Abstract
INTRODUCTION: Prognostic value of glomerular hematuria in primary membranous nephropathy (PMN) patients with nephrotic syndrome (NS) has not been well understood. We investigated the earlier improvement of hematuria in PMN patients with NS receiving immunosuppressive (IS) therapies to illuminate its prediction capacity for the treatment response and remission status at 12 months. METHODS: This is a single-center retrospective study. From 1 January 2021 to 30 June 2024, patients with biopsy-proven PMN and NS starting IS therapy after renal biopsy were recruited. The main exposures were baseline hematuria and hematuria disappearing at 6 months. The outcome was nephrotic remission status at 12 months. Binary logistic regression models were used to estimate the relationship between exposures and outcomes. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of exposures. RESULTS: Overall, 127 patients met the eligibility criteria. Overall, 112 patients (88.2%) had glomerular hematuria at the renal biopsy. Patients with hematuria had higher ages (57.2 ± 12.4 vs. 47.9 ± 12.7, p = 0.007), higher serum h-CRP levels (1.14 [0.66, 2.11] vs. 0.41 [0, 0.91], p = 0.004), and lower remission rate at 12 months (66/112 [58.9%] vs. 13/15 [86.67%], p = 0.037). In the subgroup of patients with glomerular hematuria, baseline hematuria levels were 18 (8, 25) RBC/μL. No significant correlations were found between baseline hematuria levels and other clinical indexes. At 6 months, 31 out of 112 (27.7%) patients had negative conversion of hematuria, and they had lower baseline PLA2R Ab titer (43.6 [0, 78.2] vs. 67.5 [10.8, 191.4], p = 0.025) and higher nephrotic remission rates at 12 months (26/31 [83.9%] vs. 40/81 [49.4%], p = 0.037), compared with those without. There were no significant differences among IS agents between the groups. Binary logistic regression demonstrated that hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months (OR = 0.211, 95% CI: 0.070-0.635, p = 0.006). ROC curve analysis revealed that the area under the curve for forecasting nephrotic remission at 12 months was 0.643 (p = 0.010) independently by the hematuria disappearance at 6 months and 0.781 (p < 0.001) combined with PLA2R Ab titer and IS therapeutic programs. CONCLUSIONS: Patients with PMN and NS have high prevalence of glomerular hematuria. Patients without hematuria or negative conversion of hematuria at 6 months after IS treatment have higher nephrotic remission rates at 12 months. For patients with hematuria, hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months.