低分子和高分子量尿蛋白作为预测膜性肾病患者对利妥昔单抗反应的指标：一项前瞻性研究。
Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study.
机构信息
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA.
出版信息
Nephrol Dial Transplant. 2013 Jan;28(1):137-46. doi: 10.1093/ndt/gfs379. Epub 2012 Sep 17.
BACKGROUND
Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN).
METHODS
We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulin IgG and IgM and/or anti-phospholipase 2 receptor (PLA(2)R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA(2)R with these urinary biomarkers.
RESULTS
Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m(2) × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (μg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA(2)R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response.
CONCLUSIONS
The results suggest that in patients with MN, quantification of low-, medium- and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes.
背景
选择性尿生物标志物被认为优于总蛋白尿，可预测膜性肾病（MN）患者对治疗的反应和结局。
方法
我们前瞻性地检测了尿（U）视黄醇结合蛋白（RBP）、α1-微球蛋白（α1M）、白蛋白、免疫球蛋白 IgG 和 IgM 和/或抗磷脂酶 A2 受体（PLA2R）水平的排泄是否可以比 MN 中的标准措施更好地预测利妥昔单抗（RTX）治疗的反应。我们还将抗 PLA2R 抗体的变化与这些尿生物标志物相关联。
结果
20 例蛋白尿（P）>5 g/24 h 的 MN 患者接受 RTX（375 mg/m2×4）治疗，在 12 个月时，1 例患者完全缓解（CR），9 例部分缓解（PR），5 例缓解有限（LR），4 例无反应（NR）。24 个月时，4 例 CR，12 例 PR，1 例 LR，2 例 NR，1 例复发。通过简单线性回归分析，基线时（mg/24 h）的 UIgG 是 12 个月时蛋白尿变化（Δ尿蛋白）的显著预测因子（P = 0.04）。此外，IgG 的分数排泄（FE）、尿α1 微球蛋白（Uα1M）（mg/24 h）和 URBP（μg/24 h）也是反应的预测因子（P = 0.05、0.04 和 0.03）。另一方面，UIgM、FEIgM、白蛋白和 FE 白蛋白均不能预测反应（P = 0.10、0.27、0.22 和 0.20）。然而，当根据 24 个月的蛋白尿分析结果时，在 12 m 时预测反应的所有 U 标志物都不能预测 24 m 的反应（P = 0.55、0.42、0.29 和 0.20）。抗 PLA2R 水平的下降与尿生物标志物反应相关，且通常先于其发生，但基线阳性不是蛋白尿反应的预测因子。
结论
结果表明，在 MN 患者中，低、中、高分子量尿蛋白的定量可能与 RTX 反应率相关，但与长期结局无关。
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