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)

We have utilized specific, irreversible inhibitors of cysteine proteinases to examine the role of renal cathepsin B and cathepsin L in the proteinuria which occurs in an experimental model of human glomerular disease. Administration of trans-epoxysuccinyl-L-leucylamido-(3-methyl)butane (Ep475) a specific, irreversible inhibitor of cysteine proteinases, including cathepsins B and L, significantly reduced proteinuria in rats with experimentally induced, neutrophil-independent, anti-GBM antibody disease (controls: 10 +/- 1 mg/24 h, N = 8; anti-GBM antibody disease: 203 +/- 30 mg/24 h, N = 8; anti-GBM antibody disease + Ep475: 112 +/- 13 mg/24 h, mean +/- SEM, N = 6, P less than 0.05). There was a marked reduction in the activity of both cathepsin B and cathepsin L in renal cortices obtained from Ep475-treated rats compared to either saline-treated controls or rats treated with anti-GBM IgG only. Administration of Z-Phe-Tyr(O-t-butyl)CHN2, a specific, irreversible cysteine proteinase inhibitor with a high degree of selectivity toward cathepsin L, also caused a reduction in anti-GBM antibody-induced proteinuria (90 +/- 18 mg/24 h, N = 6, P less than 0.05). This reduction in proteinuria was accompanied by a marked decrease (-84%) in the specific activity of renal cortical cathepsin L in Z-Phe-Tyr(O-t-butyl)CHN2-treated rats. However, cathepsin B activity was unchanged. There was no significant change in the renal anti-GBM antibody uptake, plasma urea nitrogen, or plasma creatinine values in the Z-Phe-Tyr(O-t-butyl)CHN2-treated rats compared to rats treated with anti-GBM IgG only or saline-treated controls. These data document the ability of cysteine proteinase inhibitors to decrease the proteinuria which occurs in a neutrophil-independent model of human anti-GBM antibody disease and suggest an important role for cathepsin L in the pathophysiology of the proteinuria which occurs in this model.
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PMID:Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis. 189 42

Proteinuria is a major manifestation of glomerular disease (glomerulonephritis, GN). We examined the effect of trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64), a specific and irreversible cysteine proteinase inhibitor, on urinary protein excretion in a complement- and neutrophil-independent model of antiglomerular basement membrane (GBM) antibody disease. A single injection of rabbit antirat-GBM IgG produced a marked increase in urinary protein excretion 24hr after injection. In two separate studies using different pools of antiGBM IgG, administration of E-64 (5mg every 6h starting 2hr prior to induction of GN) reduced proteinuria (-45 +/- 7%, and -41 +/- 14%, Mean +/- SEM, n = 6; P less than 0.001) in the 24 hour period following induction of the disease. This reduction in urinary protein excretion was accompanied by a marked decrease in the specific activity of the cysteine proteinases cathepsins B and L in glomeruli (B: -97%; L: -84%) and renal cortex (B: -87%; L: -75%) isolated from the same E-64-treated rats compared to same saline-treated controls. These data, combined with the specificity of E-64 for cysteine proteinases, suggest a potential role for cysteine proteinases in the increased GBM permeability and proteinuria in this experimental model of glomerular disease.
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PMID:The cysteine proteinase inhibitor, E-64, reduces proteinuria in an experimental model of glomerulonephritis. 317 11

We have previously reported that isoproterenol induces type 2 salivary cystatin in both submandibular glands and kidney tubule cells of rats but not in any other organs examined. In the present study, we investigated whether this salivary protein is induced in other conditions that show kidney tubule injury. Immunocytochemistry, using a monospecific antiserum to this cystatin, revealed specific staining within the proximal tubule epithelium of the cortex as well as in the inner and outer stripe of the medulla of immunologically and chemically injured rats. Cystatin could not be detected in kidneys from healthy rats by means of immunocytochemistry. Weak staining was found in 3/3 kidneys of rats treated with turpentine and in 5/5 animals treated with potassium dichromate. In rats treated with puromycin, cystatin could not be demonstrated in 5/5 animals having proteinuria of less than 100 mg/24 h; however, moderate staining was observed in 4/5 puromycin-treated rats having proteinuria greater than 100 mg/24 h. In Heymann nephritis, cystatin was present in 7/31 kidneys with proteinuria lasting 6 to 15 weeks and in none (0/7) with proteinuria of shorter duration. Strong staining was also observed in 10/10 kidneys from rats with moderate-to-severe chronic serum sickness. This study shows that elaboration of type 2 cystatin in rats is not limited to salivary glands and, with our previous study, suggests that induction of this cysteine inhibitor may represent a local response to generalized tissue injury in both submandibular and renal tissues. These findings further demonstrate that induction of cystatin in salivary glands is not unique to these glands and suggest that induction of this cysteine proteinase inhibitor may represent a local response to tissue injury caused by diverse mechanisms.
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PMID:Induction of type 2 salivary cystatin in immunological and chemical kidney injury. 837 10

Continuous efforts have been made to find out precise and simple method for determination of glomerular filtration rate (GFR). Cystatin C (cysteine proteinase inhibitor = CyC) is a low molecular weight (LMW) protein which is produced constantly by all nucleated cells independently of different pathological conditions and eliminated from the blood exclusively by glomeruli. So, CyC closely reflects the GFR. In the present study 75 patients aged between 18 and 74 (44.3 +/- 12.2) years were analyzed, with the aim to compare the reciprocal values of serum level of LMW proteins CyC and beta2-microglobulin (beta2-MG) with creatinine clearance (Ccr) as a measure of GFR. Patients were divided into groups according to sex, age (<60; >60 years) and renal diseases: patients with glomerulonephritis (GN) with and without nephrotic proteinuria, pyelonephritis (PyN), and renal transplant (Tx). High correlation between Ccr and 1/CyC (r = 0.81; p < 0.01) and Ccr and 1/beta2-MG (r = 0.80; p < 0.01) in all examined patients was found. There was significant correlation between Ccr and 1/CyC (0.82 vs. 0.79) and Ccr and 1/beta2-MG (0.85 vs. 0.76) in men as well in women, and also in two groups of patients formed according to the age (0.82 vs. 0.77; p < 0.01; 0.80 vs. 0.81; p < 0.01), without any statistical significant difference between the groups. In studied groups with different renal diseases, there were no differences in correlation coefficients between Ccr and 1/CyC and Ccr and 1/beta2-MG (p1 = 0.29; p2 = 0.21; p3 = 0.79; p4 = 0.43), without statistical differences between the groups, except significant difference in correlation coefficients for Ccr and 1/beta2-MG between patients with GN with and without nephrotic proteinuria (p < 0.032). LMW proteins, serum CyC and beta2-MG, are as good markers of GFR as Ccr, regardless sex and age. Both of these LMW proteins are good markers of GFR in patients with GN without nephrotic proteinuria, PyN and Tx patients. In patients with GN and nephrotic proteinuria serum CyC is a better marker of GFR than beta2-MG.
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PMID:Serum cystatin C and beta2-microglobulin as markers of glomerular filtration rate. 1261 40