Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombotic obstruction of glomerular capillaries causes acute renal failure in patients with hemolytic-uremic syndrome (HUS). Recanalization of occluded vessels normally occurs by activation of the endogenous fibrinolytic system, mediated by plasminogen activators, which are stored and synthesized in the endothelial cells. However, endothelial injury is considered the primary event in the pathogenesis of HUS, and this may result in impaired fibrinolysis. In five children with HUS we performed a prospective study of plasminogen activator activity and two plasminogen activator antigens: tissue-type plasminogen activator and urokinase-type plasminogen activator before and after intravenous desmopressin. Plasminogen activator inhibitor type-1 antigen was also studied. In the acute stage of HUS plasminogen activating activity was low, in spite of elevated levels of total plasminogen activator antigens. This decrease of plasminogen activating activity was due to high levels of the plasminogen activator inhibitor. Improvement of fibrinolysis paralleled recovery from HUS. We conclude that decreased fibrinolysis is an important pathophysiologic feature of HUS.
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PMID:Impaired fibrinolysis in the hemolytic-uremic syndrome of childhood. 811 Aug 78

A 46-year-old housewife with regurgitation of mitral valve developed acute renal failure due to acute thrombosis of bilateral renal arteries after cardiac catheterization. A regional fibrinolytic therapy using transarterial infusion of tissue plasminogen activator (t-PA) was performed at 8 h after the onset, and was successful. She could be taken off hemodialysis 2 weeks after the fibrinolytic therapy, and could be successfully operated on with mitral valve replacement 7 months after that. Three years after mitral valve replacement, her serum creatinine was 148 mumol/l. This is the longest follow-up case after regional transarterial fibrinolysis of acute thrombosis of renal artery using t-PA, and this therapy is a safe and good one for acute thrombosis of renal artery.
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PMID:Successful fibrinolytic therapy using tissue plasminogen activator in acute renal failure due to acute thrombosis of bilateral renal arteries. 824 31

We report the occurrence of renal failure due to cholesterol crystal embolization following thrombolytic therapy with intravenous recombinant tissue-type plasminogen activator (t-PA). No invasive vascular procedure had been performed. Although there is one case report of cholesterol crystal embolization following t-PA therapy with only extrarenal manifestations (N Engl J Med 321:1270, 1989), this is the first reported case of atheroembolic acute renal failure following t-PA therapy.
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PMID:Cholesterol crystal embolization-associated renal failure after therapy with recombinant tissue-type plasminogen activator. 850 21

Reteplase (drug code: BM 06.022) is an unglycosylated recombinant plasminogen activator variant derived from human tissue-type plasminogen activator. The main metabolic organs of reteplase are the kidneys, liver, and blood, whereas human tissue-type plasminogen activator is predominantly cleared by the liver. Recent studies showed that reteplase plasma concentrations were significantly increased in severe acute renal failure. The purpose of the present study was to evaluate whether the degree of renal failure influences the pharmacokinetic properties of reteplase. Subacute renal failure in rats was induced by bilateral 1-hr clamping of the renal arteries and recovery for 3 or 6 days. Acute renal failure was induced by bilateral surgical nephrectomy. Renal function was assessed by inulin clearance. The plasma concentration of functionally active reteplase was measured by an indirect spectrophotometric assay. Reteplase was administered as a double-bolus intravenous injection of 140 + 140 kU/kg, 30 min apart. In comparison with sham surgery, 1-hr clamping plus recovery for 6 days had the least effect on inulin clearance, followed by clamping and recovery for 3 days and bilateral nephrectomy (20.2 +/- 1.8 vs. 13.0 +/- 1.3, 8.3 +/- 0.8, and 3.1 +/- 0.2 ml center dot min-1 center dot kg-1, p < 0.01). Total plasma clearance of reteplase was significantly reduced, compared with sham surgery after 1-hr clamping plus 3-day recovery and bilateral nephrectomy (3.65 +/- 0.26 vs. 2.6 +/- 0.23 and 2.18 +/- 0.14 ml center dot min-1 center dot kg-1, p < 0.05 and p < 0.01, respectively), but not after 1-hr clamping plus 6-day recovery (3.33 +/- 0.34 ml center dot min-1 center dot kg-1, NS vs. sham surgery). There was a significant (p < 0.0001) linear correlation (r = 0.713) between the decrease of inulin clearance and the decrease of reteplase clearance. These data indicate that slight impairment of renal function does not significantly influence pharmacokinetic properties of reteplase, whereas severe renal dysfunction does.
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PMID:Influence of the degree of renal dysfunction on the pharmacokinetic properties of the novel recombinant plasminogen activator reteplase in rats. 882 Apr 18

We describe here the broad spectrum of acute renal insufficiency occurring in the course of human immunoinsufficiency virus infection. In our renal unit in Tenon hospital, 90 human immunoinsufficiency virus-infected adult patients were admitted for acute renal insufficiency between June 1988 and December 1996. Sixty out of them had a pathological diagnosis. The remaining patients did not have renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n = 11), or clinically evident hypovolemic and/or sepsis-related acute tubular necrosis (n = 17). Nine different causes of acute renal insufficiency were listed. Human immunoinsufficiency virus-associated nephropathy, the most specific human immunoinsufficiency virus-related renal disease, which was diagnosed in 14 patients, is characterized by focal and segmental glomerulosclerosis with an important hyperplasia and/or proliferation of podocytes and huge tubular distension. The rapid progression to end-stage renal failure was not a constant feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic syndrome was the other major cause of acute renal failure in these patients (32 cases) and was found to be associated with active cytomegalovirus infection. Cytomegalovirus-infected cells were present in half of the renal biopsies performed in this group of patients. Furthermore, these patients had an increased plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor was not significantly increased, as opposed to non human immunoinsufficiency virus-associated hemolytic-uremic syndrome. Half of the patients had a complete renal recovery. The other causes of acute renal insufficiency were 1) intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13 patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus-like glomerulonephritis characterized in one case by a complete clinical remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of renal diseases could be explained by the variation of human immunoinsufficiency virus-associated infections along time and by the different drugs which permit a better survival. We can hypothesize that new HIV-associated diseases will occur with the long term use of antiproteases.
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PMID:[Human immunodeficiency virus and acute renal insufficiency]. 961 98

Abnormal expression of fibrinolytic genes [e.g., tissue-type and urokinase-type plasminogen activators (t-PA and u-PA) and their specific inhibitor (PAI-1)] and of the procoagulant molecule tissue factor (TF), has been reported in various types of renal diseases. In this review, the expression pattern of these genes was demonstrated in two murine models of renal disease. One is acute renal failure due to microthrombosis under septic conditions, using endotoxin-treated mice, and the other one is lupus nephritis observed in female MRL lpr/lpr mice. Quantitative reverse transcription-polymerase chain reaction analysis and in situ hybridization were employed to investigate the expression of their mRNAs in tissues from endotoxin-treated mice or from MRL lpr/lpr mice. A dramatic increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was observed in both models, and this increase appeared to correlate with fibrin deposition in the renal microvasculature and with the progression of lupus nephritis. In addition to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in the kidneys from lupus-prone mice as a function of age. Similar changes were also observed in the kidneys from endotoxin-treated mice. The induction of PAI-1 and TF, and the decrease in u-PA expression in the kidneys of lupus-prone or of endotoxemic mice may promote the formation of renal microthrombi and thus contribute to the progression of renal damage in these models.
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PMID:Renal expression of fibrinolytic genes and tissue factor in a murine model of renal disease as a function of age. 970 58

We have previously demonstrated that gentamicin-induced acute renal failure is mediated by the consumption of renal glutathione (GSH) and accumulation of oxidized phospholipids in tubular epithelial cells as a result of inhibition of phospholipase A(2) (PLA(2)) activity. Based on these results, we tested the hypothesis that the simultaneous inhibition of PLA(2) and GSH synthesis induces acute renal failure similar in characteristics to gentamicin-induced acute renal failure. Male Sprague-Dawley rats kept under standard laboratory conditions were administered 3 mmol/kg of DL-buthionine sulfoximine (BSO; gamma-glutamylcysteine synthetase inhibitor) and 30 microg/kg of manoalide (PLA(2) inhibitor), following which significant elevations in serum creatinine and urinary lysosomal enzyme levels (elevation of N-acetyl-beta-D-glucosaminidase activity) were observed. The renal tissue GSH content was reduced in the group that received both BSO and manoalide as compared with the group that received manoalide alone. The renal tissue GSH content was also reduced in the group that received BSO alone. The renal tissue concentration of 2-thiobarbituric-acid-reactive substances increased rapidly, followed by an increase in renal tissue total phospholipid concentration in the group that received both BSO and manoalide. In contrast, the activity of PLA(2) in renal tissue decreased in the group that received both BSO and manoalide as compared with the groups that received BSO alone or physiological saline. In conclusion, concomitant administration of BSO and manoalide induces renal tubular damage and acute renal failure in rats, similar in characteristics to gentamicin-induced nephrotoxicity, whereas administration of BSO or manoalide alone did not. These results suggest that both inhibition of PLA(2) and GSH depletion are necessary for the induction of acute renal failure.
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PMID:Simultaneous inhibition of renal phospholipase A(2) and glutathione synthesis by manoalide and DL-buthionine sulfoximine induces acute tubular dysfunction in rats. 1072 47

Endothelial damage plays a central role in the development of an SIRS-related Multiple Organ Dysfunction Syndrome (MODS) as a consequence of the establishment of a hemostatic imbalance between coagulation and fibrinolysis systems. Until now, sepsis is the SIRS model that has been most studied. The aim of this study was to assess the endothelial damage and the hemostatic imbalance in early stages of an SIRS of different origins, and to study if there are any differences in these disturbances between infectious and noninfectious SIRS. The endothelial damage and hemostatic changes were studied in 40 patients with SIRS (with less than 12 h of evolution) and an acute renal failure. Infectious SIRS was diagnosed in 19 cases and noninfectious SIRS in the remaining 21 patients. Patients with SIRS presented significantly higher values (p<0.001) for factors related to endothelial damage [von Willebrand factor (vWF), thrombomodulin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) antigen], hypercoagulability [prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT)], and fibrinolysis (D-dimer and PAI activity) with respect to the control group. However, although the group with infectious SIRS presented higher values for all the factors except for the t-PA and D-dimer with respect to SIRS of other origins, none of these differences reached statistical significance (p>0.05). Our data show that patients with SIRS and associated acute renal failure, irrespective of the origin (infectious or noninfectious), show signs of intense endothelial damage and hypercoagulability throughout the process.
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PMID:Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF). 1105 12

We describe a neonate on venoarterial extracorporeal membrane oxygenation (ECMO) with acute renal failure associated with extensive aortic and bilateral renal artery thrombosis. Concurrent anticoagulation and continuous systemic thrombolytic therapy with tissue plasminogen activator (t-PA) resulted in complete thrombolysis as evaluated by Doppler flow. The relative risk and benefits of thrombolytic therapy in heparinized patients undergoing ECMO needs to be further studied.
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PMID:Successful lysis of an obstructive aortic and renal artery thrombus in a neonate on extracorporeal membrane oxygenation. 1119 May 98

The most common complication in the lethal cases of ophidian bites in Brazil is acute renal failure, but its pathogenesis is obscure. The effects of Bothrops jararacussu venom (3, 10 and 30 microg/ml) were examined using the isolated perfused kidney from Wistar rats. Dexamethasone, and WEB 2086, a triazolobenzodiazepine substance, which is a platelet activating factor receptor antagonist, were tested for a possible blockade of the renal effects in the presence of 10 microg/ml of venom. The most intense effects of the venom were noticed at 120 min after using 30 microg/ml. We observed a decrease in the perfusion pressure and in the renal vascular resistance. However, the glomerular filtration rate (GFR) and the urinary flow (UF) increased significantly. The percent of sodium (%Na(tot)(+)) and potassium (%K(tot)(+)) tubular transport were also decreased. Dexamethasone was unable to block the effects of B. jararacussu in the kidney, while WEB 2086 blocked its effect in glomerular filtration rate, urinary flow and in the percentage of total tubular potassium reabsorption. We suggest that this venom promotes diuresis independently of perfusion pressure drop. The alterations in GFR, UF and %K(tot)(+) are probably mediated by platelet activating factor. Dexamethasone did not block the renal effects maybe because of the concentration used in this work or maybe the renal effects are promoted by the myotoxin, which does not have PLA(2) activity.
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PMID:The renal effects of Bothrops jararacussu venom and the role of PLA(2) and PAF blockers. 1160 Jan 46


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