Increase In Protein Excretion Research Articles

Effects of caloric intake and dietary composition on the development of proteinuria, age-associated renal disease and longevity in the male rat.

The development of age-associated proteinuria and renal disease was studied in groups of male Wistar rats fed 12.5, 25, 50 and 75 kcal of food/day, respectively, and in calorie-restricted (40 kcal/day) rats receiving diets rich in fat, protein or carbohydrate. Proteinuria developed faster, kidneys were larger and the incidence of glomerular lesions and proteinaceous casts was greater in rats eating high calorie diets of 50 kcal/day or more. High protein diets, even when calorie-restricted, increased protein excretion and the incidence of glomerular lesions. In old rats acute food restriction (25 kcal/day) decreased protein excretion by 40% in 1 week, with no further reduction in the 2 week. Life duration was greatest in rats fed 50 kcal/day.

Morphological alterations of cell wall concomitant with protein release in a protein-producing bacterium, Bacillus brevis 47.

Bacillus brevis 47 secreted vast amounts of protein into the medium and had a characteristic three-layered cell wall. The three layers are designated, from the outermost to the innermost layer, as the outer wall (4.2 nm), the middle wall(8.5 nm), and the inner wall (2.1-3.7 nm). The inner wall might be a peptidoglycan layer. The fine cell wall structure was morphologically altered to various extents, depending on the growth period. At the early stationary phase of growth, cells began to shed the outer two layers of a limited area of the surface. This shedding was complete after further cell growth. The morphological alterations in the cell wall occurred concomitantly with a prominent increase in protein excretion. When protein secretion was severely inhibited by growing cells with Mg2+, morphological alterations in the cell wall were not observed, even at the late stationary phase of growth. This was also the case with a nonprotein-producing mutant, strain 47-5-25. When cells were incubated in buffers, the outer two layers of the cell wall were specifically removed, leaving cells surrounded only by the inner wall layer. The layers removed by incubation were recovered by high-speed centrifugation. This fraction consisted of two layers resembling the outer and middle wall layers. Protein secreted by B. brevis 47-5 consisted mainly of two proteins with approximate molecular weights of 150,000 and 130,000. Proteins released by incubating cells in buffers and proteins in the outer- and middle-wall-enriched fraction were also composed mainly of two proteins with the same molecular weights as those secreted into the medium. Therefore, we conclude that B. brevis 47 secretes proteins derived from the outer two layers of cell wall and these components are synthesized even after the shedding of the outer two layers.

Concentration of β-thromboglobulin in urine in late pregnancy

SummaryConcentrations of the platelet-specific protein β-thromboglobulin were measured in the urine of women in the third trimester of pregnancy. Urinary levels of β-thromboglobulin were greater than the 95 per cent confidence limit of the normal pregnant group in 7 out of 16 patients with moderate or severe pre-eclampsia, and this elevation could not be fully explained by an overall increase in protein excretion. One out of 15 patients with mild pre-eclampsia also had elevated urinary β-thromboglobulin levels. Levels of β-thromboglobulin were also elevated in 11 out of 88 pregnant women without hypertension or proteinuria. Eight of these 11 patients had some complication of pregnancy, namely infarcted placenta (3), intra-uterine growth retardation (2), placenta praevia (1), premature rupture of membranes (1) and ante-partum haemorrhage (1). Two individuals with normal urinary β-thromboglobulin levels developed antepartum haemorrhage

Diagnostic value of a test-strip in detecting increased urinary excretion of albumin, IgG and β2-microglobulin in patients with suspected proteinuria

Hemmingsen, L. & Skaarup, P. Diagnostic value of a test-strip in detecting increased urinary excretion of albumin, IgG and β2-microglobulin in patients with suspected proteinuria. Scand. J. clin. Lab. Invest. 41, 785—789, 1981.Test-strip screening for increased urinary protein excretion was performed in 482 patients with suspected proteinuria. The test-strip readings were compared with the urinary concentration and 24-h excretion of albumin, IgG and β2-micro-globulin (β2m), determined by an immunoprecipitin reaction, using the upper limit of the reference interval for these proteins for descriminating between normal and increased protein excretion. Increased concentration and 24-h excretion of albumin and IgG showed about 25 and 40 % false negative text-strip reactions, respectively, whereas only few false positive reactions were observed. Thus the predictive value of a negative test was low and that of a positive test high. The overall predictive value in detecting increased urinary excretion of β2m was ...

Renal tubular interactions of proteins

One of the functions of the kidney is to reclaim amino acids from filtered proteins, but under certain pathologic conditions the kidney can be affected by these filtered proteins. Low molecular weight proteins and larger polypeptides are filtered into Bowman's space and reabsorbed by the tubules, hydrolyzed by the lysosomes to amino acids, and these amino acids are reused in other proteins. This reclamation process is accelerated when the tubules are presented with large amounts of protein, such as in the nephrotic syndrome, and the kidney takes up a lesser percentage of the protein as the filtered load increases. The fraction escaping reabsorption appears in final urine, and observations of increased protein excretion are termed “proteinuria”. Recently, it has become clear that the filtration of proteins such as Bence-Jones or myoglobin, which occurs in pathologic conditions such as myeloma or crush injury, can result in the interaction of these molecules with tubular structures. This interaction can drastically alter the normal physiology of tubular cells and possibly cause acute renal failure. Our current explanation for the nephrotoxic effect of these proteins involves a change in the ionic form of proteins with isoelectric points (near pH 7) as they pass along the nephron. This change in form is related to the pH gradient along the tubule. The more acidic the tubular fluid, the more cationic the filtered protein. Proof of this hypothesis has been partially derived from experiments in which human Bence-Jones proteins were infused into rats. Those proteins with a lower isoelectric point (more polyanionic) caused less change in renal function than did those with higher isoelectric points (more polycationic). These last observations can be translated into patient prognosis. Those patients producing Bence-Jones of higher isoelectric point probably have a greater risk of renal failure than those who produce one of a more polyanionic nature. In addition, it can be speculated that treatment of a hemolytic transfusion reaction with mannitol and alkalinization of the patient prevents renal failure by dilution of the pathologic protein and also by changing its polyionic character.

Proteinuria During Long-term Captopril Therapy

Proteinuria developed in six of 81 hypertensive patients given captopril for at least four months (protein excretion, greater than 200 mg/24 hr). Two had previously elevated protein excretion. In all patients the increased protein excretion occurred by the fourth month of treatment. It subsided in four after two to nine months, despite continued therapy. In two of the four, proteinuria cleared completely within seven months after onset, while in the other two it subsided to the range of 600 mg/24 hr. However, in the remaining two patients proteinuria persisted during captopril therapy and was associated with hypoalbuminemia and hypercholesterolemia. Renal biopsy specimens showed mild membranous nephropathy in two patients, one of whom had a remittance of proteinuria during continued captopril treatment.

Increased urinary protein excretion after intravenous injection of furosemide in man.

The furosemide-induced increase in protein excretion, and its relations to 1) the size of protein molecules as reflected by three enzymes, and 2) glomerular filtration rate (GFR), plasma renin activity (PRA) and prostaglandin (PG) E2 and F2 alpha excretions were studied in 14 outpatients with normal renal function and 13 healthy males. Furosemide (120 mg) was given intravenously, and thereafter the protein excretion and the above parameters were monitored for 1--2 hours. In both groups, furosemide caused a transient increase in protein excretion. The excretion of the largest molecule, beta-glucuronidase, rose to 6.3-fold, while those of N-acetyl-beta-D-glucosaminidase and of the smallest molecule, alpha-amylase, increased by 91 and 37%, respectively. GFR increased, too, but markedly less than the protein excretion. PGE2 and PGF2 alpha excretions increased more than GFR and changed simultaneously with the excretion of proteins. Furosemide also caused a marked increase in PRA. This lasted, however, much longer than the rise in PG and protein excretion or GFR. The results suggest that the furosemide-induced increase in protein excretion is 1) related to the molecular size of proteins, 2) partly due to the rise in GFR, 3) simultaneous with the change in PG excretion. Our findings also agree with the view that furosemide causes changes in glomerular permeability.

The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney

A single intraperitoneal injection of hexochloro-1 : 3-butadiene (HCBD) at 100 mg/kg or above produced renal tubular necrosis in the rat by 24 h. Histological examination of the kidneys indicated damage to the straight portion of the proximal tubules. Urinary analysis showed diuresis, increased proteinuria and an increase in the excretion of N-acetyl-beta-D-glucosaminidase, and alkaline phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only a mild increase in protein excretion was observed. Twenty-four hours after 200 mg/kg HCBD, i.p., there was a marked decrease in the glomerular filtration rate (inulin clearance) and in the clearance of the organic anion (p-aminohippuric acid, PAH) and the organic cation (tetraethylammonium bromide, TEA) by the kidney. HCBD did not affect the accumulation of PAH or TEA by renal cortical slices when added in vitro at a concentration up to 0.1 mM. However, a decrease in PAH, but not TEA accumulation, was seen in renal cortical slices from rats treated with HCBD 24 h previously. Mercuric chloride (HgCl2), a known nephrotoxin, was used as a positive control for these studies. HCBD appears to specifically damage the straight portion of the proximal renal tubule and thereby selectively damage the organic anion transport system.

MECHANISMS OF ACIDOSIS-INDUCED PROTEINURIA

For more than 50 years it has been noted that systemic acidosis induces proteinuria. Proteinuria was found to increase with increasing acidosis (Gardner, JCI, 1961, 40:525) and was attributed to an increase in filtered load. The present study was designed to delineate the mechanisms for this increase. Acute (<6 hr) and chronic (10-20 d) acidosis was produced in rats by oral feeding of NH4Cl. Acute and chronic acidosis was associated with an increase in protein excretion (41.2±15.8 vs 22.0±5.1 (SD) μgm/min p<.02). This was predominantly due to an increase in albuminuria (12.90±8.50 vs 3.26±1.63 μgm/min p<.02), so that in acidosis albumin represented a greater proportion of total urine protein. Non-albumin proteinuria increased to a lesser extent. Acidosis was not associated with any significant change in GFR (2.29±0.52 vs 2.66±0.63 ml/min). filtration fraction (32.8±10.2 vs 36.0±9.14%), or total serum protein (6.73±0.74 vs 6.73±0.18 gm/dl). Glomerular polyanion as determined by staining with both colloidal iron and alcian blue was not altered in acute acidosis but appeared to decrease with chronic acidosis. Glomerular permeability to inert polydisperse polyvinyl pyrrolidone (mol.size 20-45 8)was increased significantly in acidotic rats.We postulate that the proteinuria of acidosis results from the documented alteration in glomerular permeability. The conformational changes in protein molecules associated with pH changes may also contribute. Both of these mechanisms would increase the filtered protein load resulting in proteinuria.

Urinary Excretion of Ten Plasma Proteins in Patients with Renal Carcinoma

Urinary and serum proteins were studied preoperatively in 48 patients with renal carcinoma, using an automated immunoprecipitin reaction. The 24 h excretion and the renal clearance of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the 24 h excretion of the immunoglobulin lambda and kappa free light chains and beta2-microglobulin were significantly increased compared with a control group. The excretion of lysozyme was also increased, but not significantly. Increased protein excretion was the most common urinary finding in patients with renal carcinoma. The protein excretion was predominantly of the glomerular type, implying a glomerular injury. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with stage III and IV tumours compared with patients with stage I and II tumours. Abnormal serum concentrations of albumin, transferrin, and haptoglobin were indicative for advanced renal carcinoma.

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Functional and morphological study on the onset of proteinuria in experimental diabetes mellitus.

In latent hereditary diabetes mellitus increased protein excretion has been found in male diabetic mice compared to controls. This proteinuria is partly due to an increased excretion of higher molecular weight proteins, which could be identified as deriving from plasma. The suggested glomerular proteinuria has been verified by an increase in the renal excretion of high molecular weight PVP. No changes in GFR occurred in this early stage of diabetic glomerulopathy. No changes in morphology could be detected, suggesting some changes in the biochemical membrane structure that cause the findings of increased permeability of the diabetic basement membrane for plasma proteins.

Observations on the kidneys and urine of the wild Norway rat, Rattus norvegicus.

The kidneys of 39 wild Norway rats ( Rattus noryegicus), 9 months or older, were examined for evidence of chronic progressive nephrosis, which commonly affects year-old albino rats. An infectious process resembling pyelonephritis was found in two rats. Protein absorption droplets, intranuclear inclusion bodies resembling those of lead intoxication, and large ‘aberrant’ nuclei were seen in the epithelial cells of the proximal convolutions. The nematode, Trichosomoides crassicauda, was found in the renal pelvis of approximately one fourth of the rats. Basement membranes of the glomerular tufts, Bowman's capsule and proximal tubule were examined in four rats by electron microscopy. The mean thickness of basement membranes of peripheral glomerular loops was 0.28 ± 0.09 μm, which is comparable to that of young healthy Sprague-Dawley rats. The protein content in 65 determinations of 24-hour serial collections of urine ranged from less than 1 to 3.9 mg/ml. No tendency was observed toward increased protein excretion or progressive deterioration of the kidneys, such as occurs in older Sprague-Dawley rats.

Proteinuria in non-renal infectious diseases.

Abstract. The urinary excretion of total protein, orosomucoid, albumin, transferrin, and IgG, has been determined in 19 children and 23 adults with various nonrenal infectious diseases. Furthermore urine muramidase was estimated in 39 of these patients (16 children, 23 adults). An often considerably increased urinary protein excretion (“febrile proteinuria”) was found in 74% of the children, with a maximal output of 2283 mg/24 h, and in 83% of the adults, maximal output 3350 mg/24 h. In all cases an increased excretion of orosomucoid was found, but in many cases the excretion of the other proteins determined was increased as well, which excludes a prerenal mechanism as the only factor responsible for the increased protein excretion. The hypothesis is put forward that infections result in an immunological injury of the glomerular and/or tubular basement membrane, which might be of pathogenetic importance in the development of renal diseases.

The resolution of urinary or serum proteins by chromatography on DEAE cellulose columns with particular reference to urinary proteins after thermal burns.

Serum proteins were separated into the usual electrophoretic fractions by the starch block technique. Each fraction was then examined by DEAE cellulose chromatography and by starch gel electrophoresis. The combination of starch block electrophoresis and DEAE cellulose chromatography was able to distinguish 22 different serum proteins.The application of DEAE cellulose to the chromatographic resolution of urinary proteins is described. The urine was filtered and the protein was concentrated by ultrafiltration. After dialysis, a suitable aliquot was adsorbed on a DEAE cellulose column and eluted by buffers with a progressively increasing hydrogen ion concentration and ionic strength. Some illustrative chromatographs are given.A number of urines from patients with severe burns were examined by this procedure. The increase in protein excretion was found in all sections of the chromatographs with particular increases in the γ globulin and acid mucoprotein zones.

Nature of proteinuria induced by uranium in rats.

Following administration of uranium parenterally into rats in an acute dose, the increase in protein excretion consisted not only of an increase in the normally occurring albumin but to a greater extent an increase in the various globulins. At the height of proteinuria, the electrophoretic pattern of the excreted proteins strongly resembled the pattern of the serum proteins. The appearance of these serum-like urinary proteins suggests a defect in the glomerulus filtration apparatus and provides further evidence that the glomerulus, as well as the tubule, is altered by uranium administration.

Effect of hypothermia on tubular transport mechanisms.

Five mongrel dogs were cooled artificially to 20°C and then rewarmed to 37°C, while changes in the concentration of glucose, phosphorus, amino acid nitrogen, protein and creatinine in both plasma and urine as well as changes in urine flow were studied periodically. A decrease in serum amino acid nitrogen concentration occurred with cooling. The reverse was seen upon rewarming. Serum creatinine and protein levels were essentially unchanged. Urine flow increased with cooling and the U/P ratios of phosphorus, amino acid nitrogen and creatinine decreased. There was minimal increase in protein excretion while all of the filtered glucose appeared in the urine. The changes in urinary composition indicate that two transport mechanisms are involved in the reabsorption of amino acids and phosphorus from glomerular filtrate. Only one of these is affected by cooling. The mechanism responsible for glucose reabsorption is paralyzed by cold, while the effect of cold on protein reabsorption could not be quantitated by these studies.

Renin protein uria in the rat; evidence that renin does not interfere with the tubular resorption of purified human hemoglobin or bovine albumin.

The intraperitoneal injection of renin together with purified human hemoglobin or bovine albumin increases the weight of the kidneys and increases the number of athrocytosed particles of protein in the cells of the proximal convoluted tubules. In the case of bovine albumin administration there is a threefold increase in protein excretion in those rats given renin as compared with those given bovine albumin alone. A possible explanation of these effects is given.