Limitations of Total Protein Measurements in the Evaluation of Proteinuria in Plasma Cell Disorders

Plasma cell disorders often have urinary excretion of monoclonal immunoglobulins and renal injury that are evaluated using total protein assays and electrophoresis. Proteinuria was evaluated for 100 patients with plasma cell disorders and 24 h collections. A turbidimetric method on the Abbott Alinity quantified protein. Electrophoresis used agarose gels. Most specimens (66%) had protein concentrations below the manufacturer’s limit of quantitation (LOQ), 6.8 mg/dL (68 mg/L). After validating an LOQ of 3 mg/dL (30 mg/L), 34% of urine specimens still were below the LOQ. After excluding 40 patients with other causes of increased protein excretion (decreased estimated glomerular filtration rate (eGFR), diabetes mellitus, or overflow proteinuria), almost all patients had protein excretion below an upper reference limit of 150 mg/d. Median total protein excretion for these 60 patients was 75 mg/d; only one patient excreted >132 mg/d. However, 32% of these patients without increased total protein excretion had albumin excretion ≥ 30 mg/d, suggestive of kidney injury. Electrophoretic patterns included glomerular, tubular, and overflow proteinuria; 32 specimens contained monoclonal immunoglobulins. Protein concentrations of urine are often below LOQs of total protein assays, raising questions about whether LOQs should be improved. Urine albumin measurements and electrophoretic patterns may serve as more sensitive indicators of kidney injury in patients with plasma cell disorder than measurements of total protein excretion or increased serum creatinine.