propylthiouracil and Acute-Kidney-Injury

Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation.. We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature.. A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T. Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

Topics: Acute Kidney Injury; Aged; Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Nephrotic Syndrome; Propylthiouracil

Clinical recognition of drug-induced vasculitic and lupus-like syndromes is very important because continued use of the offending drug can lead to irreversible and life-threatening vasculitic organ damage (e.g. end-stage renal disease or pulmonary haemorrhage). Withdrawal of the drug often leads to spontaneous recovery, meaning that immunosuppressive therapy can be avoided. The presence of myeloperoxidase-antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare.

Topics: Acute Kidney Injury; Antibodies, Anticardiolipin; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Churg-Strauss Syndrome; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Immunoglobulin M; Kidney; Lupus Erythematosus, Systemic; Methimazole; Propylthiouracil; Skin; Thrombophilia; Vasculitis, Leukocytoclastic, Cutaneous

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

Topics: Acute Kidney Injury; Adult; Anti-Inflammatory Agents; Antithyroid Agents; Female; Humans; Hyperthyroidism; Kidney Function Tests; Male; Nephritis, Interstitial; Prednisolone; Propylthiouracil; Renal Dialysis

To define the relationship between renal epidermal growth factor (EGF) expression and thyroid hormones in acute renal failure, we performed an analysis of the renal thyroid hormone-EGF axis following acute ischemic renal injury in rats. Levels of mature EGF extractable from kidney were elevated 24 h postinjury, and levels of membrane-associated EGF precursor were reduced. Administration of triodothyronine (T3) to rats, either prior to or immediately following the induction of injury, did not further increase levels of extractable EGF. Levels of EGF mRNA in kidneys were reduced 24 h following acute ischemic damage and not affected by administration of T3. Enhanced production of mature EGF from EGF precursor occurred in membranes isolated from kidneys of rats 24 h postinjury compared with production in membranes from kidneys of normal rats. In addition, levels of thyroxine 5'-deiodinase activity in renal membranes were increased 24 h following injury. Levels of circulating total thyroxine (T4), free T4, and free T3 were reduced postischemic injury. Total T3 was unchanged. The administration of T3 to normal rats increased renal 5'-deiodinase activity and EGF precursor cleavage. Administration of propylthiouracil to rats inhibited renal 5'-deiodinase activity and prevented the increase in extractable EGF postischemic injury. We conclude that the increase in levels of mature EGF extractable from kidneys of rats postischemic injury results from enhanced activity of the serine protease that cleaves the EGF precursor. This activity may be stimulated by T3 produced in kidney. These alterations in renal T4 metabolism and EGF expression could serve to facilitate recovery of renal function following ischemia.

Topics: Acute Disease; Acute Kidney Injury; Animals; Epidermal Growth Factor; Hyperthyroidism; Iodide Peroxidase; Ischemia; Kidney; Male; Propylthiouracil; Rats; Rats, Sprague-Dawley; Renal Circulation; RNA, Messenger; Serine Endopeptidases; Thyroxine; Time Factors; Triiodothyronine

Propylthiouracil therapy is associated with a variety of adverse reactions. Renal involvement, although rare, has occurred, but neither acute interstitial nephritis nor severe acute renal failure has been reported previously. We report a case of fulminant acute interstitial nephritis with renal failure following treatment with propylthiouracil.

Topics: Acute Disease; Acute Kidney Injury; Adult; Humans; Male; Nephritis, Interstitial; Propylthiouracil

The effect of hypothyroidism on ischemic acute renal failure was studied in rats. Ten days after thyroidectomy with parathyroid reimplantation, rats underwent right uninephrectomy followed by occlusion of the left renal artery for 60 min. Plasma creatinine was lower in thyroidectomized than control rats 24 hr after ischemia; 1.3 +/- 0.5 vs. 3.2 +/- 0.6 mg%; P less than 0.05. Twenty-four hours after ischemia, inulin clearance was higher in thyroidectomized than control animals (0.40 +/- 0.06 vs. 0.17 +/- 0.03 mliter/min; P less than 0.01), despite an initially lower inulin clearance in thyroidectomized animals (0.81 vs. 1.1 +/- 0.07 mliter/min; P less than 0.05). Administration of the antithyroid drug prophylthiouracil for 14 days also resulted in lower plasma creatinine after ischemia. Kidneys from thyroidectomized animals showed less histologic damage 24 hr after ischemia. Renal cortical content of the lipid peroxidation product malondialdehyde was increased less in thyroidectomy than control kidneys after 60 min ischemia plus 15 min reflow (0.08 +/- 0.02 vs. 0.42 +/- 0.1 nmole/mg protein; P less than 0.005). Renal cortical glutathione content was higher in thyroidectomized animals by approximately 36%, 650 +/- 46 vs. 479 +/- 32 nmole/mg protein (P less than 0.02). In normal rats, glutathione infusion also increased renal cortical glutathione content and resulted in lower plasma creatinine 24 hr after renal artery ischemia. Therefore, hypothyroidism resulted in functional and histologic protection against injury after ischemia. Post-ischemic renal lipid peroxidation was reduced in thyroidectomized animals, perhaps the result of increased scavenging of reactive oxygen species (oxygen free radicals and H2O2) by glutathione.

Topics: Acute Kidney Injury; Animals; Free Radicals; Glutathione; Hypothyroidism; Ischemia; Kidney; Lipid Peroxides; Male; Propylthiouracil; Rats