M. Bonomini

Involvement of phosphatidylserine exposure in the recognition and phagocytosis of uremic erythrocytes

Cell surface-exposed phosphatidylserine (PS) represents a signal for macrophage recognition and cell phagocytosis. This study examines PS exposure and susceptibility to erythrocyte phagocytosis in patients with chronic uremia in an attempt to assess the possible pathogenic mechanism behind cell removal in a condition associated with shortened erythrocyte life. Both PS-expressing erythrocytes and erythrophagocytosis (human monocyte-derived macrophages ingesting one or more erythrocytes) were significantly increased in uremic patients compared with healthy controls. Phagocytosed uremic erythrocytes appeared intact, suggesting they were identified before lysis through some surface change recognized by the macrophages. The degree of phagocytosis was markedly greater for PS-positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic erythrocytes. A significant correlation (r = 0.655) was found between the percentage of PS-expressing red blood cells (RBCs) and the percentage of phagocytosing macrophages in uremic patients. Reconstitution experiments showed the ability of uremic plasma to promote both PS exposure and erythrophagocytosis, the latter without direct interaction with the macrophage population. Phagocytosis of uremic erythrocytes was strongly inhibited when the macrophages were preincubated with glycerophosphorylserine (GPS), a structural derivative of PS, but this was not the case with the equivalent derivative of phosphatidylethanolamine, glycerophosphorylethanolamine. This inhibition appeared to be specific because GPS failed to inhibit the phagocytosis of opsonized uremic erythrocytes that occurs through an Fc receptor-mediated pathway. These findings suggest that a PS-recognition mechanism may promote the susceptibility of uremic RBCs to phagocytosis and thus be involved in the shortened erythrocyte life span of uremia.

Leukocyte adhesion molecules and leukocyte-platelet interactions during hemodialysis: effects of different synthetic membranes.

Membranes made from synthetic polymers, in general, are considered as being biocompatible membranes and tend to be treated as a homogeneous group. However, all of these membranes have multiple and different characteristics that may contribute to interactions with blood components. As a consequence, the biocompatibility profile of synthetic membranes may vary. In the present cross-over study, we examined by flow cytometry the effects (expressed as % change from predialysis values) of three different synthetic polymers (polysulfone, PSF; polyacrylonitrile-co-sodium methallyl sulfonate, AN69; ethylenevinylalcohol, EVAL) on the expression of leukocyte adhesion molecules (CD11b/CD18, CD15s) and the interactions between leukocytes and platelets under conditions of routine clinical use. For neutrophils, a statistically significant difference was found in CD15s expression for EVAL as compared to AN69 (p<0.05) and in CD11b/CD18 expression for PSF as compared to both EVAL (p<0.01) and AN69 (p<0.05). No difference between membranes was found on the expression of such adhesive molecules on monocytes. Significant differences in platelet-neutrophil (but not in platelet-monocyte) coaggregate formation were observed between PSF and both EVAL (p<0.001) and AN69 (p<0.01). Reactive oxygen species production by neutrophil population during hemodialysis was significantly different between each pair of synthetic polymers (PSF vs EVAL, p<0.001; PSF vs AN69, p<0.001; AN69 vs EVAL, p<0.05). Our data demonstrate that in terms of leukocyte adhesion receptors and platelet-leukocyte interactions, the biocompatibility profile of the synthetic membranes polysulphone, AN69 and EVAL shows many similarities but also several significant differences. Our results support the concept that biocompatibility evaluation of each membrane should be based exclusively on data generated by that membrane in order to avoid errors based on assumptions about group characteristics.

Neurological and Psychiatric Disorders in Renal Diseases

Neurological abnormalities specifically related to uremia constantly occur in patients with end-stage renal disease (ESRD), although they only become clinically well defined in severe acute renal failure (ARF) or late in the course of chronic renal failure (CRF) and sometimes in connection with metabolic acidosis and/or electrolyte disturbances secondary to renal disease (1–5).

Quando il trapianto renale fallisce: necessità di pianificazione di un percorso assistenziale al paziente che riprende il trattamento sostitutivo emodialitico

Scopo dello studio è stato quello di cercare di migliorare la qualità di vita di pazienti portatori di grave insufficienza d’organo, attraverso un percorso tale da permettere un adeguato supporto assistenziale medico ed infermieristico. Dare definizioni della qualità di vita è particolarmente difficile perché strettamente correlato con la percezione soggettiva alla quale concorre I’intera personalità. Infatti non sono tanto gli eventi in sé a condizionare la qualità della vita, quanto il significato dato all’evento stesso con valenze emotive positive o negative. A tal proposito I’Organizzazione Mondiale della Sanità per qualità di vita intende «una percezione soggettiva che un individuo ha della propria posizione nella vita, nel contesto di una cultura e di un insieme di valori nei quali egli vive anche in relazione ai propri obiettivi o aspettative», modificabili dalla percezione della propria salute fisica e/o psicologica, dal livello di indipendenza, dalle relazioni sociali e dalla interazione con il proprio specifico contesto ambientale.

Electrophysiological and Biofunctional Abnormalities in Uremic Neuropathy

The pathophysiology of central and peripheral nervous system dysfunctions in uremia has been extensively evaluated by neurophysiological studies and biofunctional techniques during the last few years. In order to investigate uremia-related nervous alterations in our cohort of patients clinical research was supported by electrophysiology and experimental work in synaptosomes drawn from uremic rats.

Protective Effect of Calcium-Channel Blockers on the Cyclosporins (CyA)-Related Nephrotoxicity

Cyclosporine (CyA) represents an entirely different class of immunosuppressive agents (1). Acute and chronic nephrotoxicity directly attributable to CyA has tempered the initial enthusiasm surrounding this drug (1). At present the pathogenesis of CyA nephrotoxicity has not been fully elucidated but so far it has been suggested that can be divided chronologically into three broad components: 1) a functional toxicity, due mainly to afferent renal arteriolar vasocontriction (2); 2) a reversible tubulo-toxicity manifested by giant mitochondria and tubular vacuolization and dilatation (3); 3) an obliterative and irreversible arteriolopathy, eventually leading to interstitial fibrosis and nephron loss. Recently a number of reports have suggested that renal allograft recipients receiving CyA and Calcium-channel antagonists have better graft function, a lower incidence of delayed graft function and fewer rejection episodes than those receiving CyA alone (4). The use of calcium-channel antagonists as nifedipine (NIF) in combination with CyA therapy in renal transplant recipients is attractive, as hypertension is common, and because they may potentiate the inhibition of lymphocyte proliferation induced by CyA, the effects of NIF on overall glomerular and tubular functions has not been investigated in patients with stable graft function. Aim of our paper is to assess the effects of NIF on glomerular and tubular function and CyA levels in patients with stable allograft function at least six months after transplantation.

Comparison of Effects of Erythropoietin (r-HuEPO) in Patients on Hemodiafiltration (HDF) Vs Conventional Hemodialysis (SD)

As long as the use of r-HuEPO and of high-efficiency techniques as HDF raised-up, a growing interest in the complications induced by uremia on various systems and organs and mainly on the Nervous Systems seems to appear. An intense look in the Central and Peripheral Nervous System is fluorished when the effects of SD and HDF with the r-HuEPO became available and the finest modifications of these treatments could be recorded electrophysiologically and re-checked in the same patient at suitable intervals, giving the nephrologist the possibility of tracing back from the neurological impairment to the degree of uremic intoxication ([1]). It is still too early to assess the impact of long-term HDF-r-HuEPO therapy as subjective indicators of well-being, as well as patients manifested increased energy, improved appetite, taste, cold tolerance, sleeping habits and so on. The paper’s aim is to describe the main effects of SD and of HDF that allow a separate control of removal for small and larger toxins from blood. Because of the efficiency of the dialyzer/hemodiafilter and the r-HuEPO treatment the dialysis can be handled in SD and in HDF in order to explore whether part of the uremic syndrome can be attributed to the effects of uremia and anemia on the various organs and on the Central and Peripheral Nervous System (CNS). Because the treatment with r-HuEPO reduces anemia, in turn improving brain and multiorgans functions, in our study we assessed the effects of SD, HDF and of r-HuEPO on CNS and organs activity.