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

Camostat mesilate, a developed derivative of gabexate mesilate for oral use, was administered in a daily dose of 600 mg for 4 weeks to 17 patients with heavy proteinuria due to various nephropathies. Five patients had glomerulonephritis (3 patients with IgA nephropathy, one each with membranoproliferative GN and membranous nephropathy) and 3 had systemic vasculitis. These patients had been treated with glucocorticoid, cyclophosphamide, anticoagulants, and dipyridamole. Five patients had diabetic nephropathy and had been treated with conventional therapy including angiotensin converting enzyme inhibitors. Two cases with benign nephrosclerosis, one with Alport syndrome, and the rest with end-stage renal failure of undetermined cause were also included in this study. Urinary protein decreased promptly within 2 weeks (from 5.2 +/- 0.7 to 3.5 +/- 0.5, mean +/- SE, p less than 0.005), and serum total protein and albumin levels increased significantly. Serum creatinine levels did not change. Decreases in urinary protein excretion of more than 50% were observed in five out of eight patients with glomerulonephritis or systemic vasculitis, two out of five with diabetic nephropathy, and one with chronic renal failure. However, urinary protein excretion values remained at the same level in two patients with benign nephrosclerosis and a patient with Alport syndrome. We suggest that camostat mesilate caused a change in glomerular capillary permeability for macromolecules through its inhibitory effects on the kallikrein-kinin system, complement system, coagulation system, and platelet function, which contributed to the treatment of the various nephropathies.
 ...
PMID:Effect of camostat mesilate on heavy proteinuria in various nephropathies. 279 62

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparison between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P less than 0.05) UKE (3.96 +/- 0.30 vs 7.60 +/- 1.51 U/24 h) and BP (118 +/- 2 vs 135 +/- 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 +/- 0.50 vs 3.40 +/- 0.30 U/24 h) and BP increased to higher levels (117 +/- 2 vs 152 +/- 3 mmHg) than in the normal DOCA/NaCl group (P less than 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 +/- 0.40 vs 3.60 +/- 0.80 U/24 h) or BP (124 +/- 2 vs 125 +/- 2 mmHg). 3. At the end of the study, PK was decreased and PRA totally suppressed in both normal and nephritic DOCA/NaCl-treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl-treated rats (44.8 +/- 5.2 mg/day) than in control nephritic animals (15.1 +/- 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats to respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group.
 ...
PMID:Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats. 324 40

This paper discusses several tests that may permit the early detection of renal changes induced by long-term exposure to nephrotoxic industrial chemicals and may possibly serve as advance warning of pending renal damage. Some tests mainly attempt to assess the integrity of the glomerulus: high molecular weight proteinuria, glomerular basement membrane (GBM) antigens in blood and in urine, circulating anti-GBM antibodies, glomerular filtration rate after an acute oral load of proteins, and estimation of membrane negative charges (ie, glomerular polyanion). Others mainly attempt to identify functional and/or morphological changes at the tubular level: low molecular weight proteinuria, aminoaciduria, glucosuria, hyperphosphaturia, hypercalciuria, enzymuria, tubular antigen excretion, kallikrein, and prostaglandin excretion. Some of these tests are already routinely used, although controversy may still persist with regard to their clinical significance. Recently, new tests have been developed that may open new perspectives for assessing the significance of the early renal changes induced by chemicals.
 ...
PMID:Early detection of the nephrotoxic effects of industrial chemicals: state of the art and future prospects. 355 19

In order to investigate the validity of urinary kallikrein (KAL) measurement, comparative studies were performed among the values obtained by various methods of urinary KAL measurements. Daily urine samples were collected from 37 hospitalized normal subjects (NS, 21 essential hypertensives without complications (EHT) and 20 patients with renal diseases associated with proteinuria (PU). Urinary KAL excretions were determined by direct radioimmunoassay (RIA), kininogenase assay (K-genase), TAMe esterase assay (TAMe), and PPA-MCA (MCA) and PPA-NE amidase assay (NE). By the desalting procedure, urinary KAL levels showed significant changes in TAMe, MCA and NE, but not in d-RIA and K-genase in all three groups. In TAMe, MCA and NE, the recovery of added KAL in urine was significantly lower in non-desalted samples in both EHT and PU, but not in NS. Impaired recovery and correlations between d-RIA or K-genase and TAMe, MCA or NE in non-desalted samples were improved by desalting. Although good correlations were observed between d-RIA or K-genase and TAMe, MCA or NE in desalted samples, the slopes of curves were steeper in EHT and PU than in NS, suggesting that the synthetic substrate methods still have some problems in the KAL measurement in these pathological states, KAL inhibitor, aprotinin and gabezate mesilate did not suppress the esterclytic and amidolytic activities completely, but suppressed K-genase activity completely in PU urine samples, suggesting that certain kinds of non-KAL esterases might remain in PU urine samples. Thus, d-RIA and K-genase appear to be the most reliable methods in the measurement of urinary KAL quantity and activity, respectively.
 ...
PMID:A comparative study of the measurement of urinary kallikrein by various methods in patients with essential hypertension and patients with proteinuria. 364 32

Fawn-hooded (FH) rats, primarily males, develop spontaneous low-renin hypertension associated with reduced urinary excretion of kallikrein as early as 2 months of age, followed by progressive glomerular sclerosis and proteinuria as early as 3 months of age. In the present study we determined the effects of early (5-7 weeks) or late (5 months) orchiectomy on the blood pressure and nephropathy of FH rats, compared to sham-operated (control) FH males. Early orchiectomy reduced significantly the progression of glomerular sclerosis and of proteinuria and ameliorated the hypertension but had no significant effect on excretion of urinary kallikrein. Late orchiectomy, in contrast, had no significant effect on the progression of glomerular sclerosis or proteinuria but did significantly reduce the blood pressure and marginally increase the excretion of urine kallikrein. These results suggest that (a) male sex hormones may play a role in the pathogenesis of hypertension and nephropathy in the FH rats and (b) renal disease in this strain progresses in spite of improvement in blood pressure.
 ...
PMID:Contrasting effects of early and late orchiectomy on hypertension and renal disease in fawn-hooded rats. 365 Jun 58

Urinary excretion of kallikrein (UKal), sodium, potassium, protein, and creatinine, as well as the kidney content of kallikrein and renin, was studied in spontaneously hypertensive FH/Wjd (FH) male and female rats and in age- and sex-matched normal Wistar rats. With the exception of 1-month-old rats UKal excretion was significantly lower in FH rats than in Wistar rats. FH females also excreted less UKal than Wistar females. No UKal inhibitor or increased degradation of this enzyme in the urine of FH rats was detected. There was no difference in creatinine clearance, blood urea nitrogen, or serum electrolytes, and calcium between 5-month-old FH and Wistar males. Wistar rat kidneys contained about twice as much kallikrein as FH rat kidneys. From the age of 2 months FH males excreted more sodium, as well as urine, than all other groups. No differences in potassium excretion were observed. Only FH males, 4 months and older, developed proteinuria. FH males and females became hypertensive at the ages of 2 and 4.5 months, respectively. Plasma renin activity, as well as renal renin activity, was significantly lower in FH than in Wistar males. In conclusion, the decrease in UKal activity which precedes the onset of hypertension suggests that the abnormality in the renal kallikrein system may be involved in the pathogenesis of hypertension in FH rats.
 ...
PMID:Urinary and renal kallikrein in hypertensive fawn-hooded (FH/Wjd) rats. 636 17

Iodine-labeled ([125I]) rat urinary kallikrein and rat urinary TAME esterase A2 were used as probes to look for urinary and plasma proteins that bind to these enzymes. Such proteins are presumptive enzyme inhibitors. Complexes formed with labeled enzymes were identified by polyacrylamide gel electrophoresis followed by autoradiography. Urine from young (6 weeks old) Dahl salt-sensitive (S) rats showed no, or only traces, of protein binding to kallikrein. Concomitant with the slow development of hypertension and proteinuria in S rats fed normal rat chow, one of the six kallikrein-binding proteins demonstrable in plasma was readily found in S-rat urine. This kallikrein-binding protein was called "KBP-1." R rats showed either no or much less KBP-1 in the urine, compared to S rats up to 5 months of age. A partly purified preparation of KBP-1 was shown to inhibit the TAME esterase activity of rat urinary kallikrein in the radiometric TAME assay. Urine of proteinuric S rats also contained two TAME esterase-binding proteins, TEBP-1 and TEBP-2, detected with the [125I]-esterase A2 probe. As S rats aged from 3 to 8 months, free KBP-1 disappeared from the urine in spite of increased and marked proteinuria and the continued presence of KBP-1 in plasma. Concomitant with this age-related loss of urinary KBP-1 there was a marked shift in S urinary proteins binding to [125I]-esterase A2 from TEBP-1 to TEBP-2. It was speculated that KBP-1 and TEBP-1 were the same protein detectable with either labeled kallikrein or labeled esterase A2. The concomitant disappearance of free KBP-1 (TEBP-1) and the appearance of free TEBP-2 in the urine of old, hypertensive, proteinuric S rats suggests that: 1) most of the KBP-1 (TEBP-1) is bound to enzyme(s) in old rats; or 2) KBP-1 (TEBP-1) is largely converted to TEBP-2 in old rats; or 3) both are true and that binding of KBP-1 (TEBP-1) to enzymes is associated with the generation of TEBP-2.
 ...
PMID:Proteins binding to kallikrein and esterase A2 in the urine of salt-sensitive and salt-resistant rats. 675 95

S and R female rats were raised on a 1% NaCl diet, and excretion rates of urinary protein, kallikrein esterase activity, and PGE2 were measured (1) at 1 1/2 months of age, when both S and R rats were normotensive, (2) at 3 months of age, when S rats were mildly hypertensive and R controls remained normotensive, and (3) at 6 months of age, when S rats were markedly hypertensive relative to the still normotensive R rats. Urinary protein excretion rate in S compared to R rats was slightly elevated at 1 1/2 months of age and greatly elevated at 3 and 6 months of age. Urinary kallikrein was measured by hydrolysis of TAME after separation of kallikrein from nonkallikrein TAME esterases on DEAE-Sephadex minicolumns. Kallikrein TAME esterase activity was the same in 1 1/2-month-old S and R rats but became reduced in S relative to R rats at 3 and 6 months of age, concomitant with the development of hypertension and marked proteinuria. Urinary PGE2 was decreased in S rats as compared to R rats at all ages, and therefore the strain difference in urinary PGE2 preceded the development of strain differences in blood pressure and urinary kallikrein activity. We conclude that (1) reduced excretion of urinary kallikrein TAME esterase activity in S rats is probably secondary to hypertension and severe proteinuria and (2) decreased urinary PGE2 excretion in prehypertensive S rats is compatible with, but does not prove, the presence of a primary defect in intrarenal PGE2 production that could be involved in initiating hypertension.
 ...
PMID:Developmental patterns of blood pressure and urinary protein, kallikrein, and prostaglandin E2 in Dahl salt-hypertension-susceptible rats. 691 75

Previous evidence shows that salt-sensitive (S) rats have a net increase in plasma mineralocorticoid activity due to 18-hydroxy-11-deoxycorticosterone and decreased urinary kallikrein excretion compared to salt-resistant (R) rats. Since mineralocorticoids stimulate urinary kallikrein excretion, these results are inconsistent. This inconsistency was explained by the fact that, while R rats responded normally to treatment with deoxycorticosterone (DOC) by an increase in urinary kallikrein excretion, S rats showed no change in urinary kallikrein even when treated with 10 mg of DOC/day for 24 days. S and R rats responded identically to DOC with changes muscle electrolytes and relative hypertrophy of the renal distal tubule. Other measures of chronic mineralocorticoid response in S rats beside kallikrein were, therefore, intact. It was found that S rats were capable of responding to Na deficient diet with an increase in urinary kallikrein comparable to R rats. It was argued, therefore, that mineralocorticoid receptor mechanisms and distal-tubular cell responsiveness are intact in S rats. Mild glomerular and tubular scarring was found in S rats and the severity of renal lesions was increased by DOC treatment in S rats. These lesions correlated well with blood pressure and proteinuria. No such lesions were present in control or DOC treated R rats. It was suggested that failure of urinary kallikrein to respond to DOC in S rats may be a secondary phenomenon resulting from renal damage.
 ...
PMID:Anomalous response of urinary kallikrein to deoxycorticosterone in Dahl salt-sensitive rats. 691 11

Proteolytic activity, with azocasein as substrate in the presence and absence of 0.4 IU kallikrein (Padutin) was measured in the 24 h urine fractions of 100 ambulatory patients with hypertension, proteinuria or haematuria. Urinary protein and alpha 1-antitrypsin concentration have also been assayed. There was an inverse relationship between kallikrein activity and urinary alpha1-antitrypsin concentration( r = 0.84; y = 39.2 e-0.009x). Furthermore, kallikrein activity and 24 h urinary alpha 1-antitrypsin excretion were also inversely correlated (r = 0.81; y = 886,4 e-0.011x). Our data suggest an inactivation of renal kallikrein by urinary alpha 1-antitrypsin.
 ...
PMID:Inactivation of urinary kallikrein by alpha 1-antitrypsin. 697 46


<< Previous 1 2 3 4 Next >>