Revisiting the Prognosis of Patients with IgAN and Mild Proteinuria: Longitudinal Study with Unexpected Outcomes

Background: IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis and a leading cause of chronic kidney disease (CKD) globally.Current research primarily focuses on high-risk IgAN populations,while those with mild proteinuria are often considered to have a favorable prognosis. However, recent evidence suggests that patients with urinary protein excretion<0.5g/day may still be at significant risk of disease progression. Methods: Retrospective analysis of 265 biopsy-proven IgAN patients (August 2008–December 2023) with urinary protein≤0.5g/24h,≥12-month follow-up, and no steroid/immunosuppressive therapy.Patients were stratified into two groups based on the occurrence of composite renal endpoint events. Results: The study included 265 IgAN patients (50.6% male,mean age 37.5±12.0years).At biopsy,26.8% had hypertension and 64.2% received RASi.Most were CKD stage 1 (61.5%) and CKM stage 2 (68.3%).Baseline parameters:proteinuria 0.3±0.1g/24h,SCr 82.0±27.7μmol/L,eGFR 97.3±24.8mL/min/1.73m2,and TyG-BMI 202.4±39.1. Pathological findings according to the Oxford Classification included S1 in 31.3%,T1+T2 in 27.5%,C1+C2 in 35.1%.Renal arteriolar lesions were identified in 130 patients(49.1%),with Lee's grade III being most predominant(41.9%). During a mean follow-up of 90.8±52.8months,2 patients died,10 progressed to ESRD,and 15 experienced a>30% decline in eGFR.The mean annual eGFR decline rate was -2.3±11.1mL/min/1.73 m2/year.The Clinicopathological features of the composite renal endpoint event group are worse, and the CKM stage is more severe.Multivariable logistic regression identified higher creatinine levels,T1+T2 proportion,and lower TyG-BMI as independent risk factors for composite renal endpoint events.Cox regression analysis revealed that higher diastolic blood pressure,creatinine levels,renal arteriolar lesion proportion,and lower TyG-BMI were independent risk factors for composite endpoint events. Conclusion: Our study challenges the favorable prognosis assumption in IgAN patients with mild proteinuria.Over 90.8 months' follow-up,10.2% reached composite endpoints,demonstrating significant progression risk.We found that metabolic factors,such as lower TyG-BMI and higher CKM stage,are also important predictors of prognosis,in addition to traditional risk factors like baseline renal function and tubulointerstitial lesion severity.