Clinical and Histopathological Predictors of Renal Survival in IgA Nephropathy Patients with Nephrotic Range Proteinuria: A Retrospective Survival Analysis

Background: IgA nephropathy (IgAN) presents with a wide spectrum of clinical features, most commonly hematuria accompanied by subnephrotic proteinuria. Nephrotic range proteinuria is rare, observed in approximately 6% of patients at diagnosis. Limited studies have examined the relationship between clinicopathological characteristics and renal prognosis in IgAN patients with nephrotic range proteinuria. Methods: This retrospective, single-center case-control study included 114 patients diagnosed with IgAN via kidney biopsy at Şişli Hamidiye Etfal Training and Research Hospital from April 2004 to December 2016. Patients were divided into two groups: nephrotic (≥ 3.5 g/day) and subnephrotic (<3.5 g/day) proteinuria. Primary outcomes included a doubling of serum creatinine, while secondary outcomes measured the initiation of renal replacement therapy. Results: Patients with nephrotic range proteinuria had significantly lower serum albumin levels (p=0.001), higher cholesterol levels (p=0.03), and increased fibrocellular crescent formation (p=0.01). Cox regression analysis identified baseline serum creatinine, uric acid, and albumin levels, along with histopathological findings such as glomerulosclerosis and crescent formation, as significant predictors of treatment response. The Kaplan-Meier analysis showed that patients with nephrotic range proteinuria had worse renal survival, with a significantly higher proportion reaching primary and secondary endpoints compared to the subnephrotic group. Conclusion: Histopathological findings, particularly fibrocellular crescents, were more common in patients with nephrotic range proteinuria, and their presence was associated with poorer renal survival and lower treatment response rates. These patients require closer follow-up and may benefit from more aggressive therapeutic strategies.