D-penicillamine-induced glomerulonephritis with crescent formation: Remission following drug discontinuation
A 71-year-old Japanese female who had 12-year history of RA was admitted to our hospital in January 2011 because of progressive proteinuria and microscopic hematuria. A diagnosis of RA had been made in 2004, and since then, she had been receiving bucillamine, salazosulfapyridine, or minocycline as disease-modifying antirheumatic drugs (DMARDs). She also received low-dose steroid therapy (prednisolone, 5 mg/day). In November 2008, D-Pc was started at 100 mg/day to control the RA activity, and the dose was progressively increased to 200 mg/day. Her urinalysis gave a 2+ result for protein and microscopic hematuria in November 2010, and a 3+ test for protein and microscopic hematuria in December 2010. D-pc was stopped in December 2010. Her previous history included bronchiectasis and bronchiolitis. She was a never-smoker.\nOn admission to our hospital, the D-pc had been discontinued for 40 days. A physical examination revealed a 45 kg female with a normal blood pressure (125/67 mmHg). She had edema in her legs, and arthritis in her wrists and metacarpophalangeal joints. There was no fever, rash, hemoptysis or diarrhea. Investigations showed a hemoglobin of 10.4 g/dl with normal white blood cell and platelet counts. Her serum creatinine level was elevated from 0.74 mg/dl in 2010 to 1.16 mg/dl. Her blood urea nitrogen concentration was 19.4 mg/dl and the serum albumin concentration was 2.8 g/dl. The level of anti-cyclic citrullinated peptide antibody was >100 U/ml, rheumatoid factor was 23 IU/ml, C-reactive protein was 1.21 mg/dl, and serum amyloid A was 60.7 μg/ml. Her C3 and C4 levels were normal. The anti-nuclear antibody titer was 1:40. She was negative for serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA), and anti-glomerular basement membrane antibody were negative, which were confirmed by an immunoenzymometric assay (EIA). Urinalysis showed proteinuria of 1,863 mg/day. The patient’s red blood cell count was >100 cells per high power field, her hyaline cast count was two per low power field, and the granular cast count was two per low power field. Radiographs showed Steinbrocker stage III joint deformity, and her lungs had bilateral reticular shadows. Esophagogastroduodenoscopy showed an ulcer scar in the stomach, and the histopathological findings showed amyloid A deposits in the duodenal mucosa.\nIn February 2011, a percutaneous renal biopsy was performed. The kidneys showed sclerotic changes in half of the glomeruli []. In the other half of the glomeruli, focal and segmental endocapillary proliferation was observed with segmental necrotizing lesions of the capillary wall. One glomerulus had a fibrous crescentic change []. There was mild interstitial fibrosis with a mononuclear cell infiltrate. The region of the interlobular artery had amyloid deposition. An immunofluorescence (IF) study revealed deposits of IgG and C3 in the arteries.\nA few weeks later, the patients’ proteinuria disappeared, hematuria decreased, and her serum creatinine level became normal. We did not add any immunosuppressants, and therefore we concluded that this nephropathy had not been induced by amyloidosis, but by D-pc.