Glycosaminoglycans prevent the functional and morphological peritoneal derangement in an experimental model of peritoneal fibrosis.

Chronic peritoneal dialysis results in fibrosis of the peritoneal membrane, which leads to progressive reduction in dialytic efficacy. It was recently shown that the intraperitoneal administration of glycosaminoglycans (GAGs) improves the efficiency of peritoneal dialysis in CAPD patients. To verify whether the favorable effects of GAGs are purely functional or involve a morphological amelioration of the peritoneal membrane structure, a study was carried out in an animal model of plasticizer-induced peritoneal fibrosis. Rats, in which chronic renal failure had been induced by subtotal nephrectomy, received either placebo, plasticizers (i.p.), or GAGs (s.c.), or plasticizers (i.p.) and GAGs (s.c.). Urea dialysate-to-plasma equilibrium, urea and albumin peritoneal clearance, and glucose reabsorption were determined. The peritoneal membrane was evaluated morphometrically and histologically. In plasticizer-treated animals, peritoneal function tests and morphology were dramatically deranged. On the contrary, the subcutaneous administration of GAGs in plasticizer-treated rats maintained the peritoneal physiology and normal structure. The subcutaneous administration of GAGs protects peritoneal functions by affecting the remodeling of the peritoneum, rather than by a purely functional or simple mechanical effect.

Low-dosage ibopamine treatment in progressive renal failure: a long-term multicentre trial.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Assessment of the best compatible dialysis system: feasible application for bioelectrical impedance.

Since the introduction of hemodialysis procedure several attempts have been made to elucidate the material tissue interaction in order to evaluate the behaviour of immunosystem cellular and humoral responses to the material of patients on renal replacement therapy. Biochemical and sierological parameters have been considered as method for assessment of the best compatible dialysis. Nevertheless blood tests don't probably reflect the most important symptoms of clinical relevance. Thus we have applied bioelectrical impedance to assess the whole procedure/patient system. Resistance (R) changes during hemodialysis resulted strictly inversely correlated to the body weight variations during HD session (R < 0.96). Reactance (Xc) has also shown a progressive increase associated with an increment of phase angle, while Xc during clinical events such as hypotension, vomiting or cramps showed some transient falls. Also nutritional status and clinical well-being manifested a close relationship with bioelectrical parameters. It is therefore our feeling that BIA monitoring will provide a feasible tool to assess dialysis adequacy, of which biocompatibility represent a crucial aspect.

Use of glycosaminoglycans to increase efficiency of long-term continuous peritoneal dialysis.

Long-term continuous ambulatory peritoneal dialysis (CAPD) frequently induces progressive structural changes in the peritoneal membrane, leading to dialysis failure. Because heparin and glycosaminoglycans favourably remodel anatomical barriers exposed to injury, we studied the effect of intraperitoneal administration of glycosaminoglycans on peritoneal dialysis efficiency. 16 CAPD patients received glycosaminoglycans for 30 days followed by a 30-day wash-out. Glycosaminoglycans in urea and creatinine dialysate-to-plasma ratios significantly increased (means 0.86 and 0.78 at baseline, 0.92 and 0.82 at 30 days, respectively). Peritoneal protein loss was reduced, and serum albumin concentration increased. We now need to assess whether glycosaminoglycans can postpone dialysis failure in the long term.

Why the double-bag system still remains the best technique for peritoneal fluid exchange in continuous ambulatory peritoneal dialysis.

Since March 1979 (the Italian-French-Spanish meeting in Turin), we have been using the double-bag system for peritoneal fluid exchange in patients on continuous ambulatory peritoneal dialysis (CAPD). This technique, subsequently followed by many others because of the advantages to the patients, still represents the best tool in bag-exchange procedure, because it satisfies the following characteristics: single luer-lock connection; flush-before-fill; simple, safe, and aseptic manipulation; short training period; no carrying bag; good patient acceptance; and low incidence of exogenous peritonitis. In 13 years with 237 patients selected for double-bag treatment, we have observed an incidence of 1 episode of peritonitis every 26.6 patient-months. Few clinical CAPD-related complications like hypotension and alterations of Ca-P metabolism were observed, probably as a result of more personalized peritoneal fluid with high Na+ (136 mEq/L) and Ca2+ (3.5 mEqL) concentrations. In the meantime, we have also had available plasticizer-free bags, which eliminated one of the main risk factors in peritoneal sclerosis. The utilization of the plasticizer-free double-bag system, currently adopted by numerous other centers, still remains the best option from a clinical and psychological viewpoint of the patients on CAPD.

Effect of hypertriglyceridemia correction by omega-3 fatty acids on peritoneal transport in continuous ambulatory peritoneal dialysis patients.

Lipid abnormalities, both hypercholesterolemia and particularly hypertriglyceridemia (hyperTg), are common in long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Hyperviscosity and rheological alterations have been proposed as major hemodynamic problems in hyperTg patients. The aim of this study was to evaluate whether a hyperTg correction by employing omega-3 fatty acids (omega-3) affects peritoneal transport. Six hyperTg (> 700 mg/dL) CAPD patients were treated with 2-3 g/day of omega-3 until normal Tg values were achieved. The assessment of peritoneal dialysis efficacy was performed by evaluating the peritoneal equilibration test (PET) before omega-3 supplementation, when normal Tg levels were reached, and 3 weeks after stopping therapy when hyperTg returned. When normal Tg levels were reached, a small but significant improvement of urea and creatinine D/P was noted: 0.85 +/- 0.05 versus 0.93 +/- 0.03 (p < 0.05) and 0.78 +/- 0.03 versus 0.86 +/- 0.05 (p < 0.05), respectively, with negative correlation between D/P of urea and Tg. These preliminary data demonstrate that a hyperTg correction with omega-3 may induce an increase in peritoneal transport of small molecules in CAPD.

Combined hemodialysis-hemoperfusion in the treatment of secondary hyperparathyroidism of uremic patients.

Hyperparathyroidism and its related symptoms such as bone pain, soft-tissue calcifications and pruritus often get worse during dialysis treatment. We have treated 12 cases among 170 patients on regular dialysis by using coated charcoal (150 g/cartridge) in combination with standard hemodialysis. During a 6-month treatment period, without changing medical therapy and diet regime, the patients reported a marked relief from pruritus. Parathyroid hormone (PTH) levels changed from 552 +/- 86 to 364 +/- 62 pg/ml (p less than 0.001) compared to the pretreatment period, Plasma PO4(3-) changed in the same period from 6.9 +/- 1.8 to 4.6 +/- 1.5 mg/dl (p less than 0.005). The results obtained indicate a relationship between PTH, serum plasma PO4(3-) levels and pruritus. The mechanism which may be involved is that hemoperfusion removes PTH excess by absorption. Our treatment reducing PTH levels resulted in a marked relief from pruritus and other symptoms, suggesting that patients in this condition, before undergoing surgical parathyroidectomy, may be usefully treated with this therapeutic modality.

On-line bioelectric impedance during haemodialysis: monitoring of body fluids and cell membrane status.

We have measured by a computed integrated system (BIA 109, RJL AKERN) the changes of bio-impedance (BI) deriving from a tetrapolar system working on 800 microA, 50 kHz current, in 23 haemodialysed patients. Resistance (R) and reactance (Xc) have been continuously monitored during haemodialysis in each patient. Resistance was strictly inversely correlated to the decrease of body weight (r = 0.82). Also, Xc increased almost constantly. In most of the patients the increase of Xc was proportionally greater than R, resulting in an increase of phase angle (PA). However, Xc showed a transient decrease in response to seven severe symptomatic hypotensive episodes, whereas R maintained the increasing trend, causing a sharp reduction of phase angle. As Xc is an expression of storage of electrical charge by the cells acting as condensers, and phase angle quantifies the active capacitive component in relation to passive electrical resistance, these parameters may be important to evaluate cell membrane function. In fact, the univocal increase of R, Xc and phase angle observed during normal unevenful haemodialysis probably indicates improvement of cellular activities due to the depurative treatment. On the contrary, the transient reduction of Xc and phase angle observed during hypotensive crises may be an expression of cellular distress because of a too rapid ultrafiltration.

Effect of phthalate acid esters on transport in toad bladder membrane.

Sclerosing peritonitis is a serious complication in patients on long-term peritoneal dialysis; it markedly decreases transport of water and solute across the peritoneal membrane. Although the precise mechanism is unknown, organic compounds (i.e., plasticizers) from plastic tubing and dialysis bags have been suggested to be a cause of the syndrome. The effects of three such compounds on water and sodium transport in vitro were studied in the toad bladder. The compounds studied were didodecylphthalate, dioctylphthalate, and benzylbutylphthalate. After 4 hr incubation in vitro, dioctylphthalate and benzylbutylphthalate significantly inhibited vasopressin-stimulated water flow in toad bladder. Basal water flow was not affected by any of the three compounds. Sodium transport, as measured using short-circuit current, was decreased to an equivalent degree by all compounds; inhibition of short-circuit current was dose dependent and was approximately 30% at 10(-3) M. The onset of action was between 3.5 and 4 hr, and the effect on short-circuit current was not reversible. These results demonstrate that the plasticizers (to which patients of all sorts are commonly exposed) inhibit transport across living membranes. In the toad bladder these compounds decrease sodium transport and maximal water flow. Although other evidence suggests that the cumulative toxic effects of these compounds may play a causal role in sclerosing peritonitis in patients on peritoneal dialysis, our study suggests that chronic exposure to the phthalate acid esters in patients with normal renal function may result in sodium wastage, polyuria, and a concentrating defect resistant to AVP.

Removal of phosphate (Pi) by either bicarbonate dialysis or biofiltration in uremics.

The kinetics of extra and intracellular red blood cell (RBC) Pi and its removal by different therapeutic modalities were evaluated in 30 uremic patients over a 6 mo. period. Acetate hemodialysis alone, combined with hemoperfusion, or associated once a week with plasma-perfusion sessions using an activated bauxite cartridge, bicarbonate dialysis either in single pass or in recirculating system (40 L) and biofiltration, were the depurative treatments employed. The treatments with acetate buffer showed a temporary intracellular shift of Pi at the end of the sessions with post-dialytic plasma Pi rebound. This was not evident with bicarbonate buffer and biofiltration where acidosis was corrected better, and similarly during plasma perfusion treatment because blood pH remained unchanged. These findings may explain the better plasma Pi level at the end of our study with these later therapeutic models compared to acetate dialysis alone or combined with hemoperfusion. In these conditions Pi removal is limited by the correction of acidosis which implies acetate metabolism with ATP activation leading to a transient Pi intracellular influx and a subsequent efflux into the extracellular compartment.