Immune Checkpoint Inhibitor-Associated, ANCA-Negative, Pauci-immune Crescentic Glomerulonephritis with Interstitial Nephritis: A Rare Occurrence of Dual Pathology

Introduction: Immune check point inhibitors (ICIs) are associated tubulointerstitial nephritis (TIN) in 2% of patients. Rarely, ICIs can cause nephrotic glomerular lesions including minimal change disease, FSGS, or membranous nephropathy. Nephritic lesions such as pauci-immune crescentic GN are very rare, only few cases have been reported. Here we present a case of pauci-immune Crescentic GN in association with TIN related to therapy with pembrolizumab. Case Description: A 64-year-old female with stage VI non-small cell lung carcinoma, status post three cycles of pembrolizumab treatment found to have AKI with serum creatinine of 2.14 mg /dL (baseline 0.8-0.9 mg/dL). Urinalysis showed RBCs > 100 /hpf, > 25 dysmorphic RBCs /hpf , 4-10 WBCs/hpf, urine protein to creatinine ratio 0.87 g/g and urine albumin/creatinine ratio 170 mg/g. Sererological work up was unremarkable with negative ANA, dsDNA, MPO/ p-ANCA, PR3/ c-ANCA, cryoglobulins, anti-GBM antibodies, viral hepatitis serology, HIV, normal serum C3 and C4 and negative monoclonal protein study. Kidney biopsy showed pauci-immune crescentic GN and acute interstitial nephritis (Figure). She was treated with prednisone and plasmapheresis to clear pembrolizumab. Her serum creatinine improved and decreased to 0.98 mg/dL. Discussion: In patients receiving ICI and having AKI with no clear alternative etiology, TIN should be suspected. Glomerular pathology due to ICI should be suspected in the setting of active urinary sediment or heavy proteinuria. Co-occurance of TIN and cresentic glomerulonephritis due to ICI is extremely rare. Given the lack of specific clinical features for ICI related AKI, renal biopsy should be strongly considered, particularly when urine studies are suggestive of glomerular disease. The first-line treatment for ICI-related TIN is glucocorticoids and glomerular disease is treated with standard therapy for the underlying lesion. Plasmapheresis can be utilzied to clear pembrolizumab.