Improved Kidney Function in Anticoagulant-Related Nephropathy Using N-acetylcysteine

Introduction: Anticoagulant-related nephropathy (ARN) is a recognized condition marked by unexplained acute kidney injury (AKI) accompanied by hematuria while under anticoagulant therapy. Initially associated with warfarin, ARN now encompasses direct oral anticoagulants and antiplatelet agents. Its pathogenesis involves several factors, including tubular obstruction by red blood cell (RBC) casts and cytotoxicity of tubular cells due to intracellular accumulation of hemoglobin degradation products, notably free iron. Clinical outcomes are generally poor, with most patients failing to regain kidney function, leading to progressive kidney failure. Studies show a one-year mortality rate of 39%. Research in mice indicates that treatment with N-acetylcysteine (NAC) improves interstitial fibrosis and tubular atrophy (IFTA) in ARN by reducing oxidative stress. Here, we present a case of a 54-year-old woman diagnosed with biopsy-proven ARN, whose kidney function stabilized after initiating oral NAC. Case Description: Our patient was noted to have a significant increase in her serum creatinine (sCr) to 5.2 mg/dL from a baseline of 1.09 mg/dL a year earlier. Further evaluation revealed elevated anti-myeloperoxidase (MPO) antibody levels, active urine sediment with RBC casts, and subnephrotic-range proteinuria. Kidney biopsy confirmed ARN, ruling out the suspected ANCA-associated vasculitis but showing moderate mesangial IgA staining suggestive of a form of IgA nephropathy. Additionally, Prussian Blue staining revealed iron deposition in tubular epithelial cells. Her serum creatinine remained elevated, prompting a second biopsy five months later, which showed increased IFTA and more tubules with iron deposition. The patient received a six-month course of glucocorticoids and started oral NAC twice daily at this time, maintaining dialysis independence with improvements in sCr and proteinuria after 15 months. Discussion: Early recognition and intervention in ARN are crucial due to its association with accelerated chronic kidney disease progression and increased mortality rates. While treatment options remain limited, antioxidant therapy with NAC shows promise in mitigating oxidative stress-induced damage, particularly in patients requiring ongoing anticoagulation. This is significant for individuals like ours with mechanical aortic valves, where discontinuing anticoagulants is not feasible.