Hoxha Elion, Harendza Sigrid, Pinnschmidt Hans, Panzer Ulf, Stahl Rolf A K
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Institut für Medizinische Biometrie & Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
PLoS One. 2014 Oct 14;9(10):e110681. doi: 10.1371/journal.pone.0110681. eCollection 2014.
Patients with primary membranous nephropathy (MN) who experience spontaneous remission of proteinuria generally have an excellent outcome without need of immunosuppressive therapy. It is, however, unclear whether non-nephrotic proteinuria at the time of diagnosis is also associated with good prognosis since a reasonable number of these patients develop nephrotic syndrome despite blockade of the renin-angiotensin system. No clinical or laboratory parameters are available, which allow the assessment of risk for development of nephrotic proteinuria. Phospholipase A2 Receptor antibodies (PLA2R-Ab) play a prominent role in the pathogenesis of primary MN and are associated with persistence of nephrotic proteinuria. In this study we analysed whether PLA2R-Ab levels might predict development of nephrotic syndrome and the clinical outcome in 33 patients with biopsy-proven primary MN and non-nephrotic proteinuria under treatment with blockers of the renin-angiotensin system. PLA2R-Ab levels, proteinuria and serum creatinine were measured every three months. Nephrotic-range proteinuria developed in 18 (55%) patients. At study start (1.2±1.5 months after renal biopsy and time of diagnosis), 16 (48%) patients were positive for PLA2R-Ab. A multivariate analysis showed that PLA2R-Ab levels were associated with an increased risk for development of nephrotic proteinuria (HR = 3.66; 95%CI: 1.39-9.64; p = 0.009). Immunosuppressive therapy was initiated more frequently in PLA2R-Ab positive patients (13 of 16 patients, 81%) compared to PLA2R-Ab negative patients (2 of 17 patients, 12%). PLA2R-Ab levels are associated with higher risk for development of nephrotic-range proteinuria in this cohort of non-nephrotic patients at the time of diagnosis and should be closely monitored in the clinical management.
原发性膜性肾病（MN）患者若蛋白尿能自发缓解，通常预后良好，无需免疫抑制治疗。然而，诊断时的非肾病性蛋白尿是否也与良好预后相关尚不清楚，因为尽管使用了肾素 - 血管紧张素系统阻滞剂，仍有相当数量的此类患者会发展为肾病综合征。目前尚无临床或实验室参数可用于评估肾病性蛋白尿发生的风险。磷脂酶A2受体抗体（PLA2R - Ab）在原发性MN的发病机制中起重要作用，且与肾病性蛋白尿的持续存在相关。在本研究中，我们分析了PLA2R - Ab水平是否可预测33例经活检证实为原发性MN且伴有非肾病性蛋白尿并接受肾素 - 血管紧张素系统阻滞剂治疗的患者发生肾病综合征的情况及临床结局。每三个月测量一次PLA2R - Ab水平、蛋白尿和血清肌酐。18例（55%）患者出现肾病范围蛋白尿。研究开始时（肾活检及诊断后1.2±1.5个月），16例（48%）患者PLA2R - Ab呈阳性。多因素分析显示，PLA2R - Ab水平与肾病性蛋白尿发生风险增加相关（HR = 3.66；95%CI：1.39 - 9.64；p = 0.009）。与PLA2R - Ab阴性患者（17例中的2例，12%）相比，PLA2R - Ab阳性患者（16例中的13例，81%）更频繁地开始免疫抑制治疗。在这组诊断时为非肾病性患者中，PLA2R - Ab水平与肾病范围蛋白尿发生的较高风险相关，在临床管理中应密切监测。
