salicylates and Albuminuria

Salsalate, a nonacetylated prodrug of salicylate, has been shown to decrease blood glucose concentration in small studies.. To compare the efficacy and safety of salsalate at different doses in patients with type 2 diabetes.. Parallel randomized trial with computer-generated randomization and centralized allocation. Patients and investigators, including those assessing outcomes and performing analyses, were masked to group assignment. (ClinicalTrials.gov registration number: NCT00392678). 3 private practices and 14 universities in the United States.. Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (< or = 225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% treated by diet, exercise, and oral medication at stable doses for at least 8 weeks.. After a 4-week, single-masked run-in period, patients were randomly assigned to receive placebo or salsalate in dosages of 3.0, 3.5, or 4.0 g/d for 14 weeks (27 patients each) in addition to their current therapy.. Change in HbA1c was the primary outcome. Adverse effects and changes in measures of coronary risk and renal function were secondary outcomes.. Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA1c levels of 0.5% or more from baseline (P = 0.009). Mean HbA1c changes were -0.36% (P = 0.02) at 3.0 g/d, -0.34% (P = 0.02) at 3.5 g/d, and -0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated.. The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time.. Salsalate lowers HbA1c levels and improves other markers of glycemic control in patients with type 2 diabetes and may therefore provide a new avenue for treatment. Renal and cardiac safety of the drug require further evaluation.. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Topics: Adolescent; Adult; Aged; Albuminuria; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Lipids; Male; Middle Aged; Prodrugs; Salicylates; Tinnitus; Young Adult

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Topics: Acetylglucosaminidase; Adolescent; Adult; Albuminuria; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 1; Female; Glycosaminoglycans; Humans; Imidazoles; Male; Middle Aged; Salicylates

The performance of the urine dipstick, sulfosalicylic acid (SSA), and urine protein-to-creatinine (UPC) tests for the detection of albuminuria was assessed in cats with chronic kidney disease (CKD). Two hundred and thirty-nine urine samples from 37 cats with CKD were used. Test results were dichotomized as either positive or negative, compared with those for the feline-specific rapid urine albumin immunoassay and test performance variables calculated for each test. A positive urine dipstick (≥ trace) and positive SSA (≥ 5 mg/dl), positive SSA alone or ≥ 2+ urine dipstick alone were indicative of albuminuria. In these cases, protein quantification would be warranted if proteinuria/albuminuria is persistent. In the case of a negative urine dipstick result the addition of the SSA added little diagnostic value. Of the tests investigated, the single best test for the detection of albuminuria was the UP/C (≥ 0.2) in which either a negative or positive test result provided useful information.

Topics: Albuminuria; Animals; Benzenesulfonates; Cat Diseases; Cats; Enzyme-Linked Immunosorbent Assay; Female; Male; Reagent Strips; Renal Insufficiency, Chronic; Salicylates; Sensitivity and Specificity; Species Specificity

Topics: Adolescent; Adult; Aged; Albuminuria; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Lipids; Male; Middle Aged; Prodrugs; Salicylates; Young Adult

To evaluate the use of dipstick, sulfosalicylic acid (SSA), and urine protein-to-creatinine ratio (UP:C) methods for use in detection of canine and feline albuminuria.. Evaluation study.. 599 canine and 347 feline urine samples.. Urine was analyzed by use of dipstick, SSA, and UP:C methods; results were compared with those for a species-specific ELISA to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive and negative likelihood ratios.. Positive results for dipstick and SSA tests (trace reaction or greater) in canine urine had moderate specificity (dipstick, 81.2%; SSA, 73.3%) and poor PPV (dipstick, 34.0%; SSA, 41.8%). Values improved when stronger positive results (>or= 2+) for the dipstick and SSA tests were compared with ELISA results (specificity, 98.9% and 99.0% for the urine dipstick and SSA tests, respectively; PPV, 90.7% and 90.2% for the dipstick and SSA tests, respectively). Data obtained for cats revealed poor specificity (dipstick, 11.0%; SSA, 25.4%) and PPV (dipstick, 55.6%; SSA, 46.9%). Values improved slightly when stronger positive test results (>or= 2+) were used (specificity, 80.0% and 94.2% for the dipstick and SSA tests, respectively; PPV, 63.5% and 65.2% for the dipstick and SSA tests, respectively). The UP:C had high specificity for albuminuria in dogs and cats (99.7% and 99.2%, respectively) but low sensitivity (28.7% and 2.0%, respectively).. Caution should be used when interpreting a positive test result of a dipstick or SSA test for canine or feline albuminuria.

Topics: Albuminuria; Animals; Benzenesulfonates; Cat Diseases; Cats; Creatinine; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Proteinuria; Reagent Strips; Salicylates; Sensitivity and Specificity; Species Specificity

Screening for microalbuminuria is increasingly advocated as a way to diagnose early renal involvement in diabetes and other diseases. It usually entails the use of a radioimmunoassay that is expensive and not always readily available.. To assess the efficacy of three simple and inexpensive tests for ruling out microalbuminuria.. Cross-sectional study.. Outpatient clinics.. 221 patients from primary care clinics and a diabetes clinic.. Random urine specimens were tested for albumin by using Micral-Test immunoassay strips (Boehringer Mannheim, Mannheim, Germany) and for protein by using sulfosalicylic acid testing and impregnated dipsticks (Chemstrips, Boehringer Mannheim). Radioimmunoassay for albumin was used for all specimens as standard for comparison.. When less than 20 mg/L was considered the upper limit of normal for albumin concentration, Micral-Test, sulfosalicylic acid testing, and Chemstrips had negative predictive values of 99%, 95%, and 96%, respectively. Seventy-four specimens tested negative on both sulfosalicylic acid and Chemstrips; the negative predictive value of these two tests combined was 99%.. The combination of sulfosalicylic acid testing and Chemistrips was as good as and less expensive than Micral-Test in ruling out microalbuminuria.

Topics: Albuminuria; Benzenesulfonates; Cost-Benefit Analysis; Cross-Sectional Studies; False Positive Reactions; Humans; Immunoassay; Mass Screening; Predictive Value of Tests; Reagent Strips; Salicylates

Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5-day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (PGF1 alpha), and PGE2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 micrograms/min. Plasma TXB2 and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 +/- 39 vs. 52 +/- 32 pg/ml, P less than 0.02) and urine TXB2 (523 +/- 249 vs. 312 +/- 11 pg/min, P less than 0.02), without changes in PRA and UAE of 6-keto-PGF1 alpha and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Albuminuria; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprostone; Female; Glomerular Filtration Rate; Humans; Male; Platelet Aggregation Inhibitors; Renal Circulation; Renin; Salicylates; Thromboxane B2

Topics: Albuminuria; Bromphenol Blue; Cellulose; Diabetes Mellitus; Diabetic Nephropathies; Evaluation Studies as Topic; Humans; Nephelometry and Turbidimetry; Reagent Strips; Salicylates; Salicylic Acid; Sensitivity and Specificity

Topics: Adult; Albuminuria; Blood Glucose; Erythrocytes; Female; Humans; Imidazoles; Male; Middle Aged; Salicylates

Three side-room tests (latex bead immunoagglutination test, LBT; 25% sulphosalicylic acid test, SST; microalbutest, MAT) for the detection of microalbuminuria in diabetics are described and their screening potential and practicability assessed. One hundred insulin-dependent diabetics attending a diabetic clinic provided an early morning urine sample (Albustix-negative) which was subjected to each of the three tests, and urinary albumin concentration (UA) was assayed by RIA. Tests were assessed in random order by two trained operators using a semiquantitative grading scale with 100% concordance between 10 observers. All test results greater than or equal to trace +ve were sufficiently sensitive (sensitivity greater than or equal to 90%) in detecting UA greater than 15 mg/l, but MAT exhibited a significantly reduced specificity (69%) and positive predictive value (58%). For a reference UA greater than 30 mg/l, LBT and SST results greater than or equal to trace +ve and MAT results greater than or equal to +ve showed a sensitivity of 100%, a specificity greater than 85% and a positive predictive value greater than 60%. Reagent shelf-life was shortest with LBT. SST involved centrifugation or filtration. Technical skill required was highest with LBT and lowest with MAT. Costs were slightly higher with LBT than SST and were not available for MAT.

Topics: Albuminuria; Benzenesulfonates; Colorimetry; Diabetes Mellitus; Humans; Indicators and Reagents; Microchemistry; Salicylates

Topics: Albuminuria; Autoanalysis; Benzenesulfonates; Globulins; Humans; Nephelometry and Turbidimetry; Salicylates; Trichloroacetic Acid

The effect of a single oral dose (1 g) of acetylsalicylic acid (ASA) on renal function and hepatic enzymes as well as prothrombin time was studied in two series of experiments on normal human volunteers. Radioimmunoassay of albumin and beta 2-microglobulin excretion rates in urine revealed a statistically significant increase in both beta 2-microglobulin and albumin excretion rates within 2 h after dosage. Hepatic enzymes were not influenced by a single dose of ASA, while a statistically significant reduction in prothrombin time was registered. High-pressure liquid chromatography was used for measuring serum levels of ASA and salicylic acid (SA). Peak levels of 500 mumol/l and 150 mumol/l for SA and ASA, respectively, were found.

Topics: Adolescent; Adult; Alanine Transaminase; Albuminuria; Aspartate Aminotransferases; Aspirin; beta 2-Microglobulin; Female; Humans; Kidney; Liver; Male; Middle Aged; Proteinuria; Prothrombin Time; Salicylates; Salicylic Acid

Our examination of urine components separated by gel filtration revealed the presence of an inhibitor that decreases the analytical recovery of protein in a turbidimetric assay involving sulfosalicylic acid as reagent (Proc. Soc. Exp. Biol. Med. 92: 748, 1956). The apparent relative molecular mass of this inhibitor was in the range 160 000-240 000. A study with purified proteins showed a similar inhibition by gamma-globulin, glycoprotein, and beta-lipoprotein in the assay of albumin by the same turbidimetric method. In contrast, measurement of protein by a dye binding method was not affected by these materials. The low values for apparent urinary protein given by the turbidimetric method as compared with those by the dye-binding method are at least partly ascribable to the inhibitor.

Topics: Albuminuria; Benzenesulfonates; Chromatography, Gel; Humans; Nephelometry and Turbidimetry; Proteinuria; Rosaniline Dyes; Salicylates; Urine

Two types of urine protein dipsticks and the sulfosalicylic acid method were compared for their accuracy and specificity, with use of urine samples supplemented with various proteins. Dipsticks yield accurate results when the protein under consideration is restricted to albumin; the sulfosalicylic acid method accurately determines many kinds of proteins in addition to albumin. Detergents affect each of the methods, but changes in salt concentration only affect results by dipstick procedures. Dipsticks, which are based on the protein-error principle for indicators, are subject to some of the conditions that apply to the bromcresol green method for serum albumin determination.

Topics: Albuminuria; False Negative Reactions; False Positive Reactions; Methods; Proteinuria; Reagent Strips; Salicylates

Topics: Adolescent; Adult; Albuminuria; Animals; Chemical Precipitation; Child; Child, Preschool; Electrophoresis; Evaluation Studies as Topic; Female; Hot Temperature; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Male; Methods; Middle Aged; Nitrites; Proteinuria; Rabbits; Salicylates; Sulfanilamides

Topics: Albuminuria; Centrifugation; Chemical Precipitation; Humans; Methods; Muramidase; Salicylates

Topics: Albuminuria; Benzenesulfonates; Humans; Indicators and Reagents; Naphthalenes; Peptides; Salicylates