Lorena Nostro

Dialysis-related genotoxicity: sister chromatid exchanges and DNA lesions in T and B lymphocytes of uremic patients. Genomic damage in patients on hemodiafiltration.

Background/Aims: Patients with chronic renal failure show the presence of massive oxidative genome damage but the role played by dialysis is still a controversial issue. The aim of our study was to verify the genomic damage in B- and T-lymphocyte subpopulations of uremic patients after a single hemodiafiltration session. Methods: We enrolled 30 patients on maintenance acetate-free biofiltration and 25 age-matched healthy volunteers and studied chromosomal alterations. Results: Our data show that the basal levels of DNA damage, the number of sister chromatid exchanges and basal high-frequency cells levels are significantly higher in patients on hemodiafiltration than in controls and in T lymphocytes than in B cells. Conclusions: These findings suggest that hemodialytic treatment could represent a potential source of damage, maybe through the oxidative action of the extracorporeal circuit components, which might explain the well-known T-specific immunodeficiency correlated with uremia.

Effects of haemodialysis on circulating endothelial progenitor cell count

During haemodialysis (HD) the endothelium is the first organ to sense and to be impaired by mechanical and immunological stimuli. We hypothesized that a single HD session induces mobilization of endothelial progenitor cells (EPCs) and that cardiovascular risk factors may influence this process. We quantified EPCs at different maturational stages (CD34+, CD133+/VEGFR2+) in blood samples from 30 patients, during HD and on the interdialytic day, and in 10 healthy volunteers. Samples were drawn at the start of HD, 1, 2 and 3 h after, at the end of HD and at 24 h on the interdialytic day. Patients were divided into two groups based on a recent risk scoring system (SCORE project): low-risk (LR) and high-risk groups (HR). HD patients showed a significantly reduced basal number of EPCs with respect to healthy volunteers. In contrast, we observed increasing EPCs during HD whereas they diminished on the interdialytic day. The EPC number was directly correlated with HD time progression. The EPC number during HD was increased in the HR group with respect to the LR group. We had a direct correlation between risk score and number of EPCs. Cardiovascular risk factors influenced the mobilization of stem cells from the bone marrow. This feature could be the direct consequence of an augmented request of stem cells to respond to the most important endothelial impairment but could also show a defective capacity of EPCs to home in and repair the sites of vascular injury.

Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension.

SUMMARY Introduction: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow. Material and methods: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 ± 3 years, mean body mass index (BMI) 27 ± 0.5 and 22.3 ± 0.3 kg m2, respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120±8mmHg).The other 37 (18 men, 19 women; mean age 39 ± 3 years; BMI 23.8 ± 0.5 kg m2 and 22.8 ± 0.5 kg m2, respectively were normotensive healthy volunteers (mean arterial blood pressure 89 ± 2 mm Hg).All the patients and subjects were untreated for at least 4 weeks before blood sampling. Results: Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux. Conclusion: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.

Flowing time on the peritoneal membrane

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QTc interval and QTc dispersion during haemodiafiltration

Background and Aim:  Our aim was to evaluate QTc interval and QTc dispersion in 27 end‐stage renal disease (ESRD) patients undergoing Acetate Free Biofiltration (AFB) in order to ascertain any correlations between the electrrocardiographic (ECG) parameters, serum Na+, K+, Ca++, Mg++ and intraerythrocytic Mg++ (Mg++e) concentrations. All measures were made at t0 (session beginning), t1 (first hour), t2 (second hour), t3 (third hour), and t4 (session end).

Circadian rhythm of hydration in healthy subjects and uremic patients studied by bioelectrical impedance analysis.

Background: Healthy subjects and patients after successful kidney transplantation show a circadian rhythm for glomerular filtration rate and for the glomerular transport of macromolecules. We aimed to evaluate by bioelectrical impedance analysis (BIA) whether body hydration status also follows a circadian rhythm in patients with impaired renal function. Methods: The study was conducted on 28 subjects divided into 3 groups: 8 healthy volunteers, 8 patients affected by chronic kidney disease and 12 end-stage renal disease (ESRD) patients on hemodialysis. During 24 h, 9 BIA measurements were taken in every subject every 180 min. Results: BIA findings demonstrate that normal subjects have a circadian rhythm in hydration status that reaches maximum body water content at night, between 21.00 and 23.00 h. In patients with chronic kidney disease, this rhythm, with maximum at night, is maintained. The rhythm is also present in ESRD patients, if the residual diuresis is at least 500 ml/day, while there is no rhythm when residual diuresis is <300 ml/day. Conclusions: In normal subjects, body hydration status shows a circadian rhythm, which is weakened or lost in oligoanuric patients on dialysis, but partially maintained in subjects with preterminal uremia and in hemodialyzed patients with residual diuresis >500 ml/day.

A case-by-case protocol of membranous nephropathy treatment with endovenous infusion of high doses of human immunoglobulins.

The treatment of membranous nephropathy is a highly controversial issue. As some patients may have spontaneous remission, in about 50% of cases the risk of treating patients with drugs that may have severe side effects is higher than the potential benefit of arresting disease progression. Some authors therefore propose exclusively symptomatic treatment; other authors use steroids and immunosuppressive drugs, alone or in association with high risk of adverse effects and often uncertain benefits. The intravenous administration of high doses of human immunoglobulins (IVIg) has been also extended to a growing number of kidney diseases including membranous nephropathy. The mechanisms through which IVIg carry out their therapeutic effect are still unclear. The present study is a retrospective and uncontrolled trial, the aim of which was firstly to verify if some patients could respond to extremely short treatment protocols, stopped when they appear to have a stable remission, thereby avoiding expensive continuation of treatment. Secondly, we aimed to verify if some patients, judged as nonresponders to a classical protocol of IVIg therapy, could respond to a more prolonged treatment.

Management of patients after renal graft loss: an open question for nephrologists.

Patients undergoing renal graft failure and returning to dialysis are often regarded to like facing for the first time a substitutive treatment, without considering the technical complications, the economical impact, and the psychological implications. This review attempt, to give answers to various questions, concerning the management of vascular access, the immunosuppressive therapy, the transplantectomy, the emotional and neuropsychic aspects, and the quality of life of graft-failed patients.