salicylates and Kidney-Diseases

Topics: Acetaminophen; Aged; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents; Apazone; Aspirin; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Diclofenac; Drug Hypersensitivity; Gastrointestinal Diseases; Hematologic Diseases; Humans; Ibuprofen; Indomethacin; Ketoprofen; Kidney Diseases; Kinetics; Naproxen; Phenylbutazone; Piroxicam; Salicylates; Thiazines

The hair cells of the cochlea (neuroepithelium) represent the primary target in most drug-induced ototoxic adverse effects on hearing (e.g. aminoglycoside antibiotics). To what extent an exogenically-induced morphologic damage to hair cells is reversible is not known. In aging structurally altered hair cells can persist for years likewisely not any longer participating in sensory transduction as the hair cells degenerate, secondary changes occur in the spiral ganglion cells and the neuronal pathways. Following heavy metal poisoning an adverse effect is observed on both central and peripheral innervation of the cochlea and only minor primary changes occur in the receptor cells. The link between function and morphology in the cochlea is very obvious regarding the high and middle frequencies with a distinct tonotopic localisation whereas for low frequencies (below 1 khz) such a specific morphologic correlation is lacking. Ototoxic effects primarily affecting the source for the production of endolymph, i.e. the stria vascularis, become manifest at all frequencies and at a rather early stage. Independent of type of substance penetrating into the inner ear, the substance has a considerably slower elimination rate as compared with all other compartments in the body. The toxicity of the drugs seems to be more related to its tissue binding capacity and saturation of receptor sites than related to the concentration of the drug in endo-or perilymph.

Topics: Age Factors; Aminoglycosides; Animals; Anti-Bacterial Agents; Antimalarials; Antineoplastic Agents; Cochlear Implants; Diuretics; Drug Evaluation; Drug Evaluation, Preclinical; Embryo, Mammalian; Endolymph; Fever; Hair Cells, Auditory; Hearing Loss, Sensorineural; Humans; Kidney Diseases; Kinetics; Labyrinth Diseases; Metals; Rats; Salicylates; Stria Vascularis

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

Several classes of drugs have been identified as having ototoxic potential: aminoglycoside antibiotics, other basic antibiotics, antimalarial drugs, loop diuretics, and salicylates. Various chemicals have also been implicated in causing ototoxicity. If certain predisposing conditions are present when a potentially ototoxic drug is administered, the risk of ototoxicity is increased. These conditions include impaired renal functioning, pregnancy, previous or concomitant treatment with another potentially ototoxic drug, inherited susceptibility to ototoxicity, and the effects of noise. Other conditions that have been associated with ototoxicity for which there is a lack of strong scientific support are age, sex, and pre-existing hearing loss. The physician's awareness of predisposing conditions combined with rational drug usage can reduce ototoxic risk to the individual.

Topics: Age Factors; Aminoglycosides; Anti-Bacterial Agents; Antimalarials; Child, Preschool; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Ear, Inner; Female; Hearing Disorders; Humans; Infant, Newborn; Kidney Diseases; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Salicylates; Sex Factors

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

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Kidney Diseases; Kidneys, Artificial; Male; Salicylates

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antipyretics; Arsenic; Bismuth; Cadmium; Carbon Tetrachloride Poisoning; Contrast Media; Glycols; Gold; Heat Exhaustion; Insecticides; Kidney Diseases; Lead Poisoning; Mercury Poisoning; Metals; Poisoning; Radiation Injuries; Salicylates; Sulfonamides; Toxicology; Uranium; Venoms

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Aminobenzoates; Arthritis, Rheumatoid; Aspirin; Blood Coagulation; Buffers; Dyspepsia; Gastritis; Gastrointestinal Hemorrhage; Humans; Intestinal Absorption; Kidney Diseases; Placebos; Salicylates; Sodium Salicylate; Tablets, Enteric-Coated

Topics: Adolescent; Adult; Age Factors; Aged; Bacteriuria; Female; Hematuria; Humans; Kidney Diseases; Mass Screening; Middle Aged; Occupations; Personnel, Hospital; Proteinuria; Pyelonephritis; Salicylates; Urinary Tract Infections; Urine

Renal pigmentation due to the administration of exogenous compounds is an uncommon finding in most species. This report describes renal pigmentation and intranuclear inclusions of the proximal convoluted tubules due to chronic bismuth administration in a rhesus macaque. An 11-year-old Indian-origin rhesus macaque with a medical history of chronic intermittent vomiting had been treated with bismuth subsalicylate, famotidine, and omeprazole singly or in combination over the course of 8 years. At necropsy, the renal cortices were diffusely dark green to black. Light and electron microscopy revealed intranuclear inclusions within the majority of renal proximal tubular epithelial cells. These inclusions appeared magenta to brown when stained with hematoxylin and eosin and were negative by the Ziehl-Neelsen acid-fast stain. Elemental analysis performed on frozen kidney measured bismuth levels to be markedly elevated at 110.6 ppm, approximately 500 to 1000 times acceptable limits. To our knowledge, this is the first report of renal bismuth deposition in a rhesus macaque resulting in renal pigmentation and intranuclear inclusions.

Topics: Animals; Antiemetics; Bismuth; Kidney; Kidney Diseases; Macaca mulatta; Male; Monkey Diseases; Organometallic Compounds; Pigmentation; Pigmentation Disorders; Salicylates; Vomiting

Paraquat-induced nephrotoxicity involves severe renal cell damage caused by reactive oxygen species (ROS), specifically via increasing concentrations of superoxide anions in the kidney. Recently, superoxide dismutase (SOD) mimetics (SODm) have been developed that display safe SOD activities but which also possess additional antioxidant enzyme (e.g., catalase) or ROS-scavenging activities. The aim of this study was to compare the effects of two such SODm, specifically, EUK-134, a SODm with catalase activity, and tempol, a SODm with ROS-scavenging properties, on paraquat-induced nephrotoxicity of renal NRK-52E cells. Incubation with paraquat (1 mM) for 24 h reduced cell viability and increased necrosis significantly. Paraquat also generated significant quantities of superoxide anions and hydroxyl radicals. Both EUK-134 (10-300 microM) and tempol (0.3-1.0 mM) were able to improve cell viability and reduced paraquat-induced cell death significantly via dismutation or scavenging of superoxide anions and reduced hydroxyl radical generation. The data presented here suggest that SODm such as EUK-134 and tempol, which possess additional catalase and/or ROS-scavenging activities, can significantly reduce renal cell damage caused by paraquat. These effects were evident at concentrations which avoid the pro-oxidant activities associated with higher concentrations of SOD. Such SODm could therefore prove to be beneficial as therapies for paraquat nephrotoxicity.

Topics: Animals; Antioxidants; Cyclic N-Oxides; Free Radical Scavengers; Herbicides; Hydroxyl Radical; Kidney; Kidney Diseases; Organometallic Compounds; Paraquat; Rats; Reactive Oxygen Species; Salicylates; Spin Labels; Superoxide Dismutase; Superoxides

Salicylate was recently shown to provide protection against cisplatin nephrotoxicity in rats. We have demonstrated that enhanced tumor necrosis factor-alpha (TNF-alpha) production mediates, in part, cisplatin nephrotoxicity. The purpose of this study was to determine if the protective effects of salicylate were mediated through inhibition of TNF-alpha in vivo and to explore the mechanism of inhibition in vitro.. The effects of treatment with cisplatin alone and in combination with sodium salicylate in mice on renal function, histology, and gene expression were determined. The effects of cisplatin and salicylate on TNF-alpha expression, nuclear factor kappa B (NF-kappa B) activity, and apoptosis were determined in vitro using cultured murine proximal tubule cells.. Salicylate significantly reduced both the functional and histologic evidence of cisplatin renal injury. Cisplatin increased the renal expression of TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule (ICAM)-1, heme oxygenase-1, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2). Treatment with sodium salicylate blunted the increase in TNF-alpha mRNA and also reduced serum TNF-alpha protein levels. Salicylate had little protective effect when administered with cisplatin to TNF-alpha-deficient mice. Cisplatin increased the degradation of I kappa B (I kappa B) in a time-dependent manner and also increased nuclear NF-kappa B binding activity. Salicylate inhibited I kappa B degradation and NF-kappa B binding activity in the presence of cisplatin. In addition, salicylate inhibited the cisplatin induced TNF-alpha mRNA increase in mouse proximal tubule epithelial (TKPT) cells.. These results indicate that salicylate acts via inhibition of TNF-alpha production to reduce cisplatin nephrotoxicity. The inhibition of TNF-alpha production may be mediated via stabilization of I kappa B.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Apoptosis; Cisplatin; Drug Interactions; Gene Expression; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Kidney Diseases; Kidney Tubules, Proximal; Leukocytes; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NF-kappa B; Receptors, Tumor Necrosis Factor; Salicylates; Tumor Necrosis Factor-alpha; Up-Regulation

Salicylate has recently been demonstrated to protect against the auditory and vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic side effects of cisplatin (CDDP). We first tested protection of the inner ear in Wistar rats receiving a single infusion of 16 mg CDDP/kg body weight with or without treatment with 100 mg/kg salicylate (bid) for 5 days beginning one day before the CDDP infusion. Cisplatin induced a threshold shift of more than 30 dB (at 14 kHz; measured by auditory evoked brain stem response) that was significantly reduced by salicylate. We then examined the protective potential of salicylate on the cochlea, peripheral nerves, and kidney in a rat model of breast cancer--Fisher344 rats implanted with highly metastatic MTLn3 breast cancer cells. Animals received 3 x 5 mg CDDP/kg (given every third day), and salicylate was administered at 100 mg/kg (bid) from 2 days before to 3 days after CDDP treatment. Salicylate significantly attenuated the CDDP-induced threshold shift from approximately 20 dB (at 16 and 24 kHz) to approximately 5 dB, and drastically reduced the loss of cochlear outer hair cells. Likewise, salicylate protected kidney function (measured as plasma blood urea nitrogen and creatinine levels) from CDDP toxicity. Protection of nerve conduction velocities of both sensory and motor nerves was minimal. The chemotherapeutic efficacy of CDDP on suppression of tumor mass and cancer cell metastasis remained unaffected by salicylate. The results suggest that administration of salicylate may become the basis of an effective therapeutic intervention against the ototoxic and nephrotoxic side effects associated with CDDP chemotherapy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Auditory Threshold; Blood Urea Nitrogen; Breast Neoplasms; Cisplatin; Drug Antagonism; Evoked Potentials, Auditory, Brain Stem; Female; Hair Cells, Auditory, Outer; Hearing Loss, Sensorineural; Kidney Diseases; Kidney Function Tests; Male; Neoplasms, Experimental; Neural Conduction; Rats; Rats, Inbred F344; Rats, Wistar; Salicylates

1. Plasma albumin concentration was measured in 118 healthy subjects (aged between 18 and 87 years), in 95 renal patients with creatinine clearances between 15 and 50 ml min-1 (aged between 14 and 79 years) and in 101 uraemic patients maintained on chronic haemodialysis (aged between 27 and 83 years). 2. There was a significant (P less than 0.001) negative correlation between albumin concentration and age in healthy subjects, but no correlation in patients with low creatinine clearance or in uraemic patients. 3. The ex vivo plasma binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (37 nM) was studied in groups of age-selected young and aged healthy subjects in patients with low creatinine clearance and in patients with uraemia. The unbound fractions of diazepam and salicylic acid were about double in old compared with young healthy subjects whereas they were similar in young and old patients with lowered creatinine clearance. In uraemic patients, ageing did not affect the binding of salicylic acid whereas the unbound fraction of diazepam was slightly but significantly greater in elderly subjects. The unbound fraction of digitoxin was independent of age in both healthy subjects and in those with renal disease. 4. Decreased plasma binding of diazepam and salicylic acid was partially corrected by extensive dialysis of plasma. The lower plasma binding of diazepam and salicylic acid associated with ageing may be ascribed to the effects of endogenous displacers and to hypoalbuminaemia. The influence of these two factors appears to be drug-dependent.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Blood Proteins; Diazepam; Digitoxin; Humans; Kidney Diseases; Middle Aged; Salicylates; Salicylic Acid; Serum Albumin

Topics: Bismuth; Cisplatin; Female; Humans; Kidney Diseases; Organometallic Compounds; Ovarian Neoplasms; Salicylates

Oral application of 700 mg/kg salicylic acid to pregnant and non-pregnant female rats caused an increase of serum Mg2+ and a decrease of serum Ca2+ concentration. The salicylate effect was drastically enhanced by Zn deficiency. The increase in serum Mg2+ is probably caused by the nephrotoxicity of salicylate. The decrease of serum Ca2+ concentration is combined with an increase of parathyroid hormone concentration in serum. Probably, salicylate and Zn deficiency inhibit Ca2+ mobilization by parathyroid hormone in bone.

Topics: Animals; Calcium; Female; Fetal Blood; Kidney Diseases; Magnesium; Parathyroid Hormone; Pregnancy; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Zinc

Substances known or suspected to cause subtle or transient anatomical alterations in renal development were administered prenatally or neonatally to rats in order to determine whether they are capable of altering renal functional development. Colchicine alters mitotic activity and cytoskeletal structure and is teratogenic in many species. Since the kidney of the newborn rat undergoes extensive cellular proliferation and nephron differentiation, it is possible that neonatal administration of colchicine may affect nephron development. Dinoseb and methyl salicylate have previously been reported to produce a high incidence of dilated renal pelvis in the term rat fetus. Colchicine was injected sc, at 75 micrograms/kg, to Postnatal Day (PD) 1 Sprague-Dawley rats. Dinoseb was administered ip to pregnant Sprague-Dawley rats on Gestation Days 10-12 at doses of 8 or 10.5 mg/kg/day, and methyl salicylate was administered ip at doses of 200, 250, or 300 mg/kg/day on Gestation Days 11-12. Renal function was examined in pups from immediately after birth through weaning. Maximal urine concentrating ability was measured after DDAVP (desmopressin acetate, a vasopressin analog) injection in suckling rats, and after 24 hr of water deprivation in weanlings. Proximal tubule transport was measured in renal cortical slices. Basal urinary parameters, including urine flow, osmolality, pH, and chloride content, were measured. Colchicine treatment had no effect on body weight or kidney weight. There was a significant decrease in maximal urine osmolality in PD 30 rats measured after 24 hr of water deprivation. The urine concentrating deficit detected in functionally mature PD 30 rats suggests that colchicine treatment during renal histogenesis causes a latent deficit in medullary function in the absence of any gross morphological effects. The 10.5 mg/kg/day dose of dinoseb caused a weight reduction in neonates which persisted after weaning. Urine volume after DDAVP challenge was increased over controls in both dose groups on PD 6, but maximal urine concentration was unaffected. On PD 14, maximal urine concentration after DDAVP injection was decreased in the 10.5 mg/kg/day group. By PD 30, urine concentrating ability was comparable to controls. Renal cortical slices from the 10.5 mg/kg/day dose group had an enhanced ability to accumulate organic anions on PD 3 and 31, but opposite effects were observed in the low-dose group. No other renal functional parameters were altered. Urine os

Topics: 2,4-Dinitrophenol; Animals; Animals, Suckling; Colchicine; Deamino Arginine Vasopressin; Dinitrophenols; Female; Fetus; Herbicides; Kidney Cortex; Kidney Diseases; Kidney Function Tests; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Salicylates; Teratogens

Topics: Benzenesulfonates; Electrophoresis, Polyacrylamide Gel; Humans; Kidney Diseases; Molecular Weight; Mucoproteins; Neoplasms; Salicylates; Solubility

The protein binding of tolfenamic acid in plasma from patients with renal and hepatic disorders was studied by equilibrium dialysis. Drug binding to the cellular components of whole blood and blood cell suspensions was also measured. Salicylic acid was used as the reference drug in all experiments. Renal and hepatic diseases increased the unbound fraction of tolfenamic acid. Free drug fractions were significantly correlated with changes in creatinine, urea, and total bilirubin, but not with those in albumin or total protein in plasma. Comparison of the theoretical binding parameters in control plasma and similar changes in protein binding in all the plasma samples studied revealed that tolfenamic acid and salicylic acid probably share a common primary binding site. The significance of the correlation permits use of salicylic acid as a model drug for predicting changes in the protein binding of tolfenamic acid. The measurements of binding properties in whole blood and blood cell--buffer suspension showed that tolfenamic acid interacts with the lipid membrane structures of blood cells, while salicylic acid is distributed into the aqueous cell space.

Topics: Adult; Aged; Erythrocytes; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; ortho-Aminobenzoates; Protein Binding; Salicylates; Salicylic Acid

Proteinuria may be the initial manifestation of serious renal disease or merely a laboratory finding of little clinical importance. Excretion of urinary protein in excess of 150 mg per 24 hours in an adult is abnormal. It may be of glomerular, tubular or overflow origin. A comparison of the dipstick and sulfosalicylic acid techniques helps distinguish the source of protein, and electrophoresis is confirmatory. Transient and intermittent proteinuria are not clinically important. Persistent proteinuria requires further investigation.

Topics: Benzenesulfonates; Child; Edema; Electrophoresis; Humans; Hypertension; Kidney Diseases; Methods; Proteinuria; Salicylates; Urinary Tract Infections; Urine

Topics: Anti-Inflammatory Agents; Arthritis; Aspirin; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Drug Interactions; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Kidney Diseases; Salicylates

To assess the effects of long-term aspirin ingestion on renal function, we studied all of the patients at the Massachusetts General Hospital Arthritis Clinic who had been taking aspirin continuously for ten or more years. Aspirin ingestion was documented by multiple, random, unannounced blood salicylate levels. Most of these 46 patients had seropositive rheumatoid arthritis. All creatinine and BUN levels were normal. Maximum recorded specific gravities were greater than 1.019 in 43 of 46 patients. These data suggest that long-term salicylate ingestion does not cause renal damage.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Creatinine; Female; History, 17th Century; Humans; Kidney; Kidney Diseases; Male; Nephritis, Interstitial; Proteinuria; Random Allocation; Salicylates; Time Factors

Topics: Adult; Analgesics; Female; Humans; Kidney Diseases; Phenacetin; Salicylates; Substance-Related Disorders; Switzerland

The effects of several potentially nephrotoxic furans on urinary levels of N-acetylglucosaminidase (NAG) were examined to determine whether this test might serve as a useful quantitative index of nephrotoxicity for this series of compounds. Whereas others have found that nephrotoxins such as sodium salicylate and biphenyl cause increases in urinary NAG, we observed that these furans, which were shown to be nephrotoxic by histological procedures, caused significant decreases in urinary levels of the enzyme. This effect was dose-related in the one case examined.

Topics: Acetylglucosaminidase; Animals; Furans; Heterocyclic Compounds; Hexosaminidases; Kidney Diseases; Male; Mice; Mice, Inbred ICR; Salicylates; Salicylic Acid

Analgesic nephropathy is recognized worldwide, but the differences in incidence in various countries, or regions, remain unexplained. Analgesic compounds may cause both functional and structural renal damage. This damage may be related to depletion of glutathione and renal vasoconstriction (probably mediated through prostaglandin depletion) and to the fact that the concentrations of glutathione and prostaglandins and their metabolites in the kidneys are manyfold their concentrations in plasma. Most patients with analgesic nephropathy are middle-aged women with histories of peptic ulcer, anemia, psychiatric disorders, headaches, and arthralgias. Investigations often show pyuria, some bacteriuria, and impaired concentrating ability, as well as other abnormalities of tubular function; caliceal abnormalities on intravenous pyelography are also frequent. It is important to discover these patients; evidence exists that with cessation of drug ingestion, renal function may stabilize and, in some cases, may improve.

Topics: Analgesics; Female; Glutathione; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Peptic Ulcer; Salicylates; Substance-Related Disorders

Topics: Acetaminophen; Adult; Analgesics; Animals; Dose-Response Relationship, Drug; Female; Humans; Kidney Diseases; Microsomes; Middle Aged; Phenacetin; Phenetidine; Prospective Studies; Rats; Salicylates

Topics: Diflunisal; Glucuronates; Humans; Hydrolysis; Kidney Diseases; Salicylates

N-acetyl-beta glucosaminidase (NAG) enzymuria was used as a marker of renal injury in patients with rheumatic disease. An elevated NAG level was particularly common in patients receiving gold or aspirin therapy. The multiplicity of drugs received and the unknown role of underlying disease in these patients led to a study in healthy volunteers. Customary therapeutic doses of aspirin, choline salicylate, ibuprofen, indomethacin and acetaminophen did not produce enzymuria. Large single doses of salicylates equivalent to 6 tablets of aspirin consistently did produce enzymuria. The size of the individual dose in relation to body weight was more important than the total daily dose. NAG enzymuria appears to be a sensitive tool for identifying potentially nephrotoxic drugs.

Topics: Acetaminophen; Acetylglucosaminidase; Adult; Anti-Inflammatory Agents; Aspirin; Gold; Hexosaminidases; Humans; Ibuprofen; Indomethacin; Kidney; Kidney Diseases; Lysosomes; Rheumatic Diseases; Salicylates

Topics: Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney; Kidney Diseases; Phenacetin; Salicylates

Analgesic drugs causing kidney functional disturbances and histologically evident kidney derangements are reviewed. Today, not the pathological changes, which have dominated the scene of pathogenesis for analgesic nephropathies are in the foreground of investigative interest, but rather the biochemical interactions of analgesics or their metabolites in the renal cell and prospective epidemiologic studies. As the term 'phenacetin nephropathy' has been replaced by 'analgesic nephropathy', it seems likely that metabolic activation responsible for renal injury caused by analgesic mixtures will be of primary importance in furture investigations as well as the unravelling of immunogenic processes for a variety of analgesics and their metabolites.

Topics: Acetaminophen; Analgesics; Humans; Kidney; Kidney Diseases; Kidney Medulla; Phenacetin; Salicylates

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

Screening procedures have achieved notoriety in recent years because of their ability to detect diseases in their early phases and also because of their expense. This paper describes a little-known but simple urine screening test which, if used judiciously, may help with diagnosis and treatment, and yet remain relatively inexpensive.

Topics: Analgesics; Humans; Indicators and Reagents; Kidney Diseases; Phenylketonurias; Reagent Strips; Salicylates

The serum protein binding of phenytoin, salicylic acid, sulfisoxazole, and warfarin was determined in normal human adults, in patients with impaired renal function (kidney donor and recipient), and in adult male Sprague--Dawley rats. The free fraction values for salicylate and sulfisoxazole were significantly correlated in all three groups. The other correlations were statistically significant in only one or two of these groups. There was a statistically significant negative correlation between albumin concentration and the free fraction values of salicylic acid and sulfisoxazole (but not of phenytoin and only under special circumstances with warfarin) in normal subjects and of phenytoin, salicylic acid, and sulfisoxazole (but not warfarin) in rats. No such correlation was observed for any of the drugs in patients with impaired renal function. These observations show that no single weakly acidic drug can serve as an index for quantitatively determining the effect of disease or species differences on the serum protein binding of other weakly acidic drugs.

Topics: Adolescent; Adult; Animals; Blood Proteins; Female; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Pharmaceutical Preparations; Phenytoin; Protein Binding; Rats; Salicylates; Serum Albumin; Sulfisoxazole; Time Factors; Transplantation, Homologous; Warfarin

A recent clinical advance has been the discovery that many drug-induced hepatic diseases result from the metabolic activation of chemically stable drugs to potent alkylating agents by the liver. In addition to the liver, however, the kidney also contains active enzyme systems capable of metabolically activating drugs and other chemicals. For this reason a systematic investigation of the possible role of metabolic activation in the pathogenesis of several drug-induced renal diseases has been undertaken. These laboratory results are reviewed in the light of the clinical spectrum of the renal injuries, and possible therapeutic implications of these new findings are briefly discussed. The potential use of these models of nephrotoxicity to probe a variety of physiologic and pathophysiologic mechanisms of renal function are noted.

Topics: Acetaminophen; Analgesics; Animals; Carbon Tetrachloride Poisoning; Cephaloridine; Chloroform; Cytochrome P-450 Enzyme System; Disease Models, Animal; Dose-Response Relationship, Drug; Furans; Furosemide; Glutathione; Humans; Kidney; Kidney Diseases; Kidney Tubular Necrosis, Acute; Kidney Tubules, Proximal; Protein Binding; Salicylates; Toxicology

Topics: Fluorobenzenes; Humans; Kidney Diseases; Kinetics; Salicylates

The effect of salicylate treatment on the kidney, particularly medullary function, was investigated. In a retrospective analysis patients with rheumatoid arthritis (RA) treated with high doses of salicylates were shown to have inferior urinary concentrating power and increased excretion of N-acetyl-beta-D-glucosaminidase (NAG) when compared with patients who had not received salicylate treatment. A prospective study of renal funcition in healthy people and patients with RA starting salicylate in therapeutic doses showed that while epithelial cell excretion was only transiently raised in both groups the excretion of NAG was increased in all cases at three days and this increase was sustained at 10 days, all values being much higher in the patients than in the healthy subjects. Thus salicylate treatment does cause renal tubular damage but this damage results in only minimal impairment of function and does not constitute a reason for withholding salicylate treatment.

Topics: Acetylglucosaminidase; Arthritis, Rheumatoid; Female; Humans; Hydrogen-Ion Concentration; Kidney Concentrating Ability; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Middle Aged; Salicylates

The adult population of a small Victorian town was interviewed for current analgesic consumption and the replies were validated by urine testing. One thousand four hundred and fifty-six subjects were ranked by stated analgesic consumption, and the 50 highest consumers matched for age and sex with non-consumers. Early morning urine specimens were collected and no significant difference in osmolality or white cell excretion rates was found between the two groups. It was concluded that the absolute risk of renal impairment on chronic analgesic consumers is low, and that patients on therapeutic regimens, including analgesics, may be reassured that any risk is minimal.

Topics: Adult; Analgesics; Aspirin; Australia; Female; Humans; Kidney Diseases; Leukocytes; Male; Middle Aged; Osmolar Concentration; Salicylates; Substance-Related Disorders; Urine

The purpose of this paper is to review the development of the mammalian kidney and to assess the influence that various perinatal manipulations may have on the developmental process either morphologically or functionally. Immature kidneys in general have less functional capacity than adult kidneys and a low rate of glomerular filtration, perhaps related to renal blood flow, which appears to limit the disposition of a fluid or solute load. Tubular reabsorption is also limited leading to the urinary loss of glucose, amino acids, bicarbonate and phosphate. Although the relatively low function of the immature kidney is a normal part of development, its capacity to respond under conditions of stress may be less adequate than in adults. An additional concern is that a variety of perinatal manipulations, such as the incidental or accidental ingestion of a chemical, may lead to varying degrees of altered morphogenesis or functional development of the kidney. Chemical induced renal anomalies may be of several types, but in typical teratology experiments hydronephrosis may be the most frequent observation. The functional consequences of these renal malformations may be lethal or inconsequential or while an animal may be able to survive and develop normally in the presence of a renal malformation, it is possible that a stressful situation would unmask a functional malformation which could compromise survival. Thus, some renal abnormalities may be subtle enough to go unnoticed without experimental tests. Without such tests it is impossible to evaluate the effect of functional alterations on successful adaptation.

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Dinitrophenols; Diphenylamine; Female; Guinea Pigs; Humans; Hydronephrosis; Infant, Newborn; Kidney; Kidney Diseases; Paraquat; Penicillins; Polychlorinated Dibenzodioxins; Polycystic Kidney Diseases; Pregnancy; Rabbits; Salicylates

Topics: Aspirin; Chemical and Drug Induced Liver Injury; Female; Heart Diseases; Humans; Kidney Diseases; Male; Pregnancy; Salicylates; Stomach Diseases

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

The nature of the original renal disease was determined in 403 consecutive cases of end-stage renal failure, in 317 of which the clinical diagnosis was corroborated by histological examination of the kidney. Five diseases accounted for 20 or more cases--glomerulonephritis (31% of the total), analgesic nephropathy (29%), primary vesicoureteral reflux (8%), essential hypertension (6%), and polycystic kidneys (5%). In only four cases did renal failure result from chronic pyelonephritis without a demonstrable primary cause. Greater use of micturating cystography and cystoscopy and routine urine testing for salicylate are advocated for earlier diagnosis of the major causes of "pyelonephritis". The incidence of end-stage renal failure in people aged 15-55 in New South Wales was estimated to be at least 34 new cases per million of total population each year.

Topics: Acetaminophen; Adult; Analgesics; Aspirin; Australia; Caffeine; Codeine; Cystoscopy; Female; Glomerulonephritis; Humans; Hypertension, Renal; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Phenacetin; Polycystic Kidney Diseases; Pyelonephritis; Renal Dialysis; Salicylamides; Salicylates; Transplantation, Homologous; Urography; Vesico-Ureteral Reflux

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity.

Topics: Analgesics; Aspirin; Caffeine; Codeine; Creatinine; Female; Follow-Up Studies; Humans; Kidney; Kidney Diseases; Pain; Phenacetin; Salicylates; Substance-Related Disorders

Urine levels of the lysosomal enzyme beta-N-acetylglucosaminidase have been measured in patients with arthritic disorders; significantly higher levels were found in patients with rheumatoid arthritis (mean: 332.9 nmol/h/mg creat.) than in those with degenerative joint disease (mean: 86.31 nmol/h/mg creat.; P less than 0.001). Analysis of the results shows that salicylates were responsible for some of this difference, but suggests that rheumatoid disease itself may cause renal damage.

Topics: Acetylglucosaminidase; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Hexosaminidases; Humans; Kidney Diseases; Salicylates

Topics: Alcoholic Beverages; Anticoagulants; Blood Transfusion; Cortisone; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Hip Joint; Humans; Indomethacin; Joint Diseases; Kidney Diseases; Liver Cirrhosis; Neoplasms; Phenylbutazone; Postoperative Complications; Prospective Studies; Salicylates; Stomach Diseases

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury.The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation.

Topics: Acetaminophen; Adult; Arthritis, Rheumatoid; Aspirin; Caffeine; Codeine; Drug Synergism; Female; Humans; Kidney Diseases; Male; Middle Aged; New Zealand; Osteoarthritis; Phenacetin; Phenylbutazone; Salicylates; Urinary Tract Infections

Topics: Allopurinol; Amino Acids; Aspirin; Autoanalysis; Creatinine; Glycosuria; Humans; Kidney Diseases; Neoplasms; Phosphates; Porphobilinogen; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Salicylates; Uric Acid; Xanthine Oxidase

Topics: Circadian Rhythm; Creatinine; Female; Humans; Kidney Diseases; Middle Aged; Probenecid; Purine-Pyrimidine Metabolism, Inborn Errors; Pyrazinamide; Salicylates; Time Factors; Uric Acid

Topics: Ampicillin; Child, Preschool; Chloramphenicol; Colistin; Diagnosis, Differential; Drug Eruptions; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Electroencephalography; Erythromycin; Female; Fever; Humans; Hydrocortisone; Infections; Kanamycin; Kidney Diseases; Male; Middle Aged; Penicillins; Pericarditis; Pertussis Vaccine; Pleural Diseases; Recurrence; Salicylates; Tetracycline; Tonsillectomy

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Catecholamines; Dextrans; Edetic Acid; Humans; Kidney; Kidney Diseases; Phenacetin; Phenindione; Phenylbutazone; Salicylates

Topics: Female; Humans; Kidney Diseases; Male; Middle Aged; Phenacetin; Salicylates; Substance-Related Disorders; Syndrome

Topics: Acute Disease; Alkaline Phosphatase; Analgesics; Animals; Anti-Inflammatory Agents; Chronic Disease; Heterocyclic Compounds; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Male; Nicotinic Acids; Phenylbutazone; Pyridazines; Rats; Rats, Inbred Strains; Salicylates; Toluidines

Topics: Diuretics; Gout; Humans; Hypertension; Hypothyroidism; Kidney Diseases; Nicotinic Acids; Nucleoproteins; Proteins; Purines; Salicylates; Thioridazine; Uric Acid

Topics: Adrenal Gland Diseases; Alkalosis; Amino Acids; Burns; Diabetes Insipidus; Diarrhea; Diet, Sodium-Restricted; Dietary Fats; Dietary Proteins; Diuretics; Endocrine System Diseases; Gastrointestinal Diseases; Glucose; Humans; Infusions, Parenteral; Kidney Diseases; Parenteral Nutrition; Salicylates; Sodium Chloride; Vomiting; Water-Electrolyte Balance

Topics: Animals; Carbon Isotopes; Half-Life; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Metabolic Clearance Rate; Rabbits; Salicylates; Skin Absorption; Skin Diseases; Sulfonamides; Time Factors

Topics: Adult; Analgesics; Anti-Inflammatory Agents; Aspirin; Fever; Gastrointestinal Hemorrhage; Humans; Intestinal Absorption; Kidney Diseases; Salicylates; Uricosuric Agents

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

Topics: Adipose Tissue; Aspirin; Brain Diseases; Chemical and Drug Induced Liver Injury; Fatty Liver; Humans; Infant; Kidney Diseases; Peritoneal Dialysis; 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: Acetates; Bence Jones Protein; Chromatography; Colorimetry; Diagnosis, Differential; Humans; Immunodiffusion; Immunoelectrophoresis; Kidney Diseases; Proteinuria; Salicylates

Topics: Aged; Anti-Bacterial Agents; Contrast Media; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Nephritis, Interstitial; Nephrosis; Phenacetin; Phenylbutazone; Salicylates; Substance-Related Disorders

Topics: Allopurinol; Colchicine; Crystallization; Diagnosis, Differential; Diet Therapy; Gout; Humans; Indomethacin; Joint Diseases; Kidney Diseases; Kidneys, Artificial; Phenylbutazone; Probenecid; Proteinuria; Purines; Radiography; Salicylates; Steroids; Sulfinpyrazone; Uric Acid

Topics: Adult; Aged; Analgesics; Bacteriuria; Creatinine; Female; Hematuria; Humans; Kidney Diseases; Male; Middle Aged; Phenacetin; Proteinuria; Retrospective Studies; Salicylates; Switzerland; Urologic Diseases

Topics: Analgesics; Animals; Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney; Kidney Diseases; Phenacetin; Salicylates

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: Allopurinol; Blood Urea Nitrogen; Enzyme Therapy; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Male; Salicylates; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

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

Topics: Aspirin; Brain Diseases; Carbohydrate Metabolism; Coma; Fatty Liver; Heart Diseases; Humans; Kidney Diseases; Salicylates; Toxicology; Viscera

Topics: Adolescent; Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Colchicine; Genetics, Medical; Gout; Intestinal Diseases; Intestinal Obstruction; Intestine, Small; Kidney Diseases; Pathology; Salicylates; Substance Withdrawal Syndrome; Substance-Related Disorders; Toxicology; Uremia; Uricosuric Agents

Topics: Anthracosilicosis; Hemorrhage; Humans; Kidney Diseases; Lung Diseases; Muscular Diseases; Penicillins; Radiography, Thoracic; Salicylates; Scleroderma, Systemic; Vitamin E

Topics: Abdomen; Abdomen, Acute; Adrenal Cortex Hormones; Colchicine; Gastrointestinal Hemorrhage; Gout; Kidney Diseases; Phenylbutazone; Salicylates; Shock; Toxicology; Uricosuric Agents; Zoxazolamine

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Colchicine; Diet; Diet Therapy; Drug Therapy; Geriatrics; Gout; Kidney Diseases; Metabolism; Phenylbutazone; Probenecid; Salicylates; Sulfinpyrazone; Surgical Procedures, Operative; Toxicology; Uric Acid; Uricosuric Agents; Zoxazolamine

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Colchicine; Diagnosis, Differential; Diet; Diet Therapy; Drug Therapy; Epidemiology; Genetics, Medical; Gout; Humans; Indomethacin; Kidney Diseases; Kidneys, Artificial; Phenylbutazone; Probenecid; Salicylates; Sulfinpyrazone; Uric Acid; Urine

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

Topics: Aspirin; Humans; Kidney; Kidney Diseases; Kidney Tubules; Salicylates; Skin Diseases