A PAS statin shows heavy “fuzzy” staining along the glomerular capillary loops
A Jones-Silver stain shows spikes along the glomerular capillary loops
Electron micrograph shows predominantly sub-epithelial dense deposits and diffuse podocyte foot process effacement.
A 25-year-old Asian woman was diagnosed with systemic lupus erythematosus more than 5 years previously. Her recent systemic symptoms include malar rash, photosensitivity, intermittent alopecia, occasional oral ulcers, and arthralgias involving various joints. She has been on steroids intermittently. She was started on losartan over a year prior and her blood pressure was around 125/70. She also takes hydroxychloroquine.
She has no history of thromboembolic events, no miscarriages/pregnancies,and is not sexually active. She recently noted trace ankle edema. Serologically, she demonstrated autoantibodies to anti-nuclear and anti-double stranded DNA antigens. She had persistently low c3 and c4 levels. Her serum creatinine level was 0.9 mg/dL and serum albumin level was 3.4 g/dL. Urine shows 3+ protein, minimal heme positivity, occasional white blood cells and no red blood cells. There were no dysmporphic red blood cell casts. Urine protein totals 3.8 grams in 24 hours (predominantly albumin).
After renal imaging was completed, a renal biopsy was performed. Representative micrographs are shown above.
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This case was provided by Kevin Harley, M.D., Assistant Clinical Professor of Medicine at the University of California in Irvine.
Austin 3rd HA, Illei GG, Braun MJ, et al. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20: 901-911.
Mok CC, Ying KY, Lau CS, et al. Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial. Am J Kidney Dis 2004;43:269-276.
Radhakrishnan J, Moutzouris DA, Ginzler EM, et al. Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 2010;77:152-160.
The renal biopsy findings in this patient reveal a class V membranous lupus nephritis. There is minimal evidence of any proliferative lesion, thus no evidence of class III or IV nephritis.
Phospholipase A2 receptor antibodies would suggest a primary/idiopathic membranous nephropathy and are usually not found in membranous lupus nephritis. IgG4 subclass staining is reported by some as more likely positive in primary/idiopathic membranous disease. IgG subclass staining is usually more disparate in secondary forms of membranous disease. Endocapillary hypercellularity would be a marker of proliferative disease which would confer a greater risk for poor renal outcomes.
Up to 20% of lupus nephritis cases may be due to pure membranous disease and is classified as class V lupus nephritis.
Mycophenolate, cyclosporine, cyclophosphamide, and azathioprine have all been studied, usually in combination with steroids, as treatment for membranous lupus nephritis. At least 1 prospective trial suggested that those treated with cyclosporine over cyclophosphamide may have higher rates of relapse in proteinuria. Another study suggests that intravenous cyclophosphamide and mycophenolate are similar in inducing complete or partial response in proteinuria.