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ANCA associated vasculitis (AAV) is a severe form of necrotizing vasculitis affecting mainly small vessels. Renal involvement consists of segmental necrotizing glomerular injury, often in association with crescents, with few or no immune deposits.. MPO-ANCA is more common in southern Europe.In order to treat this pathology, that mainly affects adults around the sixth decade of life, corticosteroids (CCT) remain a cornerstone of both induction and maintenance treatment. However, they are associated with important side effects, such as immunosuppression, hypertension, glucose intolerance and others.Avacopan, a complement C5a receptor inhibitor, has been recently proposed as an adjunctive agent that permits reduction or avoidance of CCT.
We present a case of a 76 year-old man, with multiple cardiovascular risk factors, such as hypertension, dyslipidemia, heart failure with reduced ejection fraction and permanent atrial fibrillation. He also had iatrogenic hypothyroidism following radioactive iodine therapy and bilateral hip arthrosis. In April 2022 he presented with rapidly progressive renal failure, with a maximum serum creatinine (sCr) of 2.62 mg/dl and new onset normochromic normocytic anemia (Hb: 11.2 g/dl). He denied previous history of macroscopic hematuria, dysuria, pollakiuria, hemoptysis, edema, urinary tract infection, rash or petechia. Physical examination was unremarkable and blood pressure was controlled. Urinalysis demonstrated microscopic hematuria and non-nephrotic range proteinuria (protein to creatinine ratio: 1,8 g/g). Kidney ultrasound was normal.
ANCA- MPO was detected in his serum by ELISA: 654,2 UQ (<20). Kidney biopsy was performed and 9 glomeruli were obtained, of which 1 was globally sclerosed, one had segmental sclerosis and other had extracapillary fibrocellular proliferation. There was focal periglomerulitis. Tubular atrophy and fibrosis were present in less than 10% of the sample.. Immunofluorescence was negative. MPO-ANCA vasculitis was assumed and induction treatment included three pulses of intravenous methylprednisolone plus rituximab (two 375mg/m2 weekly pulses) and maintenance oral prednisone was started (1 mg/kg/day), with good response (improved glomerular filtration rate and proteinuria remission). Six months later, avacopan was started in a dose of 30 mg twice daily and CCT were tapered over six weeks, in order to reduce CCT toxicity due to this patient cardiovascular profile.Six months later, he remains asymptomatic, kidney function is stable (sCr: 1.7 mg/dl), proteinuria is persistently less than 1g/g and MPO ANCAs are now 8,8 UQ.
Avacopan, as a C5aR antagonist that blocks the effects of C5a, may reduce AAV-induced lesions, and is a new strategy to reduce drug side effects including CCT toxicity.Due to its incidence in older patients, these tend to have more comorbidities that may be aggravated with the current therapies, namely CCT.
Avacopan has been used as an alternative in maintaining MPO-ANCA vasculitis remission, particularly in patients with an increased risk of CCT toxicity as was the case of our patient with several cardiovascular risk factors, besides the vasculitis itself, which was successfully treated with this approach.