# Serum Protein Electrophoresis and the Albumin-to-Globulin Ratio in the Differential Diagnosis of Minimal Change Disease and Focal Segmental Glomerulosclerosis

## TL;DR

This study explores how serum protein electrophoresis and the albumin-to-globulin ratio can help distinguish between two kidney diseases, MCD and FSGS, especially in severe cases.

## Contribution

The study identifies the albumin-to-globulin ratio as a novel biomarker for differentiating secondary FSGS from immune-mediated podocytopathies using routine electrophoretic profiles.

## Key findings

- Secondary FSGS has significantly higher albumin-to-globulin ratios compared to MCD and primary FSGS.
- An A/G ratio > 0.49 identifies primary FSGS with high sensitivity and specificity in severe cases.
- The inverse correlation between albumin and α2-globulin is stronger in immune-mediated diseases than in secondary FSGS.

## Abstract

Background/Objectives: Differentiating minimal change disease (MCD) from focal segmental glomerulosclerosis (FSGS) remains a diagnostic challenge. We hypothesised that differences in glomerular protein selectivity could translate into distinct serum protein electrophoresis (SPEP) profiles, particularly in severe nephrotic syndrome. Methods: We retrospectively analysed SPEP profiles of adults with biopsy-proven MCD (n = 27), primary FSGS (n = 27), and secondary FSGS (n = 20). Diagnoses were established according to KDIGO guidelines and the Mayo Clinic classification. A severe subgroup was defined by a relative albumin fraction <40% to evaluate patterns in marked hypoalbuminaemia. Results: Secondary FSGS demonstrated significantly higher albumin-to-globulin (A/G) ratios compared with immune-mediated podocytopathies (MCD and primary FSGS), yielding excellent discrimination (AUC > 0.98). In contrast, discriminatory performance between MCD and primary FSGS in the overall cohort was limited (AUC = 0.657). However, within the severe subgroup, the A/G ratio provided clinically meaningful separation (AUC = 0.787). An A/G ratio > 0.49 identified primary FSGS with 86.7% sensitivity and 81.2% specificity. Correlation analysis revealed a strong inverse association between albumin and α2-globulin fractions in immune-mediated podocytopathies (ρ < −0.8), whereas this relationship was attenuated in secondary FSGS (ρ = −0.57). Conclusions: The A/G ratio may represent a practical adjunctive biomarker in the evaluation of podocytopathies. Values > 1.0 strongly favour secondary FSGS, while markedly reduced ratios in severe nephrosis are characteristic of MCD. These findings suggest that differences in glomerular selectivity and the hepatic compensatory response are reflected in routine electrophoretic profiles.