Giorgio Bazzato

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.

Risk factors for the progression of diabetic nephropathy: role of hyperlipidaemia and its correction

Hypertension, proteinuria and hyperlipidaemia are major factors implicated in the progression of chronic renal failure towards uraemia. All of these factors are frequently more pronounced in diabetic nephropathy. We evaluated the rate of progression of renal insufficiency in 12 patients with diabetic nephropathy (DN group) and 18 patients with non-diabetic chronic nephropathy (CN group) during a 2-year period. All patients had high blood pressure on angiotensin-converting enzyme (ACE) inhibitor therapy, hypercholesterolaemia and proteinuria in the non-nephrotic range. Basal glomerular filtration rate (GFR) had an overlapping range in the two groups. The rate of GFR decline during the 2-year period was similar for the DN and CN groups (0.23 vs 0.21 ml/min per month) and correlated with the mean values of low-density lipoprotein (LDL)-cholesterol for both groups (DNr=0.569, CNr=0.511,P<0.05). After 1 year of ACE inhibitor therapy we randomly allocated a subset of patients in each group (6 DN and 9 CN) to receive HMG-CoA-reductase inhibitor (simvastatin or pravastatin 10 mg/day). We observed a decrease in total (−21%) and LDL-cholesterol (−32%) and triglycerides (−11%) and an increase in high-density lipoprotein (HDL)-cholesterol (+8%). The rate of GFR decline was lower in the statin-treated group compared with the previous period (DN−0.21 vs −0.25 ml/min per month; CN −0.18 vs −0.22 ml/min per month). Our data support the hypothesis that associated risk factors rather than diabetes per se are responsible for the rate of progression of renal failure in DN and that the correction of lipid abnormalities may play a key role in slowing the rate of renal function decline.