Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the concentrations of serum nitrates/nitrites and plasma cyclic guanosine monophosphate as markers of nitric oxide synthesis in patients with or without septic shock for 5 days following admission to intensive care. We found that nitrate/nitrite concentrations, when corrected for the effect of renal failure, were significantly higher in patients with septic shock, both on admission and in the final samples drawn. In a logistic regression analysis, the rate of change of nitrate/nitrite concentration was associated with survival to day 28 (falling in survivors). The concentration of cyclic guanosine monophosphate when corrected for the confounding effects of renal function and platelet count, was only associated with the septic shock group on admission.
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PMID:Indices of nitric oxide synthesis and outcome in critically ill patients. 1128 18

The rise of blood pressure is negatively related with the glomerullar filtration rate(GFR) in patients with terminal renal failure. Hypertension may be a mechanism to maintain renal blood flow and GFR constant by the increased driving force of blood to the kidney. Elevated levels of a so-called third factor, now designated as endogenous digitalis, are found in those patients. The most likely candidate of the endogenous digitalis is ouabain, which causes hypertension with chronic administration. On the other hand, extreme hypotension often occurs during maintenance hemodialysis, and since hemodynamic alterations closely resemble endotoxin shock, the involvement of nitric oxide(NO) over-production has been suggested. When we measured nitrate anion as the final metabolite of NO, the concentration was significantly higher in patients with marked hypotension during hemodialysis than those without hypotension. Since reflex tachycardia was not observed during hypotension, we speculated that those patients had autonomic disturbances, and assessed autonomic function by heart rate spectral analysis. Although the high frequency spectral power, regarded as the vagal tone, was not significantly different between the groups, low/high frequency spectral power ratio, which was thought to be a sympathetic component, was significantly lower in patients with hypotension during hemodialysis than that in patients without hypotension. We speculated that NO synthase may be induced by the stimuli to monocytes by tubes and dialyser membrane made of synthetic materials leading to the over production of NO during and after regular hemodialysis. Thus, cytokines may be the mediator of the induction of NO synthase. Dilated capacitance vessels decrease the venous return to the heart, which may be the direct cause of dialysis-induced hypotension.
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PMID:[Pathophysiology of blood pressure variability in patients with chronic renal failure under maintenance hemodialysis]. 1130 22

Impaired angiogenesis and decreased vascular endothelial growth factor (VEGF) expression were recently documented in the remnant kidney (RK) model of progressive renal failure. VEGF (50 microg/kg, twice daily) was administered to RK rats between weeks 4 and 8 after surgery, and rats were euthanized at week 8 for histologic study. During the administration of VEGF (n = 7) or vehicle (n = 6), systemic BP was comparable in the two groups. VEGF treatment resulted in improved renal function and lower mortality rates, compared with the vehicle-treated group. Renal histologic analyses confirmed a 3.5-fold increase in glomerular endothelial cell proliferation (0.14 +/- 0.03 versus 0.04 +/- 0.02 proliferating endothelial cells/glomerulus, VEGF versus vehicle, P < 0.05), a twofold increase in peritubular capillary endothelial cell proliferation (1.60 +/- 0.30 versus 0.78 +/- 0.17 cells/mm(2), VEGF versus vehicle, P < 0.01), a threefold decrease in peritubular capillary rarefaction (P < 0.01), and a twofold increase in endothelial nitrix oxide synthase expression (P < 0.05) in the VEGF-treated group; an eightfold increase in urinary nitrate/nitrite levels (P < 0.05) was also noted. Although the difference in glomerulosclerosis scores did not reach statistical significance (0.67 +/- 0.42 versus 1.22 +/- 0.63, VEGF versus vehicle; range, 0 to 4; P = NS), VEGF-treated rats exhibited less interstitial collagen type III deposition (9.32 +/- 3.26 versus 17.45 +/- 7.50%, VEGF versus vehicle, P < 0.01) and reduced tubular epithelial cell injury, as manifested by osteopontin expression (5.57 +/- 1.60 versus 9.58 +/- 3.45%, VEGF versus vehicle, P < 0.01). In conclusion, VEGF treatment reduces fibrosis and stabilizes renal function in the RK model. The use of angiogenic factors may represent a new approach to the treatment of kidney disease.
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PMID:Impaired angiogenesis in the remnant kidney model: II. Vascular endothelial growth factor administration reduces renal fibrosis and stabilizes renal function. 1142 73

Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m(2); P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m(2); P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73 m(2) and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.
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PMID:Defective nitric oxide production and functional renal reserve in patients with type 2 diabetes who have microalbuminuria of African and Asian compared with white origin. 1156 11

Nitric oxide synthase requires tetrahydrobiopterin for its activity. In animal models of sepsis, changes in circulating tetrahydrobiopterin concentrations precede increases in nitrate. We measured plasma tetrahydrobiopterin and nitrate concentrations on three consecutive days in 10 patients with septic shock and 10 critically ill control patients. Total nitrate concentration was measured after reduction of nitrite to nitrate. Tetrahydrobiopterin concentrations were measured using HPLC. The median (range) APACHE II score was 22 (13-27) in the patients with septic shock and 25 (7-28) in the control group. The nitrate concentration was significantly higher in patients with septic shock than in controls (P = 0.01) on all days but did not change with time. Tetrahydrobiopterin concentrations were highest in the patients with septic shock on day 1 only (P = 0.037). In the seven patients with renal failure, both nitrate and tetrahydrobiopterin concentrations tended to be higher than in the 13 patients without renal failure. The nitrate concentration correlated with tetrahydrobiopterin concentration on day 1 only (P = 0.05). In patients with septic shock, both tetrahydrobiopterin and total nitrate concentrations were higher than those in critically ill controls but were increased mainly in patients with renal failure. In summary, tetrahydrobiopterin concentration increases during septic shock, in line with increases in nitrate concentration. However, as for nitrate, concentrations
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PMID:Circulating tetrahydrobiopterin concentrations in patients with septic shock. 1157 38

In patients the progression of pathologic renal processes after the treatment of primary disease is a problem of increasing importance and therapeutic strategies are insufficient till now. The aim of this paper was to search for rat models of interstitial fibrosis as a basis for testing therapeutic strategies to prevent end-stage renal failure. Experiments were done on adult female Wistar rats (Han:Wist) to investigate long-term consequences of temporary warm ischaemia, 5/6 nephrectomy (5/6 NX) and single uranyl nitrate (UN) administration (0.3 or 0.5 mg/ 100 g body wt. intraperitoneally). Observation time was 20 weeks after injury in each group. Creatinine clearance, urinary protein excretion and hydroxy-proline (OH-proline) concentration in renal tissue were measured and light microscopic investigations were done to characterise both quality and time course of long-term renal damage in relation to matched control animals. Temporary warm ischaemia and 5/6 NX did not cause any fibrotic changes during the 20 weeks observation period. The higher UN dose led to decreased creatinine clearance, increased urinary protein excretion and enhanced OH-proline concentration in renal tissue. Morphologic investigations showed fibrotic areas containing strongly dilated and atrophic tubules with thickened basal membranes. These effects can be seen from week four after UN administration up to the end of the observation period. In conclusion, administration of one single dose of UN is a simple procedure to induce interstitial renal fibrosis as an experimental model to investigate therapeutic strategies for their prevention.
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PMID:Temporary warm ischaemia, 5/6 nephrectomy and single uranyl nitrate administration--comparison of three models intended to cause renal fibrosis in rats. 1166 57

The epileptogenic activity of imipenem was investigated in rats with experimental renal failure induced by uranyl nitrate injection by using electroencephalogram (EEG) recording and a pharmacokinetic-pharmacodynamic model including an effect compartment. Results previously obtained with healthy rats were used to estimate the dose of imipenem required to induce an observable but nonlethal EEG effect on the assumption that only the pharmacokinetic parameters of the model would be affected by renal failure. Good agreement was observed between the predicted and observed effects.
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PMID:Pharmacokinetic-pharmacodynamic modeling of electroencephalogram effect of imipenem in rats with acute renal failure. 1170 50

A number of xenobiotics and certain pathophysiological situations cause the induction of CYP2E1. The present study was designed to establish the role of plasma urea nitrogen and L-arginine on hepatic CYP2E1 expression in rats or rats with acute renal failure. Exposure of rats to a single intravenous dose of 5 mg/kg uranyl nitrate caused renal failure in 5 days (ARF), as evidenced by increases in plasma urea nitrogen level and kidney to body weight ratio. Northern and Western blot analyses revealed that hepatic CYP2E1 was 2- to 4-fold induced by ARF. Treatment of rats with either 10% glucose in drinking water for 5 days following a single injection of uranyl nitrate or two injections of recombinant growth hormone (5 units/kg, s.c., twice a day) on the 4th day after uranyl nitrate injection reduced both the rise in plasma urea nitrogen and the induction of CYP2E1. Exposure of rats to urea (approximately 225 mg/kg/day) in drinking water for 1 to 3 day(s) resulted in significant increases in CYP2E1 mRNA and protein. Furthermore, perfusion of the liver with 25 mM urea for 24 h resulted in CYP2E1 induction with an increase in the mRNA. The levels of CYP2E1 protein and mRNA were increased in rats perfused with 25 mM L-arginine for 24 h (i.e., a 4-fold increase). Hence, L-arginine, which is irreversibly hydrolyzed to urea and ornithine by arginase, also induced hepatic CYP2E1. The results of the present study provided evidence that increases in plasma urea in conjunction with L-arginine metabolism lead to the induction of CYP2E1 in the liver.
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PMID:Increase in urea in conjunction with L-arginine metabolism in the liver leads to induction of cytochrome P450 2E1 (CYP2E1): the role of urea in CYP2E1 induction by acute renal failure. 1201 4

The purpose of this investigation was to determine whether the pharmacokinetics of the angiotensin II receptor antagonist losartan is altered in renal failure. Male Wistar rats were pretreated with uranyl nitrate or subjected to bilateral ureteral ligation to produce acute renal failure (ARF). Saline-injected and sham-operated rats, respectively, served as controls. Uranyl nitrate-treated rats showed significantly higher serum concentrations of losartan after oral administration and the area under the serum concentration-time curve (AUC(0-24)) of losartan increased about 3-fold compared to control rats. The systemic clearance of losartan significantly decreased from 410 +/- 254ml/h/kg in control to 177 +/- 112ml/h/kg in uranyl nitrate-treated rats. In order to investigate the mechanisms of reduced clearance of losartan associated with ARF, a hepatic microsome fraction was prepared from normal and ARF rats. No significant difference was found in the metabolism of losartan by hepatic microsomes prepared from ARF and control rats. In addition, the metabolic activity of microsomes was examined in the presence of uremic rat serum. The unbound clearance of losartan and the unbound clearance associated with the formation of EXP3174 in the presence of uremic serum were significantly lower than those in the presence of control serum. Furthermore, the metabolism of losartan was inhibited by indoxyl sulfate, a uremic toxin, in an uncompetitive manner. These results suggest that ARF is associated with reduced clearance of losartan due to the inhibition of hepatic metabolism by accumulated uremic toxin(s).
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PMID:Effect of experimental renal failure on the pharmacokinetics of losartan in rats. 1218 13

In rats with acute renal failure induced by uranyl nitrate, the hepatic microsomal cytochrome P450 (CYP) 2E1 and CYP3A23 increased 2-4- and 4-times, respectively, CYP2C11 decreased to 80% of control, but the levels of CYP1A2 and CYP2B1/2 were not changed. It has been reported that theophylline was metabolized to 1,3-dimethyluric acid by CYP1A2 and CYP2E1 and 1-methylxanthine via CYP1A2, which was metabolized further to 1-methyluric acid via xanthine oxidase in rats. Hence, it was expected that the formation of 1,3-dimethyluric acid would show an increase in rats with renal failure as a result of induction of CYP2E1. The pharmacokinetics of theophylline were compared in control rats and rats with renal failure after intravenous administration of aminophylline, 5 mg kg(-1) as theophylline. In rats with renal failure, the plasma concentrations of theophylline were considerably lower and the resultant total area under the plasma concentration-time curve from time zero to time infinity (AUC(0- infinity )) of theophylline was significantly smaller (2,200 vs 1,550 microg min mL(-1)) compared with control rats. In rats with renal failure, the plasma concentrations of 1,3-dimethyluric acid were considerably higher and the resultant AUC(0-6 h) of 1,3-dimethyluric acid was significantly greater (44.4 vs 456 microg min mL(-1)) compared with control rats. Moreover, the AUC(0-6 h, 1,3-dimethyluric acid)/AUC(0- infinity, theophylline) ratio increased from 2.02% in control rats to 29.4% in rats with renal failure. The in-vitro intrinsic 1,3-dimethyluric acid formation clearance was significantly faster in rats with renal failure (734 vs 529 10(-6) mL min(-1)) compared with control rats using hepatic microsomal fraction. The results led us to conclude that in rats with uranyl nitrate-induced renal failure after the administration of aminophylline, 5 mg kg(-1) as theophylline, there was an increase in the formation of 1,3-dimethyluric acid as a result of an increase in CYP2E1 expression.
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PMID:Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous theophylline in rats: the role of CYP2E1 induction in 1,3-dimethyluric acid formation. 1254


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