Couser William G
Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. doi: 10.2215/CJN.11761116. Epub 2017 May 26.
Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.
膜性肾病（MN）是一种独特的肾小球病变，是非糖尿病白人成年人特发性肾病综合征最常见的病因。约80%的病例为肾脏局限性（原发性MN，PMN），20%与其他全身性疾病或暴露因素相关（继发性MN）。本综述仅关注PMN。大多数PMN病例存在循环中针对足细胞膜抗原PLA2R的IgG4自身抗体（70%），活检证据显示PLA2R染色表明近期存在免疫性疾病活动，尽管血清抗体水平为阴性（15%），或血清抗THSD7A（3%-5%）。其余10%未检测到可证实的抗PLA2R/THSd7A抗体或抗原的患者可能患有PMN，可能继发于另一种尚未明确的抗足细胞抗体。目前大量的临床和实验数据表明这些抗体具有致病性。临床上，80%的PMN患者表现为肾病综合征，20%表现为非肾病性蛋白尿。未经治疗，约三分之一的患者会自发缓解，尤其是那些抗PLA2R水平缺失或较低的患者；三分之一的患者在10年内进展为终末期肾病（ESRD），其余患者发展为非进行性慢性肾脏病（CKD）。在循环抗PLA2R/THSD7A抗体不再可检测到（免疫缓解）后，蛋白尿可能会持续数月。所有PMN患者从诊断时起就应接受支持治疗，以尽量减少蛋白质排泄。诊断时抗PLA2R/THSD7A水平升高且蛋白尿>3.5g/d的患者，以及在支持治疗6个月后未能将蛋白尿降至<3.5g/d或出现肾病综合征并发症的患者，应考虑进行免疫抑制治疗。公认的治疗方案包括类固醇/环磷酰胺、钙调神经磷酸酶抑制剂和B细胞清除。通过适当的管理，在随后的10年中只有10%或更少的患者会发展为ESRD。
