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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.

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.

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.

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.

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.

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.

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.

Lysagth et al have reported a semplified model of spontaneous plasmapheresis by placing between an A-V shunt a conventional plasmafilter. On the basis of this experience we tried to make a further semplification of this apparatus using a single venous puncture, obtaining by gravity sufficient transmembrane pressure for plasma separation. By alternatively lowering and elevating the system, plasma is separated from the blood and packed red cells are reinfused after a new pass through the filter with FFP or plasma substitutes.

Evidence for muscle protein wasting and abnormal muscle metabolism is common in uremia. Muscle DNA content is considered a reliable reference standard in normal and undernourished adults. Muscle RNA content rapidly changes during starvation and refeeding. The ratio of noncollagen alkali-soluble proteins (ASP) to DNA is considered to be an estimate of the cytoplasmic volume of a single cell, and the RNA: DNA ratio is an index of the ribosomal capacity for protein synthesis. Muscle DNA, RNA, ASP, water, and fat content were determined in muscle biopsy specimens from chronically uremic patients receiving conservative treatment (CT), maintenance hemodialysis (two centers), or CAPD. Nutrient intake was low and the anthropometric indices were decreased in all groups of patients, except in the hemodialysis patients from one center. Serum proteins and muscle ASP: DNA and RNA: DNA ratios were decreased. The nutritional status was reassessed in some malnourished CAPD patients after about one year of careful nutritional advice and was unchanged. These results suggest that chronically uremic patients on CT are often malnourished, primarily because of an inadequate protein and/or energy intake. Muscle nucleic acid and protein content are useful tools for nutritional assessment at a cellular level in humans with chronic renal failure and can be used to monitor the response to nutritional therapy.

Thyroid function was measured in 30 healthy subjects and 84 patients with various degrees of nephron loss (GRF: 70 +/- 15 m/min, 30 +/- 16 ml/min, 10 +/- 7 ml/min and 2.1 +/- 1.3 ml/min). A low T3 and T4 syndrome is evident when GRF is reduced to 30 +/- 16 ml/min while a blunted TSH response is detected earlier in the course of nephron loss. T3 response to TRH was normal and FT4 was not affected by renal dysfunction. The data indicate that in nephron loss hypothalamic-pituitary abnormalities occur.

Despite the great impact of continuous ambulatory peritoneal dialysis (CAPD) as an effective modality of treatment for uraemic patients, two limiting factors remain: the high incidence of peritonitis and the need for patients continuously to carry a bag. We have designed a new closed system with two bags connected to the permanent Tenckhoff catheter. Two clamps alternately allow outflow and inflow of peritoneal dialysate. When the exchange manoeuvre is finished the patient frees the whole system from the needle and discards it. Since December 1978, 24 patients have been treated with this technique. The results are similar to the Toronto series with a marked reduction in the incidence of peritonitis (22.5 pt/months).

The authors have compared during 4 weeks of study the effects of furosemide (F) by oral route or i.v. and muzolimine (M)/os in 10 patients with nephrotic syndrome (NS) and normal renal function. A satisfactory diuretic response was observed with i.v. F (100 mg) and M/os (30-60 mg) with respect to the basal condition (P less than 0.001), while F/os (100 mg) was ineffective in these patients. This behaviour may be explained by the different pharmacological properties of M vs. F, by gut alterations due to the oedema of mucosa or loss of some "carrier(s)" operating for intestinal absorption of these two high ceiling diuretics.

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.

Since knowledge about the pathogenesis of hepato-renal syndrome (HRS) is incomplete, the therapy is empiric and supportive. While a number of specific therapeutic measures have been attempted, none has been proved to be of practical value. We describe a very simple technique for concentration of ascitic fluid obtained with spontaneous filtration by gravity. We have been treating with this new device 4 patients affected by HRS with ascites refractory to diuretics. We obtained a rapid disappearance of ascites and improvement in clinical condition. The simplicity and the ease of operation make this technique feasible for repeated chronic ambulatory treatment.

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.

Plasma-exchange (PE) represents an effective therapeutic approach employed in several immunological nephropathies, poisonings and various other diseases. Hemodynamic changes during intermittent flow PE were studied--using the thermodilution technique--in 8 patients (3 male and 5 female) aged between 36 and 73 years (mean 46.4). The mean values for the following parameters were measured before, during every cycle--exchanging about 300 ml of fresh frozen plasma--and at the end of the session: mean arterial pressure (MAP), heart rate (HR), cardiac index (Cl), stroke index (SI), total peripheral resistence (TPR), central venous pressure (CVP), pulmonary arterial pressure (PAP) and pulmonary capillary wedge pressure (PCWP). During the first exchange the systemic circulation showed hemodynamic changes similar that of an acute hemorrhagic condition: decrease in MAP (from 106 to 97 mmHg), Cl (from 4.27 to 3.7 L/m'/m2), SI (from 53 to 49 ml/beat/m2) and CVP (from 6.9 to 4.4 mmHg); increase in TPR (from 1230 to 1339) dynes/sec/cm-5), while HR showed only mild changes. In the following cycles all the parameters progressively returned toward the previous values. During the first cycle the pulmonary circulation showed a decrease in PAP (from 15.5 to 13 mmHg) and PCWP (from 8.9 to 6.6 mmHg). PAP also increased constantly in the following cycles reaching at the end of the session levels which were higher than the initial ones. Our data demonstrate that in PE treatment especially when is employed a low volume of fluid, has to be substituted at every cycle in order to prevent the major hemodynamic complications i.e. hypovolemic shock and heart failure.