Renal Clearances of Grass Polysaccharide: Observations on Glomerular Porosity and on the Relation of This Function to Proteinuria in Renal Disease

Abstract

bridge, drew our attention in 1948 to a fructosan polysaccharide (levan) prepared from Italian rye grass. It is readily soluble in cold water, yields levulose on acid hydrolysis and is not metabolized. At that time, the fructosan was believed to be a homogeneous substance with a molecular weight somewhat greater than that of inulin, so that the suggestion was made that it might replace inulin in the measurement of glomerular filtration rate. It has since (see below) been shown to be inhomogeneous. Samples of blood and urine were collected at intervals, at first of five and 10 minutes and then at longer intervals over four to six hours. Plasma concentrations were calculated by interpolation to the mid point of each period of urine collection from a semilogarithmic graph of the determined concentrations, and these estimates were used in the calculation of plasma clearances.(b) Continuous infusion method: A small plastic catheter was placed in the femoral vein and 30 ml. of priming solution, containing usually 1 gm. each of polysaccharide and creatinine and 4 gm. of mannitol, were injected rapidly. This was followed by a sustaining solution containing saline and given at a rate of about 1 ml. per minute. The bladder was rinsed with saline 15 minutes after completion of the priming injection; this was noted as zero time. Urine samples were collected at intervals of 10 to 15 minutes and combined with the saline bladder rinses (30-50 ml.). Samples of venous blood were collected near the mid points of each urine collection. This routine was varied in detail (concentration of polysaccharide, rate of infusion and intervals of collection) in some experiments. Clearance techniques in human subjectsThe methods, except for addition of polysaccharide to the priming and sustaining media in amounts of 3 and 5 gm., respectively, are those described elsewhere (4) for the determination of plasma clearances of mannitol (Cm) and p-aminohippurate (CPAR). Some of the observations in patients include only the three periods of urine collection used in the measurement of PAH clearance at low plasma levels. PAH was omitted from most of the infusions used in normal subjects.

Normal Glomerular Permeability and Its Modification by Minimal Change Nephrotic Syndrome

“…The clearance of the polysaccharide fructosan (approximate mol wt 8,000) equals that of inulin in normal man, but averages only 60% of GFR in patients with glomerular disease, and similar observations have been made for a second larger polysaccharide (40). In addition, the ratios of hemoglobin (mol wt 68,000) to inulin clearances are reduced below normal in proteinuric patients with the nephrotic syndrome (41).…”

“…In contrast, the GBM itself appears to completely separate plasma from the glomerular filtrate. Traditionally this structure has been considered to behave as a semipermeable membrane containing cylindrical pores of [35][36][37][38][39][40][41][42] A radius or rectilinear slits of half-width 36 A (5). However, if the membrane does contain functional pores, it may be more heteroporous than originally suggested (6), and although these experiments suggest that the basement membrane contains pores, such pores have never been demonstrated.…”

Experiments Concerning the Renal Clearances of Some Fructosans in the Dog

“…These results have been confirmed and extended in a later paper [Beattie and Corcoran, 1952] [1925] from iris rhizomes grown in Essex, England.B. The two bacterial levans were isolated from the growth media of the appropriate micro-organisms.…”

“…and details of two of these are given in Table I Irisin Partition Experiments. Beattie and Corcoran [1952] suggested that irisin may consist of two or more components with differing rates of clearance. To obtain further information, the fructosan excreted during the first hour after injection was recovered and injected into a second animal.…”

“…This was done by the method described by Beattie and Corcoran [1952]. It does not differentiate between free and combined fructose (polysaccharide).…”