The Mechanism and Significance of Protein Excretion by the Normal Kidney

Sellers, Alvin L.

doi:10.1001/archinte.1956.00250300119013

Cited by 37 publications

(12 citation statements)

References 18 publications

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“…In these experiments the adult male rat was selected to represent the mammalian order, since rat urine is known to contain significant amounts of protein under normal conditions (5). In addition, the use of a laboratory animal afforded ready access to renal tissue in which the formation of "protein absorption droplets" (6) within the cells of the proximal convoluted tubules could be studied histologically.…”

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confidence: 99%

THE EFFECT OF pH ON THE FILTRATION, REABSORPTION, AND EXCRETION OF PROTEIN BY THE RAT KIDNEY*

Gardner¹

1961

J. Clin. Invest.

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In a paper discussing the protein content and acidity of human urine, von Hoesslin in 1909 suggested that a direct relationship existed between the hydrogen ion content and the protein content of human urine (1). Since then clinicians occasionally have commented on this relationship, some to confirm its existence (2, 3) and at least one to deny it (4). These comments usually have been based on the observation of patients thought to have proteinuria of the "benign" or "physiological" variety-e.g., orthostatic albuminuria. The present investigation was undertaken when a review of the pertinent publications since 1909 failed to reveal any formal laboratory study of the effect of pH on protein metabolism in the kidney. The study was designed to provide at least partial answers to two major questions. First, in mammals, do changes in the rate of urinary protein excretion accompany variations in the systemic and urinary hydrogen ion concentrations? Second, if such changes do occur, are they the result of changes in the filtration and/or reabsorption of protein within the kidney?In these experiments the adult male rat was selected to represent the mammalian order, since rat urine is known to contain significant amounts of protein under normal conditions (5). In addition, the use of a laboratory animal afforded ready access to renal tissue in which the formation of "protein absorption droplets" (6) within the cells of the proximal convoluted tubules could be studied histologically.The results of this investigation show that significant changes in urinary protein excretion accompany systemic acid-base disturbances in the male rat and suggest that this phenomenon is the * Supported by a grant from the Heart Association of Southeastern Pennsylvania. Portions of this work have appeared in abstract form (Clin. Res. 1960, 8, 228 MATERIALS AND METHODSGeneral experimental conditions. Male Wistar rats weighing 185 to 213 g were housed in individual metabolic cages. They were fed Purina Dog Chow pellets for at least 24 hours preceding each experimental period. During urine collection periods solid food was withdrawn to minimize contamination of the urine by food particles, and the animals were given a solution of 15 per cent glucose in distilled water, thus insuring adequate volumes (7) of relatively clean urine. The urines were collected from screened funnels beneath each cage over periods of time ranging from 8 to 24 hours. Toluene and mineral oil were not routinely used in the collection containers, since preliminary observations indicated that only minimal urinary pH changes took place in the absence of these preservatives. These urines provided a control baseline against which the urines from subsequent experiments were compared. Variations in the systemic and urinary pH's of these and additional animals were produced by the addition of 1 per cent NH4C1, 5 per cent NaHCO, 0.5 per cent (NHj)2C0,, or 0.04 per cent acetazolamide (Diamox 1) to the 155 per cent glucose in their drinking water. While the animals drank their assig...

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confidence: 99%

THE EFFECT OF pH ON THE FILTRATION, REABSORPTION, AND EXCRETION OF PROTEIN BY THE RAT KIDNEY*

Gardner¹

1961

J. Clin. Invest.

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“…Thus, whereas albumin is the major protein component of serum, the globulin fractions predominate in urine (1,3). The presence in urine of y-globulin at a relative concentration equal to and frequently greater than that in serum cannot be explained by current concepts concerning the origin of urinary proteins by a process of glomerular filtration of serum proteins (6,7) followed by a nonselective tubular reabsorption (8). Such a mechanism would lead to a preferential excretion in the urine of proteins of low molecular weight and would result in an increase in their concentration relative to that of the larger proteins.…”

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Physicochemical and Immunologic Studies of Gamma Globulins of Normal Human Urine*

Franklin

1959

J. Clin. Invest.

101

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Normal human urine has been shown to contain up to 150 mg. of protein in a 24 hour aliquot. Electrophoretic analyses of these proteins by a number of observers (1-3) have demonstrated the presence of components corresponding to each of the five major fractions present in serum. In general, however, the resolution of these peaks has been poor, and significant amounts of protein migrating more rapidly than albumin have been demonstrated. Immunoelectrophoretic studies of normal human urine by Grant (4) and Patte, Baldassaire and Loret (5) have revealed the presence of at least eight components which reacted with an antiserum to normal human serum and frequently gave reactions of identity with the corresponding proteins present in serum. Among the proteins identified by these observers were albumin, four a-globulins, two A-globulins and y-globulin (4).In spite of the qualitative similarities of the serum and urine proteins, quantitative differences in the relative amounts of the major fractions have been demonstrated. Thus, whereas albumin is the major protein component of serum, the globulin fractions predominate in urine (1, 3). The presence in urine of y-globulin at a relative concentration equal to and frequently greater than that in serum cannot be explained by current concepts concerning the origin of urinary proteins by a process of glomerular filtration of serum proteins (6, 7) followed by a nonselective tubular reabsorption (8). Such a mechanism would lead to a preferential excretion in the urine of proteins of low molecular weight and would result in an increase in their concentration relative to that of the larger proteins. Since the molecular weight of the major fraction of y-globulin in serum is approximately two and one-half times that of albumin, the presence in urine of relatively greater amounts of protein with the mobility of y-globulin suggested the existence of additional protein species which have not been detected in serum. The present study presents evidence for the existence in normal urine of proteins with a mobility similar to y-globulin and an approximate molecular weight of 35,000, and which are antigenically closely related to the y-globulin fraction of serum. While this work was in progress, low molecular weight y-globulin fractions have also been demonstrated in normal human urine by Webb, Rose and Sehon (9). MATERIAL AND METHODSTwenty-four hour urines were collected from 12 normal males and stored in the cold at 4°C. Following filtration to remove formed elements and insoluble precipitates, the urines were dialyzed against running tap water for 24 hours in the cold and concentrated to a volume of 10 to 15 ml. by pervaporation at 0 to 40 C. In a number of instances protein was precipitated by the addition of 650 Gm. ammonium sulfate to each liter of urine. Following centrifugation at 3,000 rpm for one hour, the precipitate was dialyzed against running tap water to remove the salt, and the protein solution was concentrated as above. Both methods yielded similar results. For large scale ...

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“…In general, proteins with a molecular weight lower than 70 000 are able to pass the glomerular membrane, while those with a higher molecular weight are not [18], the permea bility however being modified by shape and electrical charge of the molecule [19]. Some investigators consider the treatment in the kidneys to be merely a glomerular filtration without tubular ex cretion or reabsorption [20] while others believe that there is reab sorption of some of the protein which has passed the glomerular membrane [21]. We are not able to decide which theory is valid for the urinary TI, but we find a good explanation of our results in the assumption that the increased amount of urinary TI during the period of stress is excreted by a passive mechanism involving only glomerular filtration since the curves in Figure 4 and 5 are roughly straight up to high increases in serum concentration.…”

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confidence: 99%

Relationship between Serum Concentration and Urinary Output of Trypsin Inhibitor (Hyaluronidase Inhibitor) During Operative Stress

Faarvang¹,

Lauritsen²

1961

Enzymol Biol Clin

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The serum concentration and urinary output of trypsin inhibitor was followed in a period before and after operative stress in ten persons. In all subjects the values increased in the postoperative period. No correlation was recorded between the preoperative serum concentrations and urinary trypsin inhibitor outputs, but a highly significant, positive correlation was found between the postoperative increases in serum and urine, demonstrating that the urinary trypsin inhibitor originates from the blood. It is proposed that the urinary trypsin inhibitor is identical with a serum inhibitor which only constitutes a small part of the total trypsin inhibiting activity in serum in the normal state, but whose concentration is markedly increased during stress. The observations could be explained by a passive excretion of the substance in the kidneys, i.e. a glomerular filtration without tubular secretion or reabsorption. The clearance of the compound is estimated to be 0.08 ml per minute (average, for ten persons) but with large individual variations (from 0.02 to 0.12 ml/min) suggesting individual variation in the glomerular permeability to the substance.

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The Mechanism and Significance of Protein Excretion by the Normal Kidney

Cited by 37 publications

References 18 publications

THE EFFECT OF pH ON THE FILTRATION, REABSORPTION, AND EXCRETION OF PROTEIN BY THE RAT KIDNEY*

THE EFFECT OF pH ON THE FILTRATION, REABSORPTION, AND EXCRETION OF PROTEIN BY THE RAT KIDNEY*

Physicochemical and Immunologic Studies of Gamma Globulins of Normal Human Urine*

Relationship between Serum Concentration and Urinary Output of Trypsin Inhibitor (Hyaluronidase Inhibitor) During Operative Stress

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