A Case of ANCA-Associated Vasculitis with Glomerulonephritis Unmasked by Electron Microscopy

Introduction: Risk of progression to ESKD remains high in ANCA vasculitis with glomerulonephritis (AAV GN). Early diagnosis is critical for enhancing renal outcomes, yet it proves to be a challenge because active AAV GN lesions may not always be visible under light microscopy (LM), attributed to the focal nature of these lesions. We present a case where electron microscopy (EM) played a key role in identifying active necrotizing AAV GN. Case Description: A 63-year-old healthy female presented with hypertensive emergency. Creatinine was elevated to 2.1 mg/dL from 0.8 mg/dL 1.5 years prior and 1.15 mg/dL 8 months earlier. UA showed microscopic hematuria and mild proteinuria. Serologic testing showed high levels of MPO (>8 U), positive p-ANCA, equivocal PR3 and negative c-ANCA. ANA, dsDNA, GBM ab, cryoglobulin, SPEP and immunofixation, were unremarkable. After addressing hypertension, persistent hematuria and AKI indicated potential glomerular disease. A subsequent kidney biopsy revealed FSGS (10%), global glomerulosclerosis (50%) and moderate interstitial fibrosis with tubular atrophy (40-50%) under LM, suggesting a prior occurrence of AAV GN. Although LM did not identify current AAV GN lesions, the presence of high MPO antibodies and ongoing AKI led to the administration of pulse dose steroids and rituximab, which resulted in reduced creatinine levels. EM further confirmed the AAV GN diagnosis by revealing crescent formation and fibrinoid necrosis. Discussion: The case highlights the difficulties in diagnosing AAV GN accurately, emphasizing the risk of misdiagnosis resulting from the localized nature of the lesions. Recent study suggests that kidneys may continue to function adequately, even when only a small fraction of glomeruli remained unaffected in AAV GN. Precise diagnosis and prompt treatment is needed to maintain normal glomerular function and enhance renal prognosis.AAV GN on EM