Background: Secondary amyloidosis, a rare complication of Crohn disease (CD), is triggered by persistent systemic inflammation. Kidney involvement is the most frequent manifestation and is often characterized by nephrotic syndrome and kidney failure. This complication usually appears in patients with long-standing disease and is associated with increased morbidity and mortality risk. Diagnosis is by microscopic amyloid observation of tissue biopsy, and when the diagnosis is confirmed, the therapeutic objective is disease activity control. Response assessment is challenging because of a lack of reliable biomarkers. Case Report: A 56-year-old male with a long-standing history of CD treated with a tumor necrosis factor-α inhibitor presented with an acute elevation of creatinine in association with clinical and laboratory markers of nephrotic syndrome. Kidney biopsy revealed renal amyloidosis. After treatment adjustment, although a stable creatinine was achieved, the patient had persistent impaired glomerular filtration rate. Conclusion: As a systemic chronic inflammatory disorder, CD may present multisystemic morbidity, for which increased awareness among gastroenterologists is warranted. Renal amyloidosis is an infrequent extraintestinal complication of CD that may lead to chronic kidney impairment. Although evidence-based treatment is lacking, disease activity control is pivotal for management.