Urine Protein to Albumin Gap without Monoclonal Gammopathy

Introduction: The urine protein-to-albumin gap (UPAG) describes the difference between total urine protein excretion and urine albumin excretion. The UPAG is usually considered significant when less than 50% of the urine protein consists of albumin. If the UPAG is elevated, this may raise suspicion for monoclonal gammopathies such as multiple myeloma where increased immunoglobulin or light chain excretion in the urine results in proteinuria that is composed of a relatively smaller proportion of albumin. We present the case of a 61-year-old man with elevated UPAG without evidence of monoclonal gammopathies. Case Description: A 61-year-old man with a past medical history of type 2 diabetes mellitus was admitted with endocarditis in the setting of Staphylococcus aureus bacteremia from cellulitis complicated by septic shock and multiple septic emboli involving the brain. He developed acute kidney injury (AKI) and required temporary hemodialysis. His renal function improved and creatinine normalized to 0.8 mg/dL. Urinalysis during the AKI was positive for blood and protein. After resolution of the AKI, hematuria resolved but proteinuria persisted. Urine protein quantification showed a UPCR of 3.2 g/g and a UACR of 533 mg/g, resulting in a UPAG of 2.5 g with albumin only accounting for 16.7% of the proteinuria. The results were confirmed with repeat testing. Urine protein electrophoresis (UPEP) showed multiple protein bands with albumin predominating but no monoclonal immunoglobulins identified. Serum fibrinogen was 565 mg/dL and CRP 122 mg/L. Total serum protein was 6.8 g/dL with hypoalbuminemia of 2.2 g/dL. Serum protein electrophoresis showed polyclonal hypergammaglobulinemia with elevated IgG 2332 mg/dL and IgA 677 mg/dL, decreased IgM 38 mg/dL, and no monoclonal immunoglobulins identified. Discussion: A 61-year-old man who was admitted with endocarditis was incidentally found to have a UPAG without monoclonal pattern on UPEP. CRP, fibrinogen, and polyclonal IgG and IgA were elevated in the setting of endocarditis. The UPAG is best explained by inflammatory proteins released in the setting of the systemic infection. While a UPAG is commonly considered to be an indicator of monoclonal gammopathies, this case illustrates that inflammatory proteins may reach quantities that can lead to a significant UPAG when excreted in the urine.