A Case of Pulmonary-Renal Syndrome (PRS) in ANCA-Negative, Pauci-Immune Necrotizing Glomerulonephritis with High IntelliSep Index

Introduction: Pauci-Immune Necrotizing Glomerulonephritis (PING) results from inflammatory vasculitis, often associated with antineutrophilic cytoplasmic antibodies (ANCA). ANCA-negative PING is rare. The role of neutrophils with PING is highly implicated in ANCA-negative cases. We present a case of ANCA-negative PING with PRS. It highlights early recognition and postulates potential methods for utilizing IntelliSep Index (ISI), a rapid (<10 min) assay quantifying immune activation via biophysical properties of leukocytes, to support treating PING. Case Description: A 67-year-old woman with tobacco use and primary hypertension presented to the hospital with progressive dyspnea and hemoptysis. Labs included creatinine (Cr) 0.71 mg/dL, serum albumin 1.9 g/dL, Hgb 10.3 g/dL and WBC count 14.7 1000/uL; urinalysis positive for protein, large Hgb, 5-10 WBC/hpf and 10-20 RBC/hpf. Chest imaging showed bilateral moderate airspace opacities. ISI Index was 8.8, ISI Band 3. Blood and sputum cultures were negative. Given high suspicion for PRS from small vessel vasculitis, pulse dose steroids were started. Autoimmune workup including ANCA was negative. Renal biopsy revealed necrotizing crescentic glomerulonephritis with granular mesangial staining for C3, IgM, kappa and lambda, but all other stains negative. She was discharged on prednisone, cyclophosphamide (CYC) and trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis prophylaxis. She had transaminitis 6 weeks later and CYC and TMP-SMX were held. CYC was resumed 2 weeks later and prednisone reduced. She represented to the hospital with a flare 3 weeks later. Workup with proteinuria, hematuria, and Cr elevated to 1.8 mg/dL. Repeat ISI Index was 9.0, ISI Band 3. Prednisone therapy was increased to 60 mg daily. Three months later, after prolonged steroid course and taper, her Cr improved to 1.3 mg/dL, pulmonary symptoms resolved, and she was transitioned to mycophenolate mofetil. Discussion: Diagnosing PING requires high clinical suspicion to initiate therapy. Standard diagnosis of PING may take several days for biopsy and serology. This case shows a high ISI level on presentation as well as with her flare. Considering clinical context, ISI may be beneficial in stratifying patients to consider early PING induction treatment as well as monitoring treatment response.