propylthiouracil and Kidney-Failure--Chronic

To retrospectively investigate clinico-pathological features and outcomes of patients with renal involvement in propylthiouracil (PTU)-associated antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (PTU-AAV).. Clinico-pathological features and outcomes of 12 patients (female 11, average age 32.4 ± 13.8 years) who developed AAV after treatment with PTU were collected and analyzed. ANCA was detected by both immunofluorescence (IF) and enzyme linked immunosorbent assay (ELISA). All patients had renal biopsy.. Twelve patients received PTU for 2-264 months (median 42 months) when PTUAAV was diagnosed. All patients had positive serum P-ANCA, 11 of them were MPO-ANCA, 1 was MPO and PR3-ANCA double positive. All patients presented with hematuria and proteinuria, 5 of them had gross hematuria, urine protein was 1.9 ± 1.6 g/24 h, 7 of 12 (58.3%) patients had renal dysfunction, among them 3 needed initial renal replacement therapy. Renal biopsy showed pauci-immune segmental necrotizing crescentic glomerulonephritis in ten patients, segmental necrotizing glomerulonephritis superimposed on membranous nephropathy in two patients. All patients withdrew PTU and received steroid and immunosuppressive therapy. After a median follow-up of 42 months (range 21-86), 3 patients developed to ESRD, 7 patients entered complete renal remission. Serum ANCA turned negative only in 2 patients, 10 patients had persistent positive serum ANCA. Three patients relapsed with the elevation of serum ANCA level.. Renal damage of PTU-AAV could be pauci-immune necrotizing crescentic glomerulonephritis, and necrotizing glomerulonephritis coexisted with membranous nephropathy. Most patients had persistent positive serum ANCA and had a risk of relapse and progression to ESRD even after PTU withdrawal and immunosuppressive therapy.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antithyroid Agents; Child; Cyclophosphamide; Disease Progression; Hematuria; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Tubules; Male; Middle Aged; Mycophenolic Acid; Prednisone; Propylthiouracil; Proteinuria; Recurrence; Remission Induction; Renal Replacement Therapy; Retrospective Studies; Thyroid Diseases; Young Adult

Both hypothyroid (Hypo) and hypozincemia are commonly observed in patients and animals with chronic renal failure (CRF). In CRF whether the hypothyroid plays a role in the pathogenesis of hypozincemia is unclear. This study is designed to investigate the effects of hypothyroid on intestinal zinc absorption and urinary zinc excretion in 5/6 nephrectomized (Nx) rats, because plasma zinc balance is attained through a controlled rate of intestinal uptake as well as renal reabsorption. Intestinal zinc absorption was carried out in jejunum and ileum segments by an in vivo perfusion technique and the renal zinc disposal was evaluated by a conventional method using a standard formula to calculate the zinc tubular reabsorption and the excretion of urinary zinc in 5/6 Nx rats with hypothyroidism. The Hypo-NxT rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion compared with Eu-NxT rats. They also had significantly lower levels of mucosal zinc and MT as well as lower content of liver zinc than Eu-NxT rats after intestinal zinc perfusion for 80 min. Hypo-NxT rats showed low plasma zinc levels, but had a similar output of pancreaticobiliary zinc and excretion of 24-h urine zinc compared with the Eu-NxT rats. When 2% alcohol intestinal perfusion was used to produce water diuresis, the Hypo-NxT rats presented a higher excretion of urinary zinc than the Eu-NxT rats did, especially during 2% alcohol intestinal zinc perfusion. In the Hypo-NxT rats, the lower plasma zinc levels may thus result from the hypothyroid because it reduces intestinal zinc absorption. Increasing the urine flow rate may aggravate the reduction of plasma zinc level in Hypo-NxT rats because of the increased excretion of urinary zinc.

Topics: Animals; Hypothyroidism; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Male; Metallothionein; Nephrectomy; Propylthiouracil; Rats; Rats, Sprague-Dawley; Zinc

We report a case of Graves' disease in a patient on regular hemodialysis. The patient also suffered from Wolff-Parkinson-White (WPW) syndrome and paroxysmal atrial fibrillation, which may both have been manifestations of the Graves' disease because of the increased oxygen demand. To our knowledge, this is the first case to illustrate the usefulness of the antithyroid agent propylthiouracil for Graves' disease complicated by endstage renal disease (ESRD) and WPW syndrome.

Topics: Antithyroid Agents; Atrial Fibrillation; Graves Disease; Humans; Kidney Failure, Chronic; Male; Middle Aged; Propylthiouracil; Renal Dialysis; Wolff-Parkinson-White Syndrome

A 71-year-old man with acrodermatitis continua of Hallopeau was treated successfully with a combination of oral propylthiouracil and methotrexate. After 14 weeks, he developed acute pancytopenia, an uncommon idiosyncratic side-effect of propylthiouracil, and presented with a life-threatening methicillin-resistant Staphylococcus aureus pneumonia. This illustrates the potential value and associated risks of propylthiouracil in the management of this difficult condition.

Topics: Acrodermatitis; Acute Disease; Aged; Antimetabolites; Drug Synergism; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Male; Methicillin Resistance; Methotrexate; Pancytopenia; Pneumonia, Staphylococcal; Propylthiouracil; Psoriasis; Staphylococcus aureus

Topics: Adult; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Nephritis, Interstitial; Propylthiouracil; Sjogren's Syndrome; Time Factors

Topics: Adult; Antithyroid Agents; Dose-Response Relationship, Drug; Graves Disease; Humans; Kidney Failure, Chronic; Male; Pancytopenia; Propylthiouracil

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Kidney Failure, Chronic; Male; Methimazole; Pancytopenia; Propylthiouracil

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Topics: Agranulocytosis; Angina Pectoris; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Methimazole; Middle Aged; Propylthiouracil; Renal Dialysis

The simultaneous occurrence of thyrotoxicosis and renal failure has rarely been reported in the literature, and data concerning appropriate antithyroid drug management in this circumstance are limited. We studied propylthiouracil pharmacokinetics in one such patient basally and while the patient was receiving hemodialysis. On a day when the patient was not receiving hemodialysis, propylthiouracil serum levels were high, but serum propylthiouracil half-life was not prolonged. During hemodialysis, serum propylthiouracil levels were normal, and the time to peak serum levels was delayed; the disappearance of the drug from the serum was normal after hemodialysis was completed. The amount of propylthiouracil that appeared in the dialysate was approximately 5% of the administered dose. These data suggest that propylthiouracil can be administered in standard dosages to patients with thyrotoxicosis and renal failure.

Topics: Adult; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Propylthiouracil; Renal Dialysis; Thyrotoxicosis

Differences in the metabolic fate of antithyroid drugs influence the optimal frequency of administration and their therapeutic efficacy. (35)S propylthiouracil differed from the (35)S imidazoles (carbimazole and methimazole) in the more rapid absorption and excretion and the shorter biological half-life in the plasma of the former. Renal function may have a more important influence on the biological half-life of the drugs than thyroid status. Further work is required to determine the optimal frequency of administration for each compound.

Topics: Antithyroid Agents; Carbimazole; Chromatography, Thin Layer; Female; Humans; Hyperthyroidism; Imidazoles; Kidney Failure, Chronic; Methimazole; Propylthiouracil; Sulfur Isotopes