propylthiouracil and Glomerulonephritis

Topics: Alleles; alpha 1-Antitrypsin; Animals; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal; Antithyroid Agents; gamma-Globulins; Glomerulonephritis; HLA Antigens; Humans; Immunosuppressive Agents; Infliximab; Lipopolysaccharides; Mycophenolic Acid; Neutrophil Activation; Propylthiouracil; Silicon Dioxide; Staphylococcus aureus; Vasculitis

We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Glomerulonephritis; Glomerulonephritis, Membranous; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Glomerulonephritis; Hemorrhage; Humans; Propylthiouracil; Pulmonary Circulation; Radiography, Thoracic; Vasculitis

We treated a 13-year-old girl who developed myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related crescentic glomerulonephritis (GN) during propylthiouracil (PTU) treatment for Graves' disease. MPO-ANCA-related crescentic GN during PTU therapy has been described previously in only one recent report of 2 children. We report this case here and describe 15 (13 adult cases) more patients with MPO-ANCA-related GN associated with PTU found in a literature review. The mean age at onset was 41.3 years, and the length of PTU administration ranged from 2 weeks to 6 years (mean 3.5 years). Clinical signs and symptoms were hematuria (100%), proteinuria (100%), arthralgia (7 of 16 cases; 43.8%), fever (4 cases; 20.0%), purpura (2 cases; 12.5%), skin ulcer (1 case; 6.3%) and dyspnea (1 case; 6.3%). These patients were treated with steroid (15 cases; 93.8%), cyclophosphamide (8 cases; 50.0%), steroid pulse therapy (4 cases; 25.0%), or plasma exchange (1 case; 6.3%), or were not treated (1 case; 6.3%). Most patients revealed crescentic GN (15 cases; 93.8%) on renal biopsy, while one exhibited mesangial proliferative GN (6.3%). For 2 of the 16 patients (12.5%) irreversible renal dysfunction persisted and hemodialysis was started. Patients with Graves' disease treated with PTU should be observed carefully by urinalysis and monitoring of the serum creatinine level.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Graves Disease; Humans; Peroxidase; Propylthiouracil

A 68-year-old man who developed MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) treatment is reported. In 1986, he was diagnosed as having interstitial pneumonitis. Although he tested positive for antinuclear antibody and rheumatoid factor, he had no symptoms and was followed up without therapy. Five years later, the diagnosis of Graves's disease was made after complaints of body weight loss, diplopia and exophthalmos. Tests showed positivity for anti-thyroid stimulating hormone (TSH) receptor antibody, antithyroidperoxidase antibody and antithyroglobulin antibody. He was treated with PTU and prednisolone for four years. In November 1995, hematuria and proteinuria developed, and renal function deteriorated rapidly. A renal biopsy revealed crescentic glomerulonephritis and the serum titer of MPO-ANCA was markedly elevated. He was treated with a high dose of prednisolone and cyclophosphamide. Although the serum creatinine level gradually decreased, irreversible renal dysfunction persisted. In this patient, the presence of various autoantibodies had been recognized for several years before MPO-ANCA-associated glomerulonephritis developed. Polyclonal B-cell activation and PTU treatment may have played a role in the pathogenesis of MPO-ANCA-associated glomerulonephritis.

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Glomerulonephritis; Graves Disease; Humans; Lung Diseases, Interstitial; Male; Peroxidase; Propylthiouracil

We have experienced a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis induced by propylthiouracil (PTU). A 45-year-old female had been treated with PTU for 4 years after the diagnosis of hyperthyroidism. She was referred to out hospital because of abrupt macroscopic hematuria and moderate proteinuria after several days of upper respiratory tract infection. On admission, her laboratory findings showed deterioration of renal function. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes. Her serology was found to be MPO-ANCA-positive and cytoplasmic-ANCA-negative. Based of these findings, we diagnosed idiopathic crescentic glomerulonephritis. Following the initiation of steroid pulse therapy, her urinary protein excretion and renal function gradually improved in parallel with a decrease in the MPO-ANCA titer. Although steroid therapy effectively responded to their renal function without the withdrawal of PTU, it seems that PTU may be closely associated with the development of (MPO-ANCA)-related glomerulonephritis in this case. Therefore, hyperthyroidism patients treated with PTU should be paced under vigilant observation by monitoring their urinalysis and serum creatinine level.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Peroxidase; Propylthiouracil

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting with renal failure, acute hepatic failure, and cerebral angiitis is a rare yet fatal disease. Early diagnosis and management may help in reducing mortality and morbidity. Plasmapheresis and induction with either cyclophosphamide or rituximab is indicated. Understanding the pathophysiology and complex management of this disease poses challenges to clinicians.. A 42-year-old woman presented with acute renal and hepatic failure. She had been on PTU for 11 months for Graves' disease. Initial urine microscopy showed red blood cell casts. Anti PR-3 antibodies were positive. Kidney biopsy revealed pauci-immune glomerulonephritis with crescent formation. Renal and hepatic failures were attributed to PTU-induced c-ANCA production as other serological workup was negative. Pulse steroids and plasmapheresis were initiated. Later she developed pneumonia. She was also given rituximab. After the first dose of rituximab, plasmapheresis was held for 3 days. The second dose of rituximab was given in 5 days owing to removal by plasmapheresis. She got 8 sessions of plasmapheresis. She also developed seizures and MRA of her head revealed cerebral infarct, with findings suggestive of cerebral angiitis. She did not recover and expired 20 days after presentation.. PTU can cause ANCAassociated vasculitis resulting in multiorgan failure. Plasmapheresis should be held for 3 days after rituximab infusion in order to allow maximum exposure. The second dose of rituximab may be given before the recommended 7-day interval in cases in which plasmapheresis is being performed to maximize therapeutic benefit.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Murine-Derived; Antithyroid Agents; Biopsy; Combined Modality Therapy; Disease Progression; Fatal Outcome; Female; Glomerulonephritis; Graves Disease; Humans; Immunosuppressive Agents; Liver Failure, Acute; Magnetic Resonance Angiography; Microscopy, Electron; Multiple Organ Failure; Plasmapheresis; Propylthiouracil; Pulse Therapy, Drug; Rituximab; Steroids; Time Factors; Treatment Failure; Vasculitis, Central Nervous System

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

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Glomerulonephritis; Graves Disease; Humans; Propylthiouracil; Takayasu Arteritis

The patient was a 62-year-old female. In June 1999, thiamazole (MMI) was orally administered under a diagnosis of hyperthyroidism. However, drug exanthema developed. In July, oral administration of propylthiouracil (PTU) was started. On October 20, 2005, palpitation and exertional dyspnea occurred. On November 1, bloody sputum was noted, and the patient consulted our hospital on November 8. In addition to severe anemia, chest X-ray and CT revealed diffuse infiltration in the bilateral lungs. The patient was admitted for detailed examination and treatment. After admission, the myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) level was 390 EU, suggesting ANCA-associated angitis. PTU was discontinued, and steroid pulse therapy resulted in the disappearance of alveolar hemorrhage and hematuria. Transbronchial lung biopsy suggested alveolar hemorrhage, and kidney biopsy showed glomerular necrosis and interstitial infiltration of inflammatory cells, suggesting PTU-induced ANCA-associated angitis. Posttreatment with prednisolone at 30 mg/day gradually decreased the MPO-ANCA level. There has been no relapse during the 2-years follow-up.

Topics: Antibodies, Antineutrophil Cytoplasmic; Female; Glomerulonephritis; Hemorrhage; Humans; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Vasculitis

Propylthiouracil (PTU) has been known to induce myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis. Our previous study indicated that the increase of avidity of MPO-ANCA might be associated with the occurrence of clinical vasculitis in patients with PTU-induced ANCA. The current study aimed to follow-up the avidity and titre of anti-MPO antibodies in sequential sera from patients with PTU-induced ANCA-associated systemic vasculitis (AASV).. Six patients with PTU-induced vasculitis were enrolled in the current study. Serial sera in both active phase and in remission were collected. MPO-ANCA avidity was assessed by antigen-inhibition enzyme-linked immunosorbent assays (ELISAs), and avidity constant (aK) was determined as the reciprocal value of the MPO molar concentration in the liquid phase resulting in 50% inhibition of anti-MPO antibody binding to MPO in solid phase ELISA. Titres of MPO-ANCA were determined by using serial serum dilutions in MPO-ELISA.. After cessation of PTU and initiation of immunosuppressive therapy, the avidity and titre of MPO-ANCA decreased significantly during follow-up in sera from all the patients, and the avidity decreased much more quickly than the titres.. Our study indicates that avidity of anti-MPO antibodies might be more closely associated with clinical vasculitis than titre.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Affinity; Antigen-Antibody Reactions; Antithyroid Agents; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glomerulonephritis; Graves Disease; Humans; Peroxidase; Propylthiouracil; Vasculitis; Withholding Treatment

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperthyroidism; Necrosis; Plasmapheresis; Propylthiouracil; Radiography, Thoracic; Time Factors; Treatment Outcome; Vasculitis

The effect of hyper or hypoactive thyroid on the renal toxicity of arsenic trioxide has been studied in rats. It was observed that pre-treatment of rats with thyroxine stimulates arsenic excretion in urine. The anti-thyroid drug n-propylthiouracil (PTU), inhibits the accumulation of arsenic in renal tissue. Both treatments affect the renal pathology. Histopathological lesions are less severe in PTU and arsenic-treated rats in comparison to thyroxine and arsenic-treated rats. Ultrastructural studies support light microscopical observations. An adaptive response was noticed against arsenic in PTU pre-treated rats. We attribute this response to decreased glutathione-S-transferase (GSH) activity and increased GSH synthesis in the kidney. A relationship between thyroidal activity and arsenic toxicity is suggested by present observations.

Topics: Animals; Antithyroid Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Creatinine; Glomerulonephritis; Glutathione; Glutathione Transferase; Hyperthyroidism; Hypothyroidism; Kidney; Male; Necrosis; Oxides; Propylthiouracil; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Vasculitis, Leukocytoclastic, Cutaneous

A retrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody (ANCA)-positive glomerulonephritis associated with propylthiouracil treatment. Seven Japanese pediatric patients who had myeloperoxidase-specific ANCA-positive biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis associated with propylthiouracil administration were entered in the study. Three patients had nephritis alone, and four had nephritis and extrarenal organ system vasculitis. Females predominated, and the mean age at onset was 14 yr. Propylthiouracil was reduced or discontinued in all patients and was switched to methimazole in three patients. For the treatment of nephritis, five patients received corticosteroids; three had pulse methylprednisolone, one had plasma exchange, and one had plasma exchange and pulse methylprednisolone before initiating oral prednisolone. The remaining two patients received cyclophosphamide and corticosteroids, one of whom had pulse methylprednisolone before initiating oral prednisolone and cyclophosphamide. All patients achieved remission. In general, ANCA titers correlated with the response to treatment and disease activity, with some exceptions. No patient progressed to end-stage renal disease, renal dysfunction, or death during the follow-up period (58 +/- 25 mo; range, 32 to 108 mo). All but one patient remained euthyroid. In conclusion, this experience suggests that the clinical disease spectrum of ANCA-positive disease associated with propylthiouracil treatment is similar in pediatric and adult patients and that the overall prognosis may be better than that in the non-drug-induced ANCA-positive disease.

Topics: Adolescent; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biopsy; Child; Cyclophosphamide; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney; Male; Methylprednisolone; Plasma Exchange; Prednisolone; Propylthiouracil; Treatment Outcome

A 14-year-old girl developed acute renal failure after 3 years therapy with propylthiouracil (PTU) for Grave's disease. Serologic evaluation showed antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 and myeloperoxidase. Renal biopsy showed a crescentic glomerulonephritis (GN) as well as evidence of IgA nephropathy (IgAN). PTU was discontinued and the patient was treated with prednisone and cyclophosphamide. ANCA became negative and renal function improved, but did not normalize. A second biopsy showed evidence of IgA nephropathy only. Propylthiouracil use has been associated with ANCA positive pauci-immune glomerulonephritis, but not with IgA nephropathy. An overlap syndrome between IgAN and ANCA-positive GN, however, has been described. This patient may have had a preexisting IgAN, with acute pauci-immune GN secondary to PTU, or this may be the first description of an overlap syndrome of IgAN and ANCA vasculitis all caused by PTU therapy.

Topics: Acute Kidney Injury; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Glomerulonephritis; Glomerulonephritis, IGA; Graves Disease; Humans; Propylthiouracil

A teenage girl with crescentic glomerulonephritis had antineutrophil cytoplasmic antibody (ANCA) detected after she had received propylthiouracil (PTU) for hyperthyroidism without cutaneous vasculitis. ANCA was detected on admission; renal biopsy showed crescentic glomerulonephritis with focal necrotizing glomerulonephritis but no immune deposits. Administration of steroid and decreasing the dose of PTU produced a good clinical response and the ANCA disappeared. It was concluded that ANCA is closely related to the pathogenesis of crescentic glomerulonephritis and that treatment with PTU appeared to induce ANCA.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Hyperthyroidism; Necrosis; Propylthiouracil

We present a case study of a 52-year-old female patient with hyperthyroidism which had been diagnosed at the age of 35. However, the malfunction of thyroid had been poorly controlled. Thyroid function was returning to normal after the administration of propylthiouracil (PTU) 300 mg/day, however purpura appeared in both lower extremities. Renal function deteriorated rapidly, and the patient was admitted to our hospital. According to the biopsies, leukocytoclastic vasculitis in the skin was apparent, and crescent formation was observed in the glomerulus. Serological examination revealed positive antineutrophil cytoplasmic autoantibodies (ANCA) against proteinase 3 (Pr3) and myeloperoxidase (MPO). Antinuclear autoantibody was positive. After cessation of PTU and administration of prednisolone, the purpura disappeared and ANCA were becoming negative. Renal function recovered gradually. Thyroid function was kept within normal range using iodine solution. Thus, it is strongly suggested that PTU-induced rapidly progressive glomerulonephritis associated with ANCA.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Although its pathogenesis remains to be established, detection of antineutrophil cytoplasmic antibodies (ANCA) in association with this type of vasculitis has recently been described. We report here 2 patients who developed ANCA-associated crescentic glomerulonephritis without evidence of cutaneous vasculitis during propylthiouracil treatment of hyperthyroidism. Improvement of the renal function and the disappearance of ANCA were correlately found after discontinuation of propylthiouracil and by corticosteroid therapy in both patients.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glomerulonephritis; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease. After several weeks of upper respiratory tract infection or flu-like symptoms, they abruptly began to manifest proteinuria and hematuria concomitant with severe anemia. Their serum creatinine increased from normal levels to 1.2 to 3.6 mg/dL. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes (ie, pauci-immune type). Crescent formations were observed in 40% to 60% of the glomeruli in all three cases. The serum from the patients revealed positive perinuclear-ANCA and negative cytoplasmic-ANCA (C-ANCA) pattern, and myeloperoxidase (MPO)-ANCA titers were 120 to 502 ELISA Units/mL (normal, < 10 ELISA Units/mL). A withdrawal of propylthiouracil with or without immunosuppressive therapy ameliorated their renal derangements. Graves' disease patients should be placed under vigilant observation by monitoring their urinalysis and serum creatinine, especially when being treated with antithyroid drugs and when suffering from flu-like symptoms.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Glomerulonephritis; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil

Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis following treatment with propylthiouracil and carbimazole are described. Both patients had crescentic glomerulonephritis proven by renal biopsy and responded to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though systemic vasculitis associated with propylthiouracil is reported, this is the first report to our knowledge of renal biopsy-proven vasculitis associated with either of these drugs.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Carbimazole; Glomerulonephritis; Humans; Hyperthyroidism; Kidney; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis; Vasculitis

Propylthiouracil, which is commonly used in the treatment of hyperthyroidism, has been associated in adults with antineutrophil cytoplasmic autoantibody, a serologic marker of vasculitis. Severe renal disease has not been reported as a complication of therapy with this drug. We report severe antineutrophil cytoplasmic autoantibody-positive vasculitis in children receiving propylthiouracil, as well as rapidly progressive crescentic glomerulonephritis after administration of this drug.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Child; Female; Glomerulonephritis; Humans; Hyperthyroidism; Male; Propylthiouracil