubMed

    Agarwal, Rajkumar; Davis, Cresha; Altinok, Deniz; Serajee, Fatema J

    2014-05-01

    We report a patient with hemolytic uremic syndrome who presented with radiological manifestations suggestive of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome. A 13-year-old girl presented with fever and bloody diarrhea and progressed to develop hemolytic uremic syndrome. She subsequently developed encephalopathy, aphasia, and right-sided weakness. Brain magnetic resonance imaging showed presence of vasogenic edema in the left frontal lobe, in addition to T2 and fluid-attenuated inversion recovery changes in white matter bilaterally, compatible with posterior reversible encephalopathy syndrome. Magnetic resonance angiography showed beading of the cerebral vessels. Neurological deficits reversed 8 days after symptom onset, with resolution of the beading pattern on follow-up magnetic resonance angiography after 3 weeks, suggesting reversible cerebral vasoconstriction syndrome. Both posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome may represent manifestations of similar underlying pathophysiologic mechanisms. Recognition of the co-existence of these processes in patients with hemolytic uremic syndrome may aid in judicious management of these patients and avoidance of inappropriate therapeutic interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin

    PubMed Central

    Perna, Alessandra F.; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

    2017-01-01

    Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin. PMID:28075397

  13. The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin.

    PubMed

    Perna, Alessandra F; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

    2017-01-10

    Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin.

  14. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review.

    PubMed

    Vanholder, Raymond; Schepers, Eva; Pletinck, Anneleen; Nagler, Evi V; Glorieux, Griet

    2014-09-01

    A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.

  15. Molecular mechanisms for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

    PubMed

    Watanabe, Hiroshi

    2013-01-01

    Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

  16. Supplementation of Emblica officinalis (Amla) extract reduces oxidative stress in uremic patients.

    PubMed

    Chen, Tung-Sheng; Liou, Show-Yih; Chang, Yen-Lin

    2009-01-01

    Emblica Officinalis (also known as Amla or Indian Gooseberry), a natural, traditional and functional food in Asia, has physiological benefits such as hepato-, cyto- and radio- protection, as well as hypolipidemic effects. In addition, Amla often functions as a potent antioxidant due to the high level of ascorbic acid (ranging from 1,100 to 1,700 mg/100 g of fruit) in its fruit. The aim of this study was to determine whether supplementation with Amla extract could reduce oxidative stress in patients with uremia. The findings show that supplementation with Amla extract for 4 months reduced the plasma oxidative marker, 8-iso-prostaglandin, (M0 vs. M4 = 1415 +/- 1234 pg/ml vs. 750 +/- 496 pg/ml, p < 0.05) and increased plasma total antioxidant status (TAS) (M0 vs. M4 = 2.32 +/- 0.14 mM vs. 2.55 +/- 0.24 mM, p < 0.05) in uremic patients. On the other hand, there were no significant differences observed in liver function (GOP and GPT), renal function (creatinine, blood urea nitrogen and uric acid), diabetic index (plasma glucose and adiponectin) and atherogenic index (LDL/HDL ratio, total cholesterol and homocysteine) in patients treated with Amla for 4 months. Our data suggest that Amla supplementation may increase plasma antioxidant power and decrease oxidative stress in uremic patients. However, Amla extract did not influence hepatic or renal function, or diabetic and atherogenic indices in uremic patients.

  17. Observer study to evaluate the simulation of mammographic calcification clusters

    NASA Astrophysics Data System (ADS)

    Sousa, Maria A. Z.; Marcomini, Karem D.; Bakic, Predrag R.; Maidment, Andrew D. A.; Schiabel, Homero

    2016-03-01

    Numerous breast phantoms have been developed to be as realistic as possible to ensure the accuracy of image quality analysis, covering a greater range of applications. In this study, we simulated three different densities of the breast parenchyma using paraffin gel, acrylic plates and PVC films. Hydroxyapatite was used to simulate calcification clusters. From the images acquired with a GE Senographe DR 2000D mammography system, we selected 68 regions of interest (ROIs) with and 68 without a simulated calcification cluster. To validate the phantom simulation, we selected 136 ROIs from the University of South Florida's Digital Database for Screening Mammography (DDSM). Seven trained observers performed two observer experiments by using a high-resolution monitor Barco mod. E-3620. In the first experiment, the observers had to distinguish between real or phantom ROIs (with and without calcification). In the second one, the observers had to indicate the ROI with calcifications between a pair of ROIs. Results from our study show that the hydroxyapatite calcifications had poor contrast in the simulated breast parenchyma, thus observers had more difficulty in identifying the presence of calcification clusters in phantom images. Preliminary analysis of the power spectrum was conducted to investigate the radiographic density and the contrast thresholds for calcification detection. The values obtained for the power spectrum exponent (β) were comparable with those found in the literature.

  18. Malnutrition, a new inducer for arterial calcification in hemodialysis patients?

    PubMed

    Zhang, Kun; Cheng, Gang; Cai, Xue; Chen, Jie; Jiang, Ying; Wang, Tong; Wang, Jingfeng; Huang, Hui

    2013-03-18

    Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear. 68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods. 66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP. Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients.

  19. Malnutrition, a new inducer for arterial calcification in hemodialysis patients?

    PubMed Central

    2013-01-01

    Background Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear. Methods 68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods. Results 66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP. Conclusions Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients. PMID:23506394

  20. Intracranial physiological calcifications evaluated with cone beam CT

    PubMed Central

    Sedghizadeh, P P; Nguyen, M; Enciso, R

    2012-01-01

    Objectives The purpose of this study was to evaluate cone beam CT (CBCT) scans for the presence of physiological and pathological intracranial calcifications. Methods CBCT scans from male and female patients that met our ascertainment criteria were evaluated retrospectively (n = 500) for the presence of either physiological or pathological intracranial calcifications. Results Out of the 500 patients evaluated, 176 had evidence of intracranial physiological calcification (35.2% prevalence), and none had evidence of pathological calcification. There was a 3:2 male-to-female ratio and no ethnic predilection; the ages of affected patients ranged from 13 years to 82 years with a mean age of 52 years. The majority of calcifications appeared in the pineal/habenular region (80%), with some also appearing in the choroid plexus region bilaterally (12%), and a smaller subset appearing in the petroclinoid ligament region bilaterally (8%). Conclusions Intracranial physiological calcifications can be a common finding on CBCT scans, whereas pathological intracranial calcifications are rare. PMID:22842632

  1. Tissue age affects calcification in the scleractinian coral Madracis mirabilis.

    PubMed

    Elahi, Robin; Edmunds, Peter J

    2007-02-01

    In this study, two factorial experiments were used to investigate the role of tissue age in affecting the phenotypic expression of calcification in scleractinian corals. Both experiments tested whether calcification was altered by tissue age and whether corals of different ages exploit plasticity to differing degrees by altering calcification rates under new environmental conditions. To isolate age and size effects, branches of the Caribbean coral Madracis mirabilis were broken into a distal portion that was functionally young and a proximal portion that was functionally old. Fragments were transplanted from a deep (17 m) to a shallow (9 m) site in a Jamaican lagoon to test whether age affected the plasticity of calcification. Both experiments demonstrated that calcification scaled isometrically in the two age groups, and although scaling exponents were indistinguishable statistically among ages, young fragments calcified faster than old fragments. Thus, the effect of age on calcification rate was absolute and independent of size. However, the interactive effect of age and depth was not significant, demonstrating that ability to alter calcification rate (i.e., the extent of phenotypic plasticity for this trait) was unaffected by age. Together, these patterns are consistent with the hypothesis that the proximal modules (i.e., polyps) of M. mirabilis are subject to physiological senescence, as has been reported for other clonal organisms, including algae, fungi, plants, bryozoans, ascidians, and other cnidarians.

  2. Targeting vascular calcification: softening-up a hard target.

    PubMed

    Kapustin, Alexander; Shanahan, Catherine M

    2009-04-01

    Widespread vascular calcification is a ubiquitous feature of aging and is prevalent in association with a number of common pathologies including atherosclerosis, renal failure, and diabetes. Once thought of as innocuous, emerging evidence suggests that calcification is causal in precipitating vascular events and mediating chronic cardiovascular damage, independent of disease context. Importantly, a large body of data has shed light on the factors that favor the formation of calcification in vivo, as well as on the complex mechanisms that initiate and promote it. This has identified some novel targets and allowed for the possibility that calcification can potentially be blocked and ultimately regressed. Targets include local and circulating inhibitors of calcification as well as factors that may ameliorate vascular smooth muscle cell (VSMC) apoptosis. Despite this, the vasculature remains a difficult tissue to target and currently there are no effective treatments in general use. More crucially, any potential treatments will need to be carefully evaluated as they may impinge on bone metabolism. Our best hope for the near future is to normalize factors associated with accelerated calcification in pathologies such as renal failure where, aberrant mineral metabolism, as well as treatment regimes, may contribute to the initiation and progression of calcification.

  3. Skeletal maturity assessment using mandibular canine calcification stages.

    PubMed

    Džemidžić, Vildana; Tiro, Alisa; Zukanović, Amila; Redžić, Ismeta; Nakaš, Enita

    2016-11-01

    The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years). The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI), as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase. Copyright © 2016 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  4. Recent advances in research on human aortic valve calcification.

    PubMed

    Furukawa, Ken-Ichi

    2014-01-01

    Aortic valve calcification can aggravate aortic stenoses, and it is a significant cause of sudden cardiac death. The increasing number of patients with age-related calcification is a problem in developed nations. However, the only treatment option currently available is highly invasive cardiac valve replacement. Therefore, clarification of the etiology of calcification is urgently needed to develop drug therapies and prevention methods. Recent studies have revealed that calcification is not a simple sedimentation of a mineral through a physicochemical phenomenon; various factors dynamically contribute to the mechanism. Further, we are finally beginning to understand the cellular origins of calcification, which had been unclear for a long time. Based on these findings that help to clarify potential drug targets, we expect to establish drug therapies that reduce the stress on patients. In this paper, I introduce the latest findings on cells that are most likely to contribute to calcification and on calcification-related factors that may lead to the development of drug therapies.

  5. Inducers and inhibitors of biomineralization: lessons from pathological calcification.

    PubMed

    Giachelli, C M

    2005-11-01

    Ectopic calcification is a common response to soft tissue injury and systemic mineral imbalance and can lead to devastating clinical consequences when present in joints, heart valves and blood vessels. We have hypothesized that mineralization of matrices in any tissue is normally controlled by a balance between procalcific and anticalcific regulatory proteins such that abnormal deposition of apatite is avoided. Alterations in this balance induced by injury, disease or genetic deficiency are postulated to induce ectopic mineral deposition. Over the past several years, we have developed in vitro and in vivo models of ectopic calcification to investigate potential inducers and inhibitors of this process. Osteopontin, a secreted phosphoprotein, has emerged as a major inhibitor of ectopic mineralization. Osteopontin is a potent inhibitor of vascular cell calcification in vitro and mice lacking osteopontin are highly susceptible to ectopic calcification. Furthermore, osteopontin treatment of biomaterials protected against ectopic mineralization. Our studies indicate that in addition to inhibiting apatite crystal initiation and growth, osteopontin stimulates resorption of ectopic calcification via peripheral macrophages and giant cells. In contrast, inorganic phosphate has emerged as a major inducer of mineralization in these systems. Elevated inorganic phosphate (Pi) was shown to induce smooth muscle cell matrix calcification with morphological properties similar to those observed in calcified human valves and atherosclerotic plaques. Furthermore, mineralization induced by inorganic phosphate was dependent on the activity of the sodium-dependent phosphate cotransporter, Pit-1. These studies implicate controlled, transcellular transport of Pi as a major requirement for matrix calcification.

  6. Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease.

    PubMed

    Borges, Natália A; Barros, Amanda F; Nakao, Lia S; Dolenga, Carla J; Fouque, Denis; Mafra, Denise

    2016-11-01

    Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients. This was a cross sectional study. Twenty-one nondialysis patients were included (43% men, 63.0 ± 7.8 years, glomerular filtration rate: 34.4 ± 12.5 mL/min) as well as 29 hemodialysis (HD) patients [58% men, 52.7 ± 10.3 years, time on dialysis 54 (31-94.5 months)]. Total levels of uremic toxins (IS, p-CS, and IAA) were assessed by high-performance liquid chromatography with fluorescence detection. C-reactive protein, Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and calprotectin plasma levels were determined by immunometric assays. HD patients presented higher inflammatory markers and uremic toxins levels than nondialysis patients. IL-6 levels were positively correlated with IS (r = 0.49; P = .03), p-CS (r = 0.35; P = .04) and IAA (r = 0.36; P = .03). A positive correlation was also observed between MCP-1 levels with IS (r = 0.72; P = .001), p-CS (r = 0.48; P = .001) and IAA (r = 0.75; P = .0001). Linear regression showed that IS was an independent predictor for IL-6 and MCP-1 levels after adjustment. Plasma uremic toxins were associated with higher IL-6 and MCP-1 levels in CKD patients, potentially playing a role in the development of CVD. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  7. [Relationship between accelerated artherosclerosis and Treg/Teff balance in uremic apoE-/- mice].

    PubMed

    Shen, Yan; Yuan, Zu-yi; Liu, Yan; Xiao, Yan; Wu, Yue; Zhao, Yan; Tian, Yu-ling; Liu, Wei-min; Wang, Li-jun; Liang, Xiao; Chen, Tao; Geng, Tao

    2010-02-01

    To establish a uremic apolipoprotein E knockout (apoE-/-) mouse model and explore the relationship between accelerated atherosclerosis and Treg/Teff balance. Using apoE-/- mice with C57BL/6J background, uremic apoE-/- mice were created by electrocautery of the right kidney and nephrectomy of the left, and the control apoE-/- mice received a sham-operation. Two weeks after inducing uremia, the renal function of the mice were evaluated to assess the validity of the model. Ten weeks after the operation, blood samples were obtained from the mice to assess the renal function and serum total cholesterol (TCH); the serum concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interferon-gamma (IFN-gamma) were detected by ELISA, and CD4(+)CD25(+)Foxp3(+)Treg ratio in the spleen was determined by flow cytometry. RT-PCR was used to detect the expression of Foxp3 and IFN-gamma mRNA in the aorta, and oil red O staining used to investigate the relative atherosclerotic area on the frozen sections of the aortic root. The correlation between the renal function parameters and Treg quantity was analyzed. Renal function detection confirmed successful establishment of the uremic apoE-/- mouse model. Ten weeks after the operation, the relative atherosclerotic plaque area in the aortic root plaque increased significantly, the spleen Treg ratio decreased, the serum concentrations of TGF-beta(1) decreased and IFN-gamma and TCH increased, the expression of aortic Foxp3 mRNA decreased and IFN-gamma mRNA increased as compared with those in the control apoE-/- mice. A significant inverse correlation was found between the renal function parameters and Treg quantity in uremic apoE-/- mice. In uremic apoE-/- mice, accelerated aortic atherosclerosis is correlated to the T cell subset (Treg/Teff) imbalance shown by decreased quantity and impaired function of Treg and enhanced activity of Teff.

  8. Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

    PubMed

    AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

    2016-01-01

    Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

  9. Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification.

    PubMed

    Bhakta, Mayurkumar; Bruce, Charles; Messika-Zeitoun, David; Bielak, Lawrence; Sheedy, Patrick F; Peyser, Patricia; Sarano, Maurice

    2009-01-01

    The use of oral calcium supplementation among the elderly for prevention and treatment of osteoporosis and osteopenia is increasing. The incidence of aortic valve disease and coronary artery disease also is increasing. No study thus far has been done to demonstrate whether this affects the progression of calcification in both the valves and vasculature. We sought to determine whether ingestion of oral calcium supplementation has an effect on aortic valve calcification (AVC) and coronary artery calcification (CAC). We performed an independent assessment of AVC, CAC, and calcium supplementation among patients enrolled in the Epidemiology of Coronary Artery Calcification study who were >60 years of age and had baseline and 4-year follow-up AVC data. In this population-based study of Olmsted County (Minnesota) residents, AVC and CAC scores were determined prospectively by electron beam computed tomography. We evaluated baseline demographic data and analyzed whether those patients using calcium supplementation had a higher rate of progression of both AVC and CAC. We identified 257 patients (mean age, 67.8+/-5.2 years), 144 of whom were women. Twenty-five patients (all women) reported using calcium supplements. Analysis of the 144 women (25 taking calcium supplementation) showed there was no difference in the progression of AVC (mean difference in baseline and follow-up AVC score; no supplement versus supplement, 30+/-9 vs 39+/-28; P=.73) or CAC (mean difference in baseline and follow-up CAC score; no supplement vs supplement, 47+/-15 vs 112+/-22; P=.154). There were no significant differences between the 2 groups with regard to baseline AVC, serum calcium, renal function, diabetes, hypertension, cholesterol, or body mass index. In this community-based observational study with a 4-year follow-up, no significant increased progression of AVC or CAC was found in women taking oral calcium supplementation. Larger prospective, randomized studies are needed to confirm these

  10. Determinants of aortic bioprosthetic valve calcification assessed by multidetector CT.

    PubMed

    Mahjoub, Haïfa; Mathieu, Patrick; Larose, Eric; Dahou, Abdelaziz; Sénéchal, Mario; Dumesnil, Jean-Gaston; Després, Jean-Pierre; Pibarot, Philippe

    2015-03-01

    Cusp calcification is the main mechanism leading to bioprosthetic heart valve (BPV) failure. Recent studies suggest that BPV calcification is an active rather than passive process probably modulated by several mechanisms including lipid-mediated inflammation and dysfunctional phosphocalcic metabolism. To identify the clinical and metabolic determinants of BPV calcification assessed by multidetector CT (MDCT). Presence of BPV calcification was assessed by MDCT in 194 patients who had undergone aortic valve replacement. A calcification score was individually calculated and expressed in mm(3). Patients also underwent a clinical evaluation, a Doppler echocardiographic exam, and a plasma lipid and phosphocalcic profile. 46 patients (24%) had BPV calcification (cusp calcification score >0 mm(3)). After adjustment for age, gender, and time interval since BPV implantation, increased calcium-phosphorus product (OR 1.11, 95% CI 1.01 to 1.23 per 1 unit; p=0.02) and the presence of prosthesis-patient mismatch (OR 3.67, 95% CI 1.25 to 10.6; p=0.01) were the strongest independent factors associated with BPV calcification. Calcium supplement intake, age and female gender were independently associated with increased calcium-phosphorus product. This study suggests that higher calcium-phosphorus product and prosthesis-patient mismatch promote BPV calcification. Furthermore, this study reports that calcium supplements, which are extensively prescribed in elderly patients, are independently associated with higher calcium-phosphorus product. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Management of rotator cuff calcific tendinosis guided by ultrasound elastography.

    PubMed

    Lin, Yen-Huai; Chiou, Hong-Jen; Wang, Hsin-Kai; Lai, Yi-Chen; Chou, Yi-Hong; Chang, Cheng-Yen

    2015-10-01

    Ultrasound (US) elastography can provide information about the hardness of calcification and might help decide treatment strategy. The purpose of this study was to evaluate the hardness of the calcific area within rotator cuffs by US elastography as an aid for the selection of aspiration or fine-needle repeated puncture for the treatment of rotator cuff calcific tendinosis. This prospective study included 39 patients (32 males, 7 females; mean age, 52.9 years) who received US elastography and gray-scale ultrasonography before US-guided treatment for rotator cuff calcific tendinosis. The morphology of the calcifications was classified as arc, fragmented, nodular, and cystic types. US elastography using virtual touch imaging (acoustic radiation force impulse) technique was performed to examine the calcified region to obtain an elastogram that was graded dark, intermediate, or bright. The hardness of the calcifications were recorded, and graded as hard, sand-like, or fluid-like tactile patterns during the US-guided treatment, and the tactile patterns were compared with the results of US elastography and gray-scale ultrasonography. Though the morphologies of the calcifications were significantly related to the tactile pattern of the needle punctures (p < 0.001), gray-scale US could not accurately demonstrate the hardness of the calcifications. With the aid of elastography, the fluid-like tactile pattern could be predicted well as a nondark pattern by elastography (p < 0.001). Ultrasound elastography is a useful modality for evaluation of rotator cuff calcific tendinosis, and as an aid to guide management. If elastography shows the calcified area as a non-dark pattern, then fine-needle aspiration should be performed. Copyright © 2015. Published by Elsevier Taiwan.

  12. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  13. Intracranial Artery Calcification and Its Clinical Significance

    PubMed Central

    Wu, Xiao Hong; Wang, Li Juan; Wong, Ka Sing

    2016-01-01

    Intracranial arterial calcification (IAC) is an easily identifiable entity on plain head computed tomography scans. Recent studies have found high prevalence rates for IAC worldwide, and this may be associated with ischemic stroke and cognitive decline. Aging, traditional cardiovascular risk factors, and chronic kidney disease have been found to be associated with IAC. The severity of IAC can be assessed using different visual grading scales or various quantitative methods (by measuring volume or intensity). An objective method for assessing IAC using consistent criteria is urgently required to facilitate comparisons between multiple studies involving diverse populations. There is accumulating evidence from clinical studies that IAC could be utilized as an indicator of intracranial atherosclerosis. However, the pathophysiology underlying the potential correlation between IAC and ischemic stroke—through direct arterial stenosis or plaque stability—remains to be determined. More well-designed clinical studies are needed to explore the predictive values of IAC in vascular events and the underlying pathophysiological mechanisms. PMID:27165425

  14. Pathological calcifications studied with micro-CT

    NASA Astrophysics Data System (ADS)

    Stock, Stuart R.; Rajamannan, Nalini M.; Brooks, Ellen R.; Langman, Craig B.; Pachman, Lauren M.

    2004-10-01

    The microstructure of pathological biomineral deposits has received relatively little attention, perhaps, in part because of the difficulty preparing samples for microscopy. MicroCT avoids these difficulties, and laboratory microCT results are reviewed for aortic valve calcification (human as well as a rabbit model), for human renal calculi (stones) and for calcinoses formed in juvenile dermatomyositis (JDM). In calcified aortic valves of rabbits, numerical analysis of the data shows statistically significant correlation with diet. In a large kidney stone the pattern of mineralization is clearly revealed and may provide a temporal blueprint for stone growth. In JDM calcified deposits, very different microstructures are observed and may be related to processes unique to this disease.

  15. Orbital melanoma with calcification: A diagnostic dilemma

    PubMed Central

    Bains, Sukhdeep; Kim, Usha; Shanti, R

    2016-01-01

    Primary orbital melanoma is rare and has varied initial presentation. A 28-year-old female presented with proptosis and decreased vision in the left eye. Computed tomography scan showed an orbital mass with contrast enhancement and calcification around the optic nerve leading to a diagnosis of meningioma. The patient chose to be on observation. Loss of vision with an increase in proptosis was seen at 6 months follow-up. On surgical exploration, a well-defined pigmented mass was seen encasing the optic nerve. Histopathological analysis revealed a malignant melanoma. Metastatic workup was negative. Left eye lid sparing exenteration was done. A high index of suspicion is necessary in a rapidly growing suspected optic nerve sheath meningioma and a differential diagnosis including orbital melanoma be considered. PMID:28112137

  16. Calcification of in vitro developed hypertrophic cartilage

    SciTech Connect

    Tacchetti, C.; Quarto, R.; Campanile, G.; Cancedda, R.

    1989-04-01

    We have recently reported that dedifferentiated cells derived from stage 28-30 chick embryo tibiae, when transferred in suspension culture in the presence of ascorbic acid, develop in a tissue closely resembling hypertrophic cartilage. Ultrastructural examination of this in vitro formed cartilage showed numerous matrix vesicles associated with the extracellular matrix. In the present article we report that the in vitro developed hypertrophic cartilage undergoes calcification. We indicate a correlation between the levels of alkaline phosphatase activity and calcium deposition at different times of development. Following the transfer of cells into suspension culture and an initial lag phase, the level of alkaline phosphatase activity rapidly increased. In most experiments the maximum of activity was reached after 5 days of culture. When alkaline phosphatase activity and /sup 45/Ca deposition were measured in the same experiment, we observed that the increase in alkaline phosphatase preceded the deposition of nonwashable calcium deposits in the cartilage.

  17. Basic mechanisms of calcific aortic valve disease.

    PubMed

    Mathieu, Patrick; Boulanger, Marie-Chloé

    2014-09-01

    Calcific aortic valve disease (CAVD) is the most common heart valve disorder. There is no medical treatment to prevent and/or promote the regression of CAVD. Hence, it is of foremost importance to delineate and understand the key basic underlying mechanisms involved in CAVD. In the past decade our comprehension of the underpinning processes leading to CAVD has expanded at a fast pace. Hence, our understanding of the basic pathobiological processes implicated in CAVD might lead eventually to the development of novel pharmaceutical therapies for CAVD. In this review, we discuss molecular processes that are implicated in fibrosis and mineralization of the aortic valve. Specifically, we address the role of lipid retention, inflammation, phosphate signalling and osteogenic transition in the development of CAVD. Interplays between these different processes and the key regulation pathways are discussed along with their clinical relevance.

  18. [Molecular mechanism of idiopathic basal ganglia calcification].

    PubMed

    Wang, Cheng; Xu, Xuan; Li, Lulu; Wang, Tao; Zhang, Min; Shen, Lu; Tang, Beisha; Liu, Jingyu

    2015-08-01

    Idiopathic basal ganglia calcification (IBGC), also known as Fahr’s disease, is an inheritable neurodegenerative syndrome characterized by mineral deposits in the basal ganglia and other brain regions. Patients with IBGC are often accompanied with movement disorders, cognitive impairment as well as psychiatric abnormalities. So far, no therapeutic drug has been developed for the treatment of IBGC. Recently, genetic studies have identified several genes associated with IBGC, including SLC20A2, PDGFRB, PDGFB, ISG15 and XPR1. Loss-of-function mutations in these genes have been associated with disturbance in phosphate homeostasis in brain regions, the dysfunction of blood-brain barrier as well as enhanced IFN-α/β immunity. In this review, we summarize the latest research progress in the studies on molecular genetics of IBGC, and discuss the molecular mechanisms underlying the pathophysiology of mutations of different genes.

  19. An unusual case of extensive peritoneal calcification: A case report

    PubMed Central

    Roriz, Diogo; Abreu, Inês; Costa, João F.; Soares, Pedro Belo; Caseiro-Alves, Filipe

    2014-01-01

    The peritoneum is the largest serous membrane of the body and can be exposed to several injuries that may cause abnormal findings on imaging exams. Linear peritoneal calcification is remarkably rare, usually secondary to long duration peritoneal dialysis. We report an uncommon case of extensive peritoneal calcification in a 39-year-old female without long exposure to peritoneal dialysis solutions, in which peritoneal calcification could be linked to Alport syndrome and previous adverse reaction to intraperitoneal iodinated contrast. Radiologist should be aware of this and related imaging findings, know when to search for them as well as understand their clinical value. PMID:26937431

  20. Soft-tissue calcification after subcutaneus emphysema in a neonate

    SciTech Connect

    Naidech, H.J.; Chawla, H.S.

    1982-08-01

    Bilateral, almost symmetric, calcifications of the soft tissues after subcutaneous emphysema have not, to our knowledge, been described. Because of the close clinical and radiographic evaluation in our case, the finding of calcinosis was not a diagnostic problem. Several 1.5 mm computed tomographic (CT) sections of the thorax were scanned and they were confirmatory in showing the distribution of the calcifications. Since subcutaneous emphysema is commonplace, and calcification after it is apparently unknown, the literature was reviewed and an additional cause of soft-tissue calcinosis is presented.

  1. Screening of Cyanobacterial Species for Calcification

    SciTech Connect

    Brady D. Lee; William A. Apel; Michelle R. Walton

    2004-07-01

    Species of cyanobacteria in the genera Synechococcus and Synechocystis are known to be the catalysts of a phenomenon called "whitings", which is the formation and precipitation of fine-grained CaCO3 particles. Whitings occur when the cyanobacteria fix atmospheric CO2 through the formation of CaCO3 on their cell surfaces, which leads to precipitation to the ocean floor and subsequent entombment in mud. Whitings represent one potential mechanism for CO2 sequestration. Research was performed to determine the ability of various strains of Synechocystis and Synechococcus to calcify when grown in microcosms amended with 2.5 mM HCO3- and 3.4 mM Ca2+. Results indicated that although all strains tested have the ability to calcify, only two Synechococcus species, strains PCC 8806 and PCC 8807, were able to calcify to the extent that a CaCO3 precipitate was formed. Enumeration of the cyanobacterial cultures during testing indicated that cell density did not appear to have a direct effect on calcification. Factors that had the greatest effect on calcification were CO2 removal and subsequent generation of alkaline pH. Whereas cell density was similar for all strains tested, differences in maximum pH were demonstrated. As CO2 was removed, growth medium pH increased and soluble Ca2+ was removed from solution. The largest increases in growth medium pH occurred when CO2 levels dropped below 400 ppmv. Research presented demonstrates that, under the conditions tested, many species of cyanobacteria in the genera Synechocystis and Synechococcus are able to calcify but only two species of Synechococcus were able to calcify to an extent that led to the precipitation of calcium carbonate.

  2. Cerebroretinal microangiopathy with calcifications and cysts

    PubMed Central

    Xu, Wenrui; Zhao, Jiuliang; Zhu, Yicheng; Zhang, Weihong

    2017-01-01

    Abstract Rational: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is believed to be an autosomal recessive genetic disease, with disorders in multisystem organs. Its characteristic neurological disorders manifested on neuroimaging are a triad of leukoencephalopathy, intracranial calcifications, and parenchymal cysts. In this paper, we report a CRMCC patient with multisystem involvement, focusing on the neuroimaging features, to get a better understanding of the rare disease and improve our diagnostic ability. Patient Concerns: The 23-year-old female patient firstly presented with an adolescence onset of ophthalmological manifestations. Four years later, hematological and neurological disorders occurred, the latter of which demonstrated a relatively slow progression in the following 7 years preceding her presentation to our hospital. Interventions: During hospitalization, disorders involving digestive, cardiovascular and respiratory systems were also detected. In addition, a more comprehensive depiction of neurological disorders on neuroimaging was also obtained. Diagnoses: On the basis of multiple system disorders and the detection of mutations in conserved telomere maintenance component 1(CTC1) gene, a diagnosis of CRMCC was made. Outcomes: After supportive therapy during her 4-week hospitalization, the patient's general condition improved and was released from the hospital. Lessons: CRMCC could be primarily diagnosed with the aid of its multiple system disorders and remarkable neuroimaging features. Cerebral micro hemorrhages determined by the combination of CT and T2∗-weighted magnetic resonance images in our case could provide some additional information for diagnosis. Furthermore, several other associated disorders were depicted for the first time in our case, expanding the clinical spectrum of CRMCC. PMID:28072696

  3. Functional Genomic Analysis Identifies Indoxyl Sulfate as a Major, Poorly Dialyzable Uremic Toxin in End-Stage Renal Disease

    PubMed Central

    Jhawar, Sachin; Singh, Prabhjot; Torres, Daniel; Ramirez-Valle, Francisco; Kassem, Hania; Banerjee, Trina; Dolgalev, Igor; Heguy, Adriana; Zavadil, Jiri; Lowenstein, Jerome

    2015-01-01

    Background Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). Methods We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Results Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. Conclusion These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to

  4. Uremic Serum and Solutes Increase Post–Vascular Interventional Thrombotic Risk Through Altered Stability of Smooth Muscle Cell Tissue Factor

    PubMed Central

    Chitalia, Vipul C.; Shivanna, Sowmya; Martorell, Jordi; Balcells, Mercedes; Bosch, Irene; Kolandaivelu, Kumaran; Edelman, Elazer R.

    2013-01-01

    Background Stent thrombosis (ST), a postinterventional complication with a mortality rate of 50%, has an incidence that rises precipitously in patients at risk. Chronic renal failure and end-stage renal disease have emerged as particularly strong ST risk factors, yet the mechanism remains elusive. Tissue factor (TF) is a crucial mediator of injury-related thrombosis and has been implicated for ST. We posit that uremia modulates TF in the local vessel wall to induce postinterventional thrombosis in patients with end-stage renal disease. Methods and Results As a model of the de-endothelialized, postinterventional state, we exposed primary human vascular smooth muscle cells (vSMCs) pretreated with uremic serum (obtained from ESRD patients on hemodialysis) to coronary-like blood flow. vSMC TF expression, activity, stability, and posttranslational modification were examined after vSMCs were treated with uremic serum or solutes. We found significantly greater clot formation after uremic serum exposure, which was substantially reduced with the prior treatment with anti-TF neutralizing antibody. Uremic sera induced 2- to 3-fold higher TF expression and activity in vSMCs independent of diabetes mellitus. Relevant concentrations of isolated uremic solutes such as indole-3-acetic acid (3.5 μg/mL), indoxyl sulfate (25 μg/mL), and uric acid (80 μg/mL) recapitulated these effects in cell culture and the flow loop model. We show further that TF undergoes ubiquitination at baseline and that uremic serum, indole-3-acetic acid, and indoxyl sulfate significantly prolong TF half-life by inhibiting its ubiquitination. Conclusions The uremic milieu is profoundly thrombogenic and upregulates vSMC TF levels by increasing TF stability and decreasing its ubiquitination. Together, these data demonstrate for the first time that the posttranslational regulation of TF in uremia may have a causative role in the increased ST risk observed in uremic patients. These data suggest that

  5. Association of Serum Phosphate and Related Factors in ESRD-Related Vascular Calcification

    PubMed Central

    Zheng, Cai-Mei; Lu, Kuo-Cheng; Wu, Chia-Chao; Hsu, Yung-Ho; Lin, Yuh-Feng

    2011-01-01

    Vascular calcification is common in ESRD patients and is important in increasing mortality from cardiovascular complications in these patients. Hyperphosphatemia related to chronic kidney disease is increasingly known as major stimulus for vascular calcification. Hyperphosphatemia and vascular calcification become popular discussion among nephrologist environment more than five decades, and many researches have been evolved. Risk factors for calcification are nowadays focused for the therapeutic prevention of vascular calcification with the hope of reducing cardiovascular complications. PMID:21660259

  6. Humoral inhibitors of the immune response in uremia. V. Induction of suppressor cells in vitro by uremic serum.

    PubMed Central

    Raskova, J.; Raska, K.

    1983-01-01

    The mechanism of inhibition of mixed lymphocyte reaction (MLR) by serum of chronically uremic rats has been studied. The inhibitory activity of the serum has been associated with a discrete subset of very low density lipoproteins (VLDL) of Sf 100-400. The degree of the inhibitory activity of uremic serum correlates with the severity of uremia. Spleen cells from normal rats incubated for 20 hours with uremic serum or its VLDL fraction suppress the response of control syngeneic cells in the MLR. Induction of such suppressor activity does not require cell proliferation because it is not inhibited by mitomycin C. although the exact identity of the induced suppressor cells has not been established, they may be macrophages. The suppressor activity of induced spleen cells can be markedly reduced by filtration of spleen cells on glass wool or on nylon wool columns. Reconstruction experiments show that the adherent cell fraction of spleen cells exposed to uremic serum suppresses the response of the nonadherent fraction of control spleen cells. These results indicate that the immunosuppressive effects of rat uremic serum in vitro involve the induction of suppressor cells. PMID:6221666

  7. 17beta-estradiol corrects hemostasis in uremic rats by limiting vascular expression of nitric oxide synthases.

    PubMed

    Noris, M; Todeschini, M; Zappella, S; Bonazzola, S; Zoja, C; Corna, D; Gaspari, F; Marchetti, G; Aiello, S; Remuzzi, G; Marchetti, F

    2000-10-01

    Conjugated estrogens shorten the prolonged bleeding time in uremic patients and are similarly effective in a rat model of uremia. We have previously demonstrated that the shortening effect of a conjugated estrogen mixture or 17beta-estradiol on bleeding time was abolished by the nitric oxide (NO) precursor L-arginine, suggesting that the effect of these drugs on hemostasis in uremia might be mediated by changes in the NO synthetic pathway. The present study investigated the biochemical mechanism(s) by which conjugated estrogens limit the excessive formation of NO. 17beta-estradiol (0.6 mg/kg), given to rats made uremic by reduction of renal mass, significantly reduced bleeding time within 24 h and completely normalized plasma concentrations of the NO metabolites, nitrites and nitrates, and of NO synthase (NOS) catalytic activity, determined by NADPH-diaphorase staining in the thoracic aorta. Endothelial NOS (ecNOS) and inducible NOS (iNOS) immunoperoxidase staining in the endothelium of uremic aortas of untreated rats was significantly more intense than in control rats, while in uremic rats receiving 17beta-estradiol staining was comparable to controls. Thus 17beta-estradiol corrected the prolonged bleeding time of uremic rats and fully normalized the formation of NO by reducing the expression of ecNOS and iNOS in vascular endothelium. These results provide a possible biochemical explanation of the well-known effect of estrogens on primary hemostasis in uremia, in experimental animals and humans.

  8. Genetics Home Reference: familial idiopathic basal ganglia calcification

    MedlinePlus

    ... in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 ... link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012 Feb 12;44(3):254- ...

  9. [The hemodynamic characterization of the diabetic patient with arterial calcifications].

    PubMed

    Vega Gómez, M E; Ley Pozo, J; Aldama Figueroa, A; Lima Santana, B; Montalvo Diago, J; Bustillo, C; Fernández Boloña, A; Gutiérrez Jiménez, O; Ramirez Muñoz, O; Martínez Hernández, R

    1993-01-01

    This study was designed to describe the presence of calcifications according to the clinical features of the diabetic patient and the hemodynamics of the calcified arteries. With this purpose, 197 lower limbs from diabetic patients (type I and II) and carbon-hydrate intolerant patients, were studied. In all of the patients, the pressure ratio leg/arm was measured. On the same way, the arterial flow velocity was recorded using the Doppler ultrasonography on the pedia and postero-tibial arteries. The arterial calcifications, evident on the radiography of the foot, were more frequent between the type I patients and the neuro-infections diabetic foot. According to the hemodynamics point of view, we found a trend of association of more pathologic arterial flow velocity curves with the presence of calcifications (specially on the intima layer). It was also remarkable that an arterial incomprensibility was always associated with arterial calcifications.

  10. In vitro computerized evaluation of biological cardiac prosthesis calcification.

    PubMed

    Gatti, A M; Noera, G; Massini, C

    1985-01-01

    The late valvular bioprostheses failure is mainly related to leaflet calcification. This study reports a new approach to testing the biological prostheses calcification applying a computerized technique to x-ray picture. A bovine glutaraldehyde-fixed bioprostheses (BB) was implanted in two sheep in mitral position. The experimental procedure was performed on valves explanted six months after surgery. The BB x-ray pictures were tested by means of a video display computer (VDC) that can process radiographic, photographic or microscopic images and also evaluate the optical density of image quantifiable. The calcification zone assumes different values according to the calcification degree. The VDC can colour the BB x-ray images and display them on monitors (one black and white, one colour) with the colours strictly related to the grey levels of the image.

  11. Acute Calcific Tendinitis of the Rectus Femoris: A Case Series

    PubMed Central

    Kobayashi, Hideo; Kaneko, Haruka; Homma, Yasuhiro; Baba, Tomonori; Kaneko, Kazuo

    2015-01-01

    Introduction: Periarticular calcific tendinitis is a common cause of Orthopedic outpatient referral. Calcific tendinitis of the rectus femoris, however, is very rare and not well known. Due to its rarity, correct diagnosis and prompt treatment are not fully understood. Case Report: Two females (38 and 40 years old) of acute calcific tendinitis of the rectus femoris with the good clinical course without any operative treatment were presented. The pain was managed with oral non-steroidal antiinflammatory drugs and/or local steroid injection. Interval radiographic assessment showed complete resorption of the calcification. Conclusion: Establishing the correct diagnosis and initiating prompt treatment are shown to be important in achieving resolution of symptoms and in avoiding unnecessary investigations. PMID:27299063

  12. Effects of. gamma. irradiation on cartilage matrix calcification

    SciTech Connect

    Nijweide, P.J.; Burger, E.H.; van Delft, J.L.; Kawilarange-de Haas, E.W.M.; Wassenaar, A.M.; Mellink, J.H.

    1980-10-01

    The effect of ..gamma.. irradiation on cartilage matrix calcification was studied in vitro. Metatarsal bones of 14- to 17-day-old embryonic mice were dissected and cultured under various conditions. Prior to culture, half of the metatarsal bones received absorbed doses of 1.0 to 30.0 Gy ..gamma.. radiation. Their paired counterparts served as controls. Irradiation inhibited longitudinal growth and calcification of the cartilage matrix during culture. In addition, a number of histological changes were noted. The inhibition of matrix calcification appeared to be due to an inhibition of the intracellular calcium accumulation. The formation of extracellular calcification foci and the growth of the calcified area already present at the moment of explanation were not inhibited during culture.

  13. Placental calcification: ultrastructural and X-ray microanalytic studies

    SciTech Connect

    Varma, V.A.; Kim, K.M.

    1985-01-01

    Calcification is common in human placentas and is widely recognized as a normal part of maturation and aging of this organ. Eleven human placentas were studied by light and electron microscopy to elucidate the mechanism of placental calcification. Earliest mineral deposits were seen along the trophoblastic basement membrane of the chorionic villi undergoing fibrinoid degeneration. Transmission electron microscopic examination revealed crystalline deposits within small membrane-bound vesicles; the latter appear to be derived from degenerating cells and were particularly numerous within the basement membrane. X-ray microanalysis of these deposits revealed calcium and phosphorus peaks and the pattern of calcium hydroxyapatite was noted by electron diffraction. This pattern of calcification, i.e., precipitation of calcium hydroxyapatite in association with extracellular membrane bound vesicles, is similar to that seen in physiologic and pathologic calcifications of other tissues.

  14. Ectopic calcification in lambs from feeding the plant Cestrum diurnum.

    PubMed

    Simpson, C F; Bruss, M L

    1979-01-01

    Hypercalcemia and ectopic calcification were induced in 5 lambs by supplementing the diet with the dried leaves of the plant Cestrum diurnum, for 8 to 9 weeks. Lambs developed mineralization of blood vessels, heart, kidneys, and lungs. These tissues were examined by light and electron microscopy. In the vascular tissue there was calcification of elastic fibers in the hyperplastic intima and the media, along with mineralization of mitochondria of aortic smooth muscle cells. Myocardial cells and their mitochondria were mineralized. In the kidney, there was calcification of the epithelium of the distal convoluted tubules and collecting tubules, Bowman's capsule, and the mesangial cells of the glomeruli. In the lung, there was mineralization of the alveolar septal walls and the bronchi and bronchioles. Feeding of the calcinogenic plant to lambs caused extensive soft tissue calcification. Results of the study indicated that degeneration was the early soft tissue lesion in this plant toxicity.

  15. ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

    ClinicalTrials.gov

    2014-07-14

    Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

  16. Calcific periarthritis of the elbow presenting as acute tennis elbow.

    PubMed

    Jawad, F; Jawad, A S M

    2014-01-01

    A 28-year-old woman presented with sudden acute lateral epicondylitis. There was no history of preceding trauma or repetitive use of the arm. Because of the acute onset and signs of acute inflammation, an X-ray was arranged. The X-ray showed a hyperdense calcified elongated globule distal to the lateral epicondyle. A diagnosis of calcific periarthritis (calcium apatite) of the elbow was made. Calcific periarthritis has rarely been reported as a cause of acute elbow pain.

  17. A Review of the Effect of Diet on Cardiovascular Calcification

    PubMed Central

    Nicoll, Rachel; Howard, John McLaren; Henein, Michael Y.

    2015-01-01

    Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification. PMID:25906474

  18. Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

    PubMed

    Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

    Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  19. A review of the effect of diet on cardiovascular calcification.

    PubMed

    Nicoll, Rachel; Howard, John McLaren; Henein, Michael Y

    2015-04-21

    Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

  20. Gated cardiac tomographic visualization of coronary artery calcification

    SciTech Connect

    Markivee, C.R.; Hoyt, T.S.; Francis, R.A.; Burns, J.; Ruark, B.

    1984-07-01

    Coronary artery calcification (CAC) is usually detected by fluoroscopy or on cine films during coronary angiography, but measurement of the calcification is not possible. Gated tomography of the heart provides a full sized image with high contrast spatial resolution of 0.76 mm. The radiation exposure to the heart is between 1-5% of that experienced with coronary cinefluorography. Measurement of the diameter of calcium deposits is possible and calcium that could be related to arterial stenosis may be identified.

  1. Vascular Calcification: Current Genetics Underlying This Complex Phenomenon

    PubMed Central

    Pérez-Hernández, Nonanzit; Aptilon-Duque, Gad; Blachman-Braun, Ruben; Vargas-Alarcón, Gilberto; Rodríguez-Cortés, Adrián Asael; Azrad-Daniel, Shely; Posadas-Sánchez, Rosalinda; Rodríguez-Pérez, José Manuel

    2017-01-01

    Objective: Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima (atherosclerotic calcification) or tunica media (Mönckenberg's sclerosis). Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Data Sources: We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords “genetics and vascular calcification”, “molecular pathways, genetic and vascular calcification” and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Study Selection: The most valuable published original and review articles related to our objective were selected. Results: Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. Conclusion: Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease. PMID:28469108

  2. Extracellular vesicles in cardiovascular calcification: expanding current paradigms.

    PubMed

    Krohn, Jona B; Hutcheson, Joshua D; Martínez-Martínez, Eduardo; Aikawa, Elena

    2016-06-01

    Vascular calcification is a major contributor to the progression of cardiovascular disease, one of the leading causes of death in industrialized countries. New evidence on the mechanisms of mineralization identified calcification-competent extracellular vesicles (EVs) derived from smooth muscle cells, valvular interstitial cells and macrophages as the mediators of calcification in diseased heart valves and atherosclerotic plaques. However, the regulation of EV release and the mechanisms of interaction between EVs and the extracellular matrix leading to the formation of destabilizing microcalcifications remain unclear. This review focuses on current limits in our understanding of EVs in cardiovascular disease and opens up new perspectives on calcific EV biogenesis, release and functions within and beyond vascular calcification. We propose that, unlike bone-derived matrix vesicles, a large population of EVs implicated in cardiovascular calcification are of exosomal origin. Moreover, the milieu-dependent loading of EVs with microRNA and calcification inhibitors fetuin-A and matrix Gla protein suggests a novel role for EVs in intercellular communication, adding a new mechanism to the pathogenesis of vascular mineralization. Similarly, the cell type-dependent enrichment of annexins 2, 5 or 6 in calcifying EVs posits one of several emerging factors implicated in the regulation of EV release and calcifying potential. This review aims to emphasize the role of EVs as essential mediators of calcification, a major determinant of cardiovascular mortality. Based on recent findings, we pinpoint potential targets for novel therapies to slow down the progression and promote the stability of atherosclerotic plaques. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. Role of Gut-Derived Protein-Bound Uremic Toxins in Cardiorenal Syndrome and Potential Treatment Modalities.

    PubMed

    Lekawanvijit, Suree

    2015-01-01

    Uremic toxins have been increasingly recognized as a crucial missing link in the cardiorenal syndrome. Advances in dialysis technologies have contributed to an enormous improvement in uremic toxin removal, but removal of protein-bound uremic toxins (PBUTs) by current conventional dialysis remains problematic because of their protein-binding capacity. Most PBUTs that have been implicated in cardiorenal toxicity have been demonstrated to be derived from a colonic microbiota metabolism pathway using dietary amino acids as a substrate. Currently, indoxyl sulfate and p-cresyl sulfate are the most extensively investigated gut-derived PBUTs. Strong evidence of adverse clinical outcomes, as well as biological toxicity on the kidney and cardiovascular system attributable to these toxins, has been increasingly reported. Regarding their site of origin, the colon has become a potential target for treatment of cardiorenal syndrome induced by gut-derived PBUTs.

  4. Dietary potassium regulates vascular calcification and arterial stiffness.

    PubMed

    Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E; Dell'Italia, Louis J; Sanders, Paul W; Agarwal, Anupam; Wu, Hui; Chen, Yabing

    2017-10-05

    Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.

  5. Dual energy subtraction method for breast calcification imaging

    NASA Astrophysics Data System (ADS)

    Koukou, Vaia; Martini, Niki; Fountos, George; Michail, Christos; Sotiropoulou, Panagiota; Bakas, Athanasios; Kalyvas, Nektarios; Kandarakis, Ioannis; Speller, Robert; Nikiforidis, George

    2017-03-01

    The aim of this work was to present an experimental dual energy (DE) method for the visualization of microcalcifications (μCs). A modified radiographic X-ray tube combined with a high resolution complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) X-ray detector was used. A 40/70 kV spectral combination was filtered with 100 μm cadmium (Cd) and 1000 μm copper (Cu) for the low/high-energy combination. Homogenous and inhomogeneous breast phantoms and two calcification phantoms were constructed with various calcification thicknesses, ranging from 16 to 152 μm . Contrast-to-noise ratio (CNR) was calculated from the DE subtracted images for various entrance surface doses. A calcification thickness of 152 μm was visible, with mean glandular doses (MGD) in the acceptable levels (below 3 mGy). Additional post-processing on the DE images of the inhomogeneous breast phantom resulted in a minimum visible calcification thickness of 93 μm (MGD=1.62 mGy). The proposed DE method could potentially improve calcification visibility in DE breast calcification imaging.

  6. Vascular calcification in chronic kidney disease: a clinical review.

    PubMed

    Eddington, Helen; Sinha, Smeeta; Kalra, Philip A

    2009-03-01

    Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all-cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD-mineral bone disorder and are thought to be part of the same disease process in CKD. Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.

  7. Computed tomography study of pineal calcification in schizophrenia.

    PubMed

    Bersani, G; Garavini, A; Taddei, I; Tanfani, G; Nordio, M; Pancheri, P

    1999-06-01

    Computed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21-25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with 'non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear.

  8. Deep-penetration photoacoustic array imaging of calcifications

    NASA Astrophysics Data System (ADS)

    Hsiao, Tsai-Chu; Cheng, Yao-Yu; Tein, Wan-Ting; Luo, Shih-Bin; Chiou, De-Yi; Chung, Ren-Jei; Li, Meng-Lin

    2013-06-01

    Calcifications are one of the most important indicators for early breast cancer detection. We explore the feasibility of deep-penetration photoacoustic (PA) imaging of calcifications based on a medical ultrasound array imaging platform. Intralipid and chicken breast phantoms embedded with different-sized hydroxyapatite (HA) particles, which are the major components of calcifications, were imaged to verify the equipment's capability and penetration depth for the visualization of calcifications. An optimal near-infrared excitation wavelength was selected to maximize PA signals of HAs, resulting in a better HA signal-to-blood ratio. We demonstrated that PA imaging is capable of visualizing 0.5-mm HA particles at a depth of 3 cm in chicken breast phantoms. The noise-equivalent penetration depth of the system for visualizing 0.5-mm HA particles in the human breast was estimated to be about 2.9 to 3.5 cm, which is clinically relevant as calcifications are usually found at a depth of 0.6 to 3.0 cm. Moreover, the feasibility of differentiating HA from blood by the PA spectroscopic technique was presented and the mechanism of the HA signal generation was discussed. The results show that PA imaging is a promising technique for real-time visualization of breast calcifications.

  9. Characterization of Dystrophic Calcification Induced in Mice by Cardiotoxin

    PubMed Central

    Zhao, Yongdong; Urganus, Annette L.; Spevak, Lyudmila; Shrestha, Sheela; Doty, Stephen B.; Boskey, Adele L.

    2010-01-01

    Dystrophic calcifications often occur after injury, infection, or onset of certain rheumatic diseases. Treatment has been limited to surgical removal following failure of medical therapy. In an attempt to establish a reproducible animal model for dystrophic calcification that permitted the screening of potential interventions, we evaluated cardiotoxin (injury)-induced calcifications in three murine strains at both the cellular and ultrastructural levels. All osteopontin null mice and tumor necrosis factor receptor null mice on a C57B6 background had calcifications at days 3 and 7 after injury compared to 75% of wild-type C57B6 mice. There was no difference in mineral content among calcifications from the three mouse strains. Osteogenesis was suggested by the expression of osteocalcin, osterix, and alkaline phosphatase in calcified murine muscle tissue. Osteoclast-like cells facilitated the removal of transient dystrophic deposits (<28 days) in all models. However, none of the models showed an association of mineral crystals with collagen, suggesting that the deposits were not bone-like. The dystrophic mechanism was validated as cell death, and mitochondrial calcifications occurred soon after skeletal muscle injury in the three murine strains. PMID:19690791

  10. Effectiveness of Anti-Calcification Technologies in a Rabbit Model.

    PubMed

    Wright, Greg; de la Fuente, Angela

    2015-05-01

    A kinetic profile revealing calcification progression is a powerful method for assessing the anti-calcification efficacy of various tissue treatments compared to the traditional analysis of a single time point in studies with rabbits. Tissue calcification was compared between test and control discs in rabbits. Test groups received either ThermaFix-processed bovine pericardium, or porcine leaflets processed with Linx, or alpha-amino oleic acid (AOA). Control groups received glutaraldehyde-treated porcine valve leaflets, and bovine pericardium. Tissue discs were implanted intramuscularly in rabbits and explanted every five days until day 75. Levels of calcium and phosphorus were then monitored in the rabbit tissues. Calcium concentrations were plotted over time, with a sigmoidal curve being used for each kinetic profile. The ThermaFix group exhibited a lower calcium plateau level compared to the bovine control (107 ± 24 versus 258 ± 120 μg Ca2+ per mg dry tissue, respectively), while the Linx group exhibited a lower calcium plateau compared to porcine controls (130 ± 34 μg versus 280 ± 80 μg Ca2+ per mg dry tissue, respectively). The AOA group showed a low level of calcification through 40 days, but this was subsequently increased to a plateau of 258 ± 135 μg Ca2+ per mg dry tissue. The study results showed that effects on the rate and level of calcification of anti-calcification technologies can be modulated. In particular, time is important when assessing tissue technology effectiveness.

  11. Ocean acidification reduces growth and calcification in a marine dinoflagellate.

    PubMed

    Van de Waal, Dedmer B; John, Uwe; Ziveri, Patrizia; Reichart, Gert-Jan; Hoins, Mirja; Sluijs, Appy; Rost, Björn

    2013-01-01

    Ocean acidification is considered a major threat to marine ecosystems and may particularly affect calcifying organisms such as corals, foraminifera and coccolithophores. Here we investigate the impact of elevated pCO2 and lowered pH on growth and calcification in the common calcareous dinoflagellate Thoracosphaera heimii. We observe a substantial reduction in growth rate, calcification and cyst stability of T. heimii under elevated pCO2. Furthermore, transcriptomic analyses reveal CO2 sensitive regulation of many genes, particularly those being associated to inorganic carbon acquisition and calcification. Stable carbon isotope fractionation for organic carbon production increased with increasing pCO2 whereas it decreased for calcification, which suggests interdependence between both processes. We also found a strong effect of pCO2 on the stable oxygen isotopic composition of calcite, in line with earlier observations concerning another T. heimii strain. The observed changes in stable oxygen and carbon isotope composition of T. heimii cysts may provide an ideal tool for reconstructing past seawater carbonate chemistry, and ultimately past pCO2. Although the function of calcification in T. heimii remains unresolved, this trait likely plays an important role in the ecological and evolutionary success of this species. Acting on calcification as well as growth, ocean acidification may therefore impose a great threat for T. heimii.

  12. Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease

    PubMed Central

    Tsujimoto, Masayuki; Nagano, Yui; Hosoda, Satomi; Shiraishi, Asuka; Miyoshi, Ayaka; Hiraoka, Shima; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2013-01-01

    In patients with end-stage renal disease, not only renal clearance but also hepatic clearance is known to be impaired. For instance, the concentration of erythromycin, a substrate of cytochrome P450 3A4 (CYP3A4), has been reported to be elevated in patients with end-stage renal disease. The purpose of this study is to elucidate the reason for the decrease in hepatic clearance in patients with end-stage renal disease. Deproteinized pooled sera were used to assess the effects of low-molecular-weight uremic toxins on CYP3A4 activity in human liver microsomes and human LS180 cells. Four uremic toxins (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) present at high concentrations in uremic serum were also studied. Simultaneous treatment of uremic serum (less than 10%) or uremic toxins did not affect testosterone 6β-hydroxylation in human liver microsomes. On the other hand, pretreatment of each serum activates CYP3A4 in LS180 cells, and the increased CYP3A4 activity in uremic serum-treated cells was smaller than normal serum-treated cells. In addition, CYP3A4 and CYP24A1 mRNA levels also increased in LS180 cells exposed to normal serum, and this effect was reduced in uremic serum-treated cells and in cells exposed to uremic serum added to normal serum. Furthermore, addition of 1,25-dihydroxyvitamin D to uremic serum partially restored the serum effect on CYP3A4 expression. The present study suggests that the decrease of 1,25-dihydroxyvitamin D and the accumulation of uremic toxins contributed to the decreased hepatic clearance of CYP3A4 substrates in patients with end-stage renal disease. PMID:23965431

  13. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.

    PubMed

    Zeng, Yu-Qun; Dai, Zhenhua; Lu, Fuhua; Lu, Zhaoyu; Liu, Xusheng; Chen, Cha; Qu, Pinghua; Li, Dingcheng; Hua, Zhengshuang; Qu, Yanni; Zou, Chuan

    2016-04-05

    Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury.

  14. TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

    PubMed

    Miao, Xu-Hong; Wang, Chun-Guo; Hu, Bao-Quan; Li, Ai; Chen, Cheng-Bin; Song, Wen-Qin

    2010-01-01

    The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3) TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

  15. Relationship among serum creatinine, serum gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease.

    PubMed

    McLeland, S M; Lunn, K F; Duncan, C G; Refsal, K R; Quimby, J M

    2014-01-01

    Chronic kidney disease (CKD) in cats is associated with gastrointestinal signs commonly attributed to uremic gastropathy. Consequently, patients often are treated with antacids and gastrointestinal protectants. This therapeutic regimen is based on documented gastric lesions in uremic humans and dogs, but the nature and incidence of uremic gastropathy in cats are unknown. Evaluate uremic gastropathy in CKD cats to facilitate refinement of medical management for gastrointestinal signs. Thirty-seven CKD cats; 12 nonazotemic cats Stomachs were evaluated for the presence of classic uremic gastropathy lesions. Histopathologic lesions were compared with serum creatinine concentrations, calcium-phosphorus product (CPP), and serum gastrin concentrations. Gastric ulceration, edema, and vascular fibrinoid change were not observed. The most important gastric lesions in CKD cats were fibrosis and mineralization. Sixteen CKD cats (43%) had evidence of gastric fibrosis of varying severity and 14 CKD cats (38%) had gastric mineralization. CKD cats were more likely to have gastric fibrosis and mineralization than nonazotemic controls (P = .005 and P = .021, respectively). Only cats with moderate and severe azotemia had gastric mineralization. CPP was correlated with disease severity; severely azotemic CKD cats had significantly higher CPP when compared with nonazotemic controls, and to mildly and moderately azotemic cats (P < .05). Gastrin concentrations were significantly higher in CKD cats when compared with nonazotemic controls (P = .003), but increased concentrations were not associated with gastric ulceration. Uremic gastropathy in CKD cats differs from that described in other species and this difference should be considered when devising medical management. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  16. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease

    PubMed Central

    Lu, Fuhua; Lu, Zhaoyu; Liu, Xusheng; Chen, Cha; Qu, Pinghua; Li, Dingcheng; Hua, Zhengshuang; Qu, Yanni; Zou, Chuan

    2016-01-01

    Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury. PMID:27003359

  17. Effect of skin care with an emollient containing a high water content on mild uremic pruritus.

    PubMed

    Okada, Kazuyoshi; Matsumoto, Koichi

    2004-10-01

    Skin care is very important for preventing uremic pruritus. However, mild uremic pruritus has usually been treated with antihistamine and urea-containing ointments. We therefore examined the effects of an aqueous gel with higher water content. Twenty hemodialysis patients with mild pruritus who were not being treated with any emollient were divided into two groups of 10 each. Patients in one group were treated with an aqueous gel containing 80% water. This emollient was applied twice daily for 2 weeks. No emollient was applied for the next 2 weeks. The other group of patients were not treated with any emollient for the 4 weeks. Visual analog scale scores for itching in the experimental group at week 2 were significantly decreased compared with that at week 0 (3.5 +/- 0.3 vs 0.6 +/- 0.2, P < 0.01). Skin dryness in the experimental group was significantly improved at week 2 compared with that at week 0. The visual analog scale score for itching increased to 1.2 +/- 0.5 and skin dryness reappeared in 40% of patients by week 4, i.e. after the emollient was stopped. There were no significant changes in the control group during the study. It is concluded that the aqueous gel with high water content reduced itching and improved xerosis in patients with mild uremic pruritus. It is reasonable that skin care with an emollient containing a high water content is first started for hemodialysis patients with xerosis, even if they do not feel itching.

  18. Cilostazol inhibits uremic toxin-induced vascular smooth muscle cell dysfunction: role of Axl signaling.

    PubMed

    Lee, Chien-Hsing; Hung, Yi-Jen; Shieh, Yi-Shing; Chien, Chu-Yen; Hsu, Yu-Juei; Lin, Chih-Yuan; Chiang, Chi-Fu; Huang, Chia-Luen; Hsieh, Chang-Hsun

    2017-03-01

    Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, and vascular smooth muscle cell (VSMC) dysfunction plays a pivotal role in uremic atherosclerosis. Axl signaling is involved in vascular injury and is highly expressed in VSMCs. Recent reports have shown that cilostazol, a phosphodiesterase type 3 inhibitor (PDE3), can regulate various stages of the atherosclerotic process. However, the role of cilostazol in uremic vasculopathy remains unclear. This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling. We investigated the effect of P-cresol and cilostazol on Axl signaling in A7r5 rat VSMCs and the rat and human CKD models. From the in vivo CKD rats and patients, aortic tissue exhibited significantly decreased Axl expression after cilostazol treatment. P-cresol increased Axl, proliferating of cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and matrix metalloproteinase-2 (MMP-2) expressions, decreased caspase-3 expression, and was accompanied by increased cell viability and migration. Cilostazol significantly reversed P-cresol-induced Axl, downstream gene expressions, and cell functions. Along with the increased Axl expression, P-cresol activated PLCγ, Akt, and ERK phosphorylation and cilostazol significantly suppressed the effect of P-cresol. Axl knockdown significantly reversed the expressions of P-cresol-induced Axl-related gene expression and cell functions. Cilostazol with Axl knockdown have additive changes in downstream gene expression and cell functions in P-cresol culture. Both in vitro and in vivo experimental CKD models elucidate a new signal transduction of cilostazol-mediated protection against uremic toxin-related VSMCs dysfunction and highlight the involvement of the Axl signaling and downstream pathways. Copyright © 2017 the American Physiological Society.

  19. Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone.

    PubMed

    Picca, Stefano; Cappa, Marco; Martinez, Chiara; Moges, Seyoum Ido; Osborn, John; Perfumo, Francesco; Ardissino, Gianluigi; Bonaudo, Roberto; Montini, Giovanni; Rizzoni, Gianfranco

    2004-01-01

    We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (+/-SD) rhGH treatment observation period was 19.9+/-5.9 months. The mean age at the start of rhGH treatment was 8.3+/-3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43-2.66] than in prepubertal patients (1.19, 95% CI 1.01-1.40). Increases in PTH levels were significantly different between the two groups (Delta=1.64, 95% CI 1.16-3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.

  20. Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany

    PubMed Central

    Rasko, David A.; Webster, Dale R.; Sahl, Jason W.; Bashir, Ali; Boisen, Nadia; Scheutz, Flemming; Paxinos, Ellen E.; Sebra, Robert; Chin, Chen-Shan; Iliopoulos, Dimitris; Klammer, Aaron; Peluso, Paul; Lee, Lawrence; Kislyuk, Andrey O.; Bullard, James; Kasarskis, Andrew; Wang, Susanna; Eid, John; Rank, David; Redman, Julia C.; Steyert, Susan R.; Frimodt-Møller, Jakob; Struve, Carsten; Petersen, Andreas M.; Krogfelt, Karen A.; Nataro, James P.; Schadt, Eric E.; Waldor, Matthew K.

    2011-01-01

    BACKGROUND A large outbreak of diarrhea and the hemolytic–uremic syndrome caused by an unusual serotype of Shiga-toxin–producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin–producing E. coli have been reported — 3167 without the hemolytic–uremic syndrome (16 deaths) and 908 with the hemolytic–uremic syndrome (34 deaths) — indicating that this strain is notably more virulent than most of the Shiga-toxin–producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli. METHODS We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates. RESULTS The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors. CONCLUSIONS Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin–producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens. PMID:21793740

  1. Sensitivity of pelagic calcification to ocean acidification

    NASA Astrophysics Data System (ADS)

    Gangstø, R.; Joos, F.; Gehlen, M.

    2011-02-01

    Ocean acidification might reduce the ability of calcifying plankton to produce and maintain their shells of calcite, or of aragonite, the more soluble form of CaCO3. In addition to possibly large biological impacts, reduced CaCO3 production corresponds to a negative feedback on atmospheric CO2. In order to explore the sensitivity of the ocean carbon cycle to increasing concentrations of atmospheric CO2, we use the new biogeochemical Bern3D/PISCES model. The model reproduces the large scale distributions of biogeochemical tracers. With a range of sensitivity studies, we explore the effect of (i) using different parameterizations of CaCO3 production fitted to available laboratory and field experiments, of (ii) letting calcite and aragonite be produced by auto- and heterotrophic plankton groups, and of (iii) using carbon emissions from the range of the most recent IPCC Representative Concentration Pathways (RCP). Under a high-emission scenario, the CaCO3 production of all the model versions decreases from ~1 Pg C yr-1 to between 0.36 and 0.82 Pg C yr-1 by the year 2100. The changes in CaCO3 production and dissolution resulting from ocean acidification provide only a small feedback on atmospheric CO2 of -1 to -11 ppm by the year 2100, despite the wide range of parameterizations, model versions and scenarios included in our study. A potential upper limit of the CO2-calcification/dissolution feedback of -30 ppm by the year 2100 is computed by setting calcification to zero after 2000 in a high 21st century emission scenario. The similarity of feedback estimates yielded by the model version with calcite produced by nanophytoplankton and the one with calcite, respectively aragonite produced by mesozooplankton suggests that expending biogeochemical models to calcifying zooplankton might not be needed to simulate biogeochemical impacts on the marine carbonate cycle. The changes in saturation state confirm previous studies indicating that future anthropogenic CO2 emissions may

  2. Magnesium modulates the expression levels of calcification-associated factors to inhibit calcification in a time-dependent manner.

    PubMed

    Xu, Jinsheng; Bai, Yaling; Jin, Jingjing; Zhang, Junxia; Zhang, Shenglei; Cui, Liwen; Zhang, Huiran

    2015-03-01

    Vascular calcification, a common complication in patients with chronic kidney disease, involves a variety of mechanisms associated with the regulation of calcification-associated factors. Previous clinical studies have indicated that magnesium is involved in the reduction of vascular calcification; however, the mechanism underlying this process remains unknown. The aim of the present study was to investigate the effects of magnesium on β-glycerophosphate (β-GP)-induced calcification and the underlying mechanisms. Primary rat vascular smooth muscle cells (VSMCs) were exposed to 10 mM β-GP in medium with or without the addition of 3 mM magnesium or 2-aminoethoxy-diphenylborate (2-APB; an inhibitor of magnesium transport), for a 14-day period. Calcium deposition and alkaline phosphatase (ALP) activity were measured by Alizarin red staining, quantification of calcium and enzyme-linked immunosorbent assay. The expression levels of core-binding factor α-1 (Cbfα1), matrix Gla protein (MGP) and osteopontin (OPN) were determined by reverse transcription-polymerase chain reaction or western blot analysis, following incubation for 0, 3, 6, 10 and 14 days with the different media. VSMC calcification and ALP activity was reduced significantly in the high-magnesium medium compared with the calcification medium, during the 14-day incubation. The magnesium-induced changes in the VSMCs included a β-GP-induced downregulation of Cbfα1 by day 3 of incubation, an effect that was gradually enhanced over the 14-day period. By contrast, magnesium produced notable increases in MGP and OPN expression levels, with an opposite pattern to that observed in the Cbfα1 expression levels. However, the addition of 2-APB appeared to inhibit the protective effect of magnesium on the VSMCs. Therefore, magnesium was able to effectively reduce β-GP-induced calcification in rat VSMCs by regulating the expression levels of calcification-associated factors in a time-dependent manner.

  3. Genomic damage in endstage renal disease-contribution of uremic toxins.

    PubMed

    Schupp, Nicole; Heidland, August; Stopper, Helga

    2010-10-01

    Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-α. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.

  4. An effective treatment of atypical hemolytic uremic syndrome with plasma exchange and eculizumab: A case report.

    PubMed

    Sengul Samanci, Nilay; Ayer, Mesut; Ergen, Abdulkadir; Ozturk, Savas

    2015-06-01

    Atypical hemolytic uremic syndrome is a rare thrombotic microangiopathy caused by chronic defective regulation of the complement activation. This activation results in systemic endothelial damage leading to renal failure. Eculizumab, an anti-C5 antibody, is effective in limiting complement activation in patients with aHUS and has recently came out as a therapeutic option for aHUS. Here we present a case showing that first-line eculizumab treatment successfully prevents the induction of the terminal complement cascade and blocked the progression of thrombotic microangiopathy in aHUS.

  5. Long-term neurological sequelae of hemolytic-uremic syndrome: a preliminary report.

    PubMed

    Qamar, I U; Ohali, M; MacGregor, D L; Wasson, C; Krekewich, K; Marcovitch, S; Arbus, G S

    1996-08-01

    Seven patients with hemolytic-uremic syndrome who had major neurological symptoms during the acute illness were neurologically and cognitively evaluated prospectively several years after recovery from the illness. Four patients showed evidence of subtle neurological sequelae, including posturing, clumsiness, poor fine-motor coordination, hyperactivity, and distractibility. Psychoeducational evaluation of all seven subjects revealed mean scores within the average range in cognitive abilities, academic achievement, single word receptive vocabulary, visual/motor planning, overall adaptive functioning, and hyperactivity. The lapse of time (minimum of 7 years) between the acute illness and the psychometric evaluation could have been responsible for our normal results.

  6. Assessment of the characteristics and quality of life of patients with uremic peripheral neuropathy
.

    PubMed

    Yu, Xiu-Zhi; Lu, Shi; Gou, Wei; Wang, Wei; Zou, Shui-Hong; Han, Yin-Xia; Wang, Wei-Wei; Zhang, Jin-Yuan

    2017-03-01

    This study seeks to examine the characteristics and health-related quality of life (HRQL) of patients with uremic peripheral neuropathy. Uremic patients undergoing maintenance hemodialysis (MHD) at our hospital were enrolled in this study. Data collection began in January 2011 and ended in June 2011. The patients were divided into two groups, the lesion group (110 cases) and the non-lesion group (168 cases), based on the presence or absence of peripheral neuropathy. To examine continuous changes in signs and symptoms in the lesion group, electromyography (EMG) was performed to measure sensory nerve conduction velocity (SCV), motor nerve conduction velocity (MCV), and distal latency (DL). Furthermore, HRQL was analyzed using the generic Short Form-36 (SF-36) questionnaire. Numbness and a burning sensation in the distal limbs were observed in the lesion group; in particular, these phenomena occurred in the upper limbs and the lower limbs in 3.6% (4/110) and 48.2% (53/110) of patients, respectively. With respect to motor symptoms, upper and lower limb weakness was observed in 1.8% (2/110) and 11.8% (13/110) of patients, respectively. Changes in physical signs were mainly evidenced by tendon reflexes, for example, areflexia, or tendon reflex loss was detected in the upper extremities, the knee tendon, and the Achilles tendon in 9.09% (10/110), 55.45% (61/110), and 35.5% (39/110) of patients, respectively. Relative to the non-lesion group, the lesion group had significantly slower average SCV and MCV as well as a longer average DL (p < 0.01 for all comparisons). Based on a clinical statistical analysis of SF-36 reports, scores on each scale were lower in the lesion group than in the non-lesion group. However, compared with the non-lesion group, the lesion group did not significantly differ with respect to overall SF-36 score (t = 1.896, p = 0.060) but did significantly differ with respect to bodily pain score (t = 5.301, p < 0.001). Typical symptoms of uremic

  7. Case report of atypical hemolytic uremic syndrome with retinal arterial and venous occlusion treated with eculizumab

    PubMed Central

    Greenwood, Gregory T

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by chronic, uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy. Renal impairment and progression to end-stage renal disease are common in untreated patients with aHUS, and extrarenal manifestations are being increasingly characterized in the literature. Ocular involvement remains rare in aHUS. This report describes a patient with aHUS with bilateral central retinal artery and vein occlusion, vitreous hemorrhage, and blindness in addition to renal impairment. The patient’s hematologic and renal parameters and ocular manifestation improved following initiation of eculizumab therapy. PMID:26508891

  8. Hemolytic uremic syndrome associated with Plasmodium vivax malaria successfully treated with plasma exchange.

    PubMed

    Keskar, V S; Jamale, T E; Hase, N K

    2014-01-01

    We report a case of hemolytic uremic syndrome (HUS) in an adult patient with Plasmodium vivax malaria. The patient presented with worsening anemia, persistent thrombocytopenia and acute kidney injury. HUS was diagnosed based on the high serum lactate dehydrogenase, elevated reticulocyte count and presence of schistocytes on peripheral blood smear. Kidney biopsy showed features of thrombotic microangiopathy. Complete hematological remission was achieved after five sessions of therapeutic plasma exchange. Renal function partially recovered and stabilized at discharge. Vivax malaria, generally considered benign, may be rarely associated with HUS.

  9. MRI findings of hemolytic uremic syndrome with encephalopathy: widespread symmetrical distribution.

    PubMed

    Nakamura, Hiroshi; Takaba, Hitonori; Inoue, Takeshi; Saku, Yoshisuke; Saito, Fumihiko; Ibayashi, Setsuro; Fujishima, Masatoshi

    2003-01-01

    The authors report the magnetic resonance imaging (MRI) findings in a 22-year-old woman with hemolytic uremic syndrome and encephalopathy secondary to verotoxin-producing Escherichia coli. Multiple lesions in the midbrain, cerebellum, occipital lobe, and basal ganglia showed high signal intensity on T2-weighted images with widespread symmetrical distribution. Most of these findings showed remarkable reduction on MRI images obtained 70 days after the onset. It is suggested that edema induced by local breakdown of blood-brain barrier might play an important role in the patient.

  10. An adult case of combined encephalopathy and hemolytic uremic syndrome caused by Escherichia coli O157.

    PubMed

    Yoshimitsu, Masashi; Hayashi, Nobuaki; Kaneko, Yoshibumi; Doyama, Hisashi

    2011-01-01

    We report a 28-year-old woman with O157 enterohemorrhagic colitis-associated hemolytic uremic syndrome in whom seizures and transient hemiparesis developed on the 12th day after admission to hospital. Her subsequent recovery was characterized by improvements in renal function and platelet count. The patient recovered after treatment with steroid pulse and plasma exchange therapy, without any sequelae. As there have been few reports on the onset of encephalopathy in adults, we report this interesting case, with reference to the literature for possible effective treatment.

  11. Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins

    PubMed Central

    Schupp, Nicole; Heidland, August; Stopper, Helga

    2010-01-01

    Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-α. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation. PMID:22069557

  12. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

    PubMed Central

    Miller, Elizabeth C.; Liszewski, M. Kathryn; Strain, Lisa; Blouin, Jacques; Brown, Alison L.; Moghal, Nadeem; Kaplan, Bernard S.; Weiss, Robert A.; Lhotta, Karl; Kapur, Gaurav; Mattoo, Tej; Nivet, Hubert; Wong, William; Gie, Sophie; de Ligny, Bruno Hurault; Fischbach, Michel; Gupta, Ritu; Hauhart, Richard; Meunier, Vincent; Loirat, Chantal; Dragon-Durey, Marie-Agnès; Fridman, Wolf H.; Janssen, Bert J. C.

    2008-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS. PMID:18796626

  13. Cerebral infarct with recurrence of hemolytic-uremic syndrome in a child following renal transplantation.

    PubMed

    Mochon, M; Kaiser, B A; deChadarevian, J P; Polinsky, M S; Baluarte, H J

    1992-11-01

    A white girl with a history of atypical hemolytic-uremic syndrome (HUS) and persistent microangiopathic anemia, and thrombocytopenia for 2 months after the initial presentation at age 7 months, received her first cadaveric renal transplant at age 3 years. During the first 2.5 days post transplant, she developed progressive thrombocytopenia and anemia followed by tonic-clonic seizures and loss of consciousness, secondary to a diffuse cerebral infarction of the left hemisphere. Renal histology showed evidence of glomerular microthrombi and microangiopathy. A large cerebral infarct, previously described in patients during their initial presentation with HUS, presented in our patient as part of the recurrence of the disease post renal transplantation.

  14. Changes of gene expression profiles across different phases of vascular calcification in rats.

    PubMed

    Jiang, Z M; Wu, X J; Liu, Y; Du, X H; Shen, S J; Xu, L Y; Sun, W X

    2013-11-26

    This study investigated the alteration of gene expression profiles in order to gain a deeper understanding into the molecular mechanism involved in different processes of vascular calcification (VC). Sprague Dawley (SD) rats were injected with 300,000 µg/kg vitamin D3 and gavaged with 25 mg/kg nicotine for 8 or 16 weeks to create 8- and 16-week VC calcification groups. Histological analysis and quantification of aortic calcium content were used to determine the severity of vascular calcification. The suppression subtractive hybridization (SSH) method was employed to screen for up and downregulated genes in early and later phases of vascular calcification. Changes in calcium and phosphorus levels in tissue were used as markers of vascular calcification. Quantification of aortic calcium content revealed that vascular calcification might regress over time. In the early phase of vascular calcification, many calcification-promoting genes were upregulated, including ossification, oxidation, and inflammatory genes. In contrast, in later phase of vascular calcification, various calcification-inhibitor genes were highly expressed, including pyrophosphoric acid synthesis genes, glutamate signal peptide-related, reduction activity, and apoptosis regulation genes. The relatively higher expression of calcification-inhibitor genes compared to that of calcification-promoting genes might explain the genetic mechanism leading to the regression of vascular calcification. Therefore, this study provides a genomic basis to facilitate understanding of the molecular mechanism underlying vascular calcification regression.

  15. Elastin Calcification and its Prevention with Aluminum Chloride Pretreatment

    PubMed Central

    Vyavahare, Narendra; Ogle, Matthew; Schoen, Frederick J.; Levy, Robert J.

    1999-01-01

    Elastin, an abundant structural protein present in the arterial wall, is prone to calcification in a number of disease processes including porcine bioprosthetic heart valve calcification and atherosclerosis. The mechanisms of elastin calcification are not completely elucidated. In the present work, we demonstrated calcification of purified elastin in rat subdermal implants (Ca2+ = 89.73 ± 9.84 μg/mg after 21 days versus control, unimplanted Ca2+ = 0.16 ± 0.04 μg/mg). X-ray diffraction analysis along with resolution enhanced FTIR spectroscopy demonstrated the mineral phase to be a poorly crystalline hydroxyapatite. We investigated the time course of calcification, the effect of glutaraldehyde crosslinking on calcification, and mechanisms of inhibition of elastin calcification by pretreatment with aluminum chloride (AlCl3). Glutaraldehyde pretreatment did not affect calcification (Ca2+ = 89.06 ± 17.93 μg/mg for glutaraldehyde crosslinked elastin versus Ca2+ = 89.73 ± 9.84 μg/mg for uncrosslinked elastin). This may be explained by radioactive (3H) glutaraldehyde studies showing very low reactivity between glutaraldehyde and elastin. Our results further demonstrated that AlCl3 pretreatment of elastin led to complete inhibition of elastin calcification using 21-day rat subdermal implants, irrespective of glutaraldehyde crosslinking (Ca2+ = 0.73–2.15 μg/mg for AlCl3 pretreated elastin versus 89.73 ± 9.84 for untreated elastin). The AlCl3 pretreatment caused irreversible binding of aluminum ions to elastin, as assessed by atomic emission spectroscopy. Moreover, aluminum ion binding altered the spatial configuration of elastin as shown by circular dichroism (CD), Fourier transform infrared (FTIR), and 13C nuclear magnetic resonance (NMR) spectroscopy studies, suggesting a net structural change including a reduction in the extent of β sheet structures and an increase in coil-turn conformations. Thus, it is concluded that purified elastin calcifies in rat

  16. Effects of Ultrasound Therapy on Calcificated Tendinitis of the Shoulder

    PubMed Central

    Takatori, Katsuhiko; Morishita, Shinichiro; Nagino, Koji; Yamamoto, Waka; Shimohira, Takahiro; Shimada, Tomoaki

    2002-01-01

    In general, surgery is recommended for calcificated tendinitis of the shoulder if the patients have symptoms after conservative treatments, including needle aspiration and physical therapy. Many researchers agree about the need for adequate physical therapy consisting of range of motion exercise, muscle strengthening exercises and electrophysical agents. Some researchers report that ultrasound (u/s) promotes angiogenesis and calcium uptake to fibroblasts, but there are few studies about u/s effects on calcificated tendinitis of the shoulder. The purpose of this study was to evaluate the u/s therapy effect on calcification, pain during active movement, and to identify factors related to improvement in a randomized controlled fashion. We used the stratified random allocation method to assign 40 consecutive patients to experimental and control groups, so each group consisted of 20 patients. The experimental group was treated by u/s therapy and therapeutic exercises, and the control group was treated with therapeutic exercises only. All patients in both groups came to our department 3 times per week and u/s therapy was performed 3 times per week until the end of the study. First, we classified the calcifications as type I (clearly circumscribed and with dense appearance on radiography), type II (dense or clearly circumscribed appearance) and type III (translucent or cloudy appearance without clear circumscription) according to the classification of Gartner and Heyer. Radiography was performed every one month, and the main outcome measure was the change from the base-line of the calcification on radiography at the end of the treatment. The three point scale of Gartner and Heyer was used, in which a score of 1 indicates no change or a worsening of the condition, a score of 2 a decrease of at least 50 percent in the area and density of the calcification, and a score of 3 a complete resolution of the calcification. We also examined the affected shoulders for presence or

  17. Energetic costs of calcification under ocean acidification

    NASA Astrophysics Data System (ADS)

    Spalding, Christopher; Finnegan, Seth; Fischer, Woodward W.

    2017-05-01

    Anthropogenic ocean acidification threatens to negatively impact marine organisms that precipitate calcium carbonate skeletons. Past geological events, such as the Permian-Triassic Mass Extinction, together with modern experiments generally support these concerns. However, the physiological costs of producing a calcium carbonate skeleton under different acidification scenarios remain poorly understood. Here we present an idealized mathematical model to quantify whole-skeleton costs, concluding that they rise only modestly (up to ˜10%) under acidification expected for 2100. The modest magnitude of this effect reflects in part the low energetic cost of inorganic, calcium carbonate relative to the proteinaceous organic matrix component of skeletons. Our analysis does, however, point to an important kinetic constraint that depends on seawater carbonate chemistry, and we hypothesize that the impact of acidification is more likely to cause extinctions within groups where the timescale of larval development is tightly constrained. The cheapness of carbonate skeletons compared to organic materials also helps explain the widespread evolutionary convergence upon calcification within the metazoa.

  18. Medial calcification (whitlockite) in the aorta.

    PubMed

    Reid, J D; Andersen, M E

    1993-07-01

    Calcified deposits in the tunica media of the human aorta have been studied in 128 cases by light microscopy and by electron microscopy and analytical methods in selected samples. Although dissolved and not visible in routine histology with alum hematoxylin stains, such calcification can be clearly seen after methylene blue staining in the form of unstained refractile particles of 1-2 microns size. These are found between the elastic laminae chiefly in the inner two-thirds of the media and appear at about age 20. By X-ray diffraction supported by energy dispersive X-ray analysis, they have been identified as whitlockite (Ca,Mg)3(PO4)2. Statistical analysis shows a significant increase in numbers with age and significant differences in severity related to county of origin but no differences between sexes or races and no correlation with deaths related to cardiovascular diseases. Among various substructures of the aortic wall, no unique crystal precursor was identified. Possible etiologic factors and clinicopathologic significance are considered.

  19. Pineal calcification: its mechanism and significance.

    PubMed

    Krstić, R

    1986-01-01

    On the basis of conventional transmission electron microscopy and ultracytochemical reactions for demonstration of calcium, for glucose-6-phosphatase, and for Ca2+-ATPase, intracellular and extracellular mineralization foci in the superficial pineal gland of the Mongolian gerbil (Meriones unguiculatus) have been described. The initial intracellular calcification sites occur in the cytoplasmic matrix, vacuoles, mitochondria and the endoplasmic reticulum of large clear pinealocytes. These loci, and particularly those within the cytoplasmic matrix, transform into acervuli by a further addition of hydroxyapatite crystals. The cells gradually degenerate, die, break down, and the acervuli reach the extracellular space. It has been suggested that the reason for a rise in intracellular calcium levels could be the incapacity of Ca2+-ATPase to eliminate this cation from the cell, so that the hypercalcemic intracellular milieu becomes favourable for the initial crystallization. The primary extracellular mineralization sites occur in the calcium-rich flocculent material. The mineralization process in the gerbil pineal gland is interpreted as a histophysiological phenomenon intimately related to the metabolic activity of the pineal gland.

  20. Vascular Calcification and Renal Bone Disorders

    PubMed Central

    Lu, Kuo-Cheng; Wu, Chia-Chao; Yen, Jen-Fen; Liu, Wen-Chih

    2014-01-01

    At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC. PMID:25136676

  1. Shunt tube calcification as a late complication of ventriculoperitoneal shunting.

    PubMed

    Salim, Abubakr Darrag; Elzain, Mohammed Awad; Mohamed, Haddab Ahmed; Ibrahim Zayan, Baha Eldin Mohamed

    2015-01-01

    Shunt calcification is a rare complication of ventriculoperitoneal shunting that occurs years later after the initial operation this condition is rarely reported in literature. Two patients with shunt calcifications were described. The first patient was 17-year-old lady who had congenital hydrocephalus and shunted in the early infancy, she was presented recently complaining of itching of the skin along the shunt track and limitation of neck movement. The patient was then operated with removal of the old peritoneal catheter and replacing it with a new one. The second patient was 17-year-old boy originally was a case of posterior fossa pilocytic astrocytoma associated with obstructive hydrocephalus, he was operated with both shunting for the hydrocephalus and tumor removal, 6 years later he presented with shunt exposure. Calcification of the shunt tube was discovered intraoperatively upon shunt removal. Shunt calcification has been observed mainly in barium-impregnated catheters. Introducing plain silicone-coated shunt tubing may reduce the rate of this condition. The usual complaints of the patients suffering from this condition are pain in the neck and chest wall along the shunt pathway and limitation of the neck movement due to shunt tube tethering, but features of shunt dysfunction and skin irritation above the shunt may be present. In this review, plain X-ray and operative findings showed that the most extensive calcification is present in the neck, where the catheters were subject to heavy mechanical stress. Disturbed calcium and phosphate metabolisms may be involved in this condition. Shunt calcification is a rare condition that occurs due to material aging presenting with features of shunt tethering, dysfunction or overlying skin irritation. Plain X-ray is needed to detect calcification while shunt removal, replacement or endoscopic third ventriculostomy may carry solution for this condition.

  2. History of hot flashes and aortic calcification among postmenopausal women.

    PubMed

    Thurston, Rebecca C; Kuller, Lewis H; Edmundowicz, Daniel; Matthews, Karen A

    2010-03-01

    Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P < 0.05). There were no significant associations between history of hot flashes and coronary artery calcification. Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

  3. History of hot flashes and aortic calcification among postmenopausal women

    PubMed Central

    Thurston, Rebecca C.; Kuller, Lewis H.; Edmundowicz, Daniel; Matthews, Karen A.

    2009-01-01

    Objective Menopausal hot flashes are considered largely a quality of life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The study aim is to ask whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use are examined in an exploratory fashion. Methods Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during the peri- and post-menopause initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997–2004. Associations between the number of visits reporting hot flashes, divided by the number of visits attended and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Results Among women using hormone therapy, a longer history of reporting hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b=2.87, SE=1.21, p<0.05). There were no significant associations between history of hot flashes and coronary artery calcification. Conclusions Among postmenopausal women using hormone therapy, a longer history of reporting hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women. PMID:20042895

  4. The association of breast arterial calcification and metabolic syndrome

    PubMed Central

    Yildiz, Seyma; Toprak, Huseyin; Aydin, Sinem; Bilgin, Mehmet; Oktay, Veysel; Abaci, Okay; Kocas, Cuneyt

    2014-01-01

    OBJECTIVES: We investigated the relationship between metabolic syndrome and breast arterial calcification detected via mammography in a cohort of postmenopausal subjects. METHODS: Among 837 patients referred to our radiology department for mammographic screening, 310 postmenopausal females (105 patients with and 205 patients without breast arterial calcification) aged 40 to 73 (mean 55.9±8.4) years were included in this study. The groups were compared with respect to clinical characteristics and metabolic syndrome criteria. Univariate and multivariate analyses identified the factors related to breast arterial calcification. RESULTS: Age, postmenopausal duration and the frequencies of diabetes mellitus, hypertension and metabolic syndrome were significantly higher in the subjects with breast arterial calcification than in those without (p<0.05). Multivariate analysis indicated that age (OR = 1.3, 95% CI = 1.1–1.6, p = 0.001) and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005) were independent predictors of breast arterial calcification detected via mammography. The independent predictors among the features of metabolic syndrome were low levels of high-density lipoproteins (OR = 8.1, 95% CI = 1.0−64.0, p = 0.047) and high blood pressure (OR = 8.7, 95% CI = 1.5−49.7, p = 0.014). CONCLUSIONS: The likelihood of mammographic detection of breast arterial calcification increases with age and in the presence of hypertension or metabolic syndrome. For patients undergoing screening mammography who present with breast arterial calcification, the possibility of metabolic syndrome should be considered. These patients should be informed of their cardiovascular risk factors and counseled on appropriate lifestyle changes. PMID:25627997

  5. Shunt tube calcification as a late complication of ventriculoperitoneal shunting

    PubMed Central

    Salim, Abubakr Darrag; Elzain, Mohammed Awad; Mohamed, Haddab Ahmed; Ibrahim Zayan, Baha Eldin Mohamed

    2015-01-01

    Shunt calcification is a rare complication of ventriculoperitoneal shunting that occurs years later after the initial operation this condition is rarely reported in literature. Two patients with shunt calcifications were described. The first patient was 17-year-old lady who had congenital hydrocephalus and sh