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)

Based on recent reports that reactive oxygen metabolites may play a role in endotoxin-induced injury in other tissues, we postulated that reactive oxygen metabolites may be important mediators of endotoxin-induced acute renal failure. Superoxide dismutase, a scavenger of superoxide, or catalase, which destroys hydrogen peroxide, did not protect against endotoxin-induced renal failure. Similarly, neither the hydroxyl radical scavenger dimethylthiourea nor the iron chelator deferoxamine (which presumably would act by preventing the generation of hydroxyl radical via the iron-catalyzed Haber-Weiss reaction) prevented the endotoxin-induced fall in renal function. In separate experiments, we found no increase in renal cortical lipid peroxidation (a marker of reactive oxygen metabolite-mediated tissue injury) in endotoxin-treated rats, providing further evidence against a role for reactive oxygen metabolites in endotoxin-induced renal injury. Finally, using the aminotriazole-induced inhibition of catalase (a measure of in vivo changes in the hydrogen peroxide generation) we found no evidence of enhanced hydrogen peroxide generation in the renal cortex in endotoxin-treated rats. Taken together, the data from these three separate experimental approaches suggest that reactive oxygen metabolites are not important mediators of endotoxin-induced acute renal failure.
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PMID:Reactive oxygen metabolites in endotoxin-induced acute renal failure in rats. 212 35

The anemia associated with renal failure has been studied for over 150 years. It results primarily from inadequate production of erythropoietin such that plasma levels in dialysis patients are only 25% of those expected for the degree of anemia. Shortened red call survival, iron and other nutritional deficiencies, and uremic inhibitors have a secondary and minor role. Recombinant human erythropoietin (rHuEPO) is now used to treat this anemia. It is heavily sialated, which permits its circulation long enough to act on the bone marrow where, in concert with other growth factors, it commits progenitor cells to the erythroid cell pathway. Major issues related to clinical use of rHuEPO are dosage, resistance, and cost. Pharmacokinetic studies predict significant weekly dose reductions (and therefore cost savings) using the subcutaneous route compared to the intravenous route permitting more patients to be treated optimally. Biological heterogeneity and not hyperparathyroidism or aluminum overload accounts for most instances in which more than 450 U/kg/wk of rHuEPO is required.
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PMID:Recombinant human erythropoietin: physiology, pathophysiology of anemia in renal failure, and economic aspects related to dosing. 226 Jun 13

It is well known that macrophages are the principle cells responsible for removal of senescent erythrocytes from circulation and are the major storage cell for body iron. Monitoring stored iron in patients with anemia secondary to renal failure and chronic hemodialysis is an important parameter used for gauging supplementing these patients with iron. We have proven that blood monocyte ferritin unlike serum ferritin reflects adequately bone marrow iron stores and thus replaces an undesirable procedure in such patients namely bone marrow punctures.
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PMID:Monocyte ferritin as a possible index of bone marrow iron stores in patients on chronic hemodialysis. 229 47

End-stage renal failure and long-term hemodialysis treatment promote the development of genetically conditioned porphyria cutanea tarda (PCT). The clinical manifestation is triggered off by unknown factors coexisting with renal insufficiency and hemodialysis. Iron overload is often associated with the disease and is thought to play a key role in its pathogenesis. Iron removal by deferoxamine infusions is regarded as the treatment of choice for patients who cannot undergo repeated phlebotomy procedures and has been successfully used in patients with normal renal function. We report a case of hemodialysis-related PCT and iron overload in whom repeated venesections were contraindicated on account of severe anemia and treatment with deferoxamine led to a striking improvement of symptoms.
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PMID:Successful treatment of hemodialysis-related porphyria cutanea tarda with deferoxamine. 237 Sep 33

Recombinant human erythropoietin (rHuEPO) was purified from the conditioned media of Chinese hamster ovary cells with a transfected human erythropoietin gene. We investigated the effects of the rHuEPO in rats with renal anemia induced by partial nephrectomy. Five-sixth nephrectomy resulted in renal failure with anemia. Twenty-five days after the operation plasma urea nitrogen was increased about 2.5 times, and the red blood cell count, hematocrit, and hemoglobin concentration fell to 85% of normal. The reticulocyte count and plasma erythropoietin level did not change such as they do in patients with anemia due to chronic renal failure. Both total red blood cell volume and the plasma iron turnover rate were depressed in five-sixth nephrectomized rats compared with normal rats. The five-sixth nephrectomized rats were injected with rHuEPO (60 IU/kg) intravenously every second day for a total of six injections. After three injections of rHuEPO, circulation volume of total red blood cells was increased from 9.9 ml to 14.6 ml, and the plasma iron turnover rate was increased from 1.03 mg/kg/day to 2.12 mg/kg/day, and the reticulocyte count was also increased. After six injections, a marked increase of the red blood cell count, hematocrit, and hemoglobin concentration were observed. Plasma urea nitrogen and the creatinine levels as indications for renal function did not change after rHuEPO administration in both normal and five-sixth nephrectomized rats. In conclusion rHuEPO has a potent erythropoietic action and it is possible to cure the anemia caused by renal failure.
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PMID:Effect of purified recombinant human erythropoietin on anemia in rats with experimental renal failure induced by five-sixth nephrectomy. 240 Jun 29

Parenteral administration of iron nitrilotriacetate (FeNTA) to rats resulted in marked loss in body weight, and increases in liver/and kidney/body weight ratios. Fatalities, due to renal failure, depended on dosage and age of the animals, and were greater (70%) after a single large dose (12 mg iron) than after repeated smaller doses (30%). FeNTA administered subchronically gave rise to an increase in ethane exhalation, and to decreased liver glutathione peroxidase activity, and decreased cytochrome P-450 concentration and benzphetamine N-demethylase activity. It also resulted in severe renal tubular necrosis, with deposition of iron in the tubular cells and loss of brush border alkaline phosphatase activity, resulting in a dose-dependent diuresis, with increased urinary excretion of glucose, iron and lipid peroxidation products, and decreased urine creatinine concentration. NTA alone had none of these effects but slightly decreased the hepatic concentration of iron.
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PMID:Effects of acute and sub-chronic administration of iron nitrilotriacetate in the rat. 257 73

Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU-e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T1/2 range of 2.3 to 7.3 h. T1/2 after the first dose of r-HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment.
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PMID:Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics. 259 53

The rate of intravascular hemolysis and associated complications was studied in 100 patients with rheumatic heart disease within 2 to 20 years after replacement of the heart valves. Hemolysis of varying intensity was recorded in 72% of patients, anemia in 5%, hemosiderinuria in 27%, cholelithiasis in 4%, and sideropenia in 36.8% of the examined. Renal failure was diagnosed in none of the patients. Thromboembolic complications were more frequently encountered in patients with hemolysis. In order to prevent anemia and sideropenia, it is recommended that control may be exercised over hemolysis and iron content in the blood of patients with prosthetic heart valves.
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PMID:[The effect of intravascular hemolysis on the body of rheumatics with heart valve prostheses]. 260 61

Renal dysfunction gives rise to a variety of hematologic disturbances, including anemia, leukocyte dysfunction, and coagulopathy. The anemia of renal failure has been attributed to a relative deficiency of erythropoietin, but contributing factors include an absolute deficiency of iron or folate. Other contributing factors include heavy metal toxicity, blood loss, and hemolysis. The treatment of the anemia of renal disease has advanced with the development of recombinant human erythropoietin. At doses from 15-500 micrograms/kg triweekly in selected patients, normalization of hemoglobin is presently possible. Transfusion may still have a role in patients with renal disease, although more as preconditioning for renal transplantation. In non-HLA matched transplantation, donor-specific transfusion, as well as immunosuppressives, may exert some benefit in graft survival. The coagulopathy of renal disease consists of an acquired qualitative platelet defect best remedied by dialysis but also treated successfully by cryoprecipitate or DDAVP. Infectious complications of uremia include diminished leukocyte chemotaxis, phagocytosis, and bactericidal activity. Cell-mediated immune defects and hypogammaglobulinemia have also been described. The pathophysiology involved in the protean hematologic manifestations of uremia are discussed; additionally, we describe therapeutic recommendations to deal with anemia, bleeding and infectious complications of renal failure.
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PMID:Hematologic aspects of renal insufficiency. 267 32

Early investigational trials with new quinolone antibiotics revealed two important drug-drug interactions: decreased fluoroquinolone absorption when co-administered with magnesium-aluminum antacids and inhibition of theophylline metabolism. Subsequent studies have investigated the mechanisms of these interactions. With respect to the effect of antacids, the absorption of all quinolones appears to be significantly reduced by antacids containing magnesium and/or aluminum, and concomitant administration must be avoided. Other cations, such as calcium, iron, and probably zinc, appear to interact in a similar manner. Chelation between the quinolone and cation is the most likely mechanism. With respect to the effect on theophylline metabolism, quinolones inhibit specific cytochrome P-450 isozymes responsible for metabolism of methylxanthines, although there are major differences between the quinolones. Enoxacin is the most potent inhibitor, followed by ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin. Caffeine metabolism is also inhibited, although the clinical significance is uncertain. Case reports describe renal failure associated with concomitant administration of cyclosporine and ciprofloxacin, although controlled trials have not demonstrated an interaction. Enoxacin has little effect on warfarin metabolism, suggesting that other quinolones may not affect warfarin disposition. Case reports of central nervous system toxicity from administration of nonsteroidal anti-inflammatory agents and quinolones need confirmation. Patients should be monitored closely when potential interacting agents are used; it is probable that not all interactions have been identified.
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PMID:Drug-drug interactions with ciprofloxacin and other fluoroquinolones. 268 30


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