Abstract: FR-PO180
Anti-PR3 Positive Pauci-Immune Glomerulonephritis Associated With Immune Checkpoint Inhibitor Therapy and Responsive to Corticosteroid and Rituximab
Session Information
- Onconephrology: Clinical and Research Advances - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Clince, Michelle, Galway University Hospitals, Galway, Galway, Ireland
- Doheny, Jane Mary, Galway University Hospitals, Galway, Galway, Ireland
- Griffin, Matthew D., Galway University Hospitals, Galway, Galway, Ireland
- Mchale, Teresa, Galway University Hospitals, Galway, Galway, Ireland
- O'Neill, Liam, Galway University Hospitals, Galway, Galway, Ireland
- Gorey, David, Galway University Hospitals, Galway, Galway, Ireland
Introduction
Immunotherapy with checkpoint inhibitors (CPIs) enables activation of suppressed immune responses against cancer-associated antigens. Due to this mechanism of action, CPIs can trigger immune-related adverse events – including renal impairment. The most common findings on biopsy are acute interstitial nephritis and acute tubular injury. Several cases of pauci-immune glomerulonephritis, most commonly ANCA-negative, have also been reported during CPI therapy.
Case Description
A 73 year old man was admitted with hemoptysis, nausea and fatigue 5 days after his first cycle of carboplatin, paclitaxel & pembrolizumab for non-squamous cell lung cancer. Baseline serum creatinine (SCr) was 0.74mg/dL (65μmol/L). AKI was apparent on admission with SCr 1.63mg/dL (144μmol/L), initially considered pre-renal. Deterioration in renal function continued with peak SCr of 4.61mg/dL (408 μmol/L) despite adequate supportive therapy. Serological testing revealed positive assays for cANCA and anti-PR3 (35.0 U/mL). CXR showed new bilateral pulmonary infiltrates. Ultrasound-guided kidney biopsy revealed necrotising and crescentic glomerulonephritis with negative immunofluorescence microscopy, in keeping with a pauci-immune glomerulonephritis. IV Methylprednisolone 2mg/kg was administered for 5 days followed by rituximab infusions (2 x 1g, 2 weeks apart) and oral prednisolone taper. During the following 24 days, hemoptysis and systemic symptoms resolved and SCr progressively improved to nadir of 1.62mg/dL (144μmol/L). CPI therapy was not re-initiated. The patient remains in oncological remission without clinical or serological evidence (currently cANCA negative) of recurrent ANCA-associated glomerulonephritis.
Discussion
Anti-PR3+ ANCA-associated pauci-immune glomerulonephritis is an unusual cause of AKI during CPI therapy which, in this case, responded well to corticosteroid and rituximab. This case illustrates the importance of kidney biopsy in assessing and managing renal impairment associated with combined chemotherapy/immunotherapy regimens.
H&E and trichrome stain showing necrotising crescent.