[Use of oral hypoglycemic agents in patients with chronic kidney failure]. / Farmaci ipoglicemizzanti orali nei pazienti con insufficienza renale cronica.

Type 2 diabetes mellitus is one of the most common disease worldwide. Diabetes mellitus is expected to affect over 380 million people by 2025 and one third of these patients will develop chronic kidney disease (CKD). There are many categories of hypoglycemic agents available for treatment of type 2 diabetes mellitus: sulphounilureas, glinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and the new brand incretines. In nephropatic patients with CKD stage I-II, any hypoglycemic agent can be used: the choice must be linked to a careful evaluation of potential risk and benefit. In CKD stage III to V, conversely, some drugs are not recommended while other agents can be used with dose reduction due to risk of hypoglycemia. In these patients the early use of insulin may be indicated. The target of this review is to evaluate evidences about the possible use of hypoglycemic agents in patients affected by diabetes and CKD stage III-V.

[Reduced nitric oxide bioavailability in chronic renal failure: a new factor of progression?]. / Ridotta biodisponibilità di ossido nitrico nell'insufficienza renale cronica: un nuovo fattore di progressione?

Nitric oxide (NO) is a gaseous free radical and an important molecular mediator of many physiologic processes in virtually every organ. NO is produced from L-arginine by nitric oxide synthase (NOS). This enzyme is expressed as 3 isoforms, all of which have been isolated from the kidney: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). At present it is very difficult to measure authentic nitric oxide in vivo; a way to circumvent the difficulties is to study the effects of NOS stimulation and subsequent nitric oxide release directly by measurement of the resulting changes in vascular tone. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. Chronic renal failure (CRF) is a state of NO deficiency secondary to decreased NO production and/or increased bioinactivation of NO by reactive oxygen species. The purpose of this review is to examine the functions of NO in the kidney, and to discuss the effects of NO deficiency in the progression of chronic kidney disease.

Platelet-leukocyte interactions in hemodialysis patients: culprit or bystander?

The formation of circulating platelet-leukocyte complexes has been observed in a variety of conditions and may be pathophysiologically significant. Platelet-leukocyte interactions in fact facilitate metabolic cooperation and mutual activation, which may be of relevance in many biological processes including inflammation, atherogenesis and hemostasis. During hemodialysis procedure, the series of reactions that can occur upon blood contact with the foreign membrane surface may involve a variety of changes affecting almost every cellular and plasmatic component of the blood. This article reviews the evidence for abnormal interactions between circulating platelets and leukocytes in uremic patients undergoing maintenance hemodialysis and the pathophysiologic implications which may stem from such interactions.

[Census 2004 of the Italian renal and dialysis units--Abruzzo-Lazio-Marche-Molise-Umbria]. / Censimento 2004 dei Centri di Nefrologia e Dialisi Italiani. Abruzzo-Lazio-Marche-Molise-Umbria.

The Italian Society of Nephrology (SIN) promoted a national survey in order to collect detailed information from all Italian renal and dialysis units. This is the second paper, following the first one which focused on three northwestern regions, aim-ing to present the results of the survey. In this paper, data from the central regions (Abruzzo, Lazio, Marche, Molise and Umbria) are reported. The most relevant findings in the five regions were: A) epidemiology--prevalence of dialysis patients = 742, 781, 731, 814, 768 per million population (pmp); prevalence of transplanted patients = 162, 153, 296, 134, 304 pmp; incidence of dialysis patients = 175, 179, 184, 143, 162; gross mortality of dialysis patients = 12.3, 11.8, 15.9, 13.4, 14.0%; distribution of vascular access in prevalent dialysis patients: arteriovenous fistula = 90, 87, 82, 94, 80%, central venous catheter = 7, 10, 15, 4, 17%; vascular graft = 3, 3 ,3, 2, 3%. B) Structural resources--number of hospital beds = 52, 43, 39, 62, 44; dialysis places = 205, 260, 203, 301, 226. C) Personal resources--renal physicians = 50, 78, 47, 53, 47 pmp; renal nurses = 162, 172, 180, 224, 245 pmp; each renal physician takes care of 15, 10, 16, 15, 17 dialysis patients and each renal nurse cares of 4.6, 4.6, 4.1, 3.6, 3.1 dialysis patients. D) Activity--admission to hospital= 2334, 1689, 2652, 1255, 1377 pmp; renal biopsies = 59, 84, 97, 19, 80 pmp. Despite the differences we find among the regions, most indexes are similar and show a satisfactory level of renal care provided in the central regions examined.

Management of hypertension in chronic kidney disease: the Italian multicentric study.

BACKGROUND: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown. METHODS: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months. RESULTS: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%). CONCLUSIONS: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.

Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits).

AIM: Commercial glucose peritoneal dialysis solutions expose the peritoneum to hyperosmolar glucose containing variable amounts of non-enzymic breakdown products of glucose. These solutions are toxic for the peritoneum. The aim of the present study is to compare in vitro and in vivo characteristics of a new dialysis solution containing carnitine, a naturally occurring compound, as substitute of glucose. MATERIAL AND METHODS: We compared in vitro and in the rabbit a new peritoneal dialysis solution containing carnitine, with two standard bicarbonate glucose peritoneal dialysis solutions and a solution containing icodextrin. RESULTS: In vitro and in vivo the solution containing carnitine seems to be more biocompatible than standard glucose solutions and those containing icodextrin. CONCLUSIONS: In our study the peritoneal dialysis solution containing carnitine seems to prevent the mesothelial changes observed with solutions containing glucose. Since carnitine has been extensively studied and seems to be well tolerated by hemodialysis patients, even at high doses for long periods, clinical trials in humans may be planned in the near future.

Wireless capsule endoscopy in the diagnostic of small intestine angiodysplasia in chronic uremic patient.

Gastroenteric bleeding due to angiodysplasia (AD) is a relatively common occurrence in patients with end-stage renal failure. Gastric and colon angiodysplasic lesions can be easily revealed by endoscopic procedures, whereas lesions of the small intestine are more difficult to detect. Imaging modalities used in the diagnostic imaging algorithm for the detection of small-bowel AD, include non-invasive methods like enema-helical computer tomography,(99m)Tc-labelled red blood cell scintigraphy, and angiography, and invasive methods such as intraoperative enteroscopy. We report the cases of 3 hemodialysis patients with recurrent episodes of gastrointestinal bleeding, caused by small-bowel AD diagnosed by means of wireless-capsule endoscopy. In all cases, previous gastroscopy and colonoscopy were unrevealing. Wireless-capsule endoscopy consists in swallowing a capsule endoscope (11 mmx27 mm) which contains a miniature video camera, a light source, batteries, and a radio transmitter. Video images are transmitted by means of radio telemetry to aerials taped to the body that allow images to be captured. Moving images from a period as long as 6 h are stored on a portable recorder. Wireless-capsule endoscopy may prove valuable in the assessment of gastrointestinal bleeding in uremic patients with unrevealing results at gastroscopy and colonoscopy.

[Angiodysplasia of the small bowel: a possible cause of anemia even in mild chronic renal failure]. / Angiodisplasia dell'intestino tenue: una possibile causa di anemizzazione nell'IRC anche di grado lieve.

BACKGROUND: Gastroenteric angiodysplasia (AD) is a vascular lesion characterized by vascular ectasias to the submucous sheath of the gastrointestinal tract. Lesions can be flat or raised, isolated or grouped and can break or ulcerate causing acute hemorrhage or, more commonly, chronic bleeding. CASE-REPORT: We describe a 65-year-old patient with a 3-yr history of chronic renal failure (CRF), who gradually developed anemia (hemoglobin (Hb) 10 g/dl) without any episodes of clinically relevant bleeding or any exposure to bleeding risk factors. Blood pressure (BP) was normal and renal function was stable (serum creatinine (Cr) 1.9 mg/dl). Routine laboratory tests showed a slight reduction in serum iron and transferrin saturation and a slightly elevated absolute reticulocyte count. These findings were associated with a positive occult gastrointestinal blood test and raised the clinical suspicion of chronic gastrointestinal blood loss. Oesophagogastro-duodenoscopy and colonoscopy demonstrated an absence of significant lesions, suggesting the need to investigate for a lesion localized in the small intestine. Capsular endoscopy, a recently developed endoscopic technique, particularly suited for small bowel pathology, was performed, and demonstrated the presence of an angiodysplasic lesion, located in the jejunum. CONCLUSIONS: Our case report supports the necessity for a complete clinical and laboratory evaluation of the possible causes of anemia superimposed on relative erythropoietin deficiency in CRF patients. When gastrointestinal blood loss is suspected, the entire gastroenteric tract should be examined to search for the bleeding sites. Our report also demonstrates that AD could be responsible for gastrointestinal bleeding even in mild CRF and not only, as usually reported, in end-stage renal disease (ESRD). Capsular endoscopy offers the unique possibility to determine the bleeding site in the small intestine and appears as an effective diagnostic procedure in CRF patients.

Increased platelet phosphatidylserine exposure and caspase activation in chronic uremia.

Platelet activation is associated with exposure of the aminophospholipid phosphatidylserine (PS) to the outer hemi-leaflet of the plasma membrane bilayer, which seems to be involved in the coagulation process. Because platelet activation may occur in patients suffering from chronic uremia, which is frequently associated with a thrombophilic tendency, we studied whether uremic platelets show an increased propensity to expose PS on the outer membrane leaflet and whether this process is linked with important functional and molecular changes. Flow cytometric percentage of annexin V-positive platelets, a measure of PS externalization, was significantly elevated (P < 0.001) in uremic patients when compared to normal controls under both unstimulated and agonist-stimulated conditions. Uremic platelet procoagulant activity, as measured by thrombin generation, was more than twice as high (4.13 +/- 0.3 micro mL(-1)) as that found in normal controls (1.86 +/- 0.2 micro mL(-1)). Two independent assays showed that the enzymatic activity of caspase-3, a protease involved in the loss of membrane PS asymmetry, was significantly greater in the platelets of uremic subjects than in those of healthy controls. PS exposure in agonist-stimulated platelets was markedly reduced by inhibition of caspase-3 activity but was not affected by inhibition of calpain activity. These results support the view that the thrombophilic susceptibility of uremic patients may be partly ascribed to increased PS exposure to the outer membrane leaflet of platelets. This process seems to be causally linked to an increase in caspase-3 activity, particularly during platelet activation.

Platelet activation and platelet-erythrocyte aggregates in end-stage renal disease patients on hemodialysis.

Activated platelets may engage in dynamic interplay with other blood cells. We examined the evidence for platelet activation and the formation of platelet-erythrocyte aggregates in chronic hemodialysis patients. Circulating activated platelets (P-selectin/CD63-positive platelets) were higher than normal controls (p < 0.001) and further increased during hemodialysis sessions, the increase being higher when patients were dialyzed with cellulosic than with synthetic membranes. We found direct evidence of uremic platelet-erythrocyte adherence in vitro and increased levels of circulating platelet-erythrocyte aggregates in dialysis patients, which represents a new observation in uremia. Platelet-erythrocyte aggregates were subject to further increase during hemodialysis, and again higher levels were found with cellulosic than synthetic membranes. This phenomenon was reproduced in vitro by both ADP and PAF, but not by either complement factor C3a or by heparin concentrations corresponding to those used for clinical hemodialysis. We conclude that platelet-erythrocyte aggregates occur in hemodialysis patients probably owing to a primary platelet activation mechanism.

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.

Breast cancer diagnosis under the age of forty years.

The authors report on a multicentric consecutive series of 382 cases of primary breast cancer detected before the age of 40 years. Physical examination (PE) was always performed, whereas other diagnostic tests were performed in selected cases, namely mammography (M) in 334, fine needle aspiration cytology (CYT) in 188 and thermography (TH) in 123 cases. Single tests showed a high rate of false-negative/benign cases (PE, 0.23; M, 0.26; CYT, 0.37 and TH, 0.50), especially when the T1 subgroup was considered (PE, 0.34; M, 0.38; CYT, 0.42 and TH, 0.78). The poor results recorded for TH make its current diagnostic use highly questionable. The policy of extensive biopsy of all "dubious" benign lesions on PE allowed for the detection of 41 of 382 cancers and reduced the PE false-negative/benign rate to 0.12 for the total or 0.15 for T1 cancers, although about 80 unnecessary biopsies for each cancer detected were performed in this way. The association of PE to one or more tests resulted in even lower false-negative rates (0.06 for the total, 0.10 for T1 cancers). The authors criticize the aggressive policy of extensive biopsy recommendation based only on a dubious report on PE alone and stress the opportunity of the routine association of M and CYT to PE, since this combination seems to achieve a higher breast cancer detection rate even in this age group.

Platelet-neutrophil interactions during hemodialysis: a proposed biocompatibility approach.

Platelet interaction with neutrophils may occur to a significant degree during hemodialysis (HD). We have recently shown that the enhanced neutrophil reactive oxygen species (ROS) production during the early phase of HD with cuprophan (CUP) is sustained by neutrophils which have bound platelets through P-selectin (CD62P). The evaluation of platelet-neutrophil interactions during dialysis offers the novel aspect of cell-cell interactions as a new parameter for studying the biocompatibility of dialyzer membranes. By the use of flow cytometry techniques, the present study was set up to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil ROS (hydrogen peroxide) production from 6 HD patients each dialysed with CUP, cellulose diacetate (CDA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) in a cross-over clinical trial. Platelet-neutrophil coaggregate formation (percentage of neutrophil cells positive for CD62P) and ROS production by neutrophils (total population; CD62P+ cells; CD62P- cells) were determined before HD and after 10', 20'and 40'. CD62P+ neutrophils significantly increased during HD with CUP (10', 20', 40'), PMMA (20') and CDA (20), while no change was observed with PAN. The difference between CUP and the other membranes was significant at 10', 20' and 40'; at 20', PMMA vs PAN p<0.005. ROS production by total neutrophil population significantly increased with CUP (10', 20), PMMA (20) and CDA (20'). The increase with CUP was higher at 10' when compared to CDA (p<0.020) or PAN (p<0.005), and at 20' versus the other three membranes; at 20' PMMA vs PAN p<0.005. Only neutrophils gated in neutrophil-platelet coaggregate areas (CD26P+ neutrophils) produced hydrogen peroxide. ROS production by CD62P+ neutrophils significantly increased with CUP (10', 20), PMMA (20') and CDA (20'). The increase with CUP was significantly (p<0.0002) higher than the other three membranes at 10' and 20'; at 20', PMMA vs PAN p<0.02. With each membrane, ROS production by CD62P- neutrophils showed no significant change at any time point during HD. The results of the present study indicate that interactions between platelets and neutrophils can mediate some pathophysiological abnormalities associated with hemodialysis treatment. Our data show that cellulose diacetate, a modified cellulosic membrane, exhibits a biocompatibility profile in terms of platelet-neutrophil interactions improved as compared to the parent cellulose membrane and comparable to that of some synthetic membranes. Our data also show that there is considerable variability in the biocompatibility of synthetic membranes. Though cellulosic membranes are generally considered as being less biocompatible than synthetic membranes, our results indicate that classification of membranes by biocompatibility is more complex than a simple division into cellulosic and synthetic membranes, especially with the advent of modified cellulosic membranes.

Cell activation and cellular-cellular interactions during hemodialysis: effect of dialyzer membrane.

During hemodialysis (HD), circulating blood cells can be activated and also engage in dynamic interplay. These phenomena may be important factors behind dialysis membrane bio(in)compatibility. In the present prospective cross-over study, we have used flow cytometry to evaluate the influence of different dialysis membranes on the activation of circulating blood cells (leukocytes, platelets) and their dynamic interactions (formation of circulating platelet-leukocyte and platelet-erythrocyte aggregates) during in vivo HD. Each patient (n = 10) was treated with dialyzers containing membranes of cellulose diacetate, polysulfone and ethylenevinylalcohol (EVAL) in a randomized order. Upregulation of adhesion receptor expression (CD15s, CD11b/CD18) occurred mainly with the cellulosic membrane, though an increase in CD11b/CD18 circulating on neutrophils was also found with both synthetic membranes. Circulating activated platelets (P-selectin/CD63-positive platelets) increased during HD sessions with cellulose diacetate and polysulfone. An increased formation of platelet-neutrophil aggregates was found at 15 and 30 min during dialysis with cellulose diacetate and polysulfone but not with EVAL. Platelet-erythrocyte aggregates also increased with cellulose diacetate and at 15 min with polysulfone as well. Generally in concomitance with the increase in platelet-neutrophil coaggregates, there was an increased hydrogen peroxide production by neutrophils. The results of this study indicate that cellular mechanisms can be activated during HD largely depending on the membrane material, EVAL causing less reactivity than the other two membranes. It appears that each dialysis membrane has multiple and different characteristics that may contribute to interactions with blood components. Our results also indicate that derivatizing cellulose (cellulose diacetate) may be a useful way to improve the biocompatibility of the cellulose polymer and that there may be great variability in the biocompatibility profile of synthetic membranes, dialysis with polysulfone being in general associated with a higher degree of cell activation than EVAL membrane.

A new polymethylmethacrylate membrane for hemodialysis.

High molecular weight (MW) solutes are not removed during conventional hemodialysis (HD), and their accumulation is thought to play a role in some long-term HD complications (anemia, bone and joint pain, neuropathy, itching). The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate (PMMA) membrane (Filtryzer BK-F, 1.3 m2) compared to conventional PMMA (BK-P, 1.6 m2) and to cellulose acetate (CA, 1.3 m2). BK-F dialyzers, with a pore size of 100 A degrees and 62% porosity, are designed to remove high MW substances. Ten stable anuric RDT patients (53 +/- 13 years) were treated for one week with each membrane in a randomized sequence. Plasma concentrations of creatinine, BUN and beta 2-microglobulin (beta 2-M) were measured before (b) and after (a) HD to determine the reduction rate for these substances (%). Beta 2-M concentration after HD was corrected for changes in distribution volume. Samples of spent dialysate were collected after 3 minutes, 120 minutes and at the end of HD sessions, and appropriately treated and concentrated for HPLC analysis. The reduction rate for BUN and creatinine was similar for the 3 membranes. BK-F showed a higher beta 2-M reduction rate than BK-P (p < 0.005) or CA (p < 0.0001). HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons (kDa) throughout HD for BK-P and CA. Solutes > 10 kDa were infrequently detected. Peak profile during HD with BK-F was quite different, showing a predominant peak > 50 kDa which also included albumin. However, albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values, and was lower than that reported in CAPD patients. With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors. Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances, thereby preventing or controlling some long-term HD complications such as anemia or beta 2-M amyloid formation.

Biocompatibility and functional performance of a polyethylene glycol acid-grafted cellulosic membrane for hemodialysis.

In order to improve the biochemical reactivity of the cellulose polymer, which is mainly attributed to the presence of surface hydroxyl groups, derivatized cellulosic membranes have been engineered replacing or masking some or all of the hydroxyl groups in the manufacturing process of the membrane. The present study was set up to analyze both biocompatibility and functional performance of two different derivatized cellulosic membranes (cellulose diacetate; polyethylene glycol, PEG, acid-grafted cellulose) as compared to a synthetic membrane (polymethylmethacrylate, PMMA). Cellulose diacetate is prepared by substituting hydroxyl groups with acetyl groups; PEG cellulose is obtained by grafting PEG chains onto the cellulosic polymer with a smaller amount of substitution than cellulose diacetate. While the three dialyzers provided similar urea and creatinine removal, the dialyzer containing cellulose diacetate showed a reduced ability to remove 32-microglobulin compared to that containing PEG cellulose or PMMA. A transient reduction in leukocyte count was observed for both derivatized cellulosic membranes. The neutrophil and monocyte counts throughout the entire dialysis session showed a closer parallelism with the cellular expression of the adhesive receptor CD 15s (sialyl-Lewis x molecule) than with CD11b/CD18 expression. Platelet activation, as indicated by the percentage of cells expressing the activation markers CD62P (P-selectin) and CD63 (gp53), occurred with all membranes at 15 min of dialysis and also with PMMA at 30 min. An increased formation of platelet-neutrophil and platelet-monocyte coaggregates was found at 15 and 30 min during dialysis with cellulose diacetate and PMMA but not with PEG cellulose. Generally in concomitance with the increase in platelet-neutrophil coaggregates, an increased hydrogen peroxide production by neutrophils occurred. Our results indicate that derivatizing cellulose may represent a useful approach to improve the biocompatibility of the cellulose polymer, though some homeostatic reactions remain activated. Our results also indicate that there may be a great variability in the biocompatibility profile of derivatize cellulosic membranes which most likely stem from the different type of structural modification rather than from the degree of hydroxyl group replacement.

Endoscopy as a tool for diagnosing and treating gastrointestinal angiodysplasia in haemodialysis patients.

Gastroenteric angiodysplasia is an important cause of haemorrhage in chronic renal failure patients. This paper reports on 2 patients on maintenance haemodialysis with upper gastrointestinal bleeding due to different manifestations of angiodysplasic lesions (sudden appearance of haematemesis and melaena in one case, progressive anaemia with apparent resistance to erythropoietin in the other case). Exploratory endoscope examination of the first digestive tract showed in both cases the presence of bleeding angiodysplasic lesions. Both patients were there and then submitted to surgical endoscopy, during which the bleeding angiodysplasic lesion was sclerosed with physiological salt solution plus adrenaline 1/10000 and 1% polydocanol. In one patient, bleeding occurred again ten days later, making renewed surgical endoscopy necessary. In the course of this an elastic ligature was made to the superangular angiodysplasia. A year later in both cases there were no direct or indirect signs of further bleeding; an endoscopic check-up showed the treated lesions to be sclerosed. Endoscopy offers the unique possibility of being used for both diagnostic and therapeutic purposes in a single session. In expert hands, endoscope therapy is effective and markedly reduces the risk of side effects.

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.

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment.

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.