442. A case of anti-glomerular basement membrane (GBM) antibody-positive tubulointerstitial nephritis

Presentation of Case: A 65-year-old woman presented 2 weeks after antibacterial treatment for cystitis, with a severe acute kidney injury. Her serum creatinine level was 1.0 mg/dL two weeks before but had elevated to 2.8 mg/dL at admission. The urinalysis revealed proteinuria of 0.82 g/g Cr, hematuria of more than 100 red blood cells per high-power field (HPF), and a few leukocyte casts. No erythrocyte casts were found. Urine N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin levels were 10.5 U/L (normal range, 0.7–11.2 U/L) and 4179 μg/L (<290 μg/L), respectively. Autoimmune serology demonstrated positive for anti-GBM antibodies (51.3 IU/mL). Computed tomography showed no renal enlargement, hydronephrosis, urinary tract abnormality, or alveolar hemorrhage. She was clinically diagnosed with anti-GBM antibody-positive rapidly progressive glomerulonephritis. Plasma exchange was performed for four sessions over consecutive days. She also received one course of steroid pulse therapy (methylprednisolone 500 mg for 3 days) followed by oral prednisolone 40 mg per day. After the initiation of the therapy, the anti-GBM antibody decreased and was finally undetectable (<2.0 U/mL). Her proteinuria became negative and her urine β2-microglobulin level decreased. Serum creatinine improved to 1.59 mg/dL two months after the initiation of the therapy and then became stable, even after oral prednisolone tapered to 15 mg per day.

Diagnostic Testing: A renal biopsy was undertaken 23 days after admission. Light microscopy demonstrated no crescent formation in any of the eight glomeruli. Infiltration of inflammatory cells in the interstitium and tubulitis with rupture of tubular basement membrane was observed. Immunofluorescence demonstrated linear deposition of IgG and IgM on the glomerular capillary wall while no deposition in the tubular basement membrane. Electron microscopy demonstrated no thickening or deposition of the glomerular capillary wall.

Differential & Final Diagnosis: We diagnosed her with atypical anti-GBM antibody-positive nephritis without crescent formation or tubulointerstitial nephritis followed by the production of anti-GBM antibody. The possibility of the existence of crescentic glomerulonephritis could not be ruled out due to the limited number of glomeruli. A few cases of anti-GBM antibody positive-nephritis with atypical histological findings and clinical course has been reported. In these cases, immunofluorescence of renal biopsy demonstrates linear deposition of IgG of the capillary wall without crescent formation. In addition, renal function slowly deteriorates compared to typical anti-GBM antibody type glomerulonephritis. These clinicopathological characteristics were consistent with our case. We also considered the possibility of tubulointerstitial nephritis. Some of the tubular basement membranes contain type IV collagen, as do the glomerular basement membranes. The glomerular and tubular basement membranes share common antigenicity and may exhibit cross-reactivity. We considered that tubulointerstitial nephritis may have caused the production of anti-GBM antibodies.

Discussion of Management: Renal function slowly deteriorates in previously reported cases of atypical anti-GBM antibody nephritis. However, in our case, renal function deteriorated rapidly, and severe tubulitis was found. We treated her in the same way as typical anti-GBM antibody-positive type glomerulonephritis.

Conclusions: We experienced a case of anti-GBM antibody-positive tubulointerstitial nephritis. The patient did not present a typical clinical course and may have developed atypical anti-GBM antibody type nephritis.

Disclosures: None.