salicylates and Kidney-Failure--Chronic

Topics: Acute Kidney Injury; Barbiturates; Blood Volume; Child; Child, Preschool; Costs and Cost Analysis; Heart Failure; Humans; Hyperkalemia; Hypocalcemia; Hypotension; Intestinal Obstruction; Intestinal Perforation; Kidney Failure, Chronic; Metabolic Diseases; Methods; Nutrition Disorders; Peritoneal Dialysis; Poisoning; Renal Dialysis; Salicylates; Time Factors

Topics: Adult; Analgesics; Clinical Trials as Topic; Female; Humans; Hypertension; Kidney Failure, Chronic; Longitudinal Studies; Middle Aged; Phenacetin; Salicylates; Smoking; Substance-Related Disorders; Switzerland; Urinary Tract Infections

Topics: Administration, Oral; Barbiturates; Charcoal; Clinical Trials as Topic; Hepatic Encephalopathy; Humans; Kidney Failure, Chronic; Poisoning; Renal Dialysis; Salicylates

Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage. This has been linked to the toxic effects of hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating homocysteine levels did not lead to significant reductions in plasma protein damage. The hypothesis that lack of reduction in protein damage could be due to protein increased intrinsic instability, as result of interference with the uremic milieu rather than to hyperhomocysteinemia, was put forward. The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 h, 72 h, and 7 d was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out. The effect of the hemodialysis procedure on protein damage was evaluated. For investigating also the consequences of these alterations, human albumin was treated in vitro to produce an increase in deamidated/isomerized Asx residues, and the effects of albumin deamidation on protein binding were evaluated. Among the uremic toxins that are able to elicit protein damage, guanidine produced a dose-dependent increase in protein damage. No difference was found after a hemodialysis session. Deamidated albumin shows normal binding capacity to warfarin, salicylic acid, or diazepam but reduced binding to homocysteine. In conclusion, uremic toxins, especially guanidine, display an ability to induce significant protein damage, which can in turn have functional consequences.

Topics: Asparagine; Aspartic Acid; Biomarkers; Blood Chemical Analysis; Blood Proteins; Diazepam; Female; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Prognosis; Protein Binding; Renal Dialysis; Risk Assessment; Salicylates; Sampling Studies; Sensitivity and Specificity; Warfarin

We use oxalate oxidase from barley seedlings for the colorimetric determination of oxalate in plasma. The oxalate is converted to hydrogen peroxide, which, in the presence of peroxidase, is detected by a Trinder-like chromogenic system. Optimization of the assay, including deproteinization and elimination of interferences from reducing substrates, is described. Ascorbate additions (200 mumol/L) did not affect oxalate concentration in plasma, even after long frozen storage. Mean analytical recovery of oxalate averaged 102% +/- 6.9%, imprecision (CV) at 2.0 mumol/L was 7.2%, and the lower limit of quantification (CV = 20%) was 0.6 mumol/L. Results correlated well with those by chromatography (r = 0.999, Sy/x = 0.29 mumol/L, n = 32, range for x, y = 0-140 mumol/L). Plasma oxalate concentrations measured in 32 healthy subjects ranged from 0.6 to 2.9 mumol/L (mean 1.28, SD 0.71 mumol/L), which agrees with those measurable by using indirect radioisotopic dilution methods. Patients with primary hyperoxaluria and chronic renal failure exhibited markedly greater plasma concentrations of oxalate.

Topics: Adolescent; Adsorption; Adult; Ascorbic Acid; Benzenesulfonates; Blood Proteins; Charcoal; Child; Chromogenic Compounds; Colorimetry; Drug Stability; Female; Freezing; Hordeum; Humans; Hyperoxaluria; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Oxidoreductases; Quality Control; Reference Values; Salicylates; Sensitivity and Specificity

The interactions of selezen (imidazole salicylate) with human blood components were studied by equilibrium dialysis. These interactions were limited to the binding of salicylate to human serum albumin (HSA). The binding was saturable and involved several classes of binding sites with different association constants. A competition study indicated that salicylic acid at high concentration was able to displace warfarin and digitoxin but not glibenclamide from their HSA sites. On the other hand, selezen serum binding was decreased in renal impaired patients and this result was probably linked to the decreases in HSA concentration. So the use of small dosage regimens of selezen to these patients can be proposed. The same recommendation may be done for cirrhotic patients, where the decrease of selezen binding percentage was observed and due to both hypoalbuminemia and hyperbilirubinemia.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Chronic Disease; Dialysis; Erythrocytes; Humans; Imidazoles; Kidney Failure, Chronic; Liver Diseases; Salicylates; Salicylic Acid

Twenty-three patients with analgesic nephropathy and apparent cessation of drug abuse were tested for blood acetaminophen and salicylate on the occasion of routine renal control examinations. In 12 patients (mean creatinine level 2.74 +/- 1.09 mg/dl) no deterioration of renal function was noted within a 1-year observation period (Group 1). In 11 patients a significant progression of renal insufficiency was observed (mean creatinine level rose from 3.86 +/- 1.06 to 6.40 +/- 3.18 mg/dl within the same observation period; Group 2). Blood tests for acetaminophen and salicylate were positive in 2 patients of Group 1 and in 9 patients of Group 2 (chi 2 = 7.326), p less than 0.01). Our data emphasize the importance of a continuous analgesic abuse hidden from the medical staff with regard to the progression of renal insufficiency in analgesic nephropathy.

Topics: Acetaminophen; Adult; Aged; Analgesics; Austria; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Phenacetin; Prognosis; Salicylates; Substance Abuse Detection; Substance-Related Disorders

We describe a case of severe refractory hypoglycemia secondary to topical salicylate intoxication. A 72-year-old man with psoriasis and end-stage renal disease was treated with a topical cream containing 10% salicylic acid. The patient presented with encephalopathy and subsequently developed hypoglycemia refractory to infusions of large amounts of glucose. A serum salicylate concentration was elevated at 3.2 mmol/L. Emergent hemodialysis was accompanied by rapid lowering of serum salicylate concentration and resolution of refractory hypoglycemia. Salicylate is well absorbed across normal and diseased skin. Salicylate markedly impairs gluconeogenesis and increases glucose utilization, resulting in hypoglycemia. To our knowledge, this is the first article on hypoglycemia due to the application of topical salicylate.

Topics: Administration, Cutaneous; Aged; Confusion; Gluconeogenesis; Humans; Hypoglycemia; Kidney Failure, Chronic; Male; Occlusive Dressings; Ointments; Psoriasis; Salicylates; Salicylic Acid; Skin Absorption

1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesics taken at least every other day for 30 days or longer before the first symptom of renal disease was 2.89 (95% CI, 1.78 to 4.68). 3. The risk increased in relation to the use duration. 4. The previous regular consumption of combinations containing phenacetin was strongly associated with ESRD (odds ratio, 19.05; 95% CI, 2.31 to 157.4). The odds ratio for previous regular consumption of salicylates was 2.54 (95% CI, 1.24 to 5.20) and for pyrazolones 2.16 (95% CI, 0.87 to 5.32). 5. An analysis for possible confounding by a history of repeated headaches, arthritis, kidney stones, hypertension, and diabetes did not alter the results. 6. The odds ratio estimates for different pathological subgroups of ESRD patients in relation to previous use of any non-narcotic analgesic were glomerulonephritis. 10.57 (95% CI, 1.25 to 89.0), interstitial nephritis, 3.33 (95% CI, 1.21 to 9.17), cystic kidney disease, 0.71 (95% CI, 0.25 to 1.97), and unknown, 5.15 (95% CI, 2.29-11.57). 7. The results of this study suggest that the regular consumption of analgesics should be routinely considered as a risk factor for any non-congenital cause of chronic renal failure. They also suggest that the risk of ESRD associated with the regular consumption of phenacetin is much higher than the risk associated with other non-narcotic analgesics.

Topics: Adolescent; Adult; Analgesics; Case-Control Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Phenacetin; Salicylates; Time Factors

The single-dose plasma kinetics of diflunisal was studied in healthy young and old subjects, in patients with rheumatoid arthritis, and in patients with renal failure. The plasma and urine kinetics of the glucuronidated metabolites of diflunisal were studied in the healthy elderly subjects and in the patients with renal failure. In addition, the multiple-dose plasma kinetics of diflunisal was assessed in healthy volunteers and in patients with rheumatoid arthritis. After a single dose of diflunisal the terminal plasma half-life, mean residence time and apparent volume of distribution were higher in elderly subjects than in young adults. No difference was observed in any pharmacokinetic parameter between age-matched healthy subjects and patients with rheumatoid arthritis. The elimination half-life of unchanged diflunisal was correlated with the creatinine clearance (r = +0.89) and its apparent total body clearance exhibited linear dependence on creatinine clearance (r = +0.78). In patients with renal failure, the terminal plasma half-life and mean residence time of diflunisal were prolonged. The renal and apparent total body clearances were lower, the mean apparent volume of distribution was higher and the mean area under the concentration-time curve extrapolated to infinity (AUC) was greater in the renal failure patients than in controls. The plasma concentration of the glucuronidated metabolites rapidly rose to levels above those of unchanged drug in renal patients, whereas they were lower than those of unchanged diflunisal in controls. The AUC (0-96 h) of diflunisal glucuronides in the patients was four-times that in controls, and the terminal elimination half-life of the glucuronides was prolonged in them. The renal excretion and clearance of diflunisal glucuronides were reduced when renal function was impaired. After multiple dosing, the pre-dose steady-state plasma-concentration increased with decreasing creatinine clearance (r = -0.79). When the plasma concentration exceeded 200 mumols.l-1, the elimination half-life was doubled, due to partial saturation of diflunisal conjugation. This finding suggests that lower doses could be used in long-term treatment. Thus, old age and arthritic disease appear to have little influence on the kinetics of diflunisal in the absence of renal functional impairment. Ordinary doses can be given for short term treatment of elderly patients with or without RA. In patients with renal failure, however, reduced doses of di

Topics: Adolescent; Adult; Aged; Aging; Arthritis, Rheumatoid; Diflunisal; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Salicylates

A 61-year-old woman receiving long-term hemodialysis presented with symptoms of tinnitus, insomnia, malaise, and disequilibrium. On close questioning, it was discovered that she had received a prescription for salsalate (Disalcid) from a consulting physician who had evaluated her for joint pain. This tablet was similar in appearance to a dried aluminum hydroxide gel preparation (Alu-tab) that the patient was taking as a phosphate binder. She had mistakenly been taking six Disalcid tablets with each meal. Her salicylate level was 5.86 mmol/L, but she had no change in her serum electrolyte levels or acid-base status. When the salsalate treatment was stopped and regular dialysis treatments were continued, the symptoms of salicylism resolved. This case illustrates one of the potential dangers of polypharmacy in patients with chronic disease. The midl course was probably due to ongoing hemodialysis, which prevented the appearance of the usual acid-base abnormalities of salicylate intoxication.

Topics: Aluminum Hydroxide; Arthritis; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Salicylates; Tablets

We have evaluated pH, chloride, calcium and several endogenous aromatic acids as possible causes of the impaired binding of drugs by plasma albumin in renal failure. Changes in pH, chloride and calcium over the range found in renal failure had minimal or no effects on the binding of [14C]salicylate, a model probe which binds to both of the major drug-binding loci of human albumin. Hippurate and indoxyl sulfate were weak inhibitors of binding by normal plasma. Ortho-hydroxy-hippurate was undetectable or minimally elevated, except among patients with elevated plasma salicylate concentration. Although plasma hippurate and indoxyl sulfate concentrations were elevated markedly in patients with renal failure, inhibition of salicylate binding was significantly correlated only with the concentration of indoxyl sulfate. Addition of hippurate and indoxyl sulfate separately and together to normal plasma showed that these ligands could account for only 15% of the impaired binding of salicylate by azotemic plasma. The retained solutes which account for most of this binding defect remain to be identified. This uremic disorder (and perhaps others) is due not to a single chemical but to the additive effect of a family of chemicals.

Topics: Blood Proteins; Calcium; Chlorides; Creatinine; Hippurates; Humans; Indican; Kidney Failure, Chronic; Ligands; Salicylates; Salicylic Acid; Uremia

Topics: Humans; Kidney Failure, Chronic; Kinetics; Renal Dialysis; Salicylates; Sulfamethoxazole

A 1500 mg dose of salsalate (SSA) was given to five patients undergoing chronic hemodialysis on an interdialytic day and again before dialysis. Compared with control subjects, patients undergoing dialysis had a lower peak plasma SSA level (17 +/- 3 vs. 45 +/- 2 micrograms/ml; P less than 0.01) that occurred slightly later. In contrast, plasma salicylic acid (SA), the active SSA metabolite, had a similar but later peak level that remained substantially higher. Therefore, the AUC for SA was increased by 50% and the SA t1/2 was prolonged in the patients receiving dialysis (8.1 +/- 0.7 vs 3.8 +/- 0.2 hours; P less than 0.01). During a single treatment, dialysis clearance reduced plasma SA levels, removed 18% of total body SA, and returned the SA t1/2 to nearly normal. Because the elimination of SA is impaired in patients undergoing dialysis, the interdialytic SSA dosage should be reduced. Hemodialysis improves SA kinetics and may be followed by a normal SSA replacement dose. However, periodic monitoring of plasma SA levels is recommended when SSA dosing is begun in patients receiving dialysis.

Topics: Administration, Oral; Adult; Aged; Creatinine; Female; Half-Life; Hematocrit; Humans; Kidney Failure, Chronic; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Salicylates; Salicylic Acid

Diflunisal protein binding was studied by equilibrium dialysis at 37 degrees in plasma from healthy, uremic, and geriatric subjects. Binding data were computer analyzed assuming 2 classes of independent binding sites (Scatchard model). K1, the primary association constant for the diflunisal-albumin interaction, was substantially lower in uremic plasma (2.39 +/- 0.29 x 10(5) M-1) than in normal plasma (6.86 +/- 0.59 x 10(5) M-1). No difference was found between the number of primary diflunisal binding sites (N1) in uremic and normal plasma. In geriatric plasma neither K1 nor N1 differed from the normal values, indicating that decreased diflunisal plasma protein binding in the elderly is a result of lower plasma albumin concentration. Binding studies with plasma from uremic patients during hemodialysis revealed that free diflunisal rose from 0.46 +/- 0.04% at the start to 0.61 +/- 0.06% at the end of dialysis. Plasma free fatty acid concentrations rose similarly. In vitro displacement studies showed that oleic acid is a competitive inhibitor for the binding of diflunisal to human serum albumin. This may explain the decrease in diflunisal plasma binding at the end of hemodialysis treatment.

Topics: Adult; Age Factors; Aged; Binding Sites; Blood Proteins; Diflunisal; Heparin; Humans; Kidney Failure, Chronic; Kinetics; Middle Aged; Protein Binding; Renal Dialysis; Salicylates; Uremia

Topics: Diflunisal; Glucuronates; Half-Life; Humans; Kidney Failure, Chronic; Salicylates

The plasma protein binding of a representative acidic drug, salicylate, and a representative basic drug, quinidine, has been studied in patients with several diseases that are sometimes associated with uraemia or a change in serum albumin level. Decreased plasma protein binding of salicylate was observed in plasma from patients with uraemia and liver disease. Low albumin levels in these patients could only account inpart for the decreased binding. On the other hand, salicylate binding to plasma proteins appeared to be increased in patients with hypoxia. Decreased plasma protein binding of quinidine was observed in some patients with uraemia and in the majority of patients with liver disease.

Topics: Adult; Aged; Blood Proteins; Chronic Disease; Humans; Kidney Failure, Chronic; Liver Diseases; Middle Aged; Protein Binding; Quinidine; Respiratory Insufficiency; 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

For special purposes a combination of methods is described which allows to determine salicylic acid (including acetylsalicylic acid) and its main metabolites in blood plasma and urine separately and quantitatively. Salicylic acid (SA) and salicyluric acid (SU) are extracted from the acidified fluid with ether and afterwards reextracted in an aqueous phase. By fluorometry at different wavelengths, it is possible to differentiate between SA and SU. The conjugates of SA and SU are hydrolyzed with sulfuric acid and then extracted in the form of SA and SU. The four analyses (SA, SU and their conjugates) are of satisfying accuracy and sensitivity. To test the validity of the method in vivo, the concentrations of SA and its conjugates were determined in the plasma and urines of healthy volunteers. By a simplified, but nevertheless accurate, modification of the described method total salicylate in the urine can be determined.

Topics: Adult; Aspirin; Gentisates; Glucuronates; Humans; Hydrolysis; Kidney Failure, Chronic; Methods; Salicylates; Spectrometry, Fluorescence

Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

Topics: Adult; Aspirin; Blood Urea Nitrogen; Creatinine; Glucuronates; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Salicylates

Topics: Acidosis; Aged; Blood Urea Nitrogen; Bradycardia; Catheterization; Female; Heart Failure; Hepatic Encephalopathy; Humans; Hyperglycemia; Kidney Failure, Chronic; Male; Methanol; Middle Aged; Peritoneal Dialysis; Pyelonephritis; Salicylates

Topics: Aspirin; Chromatography, Thin Layer; Glucuronates; Glycine; Humans; Hydrolysis; Kidney Failure, Chronic; Salicylates

Topics: Age Factors; Antipyrine; Caffeine; Female; Humans; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Pelvis; Male; Papilloma; Phenacetin; Salicylates; Sex Factors; Substance-Related Disorders; Sweden; Time Factors

Topics: Analgesics; Humans; Kidney Failure, Chronic; Phenacetin; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Alkalosis; Alkalosis, Respiratory; Arteries; Asthma; Carbon Dioxide; Education, Medical; Female; Heart Arrest; Humans; Hydrogen-Ion Concentration; Infant; Keto Acids; Kidney Failure, Chronic; Male; Mathematics; Middle Aged; Pulmonary Edema; Respiratory Insufficiency; Salicylates; Teaching

Topics: Adsorption; Aged; Blood Flow Velocity; Blood Platelets; Capsules; Charcoal; Creatinine; Embolism; Female; Glutethimide; Guanidines; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Membranes, Artificial; Pentobarbital; Perfusion; Poisoning; Salicylates; Urea; Uric Acid; Water-Electrolyte Balance

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Protein Disorders; Humans; Kidney Failure, Chronic; Leukemia; Liver Diseases; Salicylates; Thrombocythemia, Essential; Uremia