Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive proteinuria has been suggested not just to reflect but also to contribute to the development of focal glomerular sclerosis. Development of proteinuria and glomerular lesions was examined up to 18 weeks after 3/4 nephrectomy in Sprague-Dawley (SDR) rats and an analbuminemic SDR variant (NAR). Nephrectomy led to a significantly lesser degree of proteinuria in NAR (42 +/- 14 SD mg/day) than in SDR (140 +/- 54 mg/day), consistent with the fact that 50-60% of urinary protein in SDR after nephrectomy is serum albumin. Nevertheless at 18 weeks NAR showed a significantly higher frequency of moderate and severe glomerular lesions than SDR. We conclude that, in this model, proteinuria itself is not a major cause of progressive glomerular injury.
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PMID:Glomerular injury in analbuminemic rats after subtotal nephrectomy. 194 21

To elucidate the pathogenetic role of hyperlipidemia per se in the development of glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and mildly hyperlipidemic male NAR were studied for a period of 37 weeks after uninephrectomy (UNX). Plasma cholesterol increased from 6.3 +/- 0.4 (week 4) to 11.9 +/- 0.6 mmol/liter (week 37) in the female NAR, and from 4.3 +/- 0.1 to 6.4 +/- 0.5 mmol/liter in the male NAR in the same period. Plasma protein concentration was also consistently higher in female NAR (60 +/- 1 g/liter) as compared to male NAR (52 +/- 1 g/liter). Plasma viscosity was higher in female NAR than in male NAR, but there were no differences in blood viscosity. Proteinuria increased progressively in the UNX female NAR from 25 weeks after surgery, reaching a final value of 141 +/- 37 mg/day. No proteinuria occurred in the UNX male NAR (final value 15 +/- 2 mg/day). Glomerular capillary pressure, measured prior to the onset of proteinuria, was not significantly different in UNX female NAR and UNX male NAR. At the end of the study glomerulosclerosis and lipid deposition was only found in the UNX female NAR. Throughout the study hyperfiltration and hyperperfusion, relative to the one-kidney clearances of the sham-operated (2K) animals, were not different in UNX male and female NAR. No differences were observed in blood pressure. Hypertrophy, evaluated by glomerular diameters, was less pronounced in UNX female NAR (174 +/- 3 microns) than in UNX male NAR (190 +/- 7 microns). Glomerular diameters in 2K female and male NAR were similar (respectively 158 +/- 2 and 157 +/- 4 microns). Plasma apo B levels were similar (2K female NAR: 204 +/- 8 U; 2K male NAR 204 +/- 13 U), but cholesterol and triglyceride content of apo B-containing lipoproteins, namely VLDL, IDL and LDL, was increased twofold in the female NAR as compared to the male NAR, implying a larger particle size in the female NAR. Deposition of apo B and apo E was observed in the glomerular mesangium of UNX female NAR, particularly in sclerotic lesions. Glomerular apo A-I deposits were localized primarily in visceral epithelial cells and were not associated with sclerotic lesions. The development of proteinuria and glomerulosclerosis after UNX in female NAR but not in male NAR may depend upon differences in plasma lipoprotein composition, but is apparently not related to differences in whole kidney hyperfiltration and hyperperfusion, glomerular capillary pressure, or blood viscosity.
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PMID:Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized female analbuminemic rats. 772 32

The nephrotic syndrome is a consequence of urinary loss of intermediate sized plasma proteins and the resulting homeostatic responses to those losses. Plasma protein composition is changed greatly. Intermediate sized proteins, including albumin, transferrin, IgG, hormone binding proteins, and low molecular weight inhibitors of the clotting cascade, are lost in the urine and their concentration in plasma reduced. Synthesis of many proteins secreted by the liver is increased either at the level of transcription or posttranscriptionally. Synthesis of several liver-derived proteins is increased in the absence of their urinary loss, suggesting that hypoalbuminemia or reduced plasma oncotic pressure (tau) stimulates the production or reduces the rate of catabolism of these proteins. Their plasma levels, including those of lipoproteins and elements of the coagulation cascade, are increased. Plasma tau falls and plasma viscosity increases because of the replacement of intermediate sized plasma proteins by larger ones. The plasma concentration of several proteins lost in the urine but not secreted by the liver, such as erythropoietin and IgG, are not defended by increased synthesis, suggesting that increased synthesis of plasma proteins is primarily confined to the liver. Loss of both liver-derived and non-liver-derived proteins may cause reduced immunity, anemia, and deficiency syndromes. Urinary loss of albumin alone is not responsible for decreased plasma pi. The relationship between plasma protein concentration and pi is greatly disturbed in nephrotic rats. In contrast, the relationship between pi and plasma protein concentration is nearly the same in rats with hereditary analbuminemia (NAR) and normal rats, despite the absence of albumin from the plasma of NAR. When proteinuria is induced in NAR the relationship between plasma protein concentration and pi becomes identical to that in nephrotic animals, although no albumin was lost in the urine of NAR.
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PMID:Plasma composition in the nephrotic syndrome. 811 87

Progression of chronic renal disease is usually more rapid in males, both in humans and in experimental animals. Estrogen-replacement studies indicate that this may be related to the beneficial effects of estrogen on the lipoprotein profile. However, in hyperlipidemic analbuminemic rats (NAR), females are more prone to develop renal injury than males, and ovariectomy tends to decrease triglyceride levels and prevent renal disease. Therefore, we studied the effects of estrogen administration on lipoproteins, and the induction of renal injury in uninephrectomized female and male NAR. Ovariectomized and orchidectomized uninephrectomized NAR were treated with estradiol implants for 24 weeks. In an additional group of ovariectomized rats, the implant was removed after 12 weeks. Both in ovariectomized and orchidectomized NAR, estradiol caused severe hypercholesterolemia (9 to 12 mmol/liter) and hypertriglyceridemia (6 to 8 mmol/liter) after six weeks. Subsequently, these rats developed severe proteinuria, reaching 209 +/- 25 and 95 +/- 43 mg/day, respectively, after 24 weeks. At this point there was severe glomerular sclerosis, with a respective score of 107 +/- 21 and 61 +/- 33. In terminal blood samples the most pronounced increase in lipid levels were observed in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). In contrast, ovariectomized NAR and orchidectomized NAR without exogenous estrogen had much lower lipid levels (cholesterol 5 to 7 mmol/liter and triglycerides 1 to 2 mmol/liter) after six weeks. These rats, or ovariectomized NAR where the estrogen treatment had been withdrawn, had practically no proteinuria (4 +/- 1, 19 +/- 11, and 13 +/- 4 mg/day, respectively) or renal damage (glomerulosclerosis score 1 +/- 0.4, 5 +/- 3 and 3 +/- 1, respectively) after 24 weeks. Thus, in hypertriglyceridemic analbuminemic rats, estrogen-treatment causes further increases in both triglycerides and cholesterol. Most probably these changes contribute to the development of renal injury by estrogen in this model. This effect of estrogen, which has also been observed in the Zucker rat, is unique for the hypertriglyceridemic state and deserves further study.
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PMID:Estrogen induces glomerulosclerosis in analbuminemic rats. 955 92