Selectivity of Protein Excretion in Patients with the Nephrotic Syndrome.

It is generally accepted that proteinuria results from increased permeability. Although no recognizable structural abnormality has been defined to indicate a pathway of protein excretion, the permeability of the glomerular membrane, under conditions of moderate and heavy proteinuria, has been interpreted in terms of distribution of "pore size" (1-3). This concept suggests the presence of "defects" or "pores" in the glomerular membrane of such dimensions that permit the passage of these proteins into the glomerular filtrate. Factors other than size and shape that may also influence the rate of diffusion of a molecule through a membrane (4) are considered negligible. Although indirectly applicable to proteins, clearance studies in animals utilizing dextrans of varying molecular weight (5, 6) have demonstrated the distribution of "pore size" in the normal glo-merulus within a range of molecular weights from 5,000 to 85,000. In addition, these studies confirm the relationship between clearance of a molecule and its molecular weight. The relationship of relative renal clearances of individual protein fractions to their corresponding molecular weight, serving as an index of glomeru-lar permeability, has been previously applied in the clinical investigation of patients with the nephrotic syndrome (7). In this investigation * this relationship has been expressed graphically as a straight line whose slope characterizes the degree of selective excretion of large or small protein molecules (Figure .1). A steep slope denotes selective filtration of small molecules, and thus suggests that the size of the glomerular "defect" is correspondingly small. Selectivity patterns of protein excretion were determined and then compared with response to steroid therapy and renal pathology in individual patients. In addition, the patterns were correlated with blood urea nitrogen, inulin and para-aminohippuric acid clearances, total 24-hour uri-nary protein, and duration of disease. The results show that those patients with the nephrotic syndrome secondary to intrinsic renal disease (primary renal disease group), demonstrating a high degree of selective protein excretion before treatment, appear to respond best to steroid therapy , irrespective of the histologic findings. Furthermore , the selectivity pattern remained fairly constant for a given patient even though the total daily urinary protein excretion was fluctuating. Although no characteristic selectivity pattern was found for any given pathologic group, those patients with more advanced histologic changes in the glomeruli appeared to have the least selective type of proteinuria. Methods Studies were carried out in 48 patients (23 males, 25 females). Forty-five satisfied Berman and Schreiner's criteria …