The Price of a Breath: First Report of Nintedanib-Induced FSGS in a Patient with Idiopathic Pulmonary Fibrosis

Introduction: Nintedanib is a tyrosine kinase inhibitor widely used for treatment of idiopathic pulmonary fibrosis (IPF). Its use in IPF is predicated on its inhibition of platelet derived growth factor receptor (GFR), fibroblast GFR, and vascular endothelial GFR, which increase fibroblast proliferation. Prior literature has identified thrombotic microangiopathy (TMA) as a rare adverse effect of nintedanib. Here we present the first reported case of nintedanib-induced focal segmental glomerulosclerosis (FSGS), expanding the spectrum of proteinuric etiologies associated with this medication. Case Description: A 77 year old male with chronic kidney disease, IPF, and heart failure presented with shortness of breath and lower extremity edema. Laboratory findings were notable for nephrotic-range proteinuria with Urine protein to creatinine ratio of 8.1g/g, hypoalbuminemia 1.2g/dL and LDL cholesterol of 268.6mg/dL. Serum Cr levels ranged from 2.19 to 2.63 mg/dL, stable from prior admissions. Further workup, including ANA, MPO, PR3 antibodies, p-ANCA, atypical p-ANCA, and hepatitis panel, was negative. CXR revealed pulmonary vascular congestion. Echocardiogram was unremarkable. The patient was discharged with daily furosemide for edema management and steroids for a suspected IPF flare. Upon follow-up in the nephrology clinic, persistent nephrotic-range proteinuria prompted a kidney biopsy, which revealed global sclerosis (50%) and segmental sclerosis (33%) on light microscopy. Nintedanib was discontinued. Six months later, serum Cr improved to 1.7 mg/dL, UPCR decreased to 1.29, and hypoalbuminemia resolved. The patient reported an improvement in his breathing and leg edema. Discussion: While nintedanib continues to play a crucial role in IPF management, this case highlights the importance of maintaining a high index of suspicion for renal complications of nintedanib, particularly in patients presenting with nephrotic range proteinuria or worsening kidney function. Clinicians should regularly monitor proteinuria and promptly rule out nephrotic syndrome in at-risk patients presenting with shortness of breath. This patient's improvement after discontinuation of nintedanib suggests a reversible FSGS. This first reported case of secondary FSGS expands the known proteinuric adverse effect profile of nintedanib.