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Aleix Cases

Publications and source records attributed to Aleix Cases.

At least 19 recordsLinked to original sources
PubMed2006

A year of advancement and reflection in nephrology science.

The 38th Annual Meeting of the American Society of Nephrology was held November 8-13, 2005, in Philadelphia, Pennsylvania, USA. The meeting offered the latest findings in basic and clinical nephrology science and was attended by more than 12,000 specialists from around the world. This year's sessions included 58 basic and clinical science symposia, 29 clinical nephrology conference sessions, 24 official symposia, 51 free communications and three poster sessions. Highlights of the meeting are discussed.

Anemia↗
PubMed2005

Prevalence, clinical correlates and therapy cost of mineral abnormalities among haemodialysis patients: a cross-sectional multicentre study.

BACKGROUND: This study evaluated the proportion of patients who met National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines for mineral status, and assessed the cost of therapy for mineral management of patients under haemodialysis treatment in Spain. METHODS: Demographic and biochemical data were collected for 1312 patients undergoing standard three-times weekly maintenance haemodialysis at six Spanish centres during December 2003. Age, gender, diabetic nephropathy, haemodialysis duration, serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone (iPTH) levels were monitored. Exploratory analyses of associations between demographic and biochemical parameters, were undertaken using bivariate and multivariate regression techniques. RESULTS: Mean age of patients was 62 years. 97% were Caucasian, 23% were diabetic. In total, 51% of patients received calcium binders, 21% sevelamer, 16% aluminium hydroxide, and 29% received no binders; 33% of patients received calcitriol. Prevalence of patients outside K/DOQI targets was: calcium 50%, phosphorus 46%; Ca x P 33%; iPTH 77%. Elevated phosphorus (>5.5 mg/dl) was independently associated with younger age [OR 0.972 (95% CI 0.963-0.980), P<0.001] and higher iPTH [OR 1.0005 (95% CI 1.0002-1.0008), P<0.001]. Elevated Ca x P (>or=55 mg(2) x dl(2)) showed a similar relationship. High iPTH levels (>300 pmol/l) were associated with female gender [OR 1.574 (95% CI 1.213-2.041), P<0.001], high serum phosphorus [OR 1.230 (95% CI 1.130-1.338), P<0.001], and longer duration of dialysis [OR 1.003 (95% CI 1.001-1.005), P<0.01]. Poorly controlled serum phosphorus, Ca x P and iPTH were associated with more expensive therapy for mineral management. CONCLUSIONS: One in three haemodialysis patients in Spain remains above the upper target range defined in current mineral metabolism guidelines. This abnormal profile is more common in younger patients and females and therapy is more expensive in younger patients.

Adolescent↗
PubMed2005

Dyslipidemia and the progression of renal disease in chronic renal failure patients.

Dyslipidemia is a common complication of progressive kidney disease and contributes to the high cardiovascular morbidity and mortality of chronic kidney disease (CKD) patients. Recent evidence also suggests a role for dyslipidemia in the development and progression of renal disease. Experimental studies have demonstrated that lipids may induce glomerular and tubulointerstitial injury, and that lipid-lowering treatments ameliorate renal injury. Various lipid abnormalities have been associated with the development and progression of renal disease in diabetic and nondiabetic patients. Population-based studies and studies of diabetic patients have reported associations of various lipid abnormalities with the development of renal disease. In patients with CKD, lipid abnormalities have also been associated with renal disease progression. Post hoc analyses of some large clinical trials on patients with vascular disease, diabetes, or dyslipidemia, and a meta-analysis of small, prospective, controlled studies on patients with CKD (diabetics and nondiabetics) suggest that statins may slow the progression of kidney disease. It is unclear whether the beneficial renal effects of statins are due to the reduction of serum cholesterol levels and/or their pleiotropic effects. There is also evidence for synergistic renoprotective effects between statins and renin-angiotensin system inhibitors. According to the results of post hoc analysis of several studies, treatment with fibrates does not seem to confer renoprotection, but evidence is scarce. In summary, there is growing evidence that lipid abnormalities may be a risk factor for renal disease, and that statins appear to confer a renoprotective effect.

Anticholesteremic Agents↗
PubMed2005

Uremic platelet dysfunction: past and present.

Uremic patients develop an acquired platelet dysfunction that results in bleeding complications. The pathogenesis of this hemostatic dysfunction is multifactorial and includes effects of circulating toxins, alterations of the vessel wall, anemia, and other factors, complicated by unwanted effects of hemodialysis procedures. This review seeks to place in perspective the evolution of knowledge on uremic platelet dysfunction. It examines how investigations of the altered hemostasis in these patients have led to a better understanding of the mechanisms involved and how these advances have contributed to the development of effective therapeutic strategies. It also comments upon the fact that elevated rates of thrombotic complications are apparently emerging as the bleeding tendency is better controlled. Emphasized is the delicate balance of hemostasis in the uremic condition, in which deficient hemostasis paradoxically coexists with accelerated atherosclerosis and an enhanced risk of thrombosis.

Blood Platelet Disorders↗
PubMed2004

Biocompatibility of cellulosic and synthetic membranes assessed by leukocyte activation.

BACKGROUND/AIMS: The contact of blood with artificial surfaces may activate blood leukocytes and platelets and initiate the leukocyte inflammatory response. We have investigated the effect of a hemodialysis (HD) with a cellulosic- and a synthetic-based membrane on circulating leukocyte activation. METHODS: Samples were obtained from patients with ESRD at baseline, and at 15 and 120 min of a hemodialysis session from both the arterial and venous lines. Leukocyte respiratory burst was analyzed by luminol chemiluminescence. Actin polymerization, expression of CD11b, and heterotypic aggregation were studied by flow cytometry, leukocyte labeling with NBD phallacidin and monoclonal antibodies, respectively. RESULTS: HD with a cellulosic membrane induced a transient fall in neutrophil (1.2 +/- 0.5 x 10(9) vs. 3.6 +/- 0.6 x 10(9) cells/l; p < 0.05) and monocyte counts (0.2 +/- 0.1 x 10(9) vs. 0.7 +/- 0.1 x 10(9) cells/l; p < 0.05). There was also an increase in respiratory burst in the venous line during a HD with a cellulosic membrane, at 15 and 120 min (100 +/- 41 and 143.2 +/- 45.3 vs. 23.8 +/- 15.7; p < 0.05). Polymerized actin, expressed as fluorescence arbitrary units, was increased in baseline samples from uremic patients versus control subjects (327.8 +/- 60.8 for a cellulosic membrane, p < 0.005, and 205 +/- 26.5 for a synthetic one, p < 0.05 vs. 97.8 +/- 27.6 in controls). The percentage of CD11b+ cells increased in samples during a HD with a cellulosic membrane at the venous line at 15 and 120 min (9.6 +/- 4.5 and 18.4 +/- 7.1% vs. 3.3 +/- 1.9%; p < 0.05%). Changes in heterotypic aggregation during HD did not reach statistical significance, but levels were higher in patients treated with a cellulosic membrane at all points than in patients dialyzed with a synthetic one. CONCLUSION: There is evidence of a priming state of leukocytes from uremic patients, which is more evident in patients dialyzed with a cellulosic membrane. Cellulosic membranes also induce greater leukocyte activation than synthetic membranes during hemodialysis.

Adult↗
PubMed2004

Update in nephrology. Highlights from the 36th Annual Meeting of the American Society of Nephrology.

The 36th Annual Meeting of the American Society of Nephrology, held in San Diego, California, USA, November 12-17, 2003, presented the newest advances in basic and clinical nephrology science. Several presentations and symposia discussed many new aspects of the management of type 2 diabetic nephropathy as well as the recent advances in the treatment of secondary hyperparathyroidism in chronic kidney disease patients with cinacalcet HCl, a calcimimetic agent. New drugs that are under development for the treatment of renal anemia, such as the continuous erythropoiesis receptor activator (CERA), or for the treatment of pure red cell aplasia, a rare but severe complication of the erythropoietic treatment, were considered. The long-term safety of i.v. iron replacement therapy was also analyzed. The recent results of the Dialysis Outcomes and Practice Patterns Study (DOPPS), a large, multinational, observational study in hemodialysis patients were presented. Some complications of renal transplantation, recent advances in immunosuppressive agents and the experience of renal transplant in HIV patients recipients were also reviewed during the congress. The 36th Annual Meeting of the American Society of Nephrology offered the newest advances in basic and clinical nephrology science and was attended by more than 11,000 nephrologists from around the world. This year's sessions included 45 basic and clinical science symposia, 22 clinical nephrology conference sessions, 17 official symposia, as well as oral communications and poster sessions.

Anemia↗
PubMed2003

Interactions between vasoconstrictors and vasodilators in regulating hemodynamics of distinct vascular beds.

We examined whether interactions between angiotensin II (Ang II), endothelin (ET), nitric oxide (NO), and prostaglandins (PGs) differentially regulate perfusion to distinct vascular beds. For this, we blocked either angiotensin AT1 or ET receptors or both and then sequentially inhibited NO and PG synthesis in anesthetized dogs. Blocking Ang II or ET had similar effects on systemic hemodynamics: Mean arterial pressure fell slightly without altering cardiac output. Blocking both caused a synergistic fall in mean arterial pressure and increased cardiac output. Pulmonary vascular resistance was not altered by blocking Ang II, ET, or both but progressively increased during NO and PG blockade in group 2 (which had unblocked ET receptors), suggesting that endogenous ET exerts pulmonary vasoconstriction that is tempered by NO and PGs. In the kidney, blocking Ang II increased regional blood flow (RBF), glomerular filtration rate (GFR), and fractional excretion of sodium (FENa). In contrast, blocking ET did not alter RBF, and it decreased GFR and FENa. Combined Ang II and ET blockade markedly increased RBF without altering GFR, and FENa was maintained at the levels as when only ET was blocked. Sequentially inhibiting NO and PGs decreased RBF when Ang II or ET were blocked but had little effect when both were blocked. Finally, Ang II or ET blockade did not alter iliac blood flow. Inhibiting NO and PGs decreased iliac blood flow when Ang II or ET but not both were blocked. These results suggest that regional differences in the interactions between endogenous Ang II, ET, NO, and PGs are important determinants in systemic, pulmonary, and regional hemodynamics.

Angiotensin II↗
PubMed2003

Uraemic medium accelerates proliferation but does not induce apoptosis of endothelial cells in culture.

BACKGROUND: Chronic renal failure patients exhibit accelerated atherosclerosis, which is associated with a high incidence of cardiovascular death. We investigated the potential effect of uraemic medium on cell proliferation and apoptosis of endothelial cells in culture (ECs), two key processes in the development of atherosclerosis. Phosphorylation kinetics of the mitogen-activated protein kinase (MAPK) p42/44 and p38 were also evaluated. METHODS: ECs were cultured with growth media supplemented with pooled sera from healthy donors. Semiconfluent ECs were incubated for 24 h with media supplemented with pools of control or uraemic sera. Cell proliferation was assessed through morphometric analysis and by flow cytometry evaluation of cell cycle. To investigate if uraemic medium induces apoptosis in ECs, we used a combination of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay and activation of caspase-3 using flow cytometry. Changes in the phosphorylation levels of MAPK were evaluated in cell lysates by western blotting. RESULTS: Exposure to uraemic media caused an alteration in the morphology of ECs, showing irregular shape and size. The number of ECs at S+G(2)M phase in the cell cycle was found to be increased when exposed to uraemic media for 24 h (28.4+/-2.9 vs 20.2+/-2.6% in control ECs). There was a transient increase in levels of phosphorylation of MAPK in both cells, although these levels were significantly higher in ECs exposed to uraemic media, especially after 5 min. In contrast, no signs of apoptosis were observed in ECs incubated with uraemic medium at the conditions applied. CONCLUSIONS: Under our experimental conditions, uraemic medium accelerates proliferation of ECs, but it does not seem to induce apoptosis. The increased proliferation observed could be related to a higher MAPK activity in these cells. Although the enhanced atherosclerosis cannot be explained on the basis of an apoptotic process, the proliferative status could contribute to intimal proliferation, which is considered to be an earlier step in the development of atherosclerosis.

Apoptosis↗
PubMed2003

Darbepoetin alfa: a novel erythropoiesis-stimulating protein.

Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anemia. It is a hyperglycosylated analog of recombinant human erythropoietin with the same mechanism of action as erythropoietin, but with a three-fold longer terminal half-life after intravenous administration than recombinant human erythropoietin and the native hormone both in animal models and in humans. Clinical studies in patients with chronic renal failure either receiving or not receiving dialysis have shown that darbepoetin alfa is equivalent to recombinant human erythropoietin in terms of increases in hemoglobin concentration, percentage of patients achieving target hemoglobin concentration and average time to reach target hemoglobin concentration, although darbepoetin alfa is administered less frequently (once weekly or every other week). Clinical trials in cancer patients either receiving or not receiving chemotherapy have demonstrated that darbepoetin alfa is safe and effective in alleviating anemia at dose intervals of once every 1, 2 or 3 weeks, and results suggest that it may achieve greater and more rapid responses than recombinant human erythropoietin in cancer patients. Furthermore, an improvement in health-related quality of life has been observed in association with anemia correction using darbepoetin alfa therapy in these patients. Darbepoetin alfa has been approved for intravenous and subcutaneous administration by the European Commission and the FDA for the treatment of anemia in patients with chronic renal failure. Additionally, this product was recently approved by the FDA for the treatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. The recommended starting dose in chronic renal failure patients is 0.45 microg/kg once weekly for both intravenous and subcutaneous administration, with subsequent titration based on the hemoglobin concentration. In cancer patients, the recommended starting dose is 2.25 microg/kg once weekly by subcutaneous injection and subsequent titration. The adverse event profile of darbepoetin alfa is similar to that of recombinant human erythropoietin in both settings. There are no reports of antibody formation associated with darbepoetin alfa in chronic renal failure patients, and three cases of antibody formation, with neutralizing activity in one of the cases, have been reported in cancer patients. However, no cases of antibody-mediated pure red cell aplasia have been reported. The longer half-life of darbepoetin alfa, together with a similar efficacy and safety profile, confers the clinical advantage over recombinant human erythropoietin of allowing a less frequent dosing (once weekly or every other week versus one to three times weekly in renal patients), thus reducing health-care utilization and probably improving patient compliance.

Anemia↗
PubMed2003

Recent advances in nephrology.

The World Congress of Nephrology was held in Berlin, Germany, June 8-12, 2003. The meeting offered the newest advances in basic and clinical nephrology science and was attended by about 9,000 scientists and clinicians from around the world. During the congress, results of the treatment of Fabry's disease with enzyme replacement therapy, the results of the treatment of anemia in patients with chronic kidney disease with new erythropoietic agents (darbepoetin alfa, continuous erythropoiesis receptor activator), and the management of secondary hyperparathyroidism and calcium-phosphorus disorders in uremia with calcimimetic agents and new phosphate binders, such as lanthanum carbonate, were discussed. Furthermore, recent studies evaluating the efficacy and safety of new immunosuppressive agents and their combination for the treatment of renal transplant recipients were also presented.

Anemia↗
PubMed2002

[Analysis of heart rate as a risk factor associated with the progression of chronic renal failure].

BACKGROUND: An increased heart rate is associated with an increased risk of cardiovascular and non-cardiovascular death. However, the possible relationship between heart rate and the rate of progression of renal disease has not been assessed so far. PATIENTS AND METHOD: Twenty-four-hour ambulatory blood pressure and heart rate recordings at baseline conditions were obtained in 24 patients with non-diabetic chronic renal failure and hypertension. The rate of progression of renal disease was estimated on the basis of the slope of the reciprocal of serum creatinine concentration against time. RESULTS: After a mean follow-up of 38 months, the rate of progression of renal failure was 0.004 (0.039) dL/mg/month. Progression of renal disease showed no correlation with baseline ambulatory systolic or diastolic blood pressures, and did not differ between dipper and non-dipper patients. Twenty-four-hour (r = 0.40, p = 0.05) and day-time (r = 0.534, p = 0.007) heart rates showed a relationship with the progression of renal failure. Proteinuria displayed a correlation with night-time heart rate (r = 0.405, p = 0.05) but not with the progression of renal failure. CONCLUSIONS: Baseline ambulatory heart rate, especially day-time heart rate, is associated with the decline of renal function in non-diabetic patients with chronic renal failure, suggesting that heart rate is a risk factor (or marker) for renal disease progression. Prospective controlled studies with a larger sample of patients are needed to confirm these findings and to investigate the possible mechanisms involved in this association.

Adult↗
PubMed2002

Erythropoietin triggers a signaling pathway in endothelial cells and increases the thrombogenicity of their extracellular matrices in vitro.

We demonstrate that exposure of cultured human endothelial cells to rHuEPO resulted in a dose-dependent increase in the tyrosine kinase activity, with phosphorylation of JAK-2 followed by rapid phosphorylation of STAT-5. Simultaneously, rHuEPO induced long-lasting phosphorylation of MAPK p42/44. Activation of this signaling pathways was directly associated with an increase in the thrombogenic properties of the extracellular matrix generated by these cells, when they were exposed to flowing blood. The enhancement in the reactivity of the resulting extracellular matrix towards platelets was associated with a higher expression of tissue factor. All these effects were blocked by an antibody to the EPO receptor and by specific inhibitors of tyrosine phosphorylation. The observed action of rHuEPO on endothelial cells seemed to be specifically triggered by the subsequent events that follow receptor binding, and occurred even at pharmacological concentrations of the cytokine. Our results indicate that rHuEPO has a direct action on the endothelium, increasing the reactivity of the underlying extracellular matrix towards platelets, effect that may be attributed to an increase in the expression of TF.

Blood Platelets↗
PubMed2002

Uremic medium causes expression, redistribution and shedding of adhesion molecules in cultured endothelial cells.

BACKGROUND AND OBJECTIVES: Patients with chronic renal failure show signs of accelerated atherosclerosis and high cardiovascular morbidity and mortality. Recent investigations indicate that uremia is associated with endothelial dysfunction and a microinflammatory state. We assessed changes in the expression of adhesion molecules [ELAM-1, VCAM-1 and ICAM-1], and proteins involved in hemostasis [von Willebrand factor (vWF) and thrombomodulin (TM)] in endothelial cells (ECs) and the corresponding extracellular matrices (ECM), respectively. DESIGN AND METHODS: Cultured human umbilical vein endothelial cells were incubated in the presence of a pool of normal or uremic sera. Immunocytochemical detection of related antigens was performed with specific antibodies coupled to colloidal gold. Concentrations of soluble adhesion molecules and TM in culture supernatants were evaluated by ELISA. Modifications in the transcription of the corresponding genes were also evaluated by Northern-blotting and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Exposure of ECs to uremic media caused an increase in the presence [ELAM-1, VCAM-1] and accessibility [ICAM-1] of the adhesion receptors on EC monolayers, as well as a higher presence of their soluble molecules in culture supernatants. We found a significant increase in the presence of vWF on the extracellular matrix derived from ECs grown in the presence of a uremic medium. The presence of TM on ECs and in the ECM remained unmodified, although there was a significant increase in the presence of TM in supernatants from ECs grown in the presence of uremic sera. Northern-blot or RT-PCR studies showed increased expression of the mRNA for all the corresponding genes (ELAM-1, VCAM-1, ICAM-1, vWF and TM). INTERPRETATION AND CONCLUSIONS: Uremic medium causes inflammatory changes in ECs, which are characterized by enhanced expression, redistribution and shedding of adhesion molecules and TM, with an increased incorporation of vWF on the extracellular matrix generated.

Blotting, Northern↗
PubMed2002

Recent advances in nephrology: highlights from the 35th annual meeting of the American society of nephrology.

The 35th Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, United States (October 30 to November 4, 2002) presented the newest advances in basic and clinical nephrology science. Several presentations and symposia discussed the effects of various interventions and risk factors in clinical outcomes in dialysis patients. The recent evidences of pure red cell aplasia secondary to neutralizing antibodies against erythropoietin were also extensively discussed in a special symposium. Recent advances in the management of calcium phosphorus metabolism and secondary hyperparathyroidism, such as the clinical efficacy and safety of AMG-073, a new calcimimetic agent in the control of hyperparathyroidism in chronic kidney disease patients, or the use of sevelamer or lanthanum carbonate as phosphate binders, were presented. The results in animal models on improved sparing of renal function with rapamycin versus cyclosporin A represent a promising advance in renal transplantation. Finally, the recent discoveries with the newly identified disease gene PKHD1, which causes autosomal recessive polycystic kidney disease, were also presented at the meeting.

Anemia↗