Anti-inflammatory profile of paricalcitol in kidney transplant recipients.

Background And Objectives: Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients.

Effect of Paricalcitol on FGF-23 and Klotho in Kidney Transplant Recipients.

Background: Paricalcitol decreases intact parathyroid hormone and the frequency of secondary hyperparathyroidism after kidney transplantation. This proof-of-concept study aimed to assess the effect of paricalcitol on fibroblast growth factor-23/KLOTHO axis in renal transplants.

Methods: Twenty-nine subjects with secondary hyperparathyroidism received oral paricalcitol 1 μg/d for 3 months, and 8 patients matched by age, sex, and creatinine clearance, but with intact parathyroid hormone less than 100 pg/mL, were included as controls.

Implications of Fibroblast growth factor/Klotho system in glucose metabolism and diabetes.

Diabetes mellitus, especially type 2 diabetes, remains the dominant metabolic disease worldwide, with an expected increase in prevalence of over 50% in the next 20 years. Our knowledge about the pathophysiology of type 2 diabetes continues to be incomplete, with unmet medical need for new therapies. The characterization of the fibroblast growth factor (FGF) family and the discovery of endocrine FGFs provided new information on the mechanisms of regulation and homeostasis of carbohydrate metabolism.

Klotho in cardiovascular disease: Current and future perspectives.

Protein Klotho, beyond its role as a regulator of the phosphatemia, is also involved in the maintaining of the cardiovascular health, being associated its alterations with the development of cardiovascular damage and increased morbi-mortality. For all this, nowadays Klotho is the subject of a thorough research which is focused on uncover its intimate mechanisms of action, and in analyzing the utility of its modulation as a potential strategy with clinical applicability. Molecular mechanisms of Klotho are not well understood but an emerging research area links Klotho deficiency with vascular pathology.

Influence of Klotho gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease.

Klotho protein has been associated with beneficial effects that contribute to the maintenance of cardiovascular health. Diverse studies suggest that alterations in the levels of this molecule may be associated with pathophysiological abnormalities that result in increased cardiovascular risk. The primary aim of this proof-of-concept study was to analyse the existence of a potential link between Klotho gene polymorphisms and the expression level of this gene in the vascular wall, and additionally with the incidence of cardiovascular disease and cardiovascular risk factors.

Inflammatory cytokines in diabetic nephropathy.

Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical catastrophe of worldwide dimensions. Metabolic and hemodynamic alterations have been considered as the classical factors involved in the development of renal injury in patients with diabetes mellitus. However, the exact pathogenic mechanisms and the molecular events of diabetic nephropathy remain incompletely understood.

Implications of Klotho in vascular health and disease.

Cardiovascular disease (CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high.

Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial.

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years.

Diabetic kidney disease: from physiology to therapeutics.

Diabetic kidney disease (DKD) defines the functional, structural and clinical abnormalities of the kidneys that are caused by diabetes. This complication has become the single most frequent cause of end-stage renal disease. The pathophysiology of DKD comprises the interaction of both genetic and environmental determinants that trigger a complex network of pathophysiological events, which leads to the damage of the glomerular filtration barrier, a highly specialized structure formed by the fenestrated endothelium, the glomerular basement membrane and the epithelial podocytes, that permits a highly selective ultrafiltration of the blood plasma.

Beneficial effects of selective vitamin D receptor activation by paricalcitol in chronic kidney disease.

In chronic kidney disease patients, active vitamin D level progressively declines in the course of the disease. This phenomenon is accompanied by elevation of parathyroid hormone, resulting in secondary hyperparathyroidism (SHPT), increased phosphorus levels, and hypocalcemia. All these disorders are associated with high rates of cardiovascular morbidity and mortality in these patients.

Reduced Klotho is associated with the presence and severity of coronary artery disease.

Objective: Klotho is involved in vascular health. We aimed to analyse in a cross-sectional study the relationship between Klotho and human coronary artery disease (CAD).

Methods: The study included 371 subjects who underwent coronary angiography and 70 patients who underwent elective cardiac surgery recruited between May 2008 and June 2009.

Pathophysiological implications of fibroblast growth factor-23 and Klotho and their potential role as clinical biomarkers.

Background: Fibroblast growth factor-23 (FGF-23) and Klotho constitute the main regulatory system of phosphorus homeostasis. Beyond this physiological role, there is growing evidence suggesting that this system has relevant pathophysiological implications in different clinical processes.

Content: In this review we discuss the pathophysiological implications of the FGF-23/Klotho system and the potential utility that measurements of its components may have as clinical biomarkers in different clinical settings, such as progression of chronic kidney disease, acute renal failure, and secondary hyperparathyroidism, as well as vascular dysfunction, atherosclerosis, and cardiovascular morbidity and mortality.

Anti-inflammatory profile of paricalcitol in hemodialysis patients: a prospective, open-label, pilot study.

Inflammation is a strong predictor of increased morbidity and mortality in hemodialysis (HD) patients. Paricalcitol, a selective vitamin D receptor activator used for prevention and treatment of secondary hyperparathyroidism, has shown anti-inflammatory properties in experimental studies, although clinical data are scarce. In an open-label, prospective, single center, pilot study, 25 stable HD patients, previously receiving calcitriol, completed 12 weeks of therapy with oral paricalcitol.

FGF23/Klotho axis: phosphorus, mineral metabolism and beyond.

In this work we summarizes the steps that allowed the identification of the fibroblast growth factor (FGF) 23/Klotho axis as the principal regulator of phosphate homeostasis, exerting actions on intestine, bone, parathyroid glands, and kidney. We review the not fully understood mechanisms of action of this axis on the regulation of mineral homeostasis and, in addition, we discuss its potential role in the pathophysiology of chronic kidney disease and the associated complications. We also reflect the actual tendency to consider the components of this system as better predictors of the pathological conditions frequently associated to mineral disorders, and review some recent studies linking these components to cardiovascular disease even in population without mineral disorders.

Expression of FGF23/KLOTHO system in human vascular tissue.

Background: Fibroblast growth factor (FGF)-23 levels have been associated with impaired vasoreactivity, increased arterial stiffness, and cardiovascular morbi-mortality, whereas a protective function of KLOTHO against endothelial dysfunction has been reported. Since expression of the FGF23-KLOTHO system in human vascular tissue remains unproved, we aimed to study the expression of FGF23, FGF receptors (FGFR) and KLOTHO in human aorta. In addition, we analyzed the FGF23-KLOTHO expression in occlusive coronary thrombi.

Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients.

Background And Objectives: Hyperphosphatemia and subclinical endotoxemia are important sources of inflammation in HD. Proinflammatory cytokines are strong correlates of soluble CD14 (sCD14) concentrations, an independent predictor of mortality in this population. We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile, endotoxin concentrations, and sCD14 levels in HD patients.

Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy.

Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus, modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today. The relationships between inflammation and the development and progression of diabetic nephropathy involve complex molecular networks and processes.

C-reactive protein levels and survival in patients with moderate to very severe COPD.

Background: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease.

Objective: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease.

A simple clinical score for type 2 diabetes mellitus screening in the Canary Islands.

Aim: To develop a straightforward risk score for type 2 diabetes (DM2) screening to use in clinical practice.

Methods: A sample of 6237 adult inhabitants of the Canary Islands (Spain) was randomly divided into two subgroups: one yielded data used to develop the instrument, and the other yielded data used for validation testing. Performance of the instrument was compared in persons with clinically diagnosed DM2 and undiagnosed diabetes.

[Sedentary lifestyle: physical activity duration versus percentage of energy expenditure].

Introduction And Objectives: To compare different definitions of a sedentary lifestyle and to determine which is the most appropriate for demonstrating its relationship with the metabolic syndrome and other cardiovascular risk factors.

Methods: A cross-sectional study of 5814 individuals was carried out. Comparisons were made between two definitions of a sedentary lifestyle: one based on active energy expenditure being less than 10% of total energy expenditure, and the other, on performing less than 25-30 minutes of physical activity per day.

[Coronary risk in the population of the Canary Islands, Spain, using the Framingham function].

Background And Objective: Although ischemic cardiopathy mortality in the Canary Islands is among the highest in Spain, the specific coronary risk for its population has not been estimated. This study presents the first cardiovascular risk charts for the Canarian adult population and compares them with those previously published on Gerona, Spain.

Subjects And Method: A cross-sectional study of 4915 subjects, aged 25-74, that had been enrolled in the cohort study CDC of the Canary Islands.