The Three Faces of IgA Nephropathy: Clinicopathological Heterogeneity and Urinary Albumin-to-Protein Ratio in a Case Series.

Background/Objectives: IgA nephropathy (IgAN) is a highly heterogeneous glomerular disease with variable clinical presentation and response to therapy. Standard histopathology provides a static assessment and may not fully reflect dynamic podocyte injury. The objective of this case series was to characterize distinct clinical phenotypes of IgAN and explore the relationship between urinary protein composition assessed by the urine albumin-to-protein ratio (uAPR) and ultrastructural glomerular injury. Methods: We retrospectively analyzed three patients with distinct clinical phenotypes of biopsy-proven IgA nephropathy to examine the relationship between urinary protein composition (uAPR), ultrastructural findings, treatment response, and clinical outcomes. Results: Case 1 demonstrated a podocytopathic phenotype resembling minimal change disease (MCD) with steroid sensitivity. Case 2 showed progression to focal segmental glomerulosclerosis (FSGS) despite stable renal function. Case 3 revealed persistent predominantly non-albumin proteinuria (uAPR 0.07-0.13) preceding biopsy-proven IgAN and resistance to multiple immunosuppressive regimens. Conclusions: Differences in uAPR were observed alongside distinct clinicopathological and ultrastructural phenotypes of IgA nephropathy. These observations suggest that urinary protein composition may provide complementary information on disease phenotype; however, its relationship with specific mechanisms of glomerular injury requires prospective validation.