salicylates and Kidney-Papillary-Necrosis

Non-steroidal anti-inflammatory agents ( NSAIA ) are increasingly used in clinical practice. They exert the majority of their therapeutic and adverse effects by inhibiting prostaglandin synthesis. A variety of clinically important side effects have been described following their administration. We review the renal complications, which include sodium retention, interference with the effectiveness of diuretics, impairment of water excretion, development of hyperkalemia, interference with the therapy of hypertension, and induction of at least four different forms of renal failure. The hemodynamic variety of renal failure and the side effects affecting fluid and electrolyte homeostasis are most likely to become manifest in the context of conditions leading to decreased renal perfusion. Guidelines for use of NSAIA , detection of patients at risk, and therapeutic approaches are provided.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Inflammatory Agents; Blood Pressure; Female; Glomerulonephritis; Hemodynamics; Humans; Hyperkalemia; Hyponatremia; Kidney Diseases; Kidney Papillary Necrosis; Male; Middle Aged; Nephritis, Interstitial; Prostaglandin Antagonists; Prostaglandins; Risk; Salicylates; Water-Electrolyte Balance

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Drug Synergism; Humans; Kidney; Kidney Diseases; Kidney Papillary Necrosis; Phenacetin; Salicylates; Tissue Distribution

"Aspirin" is the most widely used medication which is considered to be safe and effective, and which can be obtained universally without prescription. A review of the literature and clinical experience reveal that many complications can be attributed to the prolonged use of it. Some of these complications involve damage to various tissues and organs (particularly the gastric mucosa, the renal papilla, red blood cells, and the inner ear) and to coagulation and body temperature control. Hemorrhagic gastritis may result with as little as 600 mg. of salicylate four times a day for 5 days. Papillitis of the renal system may result from a comparable dosage of aspirin compound mediates with phenacetin. The purpose of this article has been to call attention to some of the important complications which may result from salicylate abuse. It is hoped that many of these complications may be avoided by proper and effective indoctrination of patients to the hazards associated with prolonged or indiscriminate intake of salicylates.

Topics: Acid-Base Equilibrium; Aspirin; Blood Coagulation; Blood Platelets; Carbon Dioxide; Digestive System; Ear, Inner; Fever; Gastric Mucosa; Gastrointestinal Hemorrhage; Homeostasis; Humans; Kidney; Kidney Papillary Necrosis; Phenacetin; Salicylates

Topics: Acetaminophen; Analgesics; Animals; Aspirin; Carcinoma, Transitional Cell; Female; Humans; Kidney Neoplasms; Kidney Papillary Necrosis; Male; Microsomes, Liver; Phenacetin; Rats; Salicylates; Spermatogenesis; Substance-Related Disorders

Topics: Analgesics; Australia; Drug Combinations; Humans; Kidney Diseases; Kidney Papillary Necrosis; Nephritis, Interstitial; Nonprescription Drugs; Phenacetin; Salicylates; Substance-Related Disorders

Using a compound analgesic mixture, it was found that renal pathology could be produced in rats if the analgesic mixture was administered as a concentrated aqueous suspension, but that development of renal pathology was not favored by hot, dry environmental conditions. Determination of whole body total salicylate concentrations in rats and humans receiving various doses of aspirin revealed that twice daily doses of 24, 60 and 125 mg/kg aspirin in the rat were equivalent to human doses of 8, 20 and (approximately) 40 ordinary 325 mg aspirin tablets daily. These doses of aspirin were then employed in a subchronic study of the nephrotoxicity of aspirin in the rat using the experimental design which maximized the nephrotoxic effects of the compound analgesic mixture. Six groups of ten male and ten female rats received aspirin orally at doses of 24,60 or 125 mg/kg twice a day five days a week for 12 weeks. Two additional groups of ten male and ten female rats received only the vehicle, at a volume equivalent to that received by the high dose group, and served as controls. Four groups (one each, control, low, mid-, and high dose) were denied access to water for 16 hours daily overnight. No pathologic renal changes were observed in any of the rats. These findings are consistent with a growing body of evidence, from both animal and human studies, that aspirin alone does not produce analgesic nephropathy.

Topics: Animals; Aspirin; Caffeine; Dehydration; Drug Combinations; Female; Hot Temperature; Humidity; Kidney Diseases; Kidney Papillary Necrosis; Male; Phenacetin; Rats; Salicylates

Topics: Animals; Humans; Kidney Papillary Necrosis; Rats; Salicylates

Topics: Animals; Humans; Kidney Papillary Necrosis; Rats; Salicylates

Topics: Animals; Antipyrine; Humans; Kidney Diseases; Kidney Papillary Necrosis; Phenacetin; Salicylates

Topics: Acetaminophen; Antipyrine; Denmark; Humans; Kidney Diseases; Kidney Neoplasms; Kidney Papillary Necrosis; Legislation, Drug; Phenacetin; Pyelonephritis; Salicylates; Substance-Related Disorders; Sweden; Switzerland; Urinary Bladder Neoplasms

Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate. No renal medullary gradient for salicylate was demonstrable during both hydropenic and hydrated states. In contrast, both free and conjugated APAP concentrations rose sharply in the inner medulla during hydropenia, reaching a mean maximal value at the papillary tip exceeding 10 times the cortical concentration (P < 0.001), a distribution similar to that of urea. Salicylate had no effect on the APAP gradient, but hydration markedly reduced both the APAP and urea gradients in the medulla. The data indicate that APAP probably shares the same renal mechanisms of transport and accumulation as urea and acetamide, and that papillary necrosis from excessive phenacetin may be related to high papillary concentration of APAP.

Topics: Analgesics; Animals; Aspirin; Dehydration; Dogs; Female; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Concentrating Ability; Kidney Diseases; Kidney Papillary Necrosis; Osmosis; Phenacetin; Salicylates; Substance-Related Disorders; Urea

Topics: Analgesics; Arthritis, Rheumatoid; Diabetes Complications; Female; Humans; Kidney Papillary Necrosis; Male; Middle Aged; Phenacetin; Salicylates; Scotland; Urologic Diseases

Topics: Analgesics; Anemia; Creatinine; Female; Hemoglobinometry; Humans; Kidney Function Tests; Kidney Papillary Necrosis; Male; Middle Aged; Nephritis, Interstitial; Phenacetin; Prognosis; Salicylates; Substance-Related Disorders; Urinary Tract Infections

Topics: Adrenal Cortex Hormones; Adult; Aged; Amyloidosis; Arthritis, Rheumatoid; Female; Humans; Kidney Diseases; Kidney Papillary Necrosis; Male; Middle Aged; Nephritis, Interstitial; Phenacetin; Phenylbutazone; Pyelonephritis; Salicylates

Topics: Adult; Aged; Analgesics; Blood Chemical Analysis; Blood Pressure Determination; Duodenal Ulcer; Female; Humans; Kidney Function Tests; Kidney Papillary Necrosis; Male; Mental Disorders; Middle Aged; Phenacetin; Pyelonephritis; Salicylates; Stomach Ulcer; Urography

Four patients who had ingested large amounts of phenacetin-salicylate medications were studied during a 12-month period. Renal failure had progressed slowly over a number of years. All patients took the drug because of psychogenic headache. Considerable skill was required to elicit the history of drug habituation. The major features of the nephropathy were multiple episodes of metabolic acidosis, minimal proteinuria, pyuria but no bacteriuria, and polyuria and polydipsia early in the course of drug ingestion. Papillary necrosis was not a prominent clinical feature of this series. Discontinuation of drug ingestion by one patient was associated with recovery of a considerable degree of renal function. Preliminary experimental evidence obtained in the dog suggests that salicylate impaired the efficiency of the counter-current multiplier by decreasing sodium transport in the ascending limb of Henle, and decreased the permeability to water of the distal convoluted and collecting tubule; phenacetin had no such effect.

Topics: Acidosis; Animals; Aspirin; Bacteriuria; Biological Transport; Caffeine; Codeine; Dogs; Drug Therapy; Headache; Humans; Kidney Diseases; Kidney Papillary Necrosis; Kidney Tubules; Metabolism; Neoplasm Recurrence, Local; Neoplasms; Phenacetin; Polyuria; Proteinuria; Pyuria; Salicylates; Sodium; Toxicology