E. Gaggiotti

Morphology of the Peritoneal Membrane during Continuous Ambulatory Peritoneal Dialysis

In the last 3 years we performed 52 peritoneal biopsies (PB) in 31 patients on continuous ambulatory peritoneal dialysis (CAPD). Samples of the parietal peritoneum were obtained either during insertion of the catheter or while it was being repositioned or removed. PB was performed in 13 patients before initiating CAPD and in 27 after 7-49 months of CAPD while 7 had PB during peritonitis, and, again, in 5 of these cases, PB was repeated after 1-4 months for light, electron transmission, and scanning electron microscopy. BP after CAPD showed that mesothelial cells were irregularly spaced, and at times we observed alterations in the cellular structure. Rarely were these cells degenerating, while rarefaction and in many cases complete absence of microvilli were observed. In some cases the submesothelial layers showed rarefaction of the connective tissue and sclerosis. During peritonitis, PB showed more alterations with marked degeneration and in some cases necrosis of the mesothelium and alterations of connective tissue. PB performed some months after peritonitis showed only a partial regression of these alterations and sclerotic patches, and no microvilli were noted in the mesothelium.

Phosphatidylcholine and Peritoneal Transport during Peritoneal Dialysis

Peritoneal effluent of patients on chronic ambulatory peritoneal dialysis (CAPD) contains a surface-active material (SAM) made up of phospholipids and showing phosphatidylcholine on thin-layer chromatography. This substance drastically lowers surface tension, helps to repel water and has a lubricating effect. The presence of stratified phosphatidylcholine on the peritoneum might narrow the stagnant dialysate fluid layer and situations which can alter the quantity or composition of SAM may affect peritoneal transport and also, perhaps, the formation of adherences. This led us to verify, experimentally, the presence of phospholipids in basal conditions, after CAPD and during peritonitis and to check if addition of phosphatidylcholine to dialysis liquid is able to modify water transport in patients with low ultrafiltration and peritonitis. Phospholipids in the dialysis effluent of patients who have been on CAPD for a long time are lower than observed in the first days of peritoneal dialysis. A more drastic, significant decrease in phospholipids was observed in patients with low ultrafiltration and in patients with peritonitis. Mean ultrafiltration significantly increases in patients with low ultrafiltration and in those with peritonitis during dialysis exchanges containing phosphatidylcholine (50 mg/l) indicating that the latter is able to restore normal physiological conditions.

Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy

Abstract Some lines of evidence have suggested that the challenge to antioxidants and biomolecules provoked by pro-oxidants such as ozone may be used to generate a controlled stress response of possible therapeutic relevance in some immune dysfunctions and chronic, degenerative conditions. Immune and endothelial cells have been proposed to be elective targets of the positive molecular effects of ozone and its derived species formed during blood ozonation. On the bases of these underlying principles and against often prejudicial scepticism and concerns about its toxicity, ozone has been used in autohemotherapy (AHT) for four decades with encouraging results. However, clinical application and validation of AHT have been so far largely insufficient. Latterly, a new and more effective therapeutic approach to ozone therapy has been established, namely extracorporeal blood oxygenation and ozonation (EBOO). This technique, first tested in vitro and then in vivo in sheep and humans (more than 1200 treatments performed in 82 patients), is performed with a high-efficiency apparatus that makes it possible to treat with a mixture of oxygen–ozone (0.5–1 μg/ml oxygen) in 1 h of extracorporeal circulation up to 4800 ml of heparinized blood without technical or clinical problems, whereas only 250 ml of blood can be treated with ozone by AHT. The EBOO technique can be easily adapted for use in hemodialysis also. The standard therapeutic cycle lasts for 7 weeks in which 14 treatment sessions of 1 h are performed. After a session of EBOO, the interaction of ozone with blood components results in 4–5-fold increased levels of thiobarbituric acid reactants and a proportional decrease in plasma protein thiols without any appreciable erythrocyte haemolysis. On the basis of preliminary in vitro evidence, these simple laboratory parameters may represent a useful complement in the routine monitoring of biological compliance to the treatment. The clinical experience gained so far confirms the great therapeutic potential of EBOO in patients with severe peripheral arterial disease, coronary disease, cholesterol embolism, severe dyslipidemia, Madelung disease, and sudden deafness of vascular origin. Extensive investigation on oxidative stress biomarkers and clinical trials are under way to validate this new technique further.

A New Technique for Insertion of the Tenckhoff Peritoneal Dialysis Catheter

To eliminate the discomfort caused by surgical methods and the risks involved using the trocar, for 1 year we have been using a new technique for insertion of peritoneal catheters (PC). We devised a steel instrument, vaguely resembling a rhinoscope, composed of two semicones. The handles are connected by a screw to permit dilatation of the semicones. After local anesthesia, an introducer needle is inserted into the peritoneal cavity. A guide-wire is passed through the needle which is then withdrawn and our instrument is placed around the guide and gently pushed into the peritoneal cavity. The guide is now removed and squeezing the handles of the instrument we introduce the PC up to 2 cm beyond the first Dacron cuff. When the catheter is in place, the instrument is removed and a subcutaneous tunnel may be made. We have used this method for 25 patients. 14 were new cases while 11 underwent PC repositioning. For all patients this new method proved to be excellent with practically no leakage and PC were utilized immediately or after only 24 h. We emphasize the brief time for PC insertion, the minimum discomfort and the simplicity of the technique.

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.

Simple peritoneal sclerosis and sclerosing peritonitis: related or distinct entities?

Aim The etiopathogenesis of sclerosing peritonitis is still debated, with some sustaining that it is a rare form of progression of simple peritoneal sclerosis and others that it is a primitive form. The aim of the present research was to clarify this question. Material and Methods 438 peritoneal biopsies from 253 patients were re-examined. 174 were obtained prior to peritoneal dialysis and 224 after various periods of dialysis. Forty biopsies were from peritoneal dialysis patients who developed sclerosing peritonitis. Peritoneal morphology was studied for signs of transition from simple sclerosis to sclerosing peritonitis. Results Evidence was found sustaining the hypothesis that simple sclerosis to sclerosing peritonitis patients have distinct pathologies. Conclusions The results confirm previous observations, excluding the existence of any type of relation between simple peritoneal sclerosis to sclerosing peritonitis.

Bleeding Tendency of Chronic Uremia Improved by Vascular Factor

Complex hemostatic changes in uremic patients are characterized by platelet distress and prolonged bleeding time. Dialysis corrects platelet function and improves the bleeding time but introduces a tendency to thrombophilia. The uremic patient is thus an excellent model for the evaluation of hemostatic drugs. VUEFFE (VF) is a new hemostatic agent which reduces bleeding time without modifying clotting parameters. Changes in hemostasis and coagulation were studied in 42 hemorrhagic uremic subjects in dialysis or on conservative management. The patients were divided into two groups, one of which was given oral VF and the other oral placebo. 84% of those receiving VF ceased bleeding within 15 days (compared to 25% for placebo) and there was a significant reduction in bleeding time. The drug can be given orally or parenterally, is well tolerated and without side effects, making it suitable for administration to hemorrhagic uremic patients.

Experimental evaluation of transport force in the rabbit ureter

Background Cleaning the urinary tract by so-called “wash-out effect” and promoting high diuresis has long been advocated but has had very little scientific backing and few prospective studies in international journals. Aim To verify whether the physical laws describing the transport force of water in rivers and pipes are also valid for urinary outflow. Methods A laboratory model for measuring transport force, given liquid and solid capacity, was adapted to create an in vivo model based on the rabbit urinary tract. Results Fluid flow in the rabbit renal pelvis and ureters was found similar to flow in pipes, obeying the physical laws of water transport to some extent. When the quantity of liquid flowing in the urinary tract in unit time was doubled, the transport force increased by various orders of magnitude. When the liquid increased by a larger factor, the transport force became enormous. Conclusions The results confirm the utility of maintaining high diuresis in patients with renal calculus, but stress the utility of drinking 1–2 liters of hypotonic water in a short time to obtain an enormous increase in transport force which increases the probability of a cleansing effect.