The uraemic retention solute para-hydroxy-hippuric acid attenuates apoptosis of polymorphonuclear leukocytes from healthy subjects but not from haemodialysis patients.

Background: Disturbed polymorphonuclear leukocyte (PMNL) apoptosis contributes to the dysregulation of the non-specific immune system in uraemia. Intracellular Ca(2+) modulates PMNL apoptotic cell death. We investigated the effect of para-hydroxy-hippuric acid (PHA), an erythrocyte plasma membrane Ca(2+)-ATPase inhibitor accumulating in uraemic sera, and of cyclopiazonic acid (CPA), an inhibitor of the sarko/endoplasmatic Ca(2+)-ATPase, on PMNL apoptosis.

New insights into the regulation of iron homeostasis.

Hepcidin evolves as a potent hepatocyte-derived regulator of the body's iron distribution piloting the flow of iron via, and directly binding, to the cellular iron exporter ferroportin. The hepcidin-ferroportin axis dominates the iron egress from all cellular compartments that are critical to iron homeostasis, namely placental syncytiotrophoblasts, duodenal enterocytes, hepatocytes and macrophages of the reticuloendothelial system. The gene that encodes hepcidin expression (HAMP) is subject to regulation by proinflammatory cytokines, such as IL-6 and IL-1; excessive hepcidin production explains the relative deficiency of iron during inflammatory states, eventually resulting in the anaemia of inflammation.

Hormonal adjuvants for the treatment of renal anaemia.

Hormonal adjuvants, besides being erythropoietic agents, broaden the spectrum of therapeutic options for the treatment of the anaemia of chronic kidney disease (CKD). Lowering elevated parathyroid hormone levels by oral calcium supplementation and phosphate restriction, by varying dialysate calcium concentrations, by administration of vitamin D3 derivatives and, in the near future, by treatment with calcimimetics may prove efficient in some patients to fight extensive requirements of erythropoietic agents. Clinical evidence for a principal role of secondary hyperparathyroidism in resistance to erythropoietin, however, is lacking.

Impact of parathyroidectomy on neutrophil cytosolic calcium in chronic kidney disease patients: a prospective parallel group trial.

Objectives: Polymorphonuclear leucocytes (PMNs) of chronic kidney disease (CKD) patients display elevated basal cytosolic calcium concentrations (iCa(2+)). As parathyroid hormone is considered to substantially contribute to the inappropriate cellular entry of calcium in uraemia, we hypothesized that parathyroidectomy lowers PMN iCa(2+).

Design And Setting: Prospective parallel group trial at a tertiary care centre.

Low total vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in hemodialysis patients.

Hemodialysis patients are prone to deficiency of vitamin C, which constitutes the most abundant nonenzymatic antioxidant in blood. Because antioxidants are involved in the pathogenesis of atherosclerosis, the authors examined the association of total vitamin C plasma level with cardiovascular outcomes in such patients. One hundred thirty-eight consecutive maintenance hemodialysis patients (median age 61 yr, 90 males) were enrolled in a single-center study.

Vitamin C plasma level and response to erythropoietin in patients on maintenance haemodialysis.

Background: Intravenous vitamin C supplementation to haemodialysis patients might ameliorate responsiveness to recombinant human erythropoietin (rHuEpo). This study was performed to analyse the relation between vitamin C plasma concentration and response to rHuEpo.

Methods: In a cross-sectional, single-centre observational study including all haemodialysis patients, pre-dialysis plasma vitamin C concentrations were measured by high-performance liquid chromatography and response to rHuEpo (haemoglobin concentration/international units rHuEpo/kg/week) was recorded together with baseline laboratory data.

Differentiating factors between erythropoiesis-stimulating agents: a guide to selection for anaemia of chronic kidney disease.

Endogenous erythropoietin (EPO) consists of a central polypeptide core covered by post-translationally linked carbohydrates. Three of the four currently available erythropoiesis stimulating agents (ESA)--epoetin-alpha, epoetin-beta and epoetin-omega- are composed of an identical amino acid sequence, but glycosylation varies as a result of type- and host cell-specific differences in the production process. Epoetin-alpha and epoetin-beta resemble each other with respect to molecular characteristics and pharmacokinetic data, although epoetin-beta has a higher molecular weight, a lower number of sialylated glycan residues and possibly slight pharmacokinetic advantages such as a longer terminal elimination half-life.

Aberrant T cell activation and heightened apoptotic turnover in end-stage renal failure patients: a comparative evaluation between non-dialysis, haemodialysis, and peritoneal dialysis.

Patients in end-stage renal disease (ESRD) have a high incidence of bacterial and viral infections. Fifteen non-dialysed (ND), 15 haemodialysed (HD), 15 patients with peritoneal dialysis (PD), and 15 healthy controls were included. T cell proliferation was measured by [3H]thymidine uptake.

Immunoglobulin light chains modulate polymorphonuclear leucocyte apoptosis.

Background: Apoptosis of polymorphonuclear leucocytes (PMNLs) is important for the resolution of inflammation. Recently, we demonstrated that glucose-modified proteins increase PMNL apoptosis. No protein factors in sera of uraemic patients attenuating PMNL apoptosis have been identified to date.

High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity.

Background: Iron is essential for the formation of hemoglobin. During long-term treatment with human recombinant erythropoietin (rhEPO), the majority of end-stage renal disease (ESRD) patients will not respond adequately to rhEPO unless substituted with intravenous iron. However, concern exists about possible detrimental effects of parenteral iron on cellular host defense and iron-mediated increments of oxidative stress.

Vitamin C in chronic kidney disease and hemodialysis patients.

Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate represents one of the most prominent antioxidants both in plasma as well as intracellulary, exerting beneficial effects by an inhibition of lipid peroxidation and by reducing endothelial dysfunction. However, in the presence of transition metals like iron, ascorbate may give rise to an increased generation of oxidants, and ascorbylation may impose additional carbonyl stress to uremic patients.

Anaemia as a risk factor for the progression of chronic kidney disease.

Purpose Of Review: About a dozen controlled clinical trials examined the effect of anaemia correction on the progression of chronic kidney disease. None of these studies fulfilled the stringent criteria of a randomized controlled trial as suggested by the CONSORT statement, yet evidence emerged that anaemia sustains mitogenic and fibrogenic stimuli by lowering local partial oxygen tension. This review addresses the question of why and how anaemia could possibly enhance the progression of chronic kidney disease, and summarizes relevant clinical trials.

Intravenous iron: the iatrogenic kick to lose control over oxygen?

Effective erythropoiesis requires both erythropoietin and iron. Regular, intravenous iron supplements represent a standard adjuvant therapy for the treatment of anemia of chronic kidney disease. In this paper, the authors speculate upon potential deleterious effects of intravenous iron on cellular physiology in the setting of the increased oxidant burden of hemodialysis patients.

Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis.

Background: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse.

Homocysteine: a risk factor for cardiovascular disease in subclinical hypothyroidism?

The role of homocysteine as a causal risk factor for cardiovascular disease remains controversial. Moderately elevated total plasma homocysteine levels have been reported in patients with overt hypothyroidism, a condition that is associated with an increased risk for cardiovascular disease. Recently, subclinical hypothyroidism has been identified as an independent risk factor for atherosclerosis and myocardial infarction in elderly women.

Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis.

Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20).

Neutrophil beta(2)-microglobulin and lactoferrin content in renal failure patients.

Multiple dysfunctions of polymorphonuclear leukocytes (PMNLs) contribute significantly to the increased morbidity and mortality among patients with end-stage renal disease. In the present study, we measured the PMNL content of beta(2)-microglobulin (beta(2)m) and lactoferrin in different states of renal insufficiency and after kidney transplantation. PMNLs were lysed ultrasonically and, after centrifugation, both proteins were assayed in the supernatant by enzyme-linked immunosorbent assay technique.

Recombinant human granulocyte colony-stimulating factor after kidney transplantation: a retrospective analysis to evaluate the benefit or risk of immunostimulation.

Background: Leukopenia due to immunosuppressive drugs represents a well-known complication in graft recipients, which might put patients at an increased risk for infections. In this study, recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that selectively stimulates neutrophil colony formation and neutrophil cell differentiation, was tested for safety and efficacy.

Methods: We evaluated 30 episodes of leukopenia (<2000/mm3) in 19 kidney graft recipients treated with rhG-CSF.

[Acute coronary syndromes: physiopathology and therapeutic aspects].

This article discusses recent developments in the field of acute coronary syndromes including pathophysiological mechanisms as well as therapeutic strategies. A plaque disruption is caused by different stimuli in a plaque prone to rupture, i.e.

Effect of immunoglobulin light chains from hemodialysis and continuous ambulatory peritoneal dialysis patients on polymorphonuclear leukocyte functions.

Circulating plasma factors accumulating in the serum of uremic patients have the potential to inhibit essential functions of polymorphonuclear leukocytes (PMNL). As a consequence, these factors can contribute to the increased risk for bacterial infections generally found in uremic patients. Free immunoglobulin light chains that are present in the serum of healthy adults at low levels appear in the serum of uremic patients at significantly higher levels.

Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly in addition 5-HT1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex.

The pharmacological properties of presynaptic serotonin autoreceptors were compared in slices of rat, rabbit, and guinea-pig brain cortex. The slices were preincubated with 3H-serotonin and then superfused with medium containing fluvoxamine 3 mumol/l and stimulated four times by trains of four pulses delivered at 100 Hz. Cumulative concentration-response curves were determined and used for the calculation of agonist EC50 values and maximal effects and antagonist KB values.