propylthiouracil and Kidney-Diseases

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) has been linked with thyroid disease as a result of antithyroid medications. We assessed the prevalence of thyroid disease in our patients with AAV.. Clinical records of 279 patients with AAV diagnosed between 1991 and 2014 were analyzed.. Thyroid disease was identified in 21.5% of patients, but only 2 had previously received propylthiouracil. There was a greater proportion of female patients, patients with antimyeloperoxidase antibodies, and patients with renal disease in the group with thyroid disease.. Our data show a higher prevalence of thyroid disease in patients with AAV than the general population. This was not attributable to antithyroid drugs.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies; Antithyroid Agents; Chi-Square Distribution; Female; Follow-Up Studies; Humans; Kidney Diseases; Logistic Models; Male; Multivariate Analysis; Peroxidase; Prevalence; Propylthiouracil; Retrospective Studies; Risk Factors; Sex Factors; Statistics, Nonparametric; Thyroid Diseases

The study aimed to predict effective human jejunal permeability (P(eff)) using a biophysical model based on parametrized paracellular, aqueous boundary layer, and transcellular permeabilities, and the villus-fold surface area expansion factor (k(VF)). Published human jejunal data (119 P(eff), 53 compounds) were analyzed by a regression procedure incorporating a dual-pore size paracellular model. Transcellular permeability, scaled by k(VF), was equated to that of Caco-2 at pH 6.5. The biophysical model predicted human jejunal permeability data within the experimental uncertainty. This investigation revealed several surprising predictions: (i) many molecules permeate predominantly (but not exclusively) by the paracellular route, (ii) the aqueous boundary layer thickness in the intestinal perfusion experiments is larger than expected, (iii) the mucosal surface area in awake humans is apparently nearly entirely accessible to drug absorption, and (iv) the relative "leakiness" of the human jejunum is not so different from that observed in a number of published Caco-2 studies.

Topics: Animals; Disease Models, Animal; Dogs; Humans; Jejunal Diseases; Kidney Diseases; Models, Biological; Permeability; Porosity; Regression Analysis

ANCA is detected in several vasculitic diseases, including drug-induced systemic vasculitis: propylthiouracil (PTU), hydralazine, minocycline, penicillamine, allopurinol, procainamide, carbimazole, thiamazole, clozapine and phenytoin. All have been known to induce ANCA positive vasculitis in adult patients.. To study the clinical manifestation, renal pathology and outcome of patients with ANCA positive vasculitis associated with propylthiouracil treatment in Siriraj Hospital.. Retrospective study in 7patients with Graves' disease who were treated with propylthiouracil and developed ANCA-positive glomerulonephritis between 2000-2008.. Seven cases with Graves' disease who received propylthiouracil whose ages were 43 +/- 14 years. The duration of propylthiouracil treatment was 68.5 +/- 39 months and the doses were 50-150 mg per day. Six cases had P-ANCA and one case had C-ANCA in the serum. Proteinuria ranged from 0.49-2.9 gram per day. Mean serum creatinine was 2.05 mg/dl with creatinine clearance of 44 +/- 35 ml/min. The propylthiouracil was withdrawn in every patient and corticosteroid was administered. Renal remission was found until 1 year of follow-up.. ANCA positive glomerulonephritis associated with propylthiouracil is not uncommon. The average onset of glomerulonephritis is 2 years or more. The propylthiouracil dosage was not necessary high. Urinalysis and other glomerulonephritis symptoms should be screened for early diagnosis and appropriate treatment in patients treated with PTU.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Graves Disease; Humans; Kidney Diseases; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome

The kidney is one of the organs affected in patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. We present a series of Chinese patients with renal involvement in PTU-associated ANCA-positive vasculitis and describe their clinical and pathological characteristics.. Clinical and pathological data from patients with PTU-associated ANCA-positive vasculitis with renal involvement, diagnosed in Peking University First Hospital, were collected and analyzed retrospectively.. Nineteen patients with PTU-associated ANCA-positive vasculitis were treated at Peking University First Hospital between December 1999 and December 2005, and 15 of them had renal involvement. Of the 15 patients, 13 were female and 2 were male, with an average age of 26.3 +/- 11.8 years. All 15 patients were perinuclear ANCA positive with specificities to myeloperoxidase (15 of 15), cathepsin G (9 of 15), human leukocyte elastase (8 of 15), lactoferrin (7 of 15), azurocidin (5 of 15), and proteinase 3 (4 of 15). Duration of PTU administration was 43.0 +/- 31.2 months. All 15 patients had clinical markers of renal involvement, including hematuria (100%), proteinuria (100%), and renal function abnormality (47%). All 15 patients underwent percutaneous renal biopsy. Ten patients had necrotizing crescentic glomerulonephritis, and 7 of these 10 patients had immune complex deposition. Three patients had minimal involvement, 2 patients had immunoglobulin A nephropathy, and 2 patients had membranous nephropathy. PTU treatment was discontinued in all 15 patients. All except 2 patients with minimal renal involvement received immunosuppressive treatment. Eleven of 15 patients achieved complete clinical remission.. Renal involvement in our case series of patients with PTU-associated ANCA-positive vasculitis was heterogeneous, and nearly half our patients had renal immune complex deposition.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Humans; Immune Complex Diseases; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Vasculitis

To investigate the features, followup data, and outcomes of patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis.. Nineteen patients with PTU-associated ANCA-positive vasculitis diagnosed in our hospital from 2000 to 2006 were analyzed retrospectively.. Our data showed a female predominance among the patients. Eleven patients had involvement of more than one organ. Renal involvement was the most common manifestation. Fourteen patients underwent renal biopsy. Four patients had focal proliferative glomerulonephritis with crescent formation. Two had necrotizing glomerulonephritis with crescent formation. Two patients had minor glomerular abnormalities, 2 had IgA nephropathy, one had membranous nephropathy, one had focal proliferative glomerulonephritis, one had granulomatous interstitial nephritis, and the remaining one had focal segmental glomerular sclerosis. Immune complex glomerulonephritis was found in 3 patients. On indirect immunofluorescence, 17 patients were perinuclear-pattern ANCA-positive, one was positive for atypical ANCA, and one was positive for cytoplasmic-pattern-ANCA. By ELISA, 4 patients were positive for both myeloperoxidase (MPO)-ANCA and proteinase-3 (PR3)-ANCA, one was positive for PR3-ANCA only, and the others were positive for MPO-ANCA only. For the treatment of vasculitis, 5 patients received prednisone alone, 10 received prednisone and cyclophosphamide, and the remaining 4 did not receive prednisone or cyclophosphamide. During followup, 15 patients achieved remission, 3 patients died, and one patient depended on dialysis. In general, MPO-ANCA concentration did not correlate with disease progression, and a delayed decrease of MPO-ANCA concentration was found in most patients who achieved remission.. Most patients with PTU-associated ANCA-positive vasculitis had good outcomes; however, severe cases existed. We suggest early recognition and adequate treatment are necessary to improve outcome.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Female; Humans; Kidney Diseases; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome; Vasculitis

To date, there is no specific antidote to acetaminophen poisoning. Propylthiouracil (PTU) has been shown to be protective against acetaminophen (APAP)-induced liver damage in rats; however, the nephroprotective effect of propylthiouracil has not been studied yet.. In order to verify this, rats were given different doses of PTU (100, 200 or 400 mg/kg per body weight, orally) 1 h before a nephrotoxic dose of APAP (1,000 mg/kg per body weight, intraperitoneally (i.p.)).. Propylthiouracil pretreatment significantly reduced APAP-induced nephrotoxicity in a dose-dependant manner, as evidenced by reduction in plasma creatinine and by amelioration of renal pathology (interstitial congestion, tubular cell degeneration and necrosis).. The mechanism of protection by PTU is probably not due to the sparing effect of non-protein thiol (approximately 95% of which is reduced glutathione), as similar depletion of renal glutathione was observed regardless of PTU pretreatment; other mechanisms are suggested.

Topics: Acetaminophen; Animals; Creatinine; Dose-Response Relationship, Drug; Kidney; Kidney Diseases; Lipid Peroxides; Male; Propylthiouracil; Rats; Rats, Wistar; Sulfhydryl Compounds; Urea