Middle molecules in uremic serum, urine and dialysis fluid.

Gel filtration through Sephadex (g 75 and 15) and ultrafiltration and diafiltration through selective membrances have been carried out on 172 uremic sera, 89 normal sera, uremic and normal urines and hemodialysis fluid. The accumulation in uremic sera of substances wwith molecular weights between 500 and 3,500 (so called "middle molecules") was demonstrated. Molecular weight evaluation was verified on single effluent fractions using different added isotopes. Evaporation of serum to dry weight revealed a 2-3 fold increase in solids compared to normal values. Estimation of the fractional content of individual elements and quantitative amino acid analysis (before and after acid hydrolysis) did not show any difference between normal and uremic subjects, but there was a significant increase of peptides in uremic serum. The accumulation of peptides was confirmed by high voltage electrophoresis. Urinary excretion of substances with comparable molecular weights to those found in uremic serum was demonstrated, but there was no significant difference between urine from normal and from uremic subjects. A steady state of chronic uremia with high urinary volume is therefore consistent with a normal urinary excretion of middle molecules with increased concentrations in serum and glomerular filtrate. Tubular reabsorption may also be decreased because the urinary excretion of middle molecules increases with the development of tubular proteinuria in patients with pyelonephritis. Dialysis treatment removes moderate amounts of middle molecules; their serum concentration decreases slightly after dialysis and they are detectable in dialysis fluid. The identification, metabolism and biological effects of middle molecules are discussed in relationship to uremic toxicity and the effects of different forms of dialysis treatment.

Mesangioproliferative glomerulonephritis.

UNLABELLED: The clinical and bioptic aspects of 211 cases of primary mesangioproliferative glomerulonephritis with urinary abnormalities lasting mre than 1 year were reviewed. We observed the following clinical syndromes: 1) Persistent proteinuria, isolated or with microhematuria: - a) with latent onset: 39% with hypertension (H); 10% with renal failure (RF); - b) with acute nephritic syndrome at onset: 31% with H; 6% with RF; 2) Recurrent macroscopic hematuria: 26% with H; 10% with RF; 3) Nephrotic syndrome: 70% with H; 29% with RF. The histological lesions, diffuse in all cases, appeared unrelated to the clinical syndromes and/or immunofluorescent patterns. In 65 cases with prevalent mesangial deposits of IgA, 46% showed persistent proteinuria with latent onset, 23% persistent proteinuria with acute nephritic syndrome at onset, 28% recurrent hematuria and 3% nephrotic syndrome. 37% of such patients developed H, 14% RF and 6% remission (R). On the other hand in 65 patients with other deposits the clinical aspects were as follows: persistent proteinuria with latent onset: 46%; persistent proteinuria with acute nephritic syndrome at onset: 31%; recurrent hematuria: 17%; nephrotic syndrome: 6%. 35% of these cases displayed H; 9% RF and 8% R. CONCLUSION: primary mesangioproliferative glomerulonephritis appears to represent a heterogeneous group with only the morphological aspects in common and associated with one of the three above-mentioned clinical syndromes. Immunohistology shows different Ig and/or complement which bear no specific relationship with clinical courses. In particular IgA deposits are present in 50% of the cases and are only related to higher incidence of recurrent hematuria and abnormal IgA serum levels.

The kinetics of aminosidine in renal patients with different degrees of renal failure.

The plasma concentration and urinary excretion after a single 500 mg dose of Aminosidine have been studied in 12 patients with different degrees of renal failure and 4 normal subjects. In normal subjects the plasma half-life is 2.47 hr; in patients with creatinine clearance (Ccr) of 30-60 ml/min, its 6.7 hrs.; in patients with Ccr of 10-30 ml/min, it is 16.7hrs.; in patients with Ccr less than 10 ml/min, it is 36.6 hrs. A dose of 0.5 g of Aminosidine should be given to normal subjects every 12 hr. When renal function is reduced, the interval (in hr) between doses should be the following: Ccr 60-40 ml/min: 19-28;Ccr 40-30 ml/min; 28-35; Ccr 30-20 ml/min: 35-47; Ccr 20-10 ml/min: 47; Ccr less than 10 ml/min: 76.

[Fabry's disease and familial lymphedema. Description of 2 cases]. / Malattia di Fabry e linfedema familiare. Descrizione di due casi.

Two cases of Fabry's disease (FD) with lymphedema of the lower limbs are reported. On the basis of lymphographic investigations showing lymphatic aplasia, the hypothesis of an inborn error in the development of the lymphatic system of the lower limbs--Familial Lymphedema--controlled by a gene associated with FD gene on the same chromosome, is suggested.