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)

Immunologic mechanisms of proteinuria were investigated in guinea pigs (GP) injected with sheep antiserum (NTS) to GP glomerular basement membrane (GBM). Linear deposition of sheep gamma 1 and gamma 2 IgG led to a prompt but transient (36 hr) increase in albumin excretion from control values of 0.026 +/- 0.013 mg/hr to maximal values of 26+/-12.1 mg/rh at six hours without detectable histologic or electron microscopic changes except for decreased staining for glomerular polyanion and epithelial cell foot process fusion. GBM permeability to anionic ferritin was not increased during proteinuria. Anti-GBM antibody deposits did not fix GP C3 or C4 in vivo or in vitro. NTS-induced proteinuria was the same in guinea pigs that were normal, greater than 95% depleted of C3 through C9, genetically deficient in C4, and depleted of circulating polymorphonuclear leukocytes (PMN). Prior administration of antihistamines, steroids, azathioprine, colchicine, indomethacin, heparin, aprotinin (Trasylol), and niridazole also failed to reduced proteinuria. Initial proteinuria subsided by 36 hr, did not recur despite linear deposition of GP gemma 1 and gemma 2 after day seven, and antibody to GMB-bound sheep globlin. In the GP nephrotoxic nephritis model, anti-GBM antibody deposits apparently mediate increased permeability to albumin by a currently undefined mechanism which is independent of complement, PMN, and other know mediators of inflammation.
 ...
PMID:Complement-independent nephrotoxic nephritis in the guinea pig. 1 57

Increased renal ammoniagenesis is pathogenic in animals. Thus, tubular degradation of filtered proteins to ammonia might link proteinuria to disease progression. The tubular uptake, metabolism and fractional degradation of aprotinin 99mTc (Trasylol), were measured in 26 glomerulonephritic patients with normal renal function, 10 with proteinuria > 5 g/24 h. In addition, urinary ammonia pH, and titratable acidity were measured. Patients with heavy proteinuria had a higher tubular metabolism, a lower uptake and a higher fractional degradation of aprotinin. Urinary ammonia and titratable acidity were also increased. Fractional degradation and urinary ammonia were strongly correlated as were urinary ammonia and proteinuria.
 ...
PMID:Tubular metabolism of aprotinin 99mTc and urinary ammonia: effects of proteinuria. 128 13

1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject. 2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3-6 g of lysine, followed by an infusion over 1 h of 0.3-1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope. 3. At the low dosage of lysine (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 +/- 0.2% of dose/h with no lysine to 0.9 +/- 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 +/- 0.006 to 0.03 +/- 0.006 h-1 (P < 0.005) between 3.75 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man. 138 15

Albuminuria (UAlbV) can be reduced by converting-enzyme inhibitors (CEI), but the hormonal mechanism responsible for this effect has not previously been defined. Since CEI increase kinin activity as well as reduce angiotensin II (ANG II) activity, experiments were performed to determine the effect of isolated alterations in kinin and ANG II metabolism on UAlbV in rats with passive Heymann pephritis. Phosphoramidon was used to potentiate kinin activity without altering ANG II synthesis. Aprotinin was utilized in combination with the CEI, enalapril, to prevent the increase in kinin activity caused by CEI. UAlbV and the fractional renal clearance of albumin (FCAlb) decreased significantly after either phosphoramidon or enalapril, although only enalapril reduced blood pressure. Glomerular filtration rate (GFR) was not affected by either drug. Phosphoramidon did not affect plasma renin activity (PRA) or the pressor response to angiotensin I (ANG I), indicating that ANG II synthesis was not altered. Aprotinin prevented the reduction in UAlbV and FCAlb produced by CEI but not the hypotension, elevated PRA, or ANG I pressor blockade produced by CEI. Aprotinin alone had no effect on UAlbV, GFR, PRA, or blood pressure. UAlbV can be reduced by increasing kinin activity by a mechanism that is not dependent on suppression of ANG II activity or reduction in GFR or blood pressure. CEI may reduce proteinuria as a result of their action on the kallikrein-kinin system rather than on the renin-angiotensin system.
 ...
PMID:Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome. 169 47

1. The novel method recently developed to measure renal tubular degradation of filtered proteins in man using radiolabelled aprotinin (Trasylol) has been modified to allow the fate and the significance of the renal catabolism of radiolabelled aprotinin to be determined beyond 24h. 2. Ten renal patients with normal kidney function and variable proteinuria each received two separate intravenous injections of radiolabelled aprotinin, 5.0 mg of 99mTc-labelled aprotinin (40MBq) and 0.5mg of 131I-labelled aprotinin (5MBq). Chromatography (Sephadex-G-25-M) was used to separate undegraded radiolabelled aprotinin from the free isotope in urine and plasma. Renal uptake from gamma-camera images (24h for 99mTc-labelled aprotinin and up to 96h for 131I-labelled aprotinin) and urinary activity (48 and 96h, respectively) were measured. 3. The renal handling of radiolabelled aprotinin was similar with the two isotopes. Chromatography showed that all plasma activity was undegraded radiolabelled aprotinin, and urine activity was only the free isotopic label. 4. Kidney uptake of 131I-labelled aprotinin was prompt, reaching a cumulative maximum of 37.1 +/- 3.0% of dose at 24h, but falling exponentially thereafter to 5.6 +/- 1.0% of dose at 96h. 5. The rate of excretion of the free label in urine, i.e. the metabolic rate of radiolabelled aprotinin, was relatively constant over the first 24h (1.6 +/- 0.09% of dose/h), but then fell in parallel with the diminishing activity over the kidney, i.e. to 1.0 +/- 0.1% of dose/h over 24-48h and to only 0.4 +/- 0.08% of dose/h over 72-96h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Observations on the early renal uptake and later tubular metabolism of radiolabelled aprotinin (Trasylol) in man: theoretical and practical considerations. 767 59

Sub-diabetogenic doses of streptozotocin (STZ) produce insulitis, beta cell destruction and diabetes in mice. Since kinin have been proposed as an inflammatory mediator in several diseases, we decided to evaluate the role of the kallikrein-kinin system in the evolution of insulitis. Male C 57 BL/KsJ mdb mice were injected with STZ (40 mg/kg) for 5 consecutive d. Aprotinin (4000 KIU/d) was injected simultaneously with STZ during 10 d. Plasma and urine samples collected on day 15 were assayed for glucose concentration and proteins, nitrites and kallikrein. Diabetic mice showed hyperglycemia and increased diuresis, marked proteinuria, nitrites and kallikrein. Administration of aprotinin, a potent tissue kallikrein inhibitor, to STZ mice, reduced the hyperglycemia and the altered renal function of the diabetic mice to level no different from normal mice. The present studies are consistent with the hypothesis that the over-production of tissue kallikrein in insulitis could be controlled by the effect of aprotinin.
 ...
PMID:Effects of aprotinin on the kallikrein-kinin system in type I diabetes (insulitis). 940 44

1. Progression to renal failure may be linked to the degree of proteinuria through tubulo-interstitial mechanisms. However, there are no data in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril. We developed a method to allow such studies, and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretion. 2. In this study, 10 patients with mild renal impairment (51Cr-EDTA clearance 63.7 +/- 8.3 ml.min-1.1.73 m-2) and heavy proteinuria (8.2 +/- 2.3 g/ 24 h) were given lisinopril (10-20 mg) for 6 weeks. Renal tubular catabolism of intravenous aprotinin was measured before and after lisinopril by renal imaging and urinary excretion of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Fresh timed urine collections were also analysed for ammonia excretion every fortnight from 6 weeks before treatment. Total urinary N-acetyl-beta-D-glucosaminidase and the more tubulo-specific N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme were also measured. 3. After lisinopril proteinuria fell significantly as expected (from 9.5 +/- 1.6 to 4.5 +/- 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism over 26 h (from 1.7 +/- 0.1 to 1.2 +/- 0.1% dose/h, P < 0.01) and in fractional degradation of aprotinin (from 0.08 +/- 0.02 to 0.04 +/- 0.007/h, P < 0.04). Ammonia excretion also fell significantly (from 1.2 +/- 0.1 to 0.6 +/- 0.1 mmol/h, P < 0.0001), as did both total urinary N-acetyl-beta-D-glucosaminidase (P < 0.0001) and the N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme (P < 0.015). These observations after lisinopril treatment have not been described previously. There was no significant change in blood pressure nor in glomerular haemodynamics.
 ...
PMID:Proximal renal tubular peptide catabolism, ammonia excretion and tubular injury in patients with proteinuria: before and after lisinopril. 964 Mar 48

Chronic vascular rejection (CR) is the commonest cause of renal transplant loss, with few clues to etiology, but proteinuria is a common feature. In diseased native kidneys, proteinuria and progression to failure are linked. We proposed a pathogenic role for this excess protein at a tubular level in kidney diseases of dissimilar origin. We demonstrated in both nephrotic patients with normal function and in those with failing kidneys increased renal tubular catabolism and turnover rates of a peptide marker, Aprotinin (Apr), linked to increased ammonia excretion and tubular injury. These potentially injurious processes were suppressed by reducing proteinuria with Lisinopril. Do similar mechanisms of renal injury and such a linkage also occur in proteinuric transplanted patients with CR, and if so, is Lisinopril then of beneficial value? We now examine these aspects in 11 patients with moderate/severe renal impairment (51CrEDTA clearance 26.2+/-3.3 mL/min/1.73 m2), proteinuria (6.1+/-1.5 g/24 h) and biopsy proven CR. Lisinopril (10-40 mg) was given daily for 2 months in 7 patients. Four others were given oral sodium bicarbonate (Na HCO3) for 2 months before adding Lisinopril. Renal tubular catabolism of intravenous 99mTc-Apr (Apr* 0.5 mg, 80MBq), was measured before and after Lisinopril by gamma-ray renal imaging and urinary radioactivity of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Total 24 h urinary N-acetyl-beta-glucoaminidase (NAG) and ammonia excretion in fresh timed urine collections were also measured every two weeks from two months before treatment. After Lisinopril proteinuria fell significantly (from 7.8+/-2.2 to 3.4+/-1.9 g/24 h, p<0.05). This was associated with a reduction in metabolism of Apr* over 26 h (from 0.5+/-0.05 to 0.3+/-0.005% dose/h, p < 0.02), and in fractional degradation (from 0.04+/-0.009 to 0.02+/-0.005/h, p<0.01). Urinary ammonia fell, but surprisingly not significantly and this was explained by the increased clinical acidosis after Lisinopril, (plasma bicarbonate fell from 19.1+/-0.7 to 17.4+/-0.8 mmol/L, p < 0.01), an original observation. Total urinary NAG did fall significantly from a median of 2108 (range 1044-3816) to 1008 (76-2147) micromol/L, p < 0.05. There was no significant change in blood pressure or in measurements of glomerular hemodynamics. In the 4 patients who were given Na HCO3 before adding Lisinopril, both acidosis (and hyperkalemia) were reversed and neither recurred after adding Lisinopril. These observations in proteinuric transplanted patients after Lisinopril treatment have not been previously described.
 ...
PMID:Renal tubular peptide catabolism in chronic vascular rejection. 1149 66