Department of Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Department of Nephrology, Daini Osaka Police Hospital, 2-6-40, Karasuga-tsuji, Tennoji, Osaka, 543-8922, Japan.
BMC Nephrol. 2021 Jul 6;22(1):253. doi: 10.1186/s12882-021-02457-0.
Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient's clinical course.
A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission.
This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.
磷脂酶 A2 受体 1(PLA2R1)和血小板反应蛋白 1 型结构域包含 7A(THSD7A)是膜性肾病(MN)的两个主要致病抗原。据报道,THSD7A 相关的 MN 比 PLA2R1 相关的 MN 合并恶性肿瘤的患病率更高。在此,我们报告了一例 MN 患者,其病因在患者的临床过程中可能从特发性变为恶性肿瘤相关。
一名 68 岁男性因肾病综合征行肾活检诊断为 MN。免疫组化显示肾脏标本 THSD7A 阴性。皮质类固醇治疗的第一疗程达到部分缓解;然而,1 年后肾病综合征再次复发。2 年后,他的腹部超声检查发现膀胱肿瘤,但他不想接受进一步的诊断检查。由于蛋白尿连续增加,再次开始皮质类固醇治疗,但未能缓解。再次进行肾活检,显示 MN,THSD7A 染色阳性。两次活检 PLA2R1 染色均为阴性。由于他的膀胱肿瘤逐渐增大,他同意行膀胱肿瘤切除术。病理检查显示肿瘤为 THDS7A 阳性膀胱癌。随后,他的蛋白尿减少并保持缓解。
本病例提示 MN 的病因在治疗过程中可能发生改变。对于蛋白尿意外复发和/或治疗反应改变的患者,可能需要更积极地筛查恶性肿瘤。