Rare Case of Fibrillary Glomerulonephritis with Concomitant Acute Interstitial Nephritis Related to Cemiplimab Use

Introduction: Immune checkpoint inhibitors (ICPI) can cause immune-related kidney injury. Acute tubulointerstitial nephritis (AIN) is commonly caused by ICPIs, although rarely, glomerular injury may also be seen. Fibrillary glomerulonephritis (FGN) is a rare glomerular disorder characterized by the presence of Congo red (CR) negative, non-amyloid fibrillary deposits in the glomeruli. DnaJ homolog subfamily B member 9 (DNAJB9) is a highly sensitive and specific biomarker for FGN. We describe a unique case of FGN accompanied by AIN, hypothesized to be attributable to cemiplimab use. Case Description: A 63-year-old male with recurrent SCC of the skin treated with cemiplimab (PD-1 inhibitor) presented with non-oliguric AKI. On admission, Sr 13 mg/dL, Sr albumin 4 g/dL, UACR 52 mg/g, and UPCR 513 mg/g. Urinalysis revealed acanthocyturia and RBC casts. The patient had no underlying hypertension or diabetes. Comprehensive serological workup was negative. Kidney biopsy revealed AIN with moderate to severe acute tubular injury and 5-10% IFTA. IF: Trace to 1+ smudgy segmental mesangial staining for IgG, C3, kappa, and lambda. EM revealed mesangial matrix expansion containing segmental nonbranching, randomly arranged fibrillary deposits, ranging in size from 11-17nm in diameter. No usual immune complex deposits or fibrillary deposits were identified along the tubular basement membranes. CR staining was negative. DNAJB9 immunohistochemical staining was positive in the glomeruli. Cemiplimab was discontinued and high-dose glucocorticoids tapered over 6 weeks were given. After 9 weeks, Sr Cr was 2.5 mg/dL with a bland urinalysis. Discussion: FGN has been associated with malignancy in approximately 9% cases. Given this association, it is recommended to screen patients with FGN for malignancy. Our patient’s history of recurrent squamous cell carcinoma may have predisposed him to FGN. Additionally, treatment with cemiplimab, an ICPI, adds complexity due to its potential for drug-induced AIN. While ICPIs are known to cause widespread organ inflammation, isolated AIN are rare, but have been reported. This case underscores the complexity of diagnosing and managing FGN, particularly when present concomitantly with AIN potentially induced by cemiplimab. It also highlights the importance of personalized treatment strategies in managing complex clinical scenarios.