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Title: Glomerular selective permeability to protein, dextran, and polyvinylpyrrolidone in health and disease
Author: Petrie, J. J. B.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1971
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This thesis presents the results of six year's work on macromolecular clearance determinations. This work is placed in context by an introductory review of literature relating to the physiology of protein excretion. Early concepts of the mechanisms involved in proteinuria are discussed. Among the studies reviewed are observations on micropuncture of the glomeruli and proximal tubules, clearance experiments, stop-flow analyses, histochemicai findings, and electron microscopy studies, It is concluded from this review of the literature that some protein is filtered at the glomeruli, but that in health virtually all of this is reabsorbed by a process which, for albumin and molecules larger than albumin, is non-selective, Reasons are given for the opinion that tubular secretion of protein is unimportant. The immunodiffusion method used in protein clearance studies is then described, along with the gel filtration technique used to determine protein, dextran, and polyvinylpyrrolidone clearances. The errors involved in these techniques are discussed. Results are presented for protein clearance studies carried out in parallel by the two techniques. From an analysis of these results it is concluded that in patients excreting over 1.OG of protein daily, -K (the index of protein selectivity by the immuno-diffusion technique) is related to Δ (the index of selectivity by the gel filtration technique) by the formula Δ = 0.73 (-K). Dextran and protein selectivity values are compared in normal subjects, in proteinuria induced by plasma infusion, and in a variety of disease states. In minimal lesion glomerulonephritis, membranous glomerulonephritis and in induced proteinuria, dextran and protein selectivity values are in substantial agreement. In normal subjects under normal conditions, in proliferative glomerulonephritis, in postural proteinuria, and in acute ischaemic renal failure, dextran selectivity values are consistently and considerably higher than protein selectivity values. These findings are explained in terms of differences in the renal handling of protein and dextran and in terras of differences in the mechanisms involved in proteinuria in the various conditions described. From the experiments on induced proteinuria it is concluded that the filtration of protein at the normal glomerulus, like that of dextran, is highly selective. The results of protein selectivity determinations in 207 patients with major proteinuria are presented and related to the histological diagnoses. Selectivity values in minimal lesion glomerulonephritis are consistently high, while in patients with renal failure proteinuria is uniformly unselective. The relationship between protein selectivity and prognosis is assessed in 197 patients. A very high selectivity (-K over 2.6) is associated with a very good prognosis (3 year survival with functioning kidneys of 96%). A very low selectivity (-K less than 1.4) is associated with a poor prognosis (3 year survival of 27%). The relationship between selectivity and responsiveness to steroid therapy is assessed in 82 treated patients. In our experience, a selectivity value of 2.0 or less is consistently associated with unresponsiveness to steroid therapy• While prompt abolition of proteinuria following steroid therapy is to be expected only in patients with minimal lesion glomerulonephritis, comparison of the outcome at 8 weeks in 30 treated proliferatives with findings at 8 weeks in 26 untreated controls with similar histology shows a significant reduction in proteinuria in response to steroids in patients with proliferative histology and selective proteinuria.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available