[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.

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.

Production of tumor necrosis factor-alpha and interleukin-1 by alveolar macrophages from HIV-1-infected persons.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are potent immunomodulatory cytokines which are produced principally by cells of the macrophage-monocyte lineage. We conducted an investigation to assess the secretion of these cytokines by bronchoalveolar macrophages from patients with progressive stages of human immunodeficiency virus (HIV-1) infection. The mean level of TNF-alpha produced by macrophages from 9 patients with AIDS was significantly reduced compared with the responses of macrophages from 6 healthy HIV-1-seronegative persons, 6 patients with either asymptomatic HIV-1 infection or persistent generalized lymphadenopathy, and 6 patients with AIDS-related complex (ARC). The four study groups did not differ in their mean IL-1 beta responses. However, within the HIV-1-infected patient population, macrophages from 4 patients, 3 of whom had AIDS and 1 with ARC, failed to secrete detectable levels of IL-1 beta. All 4 patients were also nonresponsive in assays for TNF-alpha. These data establish that advanced HIV-1 infection may result in a pronounced dysfunction in the cytokine responses of alveolar macrophages.

Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

N-3 polyunsaturated fatty acid supplementation in chronic progressive renal disease.

Chronic renal failure (CRF) may be accelerated by secondary lipid and immune abnormalities which could be antagonized by polyunsaturated fatty acid (PUFA). We examined 20 CRF patients on conservative treatment, randomized in two groups: G1 consisted of 10 control patients and G2 10 patients supplemented for 12 months with a 3.4 g daily dose of PUFA. In basal conditions and after 12 months the following parameters were checked: creatinine clearance (CCr), daily urinary protein excretion per unit of residual renal function (UProt/CCr), rate of progression of renal insufficiency (delta CCr); triglycerides (TG), total (TC), HDL (HDALC) and LDL (LDLC) cholesterol, apolipoproteins Apo Al, Apo B, lipoprotein(a) Lp(a); lymphocyte subpopulations; spontaneous (c) and stimulated (s) cytokines IL-1 beta, IL-2, tumor necrosis factors TNF-alpha secretion by peripheral mononuclear cells. The groups did not differ in their basal parameters, which did not change in G1 during follow-up. In G2 the following parameters, initially higher than normal significantly decreased after 12 months: TG (2.9 +/- 0.45 to 2.6 +/- 0.3 mmol/l p < 0.005), Apo B (1.40 +/- 0.37 to 1.22 +/- 0.36 g/l, p < 0.05), c TNF-alpha (1008.1 +/- 534.9 to 726.8 +/- 458.7 pg/ml, p < 0.05). Spontaneous (c) IL-1 beta (216.7 +/- 116.2 to 150.5 +/- 107.8 pg/ml, p < 0.05), c IL-2 (124.5 +/- 43.8 to 101.6 +/- 25.8 pg/ml, p < 0.05), and s TNF-alpha (2456.4 +/- 908.3 to 1632.2 +/- 497.1 pg/ml, p < 0.005) also decreased, although already within the normal range at baseline. G2 patients experienced a steady monthly reduction of CCr whereas it rose progressively in G1 (p < 0.05), with a simultaneous increase in UProt/CCr (p < 0.05). PUFA are beneficial on the lipid and immune abnormalities secondary to CRF and may also have a useful effect on the progression of chronic renal damage.

Electrophysiological aspects of nervous conduction in uremia.

Some neurophysiological techniques have been employed in clinical nephrology to record abnormalities of nervous conduction in central and peripheral pathways. The electrical monitoring on the peripheral and central nervous systems has allowed the detection of uremic neural injury, the diagnosis of specific electrophysiological abnormalities, the evaluation of various treatments employed and the identification of those abnormalities that uremia can induce. A group of 156 subjects subdivided into four groups were examined: 100 healthy subjects (64 M, 36 F); 56 patients (21 glomerulonephritis, 14 pyelonephritis, 5 nephrolithiasis, 5 polycystic kidney, 4 nephroangiosclerosis, 7 undetermined) with chronic renal failure treated with a conventional low nitrogen diet (CLND, 0.6 g/kg b.w./d. of proteins), 8 of whom passed from CLND to a very low nitrogen diet supplemented with alpha-keto-analogues; a group of 22 of these 56 underwent a regular dialysis treatment for 12 to 15 hours/weekly for 40.5 +/- 10.2 months. Three patients of the CLND group and 13 patients underwent renal transplantation after a variable period of RDT. In the uremic patients we found different populations of motor unit potentials; a decreased MNCV was found in 35% of the CLND patients, RDT patients had slowed MNCV in 42%. The SNCV was compromised more frequently than the MNCV. An increased duration of evoked potentials was sometimes observed in CLND and RDT patients inducing us to consider this a hallmark of uremic syndrome. The alpha-keto-analogues and HD/HP treated patients showed an improvement in several features.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

New electrophysiological assessments for the early diagnosis of encephalopathy and peripheral neuropathy in chronic uraemia.

The clinical manifestations of neuropathy in chronic uraemia are late in occurring. However, at an early stage it is possible to detect damage to either the central or peripheral nervous system by means of modern electrophysiological investigation methods. We examined 29 patients with CRF (plasma creatinine 7.0 +/- 4.0 mg%) on conservative diet. The following electrophysiological tests were carried out at least once: Electroencephalogram (EEG), Electromyogram (EMG), Motor Nerve Conduction Velocity (MNCV), Sensory Nerve Conduction Velocity (SNCV), Visual Evoked Potentials (VEPs) using the pattern reversal transient stimulation method. At the same time the following blood tests were performed: BUN, creatinine, uric acid, glucose, cholesterol, triglycerides, lipid electrophoresis, total protein (electrophoretic method), Na, K, Ca, P, red cells blood count and PTH. MNCV, SNCV and VEPs appeared to slow down early, sometimes even where there were no clinical symptoms. In addition, there is a direct correlation with decreasing renal function. MNCV and SNCV were correlated directly, reciprocally although the compromise of SNCV appeared an earlier phenomenon. The significant direct correlation between MNCV, SNCV and serum PTH suggests that the latter has an important peripheral neurotoxic role. VEP recording permits detection of early abnormalities in the central nervous system with residual renal function values around 40%.

Making the most of on-line recruiting.

Ninety percent of large U.S. companies are already recruiting via the Internet. By simply logging on to the Web, company recruiters can locate vast numbers of qualified candidates for jobs at every level, screen them in minutes, and contact the most promising ones immediately. The payoffs can be enormous: it costs substantially less to hire someone on-line, and the time saved is equally great. In this article, Peter Cappelli examines some of the emerging service providers and technologies--matchmakers, job boards, hiring management systems software, and applicant-screening mechanisms that test skills and record interests. He also looks at some of the strategies companies are adopting as they enter on-line labor markets. Recruiting needs to be refashioned to resemble marketing, he stresses. Accordingly, smart companies are designing Web pages, and even product ads, with potential recruits in mind. They're giving line managers authority to hire so that candidates in cyberspace aren't lost. They're building internal on-line job networks to retain talent. Integrating recruiting efforts with overall marketing campaigns, especially through coordination and identification with the company's brand, is the most important thing companies can do to ensure success in on-line hiring. Along the way, Cappelli sounds two cautionary notes. First, a human touch, not electronic contact, is vital in the last steps of a successful hiring process. Second, companies must make sure that on-line testing and hiring criteria do not discriminate against women, disabled people, workers over 40, or members of minority groups. When competition for talent is fierce, companies that master the art and science of on-line recruiting will be the ones that attract and keep the best people.

[On-line HFR and removal of uremic toxins inducing the loss of phospholipidic asymmetry of the erythrocyte membrane]. / HFR on-line e rimozione di tossine uremiche inducenti la perdita dell'asimmetria fosfolipidica della membrana eritrocitaria.

The phospholipids of the erythrocyte membrane are normally distributed asymmetrically in the double layer with the aminophospholipid phosphatidylserine (PS) present only on the inside of the membrane, since its exposure on the outside has numerous physiopathological consequences. In previous studies we have observed that solutes retained in uremia cause increased exposure of PS on the outer surfaces of the erythrocyte membrane and that this phenomenon may be involved in the uremic physiopathology, reducing erythrocyte survival and encouraging abnormal erythrocyte-endothelium interactions. The capability of the extracorporeal blood clearance treatment in removing the circulating uremic factors, responsible for the increased exposure of PS in red blood cells (RBC), was evaluated in 6 chronic uremic patients treated with haemodialysis (HD) or with on-line HFR in a random cross-over perspective study. The PS removal was evaluated indirectly by measuring the expression of PS in normal RBC incubated with uremic plasma obtained at various moments of the clearance session. The capability of the uremic plasma to expose PS on the RBC of healthy subjects (n-times increase compared to incubation of normal RBC with autologous plasma) was essentially unmodified during HD (3.3 +/- 0.2 pre HD; 3.3 +/- 0.1 after 2 hours; 3.1 +/- 0.2 at the end of the session) but was reduced during HFR (3.1 +/- 0.2 pre HD; 2.3 +/- 0.1 after 2 hours; 1.6 +/- 0.1 at the end of dialysis; p<0.001 at the end of dialysis vs pre and after 2 hours and p<0.001 vs HD at 2 hours and at the end of the session). The reduced capability of the uremic plasma obtained during the HFR session to expose PS in normal RBC, proves removal of the plasmatic uremic factors able to externalize the PS. To assess whether this removal effect is linked to the cartridge containing styrene resin used in the treatment with HFR, samples of ultrafiltrate were taken before and after the cartridge and its capability to express PS on normal RBC was measured. The absolute RBC values expressing PS (%) were (pre-cartridge vs post-cartridge) 8.6 +/- 0.3 vs 3.8 +/- 0.2 after 5 minutes from the start of the session; 3.9 +0.1 vs 1.6 +0.2 halfway through the session; 3.1 +/- 0.1 vs 1.3 +/- 0.66 at the end of the session (p<0.005 pre vs post at all times). Our results show that uremic compounds able to cause increased exposure of PS in RBC can be removed during on-line HFR, mainly thanks to the adsorption properties of the cartridge containing resin. This removal might be of benefit to uremic patients, improving the anaemic condition and reducing abnormal RBC-endothelium interactions which may contribute to endothelial disorder during uremia.

Preliminary report on the efficiency of combined haemodialysis-haemoperfusion treatment in chronic uraemia.

The use of activated charcoal haemoperfusion can play a complementary role in the substitutive treatment of chronic uraemia. This study reports the preliminary results of a regular combined haemodialysis-haemoperfusion treatment. The effectiveness of this treatment was observed on the subjective symptomatology (anorexia, nausea, asthenia) and on the polyneuropathy evaluated by electrophysiological assessments. The biocompatability of the system proved satisfactory.

Role of dyslipidemia in the progression of chronic renal disease.

The connection between lipids and the rate of progression of chronic renal disease was retrospectively examined in 70 patients who were divided into 2 groups according to their baseline creatinine clearance (CCr): Group 1 (Gp1) contained 30 patients with CCr 60-40 mL/min followed for 40.0 +/- 13.3 months; Group 2 (G2) contained 40 patients with CCr 39-15 mL/min followed for 39.0 +/- 18.2 months. The following parameters were considered: basal and final CCr proteinuria per unit of CCr (UProt/CCr); the difference between final and basal UProt/CCr (delta UProt/CCr); the change in CCr/month (delta CCr); baseline triglycerides (TG), total (TC), HDL (HDLC) and LDL (LDLC) cholesterol, Apo AI, Apo B, Lp(a). Besides in basal CCr the 2 groups significantly differed in the final CCr, final UProt/CCr, delta UProt/CCr, delta CCr. No differences were observed concerning lipid parameters except for Lp(a) (G1 14.8 +/- 13.6, G2 28.7 +/- 27.4 mg/dL; p < 0.05). Baseline TG (G1 184.1 +/- 61.3, G2 187.5 +/- 72.1 mg/dL) and Apo B (only G2 1.05 +/- 0.32 g/L) were significantly higher than normal subjects and the Apo AI/Apo B ratio (G1 1.42 +/- 0.43, G2 1.33 +/- 0.45) were significantly lower than in normal subjects. delta CCr, while inversely correlated in both groups with delta UProt/CCr (p < 0.01), only in G2 did it correlate directly with the Apo AI/Apo B ratio (p < 0.05) and inversely with Apo B and LDLC (p < 0.05). Although a correlation between Lp(a) and delta CCr was not found, 20/22 patients (3/5 G1, 17/17 G2) with a level > 30 mg% ran a progressive course. A natural progression of CRI, heralded by an increasing UProt, is highly frequent when baseline CCr is < 40 mL/min; only then lipids seem to add a burden to the renal damage.

Computerised non-invasive monitoring of cardiovascular stress in haemodialysis patients.

Haemodynamic instability is one of the most frequent problems occurring during dialysis treatment. Ten clinically stable patients (8 M and 2 F) undergoing chronic maintenance haemodialysis for at least 6 months were investigated. Two groups of five patients each, were selected on the basis of presence (IG) or absence (SG) of cardiovascular instability during dialysis. The cardiovascular function was assessed by computerised electrical bioimpedance performed during dialysis setting and by echocardiography immediately pre- and post-dialysis. In SG dialysis treatment did not change cardiac index (CI), stroke index (SI) and systemic vascular resistances index (SVRI). However CI, SI and SVRI, tended to decrease in IG patients; the reduction in CI was primarily due to a decrease in SI. Ejection velocity index increased significantly in SG but not in IG. Evaluation of cardiac function by Döppler echocardiography revealed a significant increment in fractional shortening, mean velocity of circumferential fiber shortening and Suga' index in SG with dialysis but not in IG. Stress index decreased significantly in both groups. Hormonal and biochemical parameters were not significantly different before and after dialysis in both groups. In IG the decrease in mean blood pressure, due to a reduction of SI, recognises in the inadequate response of myocardial contractility to volume subtraction, the genesis of its drop. Finally, impedance cardiography in uraemic patients helps to identify the factors that contribute to the impairment of cardiac performance and that should be studied before selecting new and advanced dialysis programmes.