Assessing the Selectivity of Urinary Proteins Using Albumin as an Alternative to Transferrin

Background: Since the 1960s, the utility of urinary protein selectivity in diagnosing and predicting the prognosis of glomerular diseases has been reported. Urinary protein selectivity has traditionally been assessed using the Selectivity Index (S.I.), which compares the clearance of high molecular weight protein IgG to that of medium molecular weight protein transferrin. Although albumin is a major medium molecular weight urinary protein, its measurement accuracy was initially low, leading to the use of transferrin in calculating the S.I. However, recent improvements in the measurement accuracy of albumin have been noted. At our institution, serum albumin is measured using the modified bromocresol purple (BCP) method, while urinary albumin is measured using an immunoturbidimetric assay. Methods: In this study, we analyzed data from 224 patients, comprising both outpatients and inpatients at our institution, whose concentrations of IgG, transferrin, and albumin in serum and urine were measured simultaneously between January 2014 and December 2023. Results: Firstly, we calculated the S.I. using albumin (S.I. (Alb)) and S.I. using transferrin (S.I. (Tf)) and then analyzed their correlation. The results of linear regression analysis revealed a significant correlation, with S.I. (Alb) = S.I. (Tf) × 1.077 + 0.00295 (p < 0.0001, R2 = 0.7077) in patients with trace albuminuria or more, and S.I. (Alb) = S.I. (Tf) × 0.9570 + 0.0360 (p < 0.0001, R2 = 0.7516) in those with massive proteinuria equivalent to nephrotic syndrome (3.5g or more). Subsequently, we performed the receiver operating characteristics (ROC) analysis to examine the utility of the S.I. for the diagnosis of minimal change disease, characterized by its high selectivity for urinary protein. According to the ROC analysis, the AUC of S.I. (Tf) was 0.85 (95% CI, 0.74 – 0.95), and the AUC of S.I. (Alb) was 0.85 (95% CI, 0.74 – 0.96). Conclusion: The findings suggest that the versatile S.I. (Alb) may be as useful as S.I. (Tf) in diagnosing glomerular diseases.