Title

A refractory case of rapidly progressive glomerulonephritis due to microscopic polyangiitis

Authors

Virginia L. Hoch, MD (1); Peter Burke, DO (2); Ajeetpal Hans, MD (3). (1) Christiana Care, Newark, DE. (2) Christiana Care, Newark, DE; Nephrology Associates, P.A., Newark, DE. (3) Christiana Care, Newark, DE.

Introduction

Acute kidney injury is a common diagnosis in the inpatient setting, occurring in about 23% of hospitalized patients, and is associated with increased mortality. Frequently, this condition can be managed conservatively and does not require intensive diagnostic work up. In certain instances, however, it is essential to make a timely diagnosis in order to guide more aggressive treatment. This is exemplified when a patient presents with rapidly progressive glomerulonephritis (RPGN), a condition that puts them at risk of progressing to end stage renal disease (ESRD) in a short period of time. In the present study, we present a case of RPGN due to ANCA-associated vasculitis (AAV) with suboptimal response to initial induction therapy, requiring consideration of novel therapy options.

Case Presentation

A seventy-five-year-old woman with no history of renal disease presented to the hospital for chest discomfort and dyspnea. She was found to be in acute renal failure with a creatinine of 5.1 (increased from a baseline of 0.9 three months prior), associated with proteinuria and hematuria. Work-up revealed RPGN due to microscopic polyangiitis (MPA), evidenced by positive p-ANCA and myeloperoxidase antibody titers, with renal biopsy showing necrotizing crescents in 12 of 14 glomeruli. Pulmonary manifestations included an exudative pleural effusion which required thoracentesis, as well as interstitial lung disease with multiple irregular nodular opacities. Despite aggressive treatment with plasmapheresis, high-dose prednisone and, later on, rituximab infusions, renal function did not improve, and she required initiation of hemodialysis. She was ultimately discharged on a prednisone taper with plans to continue outpatient rituximab infusions and hemodialysis. Due to her refractory course, initiation of a new targeted immunomodulator known as avacopan, a complement 5a receptor antagonist, was considered for the outpatient setting.

Discussion

AAV is an autoimmune disease in which Anti-Neutrophilic Cytoplasmic Autoantibodies (ANCAs) affect small blood vessels, causing a necrotizing vasculitis with few or no immune deposits. When the renal vasculature is affected, this can result in hematuria, proteinuria, impaired renal function, and—in severe cases— RPGN. The two major entities causing AAV are granulomatosis with polyangiitis (GPA) and MPA. Prognosis for patients diagnosed with AAV is poor without initiation of aggressive immunosuppressive treatment, with a one-year mortality rate of up to 80% (1). Patients with severe AAV should undergo induction with glucocorticoids and either rituximab or cyclophosphamide. Plasma exchange may also be considered as well in an effort to reduce circulating serum ANCA levels. However, these aggressive immunosuppressive regimens put patients at risk for other serious complications including infection, which is another leading cause for mortality in this population. For this reason, more targeted immunosuppressive therapy is under investigation to help reduce toxicity and risk for infection. Avacopan, a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor, is one such new drug. Several studies have found avacopan to be noninferior and even superior to prednisone at achieving sustained disease remission (2). For many patients, especially those showing poor response to initial therapy—such as ours described in the case above—this medication may provide a safer and potentially more efficacious treatment for AAV.

References

1) Samman, K. N., Ross, C., Pagnoux, C., & Makhzoum, J. P. (2021). Update in the management of ANCA-associated vasculitis: recent developments and future perspectives. International Journal of Rheumatology, 2021, 1-14. 2) Jayne, D. R., Merkel, P. A., Schall, T. J., & Bekker, P. (2021). Avacopan for the treatment of ANCA-associated vasculitis. New England Journal of Medicine, 384(7), 599-609