Among the several theories on the pathophysiology of progressive nephropathies [1—41, the most convincing one [1, 2] suggests that the initial reduction in nephron number progressively dam-ages the remaining ones, which suffer the consequences of adaptive increases in glomerular pressure and flow. Glomerular capil-lary hypertension is normally accompanied by enhanced transglomerular protein traffic [5—7] and both are prevented in experimental animals by a low protein diet or antihypertensive drugs [6—10]. In the past the amount of protein found in the urine, taken as an indicator of the underlying abnormality in glomerular permeability, was considered by most nephrologists simply as a marker of the severity of renal lesions. Today the results of many studies [4, 11—14] indicate that proteins filtered through the glomerular capillary may have intrinsic renal toxicity, which together with other independent risk factors such as hypertension, can play a contributory role in the progression of renal damage [reviewed in 15]. More proteins filtered through the capillary barrier means—within certain limits—more proteins excreted in the urine. If one believes in the intrinsic toxicity of filtered proteins, urinary protein factored for creatinine excretion rate can become a practical way of monitoring an individual patient's tendency to progress. Treatments which simultaneously reduce urinary pro-teins and the filtration fraction [16] are likely to have a beneficial impact on the decline of the glomerular filtration rate (GFR) and can be used to identify subcategories of patients with proteinuric renal diseases whose tendency to progress can be limited by therapeutic intervention.

According to the most widely used models of glomerular size selectivity, the glomerular capillary can be considered as being perforated by hypothetical cylindrical pores with different radii [17, 18]. Different pore-size distribution probabilities have been proposed so far as those that best replicate the curves of tracer molecules used to predict the sieving coefficient of the membrane in human glomerular diseases.