salicylates and Renal-Insufficiency

This is a review of the available information about drugs which cause an increase in plasma creatinine concentration without decreasing glomerular filtration rate (GFR). The GFR is the main, but not the single, determinant of the plasma creatinine levels. Several drugs, such as cimetidine, trimethoprim, corticosteroids, pyrimethamine, phenacemide, salicylates and active vitamin D metabolites, have been reported to increase plasma creatinine without influencing its glomerular filtration. Cimetidine, trimethoprim, pyrimethamine and salicylates can inhibit secretion of creatinine by the proximal tubule. Corticosteroids and vitamin D metabolites probably modify the production rate and the release of creatinine. The exact mechanism of phenacemide-creatinine interaction is not fully explained. These drug-induced alterations in plasma creatinine concentration have clinical significance when GFR is estimated by using plasma creatinine.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Benzeneacetamides; Cimetidine; Creatinine; Drug-Related Side Effects and Adverse Reactions; Glomerular Filtration Rate; Histamine H2 Antagonists; Humans; Pyrimethamine; Renal Insufficiency; Salicylates; Trimethoprim; Urea; Vitamin D

Topics: Acute Kidney Injury; Ascites; Dialysis; Ethanol; Methanol; Nephritis; Peritoneal Cavity; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Toxicology

Many acyl glucuronides are labile, reactive and form covalent adducts with proteins. In the present experiment, the stability of salicyl acyl glucuronide (SAG), its reactivity with serum albumin in vitro and the influence of renal failure in rats on the disposition of SAG and covalent binding of salicylate (SA) to rat plasma proteins were investigated. In vitro studies showed that SAG was hydrolyzed to SA or undergoes isomerization to positional isomers. The half-life of SAG was 1.3 hr in 0.15 M phosphate buffer at pH 7.4 and 37 degrees C, but the stability of its isomers was much greater with an apparent half-life of 19 hr. Incubation of SAG in solutions of human serum albumin revealed the formation of covalent adducts with the protein, with maximal binding of 2.8% of total SA equivalents added to the solution. For in vivo studies, one group of rats was administered 5 mg/kg of uranyl nitrate i.p. to induce renal failure. After administration of 100 mg/kg of SA i.v., the AUC 0-26 hr of SAG in rats with renal failure was 9 times higher than that observed in control rats. The apparent clearance of SA decreased from 64 +/- 21 ml/hr in control rats 28 +/- 8.7 ml/hr in rats with renal failure. The level of SA covalent adducts with plasma proteins reached about 0.5 ng/mg of protein in control rats, whereas in rats with renal failure the binding was increased significantly and achieved an average peak concentration of 18 ng/mg of protein when measured 26 hr after dosing. The data indicate that reactive SAG can accumulate in renal failure which then increases covalent addition of SA to proteins. Such binding may have a role in enhancing the potential for toxicity of acidic drugs such as SA in renal disease.

Topics: Animals; Binding, Competitive; Blood Proteins; Glucuronates; Rats; Renal Insufficiency; Salicylates

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Acute Kidney Injury; Barbiturates; Dialysis; Kidneys, Artificial; Peritoneal Dialysis; Peritoneum; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Toxicology

Topics: Acute Kidney Injury; Aspirin; Blood Chemical Analysis; Bronchopneumonia; Coma; Diagnosis, Differential; Diuresis; Gastric Lavage; Heart Arrest; Heart Failure; Humans; Infusions, Parenteral; Kidney; Kidneys, Artificial; Phenacetin; Poisoning; Pulmonary Edema; Renal Insufficiency; Salicylates; Statistics as Topic; Toxicology

Topics: Colchicine; Gout; Humans; Kidney Diseases; Phenylbutazone; Renal Insufficiency; Salicylates; Uric Acid