Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

The nature of intracytoplasmic lipid inclusions found in cultured rabbit and rat peritoneal mesothelial cells was examined by ultrastructural and biochemical techniques. Transmission electron microscopy also demonstrated extracellular release of these lipid bodies. Differential fixation with tannic acid revealed 2 types of inclusions, lamellated (lamellar bodies) and nonlamellated (homogeneous). The lamellar bodies were found near or in the Golgi apparatus and on the cell surface where occasionally they were observed in exocytotic pouches. The homogeneous inclusions were the predominant species being found primarily intracellularly. Lipid bodies obtained from the culture media over the cells displayed on electron microscopy the same morphological characteristics as those seen intracellularly. Exposure of confluent cultures of mesothelial cells to the vital lipid stain Nile Red caused the appearance of intensely fluorescent droplets in or on the cells at wave lengths consistent with staining for phosphatidylcholine-rich vesicles. Incubation of the cells with r4C)-choline an d subsequent analysis of phospholipid formation revealed high rates of r4C)-phosphatidylcholine addition to both intra and extracellular lipid pools. Taken together, mesothelial cells exhibit lipid bodies similar in ultrastructure to the surfactant containing organelles of Type II pneumocytes.

Pseudomonas species infections in the peritoneal dialysis population consist primarily of peritonitis or exit site infections. These organisms have traditionally proven difficult to eradicate, and the standard antibiotic regimen has carried the potential for nephrotoxicity.

At our institution, all peritoneal dialysis patients with Pseudomonas exit site infections or peritonitis were treated with an antibiotic combination of intraperitoneal ceftazidime and oral ciprofloxacin. Treatment duration was dependent upon the site of infection. Recurrent exit site infections were treated with a repeated course of the antibiotics, and with surgical debridement and subsequent shaving of the external cuff of double-cuffed catheters.

We saw a total of 11 Pseudomonas aeruginosa exit site infections in 7 patients (4 recurrent). Patients with recurrent infections were subsequently cured with the regimen as outlined above. Of 7 patients with Pseudomonas species peritonitis (aeruginosa, fluorescens, stutszeri, and maltophilia), 5 were cured with the initial antibiotic regimen. The 2 failures were both infected with Pseudomonas maltophilia, which is consistent with observed organism sensitivity data.

The combination of ceftazidime and ciprofloxacin with the option for surgical debridement of the external cuff (in exit site infections) appears effective in the treatment of Pseudomonas species infections in the peritoneal dialysis population. Sensitivity data should be used to adjust the antibiotic regimen when appropriate.

The transperitoneal transport of macromolecules is dependent on both effective peritoneal surface area and intrinsic permeability of the peritoneum. For passage of small solutes, the effective surface area is the main determinant. We hypothesized that day-to-day variations in peritoneal clearances are caused by changes in the effective surface area and not in the intrinsic permeability. Four CAPD {continuous ambulatory peritoneal dialysis) patients without peritonitis were investigated on 28 consecutive days. Concentrations of beta-2-microglobulin, albumin, IgG, and alpha-2-macroglobulin were determined daily in dialysate {night bags) and weekly in serum. Clearances and their coefficients of variation were calculated. Mean coefficients of the intraindividual variation of protein clearances increased, the higher the molecular weight: they ranged from 12% for beta-2microglobulin clearance to 22% for alpha-2-macroglobulin clearance. Correlations were present between the clearances of albumin, IgG, and alpha-2-macroglobulin, but not between any of these and beta-2-microglobulin clearance. In all patients, protein clearance {C) was a power function of the free diffusion coefficient in water {D) according to the equation: C=a. Db in which b represents the restriction coefficient of the peritoneum, and thus intrinsic permeability. The coefficient of variation of the restriction coefficient was low (range 4–6%). This supports our assumption that the intrinsic permeability is fairly constant on the short term. Day-to-day variations in protein clearances are thus mainly caused by alterations in the effective peritoneal surface area. Longterm follow-up of the restriction coefficient in individual patients might identify those at risk for the development of structural changes in the peritoneal membrane.

This paper describes the use of glycylglycine to prepare dialysis solution containing bicarbonate, calcium and magnesium. Bicarbonate with glycylglycine form a buffer with a constant pH of 7.35, which prevents reaction with calcium or magnesium and the formation of insoluble carbonate salts. This bicarbonate-based solution is stable over long periods and can be used with the same simplicity and convenience as lactate solution for peritoneal dialysis (PD) in humans.

We have attempted to determine whether human mesothelial cells (MC) have the power to influence their own proliferation. A serum -free medium was conditioned with the mesothelial monolayer for 24 hours and then applied to proliferating MC. Conditioned medium increased proliferation rate of MC. When the medium was heated at 60°C for 60 minutes, the growth-promoting activity of the conditioned medium decreased by 50%, suggesting that MC produce at least 2 growth factors, 1 heat-Iabile and the other heat-stable. When MC were exposed continuously to a medium containing 90 mM glucose growth factor, production was decreased by 35%. However, when the cells were exposed to glucose only on alternate days, growth-factor production was similar to that in the control medium. On the other hand, MC exposed continuously for 10 days to 90 mM of glucose exhibited a weaker response to endogenous growth factor, even in a normotonic medium with low glucose concentration. Our results suggest that MC syn thesize factor(s), which stimulate their own proliferation, and that high glucose concentrations interfere with this production and the subsequent action of growth factor.

Fluoroquinolones may be a good alternative for the treatment of bacterial peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). To test their efficiency against Gram-positive bacteria, we treatedwith intraperitoneal (i.p.) ciprofloxac in 30 episodes of Gram-positive bacterial peritonitis without manifest tunnel infection of the peritoneal catheters. Treatment was sustained for 5 days, then orally for 10 further days. Clinical and bacteriological responses were satisfactory in 25 cases, but resolution of infection was slow in 5 cases of Staphylococcus aureus. The minimal inhibitory and bactericidal concentrations were 0.06250.50 and 0.125-1.0 μg/mL respectively, lower than the plasma and dialysate concentrations of the drug. Side effects were negligible. We conclude that ciprofloxacin provides a good therapeutic alternative to more widely used antibiotics for the empirical treatment of peritonitis in patients undergoing CAPD. However, combinations of antibiotics may be necessary, in Staphylococcus aureus peritonitis.

There is scanty knowledge of the morphology of peritoneal dialysis catheter tunnels in humans, even though such knowledge may impact on peritoneal catheter design, implantation and postimplantation care. Past descriptions of catheter tunnels are based mainly on data from animal experiments. Based on these data, it has been assumed that epidermal spreading is inhibited by collagen fibers ingrown into the cuff. Our preliminary investigation indicated that this may not be the case in humans and led us to study catheter tunnel morphology in more detail. Eighteen catheter tunnels (2 -Smm of tissue around the catheters) were removed in 17 peritoneal dialysis patients. The catheters were inserted 30 to 2013 days prior to removal (median 366 days). The catheters were removed electively or because of infectious or noninfectious complications. Contrary to the observations in animals, in only 1 case did epithelium extend to the cuff with only a minimal amount of granulation tissue present at the end of a 9 mm long sinus tract. In the remaining cases, the leading edge of the epithelium always met granulation tissue 1 −14 mm from the exit, and the cuffs were found 8 33 mm from the exit. In tunnels older than 197 days, dense fibrous tissue was ingrown into the cuffs, and a dense fibrous capsule surrounded the cuff. The uninfected intercuff segment formed a pseudosheath, indistinguishable from a tendon sheath or synovial membrane. Infection in the catheter tunnel propagates through the part of the cuff adjacent to the tubing inside the capsule, suggesting that the cuff per sedoes not constitute a major barrier for spreading infection. This observation, by exclusion, infers that the beneficial role of an external cuff in decreasing exit infections is by providing firm anchorage of the catheter resulting in restriction of its piston like movement and thereby minimizing trauma and inward conveyance of outer sinus tract flora.

A multitude of therapeutic regimens have been proposed for the management of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). There are, however, few clinical trials that have evaluated the efficacy of these proposed regimens in a prospective, comparative fashion. This retrospective report is a tabulation of the published data on antimicrobial treatment of CAPD-related peritonitis. The results are presented for combination and mono-drug therapies; Gram-positive bacterial, Gram -negative bacterial and fungal infections; intravenous, oral and intraperitoneal (i.p.) routes of drug administration; various dosages and dosing intervals; and clinical response and relapse rates. The apparent optimal combination regimen for empiric treatment of peritonitis is vancomycin administered in 1 dialysis exchange/week with ceftazidime. This regimen avoids the toxicity associated with the use of aminoglycosides while maintaining effectiveness.

In the present study, we evaluated the relationship between 1. the volume and rate of dialysis outflow and subsequent inflow, 2. the patient's impression of the location of the catheter tip and 3. the stability of the catheter tip location. Thirteen patients were studied on 2 random occasions (periods 1 and 2). Inflow (L/min) was significantly faster than outflow (p<0.05). No catheter tips were located in the far upper part of the abdomen. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p<0.02). Two patients were able to feel the catheter tip at Period 1, and 4 at Period 2, but only 1 patient was able to state the exact location identical to fluoroscopy. Ninety-two percent of the fluoroscopic evaluations showed catheter tips located in the same anatomical regions in upright as well as supine positions. If vertical “neighbour” anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located at the same or the vertical “neighbour” region in the 2 study periods.

Functional activity of peritoneal macrophages of 50 patients with end-stage renal failure on intermittent peritoneal dialysis (IPD) and of 30 control subjects with normal renal function was determined. Phagocytosis of latex particles by macrophages of dialyzed patients was significantly lower as compared with the controls. Further depression of the phagocytic activity was observed during bacterial peritonitis. Macrophages from the dialyzed patients also showed nonsignificantly decreased functional expression of Fc receptors (FcR) and increased spontaneous nitro blue tetrazolium (NeT) reduction.

Epidermal growth factor (EGF) was measurea In the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65±0.009 nmol/L compared with 0.99±0.24 nmol/L in nondialyzed CRF patients, 1.15±0.23 in hemodialyzed patients and 1.96±0.25 (p < 0.01, Wilcoxon Rank Sum Test) in CAPO-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPO.

In 1989, a conference was held to discuss the current status of technique survival for patients treated with continuous ambulatory peritoneal dialysis (CAPO). Major reasons for patient drop -out from CAPO -peritonitis, inadequate dialysis, catheter-related problems and psychosocial factors -were reviewed, as were constructive techniques for dealing with these problems and areas for future investigation.