Multifocal Stroke as the Presenting Symptom of Membranous Nephropathy

Introduction: Ischemic stroke is a common diagnosis that affects almost 800,000 Americans per year. In older adults, the last thing that someone would expect as the primary culprit would be nephrotic syndrome, but this is a cause that should not be ignored. Case Description: A 64-year-old man with a history of hypertension, hyperlipidemia, and moderate aortic stenosis presented with left sided weakness was found to have new and subacute strokes with brain imaging showing multifocal areas of ischemia consistent with embolic phenomenon. Afib was not shown during the hospital stay nor on a 30-day cardiac event monitor soon after nor was an intracardiac thrombus. Other work up included an echocardiogram showing a bicuspid aortic valve with severe aortic stenosis and CT imaging with bilateral carotid stenosis. While these findings were consistent with risk factors that may have contributed to his stroke, brain imaging with concern for embolic phenomenon were not explained. By chance, the patient was also found to have a severely decreased serum albumin of 1.4g/dL and proteinuria quantified as 15g on a spot urine sample. The patient was on anticoagulation with a high risk for recurrent stroke so a PLA2R titer was measured in place of kidney biopsy which was elevated at 1:320. Membranous nephropathy was diagnosed and the patient was treated with rituximab and achieved partial remission, but proteinuria persisted at 3-5g. An eventual kidney biopsy was performed and confirmed the diagnosis of primary membranous nephropathy. Discussion: Membranous nephropathy is a well-known hypercoagulable condition that can increase the risk of arterial thromboembolism. This case is a rare example of a patient with undiagnosed membranous nephropathy presenting with a stroke as the initial sign of nephrotic syndrome (NS). As previously described, membranous nephropathy has been implicated as the inciting factor leading to ischemic stroke. The arterial thrombotic risk in NS was 8 times higher in patients with NS compared to age matched controls. Mechanism for hypercoagulability is due to urinary loss of anti-coagulation proteins (AT3, protein C and S), increased hepatic production of proteins such as fibrinogen, and increased platelet activation. Less is known about arterial thromboembolism compared to venous thromboembolism in NS and this case shows the importance of considering this diagnosis when treating stroke.