Hong Ling, Wang Lin, Wang Honglei, Wang Qihua, Yang Shicong, Tian Tian, Cui Tianjiao, Yue Shuling, Hou Xiaotao, Zheng Zhihua, Chen Wenfang
Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Kidney Int Rep. 2023 Sep 22;8(12):2742-2753. doi: 10.1016/j.ekir.2023.09.014. eCollection 2023 Dec.
Podocyte infolding glomerulopathy (PIG) is a newly recognized rare glomerular injury. The clinical significance and mechanism of this injury pattern remains unclear.
We conducted a retrospective study of renal biopsies from January 2018 to December 2020 in Kingmed Diagnostics. The renal biopsy features and clinical data were reviewed. Laser scanning microdissection and mass spectrometry (LMD/MS) was conducted to analyze the potential mechanism.
A total of 116 (0.092%) out of 126,086 biopsies were diagnosed as PIG during the period. Of these, 89 (76.7%) cases were found to have PIG coexisting with immune-complex associated glomerulonephritis (IC-PIG) whereas 27 (23.3%) were identified as isolated PIG without immunoglobulin or complement deposition. Systemic lupus erythematosus (SLE), especially with membranous lupus nephritis (LN), was diagnosed in most (70.8%) IC-PIG cases. Of the isolated PIG cases, 51.9% had no known underlying conditions; however, a relatively high positive rate (42.1%) of antinuclear antibody (ANA) was detected. Nearly half (47.5%) of the patients presented with nephrotic syndrome (NS). PIG grade was associated with proteinuria in isolated PIG ( = 0.035). LMD/MS revealed dysregulated cytoskeletal protein α-actinin4 (ACTN4) and tubulin beta-4 chain in PIG compared with normal donor kidney and minimal change disease (MCD). The displacement of ACTN4 into the glomerular basement membrane (GBM) was confirmed by the confocal microscope.
PIG is a rare podocyte injury that can exist alone without underlying disease or be concurrent with various diseases, especially SLE. Podocyte cytoskeletal protein ACTN4 and tubulin beta-4 chain were dysregulated, which may be involved in the mechanism of PIG.
足细胞内褶性肾小球病（PIG）是一种新发现的罕见肾小球损伤。这种损伤模式的临床意义和机制尚不清楚。
我们对金域检验2018年1月至2020年12月期间的肾活检进行了回顾性研究。回顾了肾活检特征和临床资料。采用激光扫描显微切割和质谱分析（LMD/MS）来分析潜在机制。
在此期间，126,086例活检中有116例（0.092%）被诊断为PIG。其中，89例（76.7%）病例被发现PIG与免疫复合物相关肾小球肾炎（IC-PIG）共存，而27例（23.3%）被确定为无免疫球蛋白或补体沉积的孤立性PIG。大多数（70.8%）IC-PIG病例被诊断为系统性红斑狼疮（SLE），尤其是合并膜性狼疮性肾炎（LN）。在孤立性PIG病例中，51.9%没有已知的基础疾病；然而，抗核抗体（ANA）检测阳性率相对较高（42.1%）。近一半（47.5%）的患者表现为肾病综合征（NS）。PIG分级与孤立性PIG中的蛋白尿相关（P = 0.035）。与正常供体肾和微小病变肾病（MCD）相比，LMD/MS显示PIG中细胞骨架蛋白α-辅肌动蛋白4（ACTN4）和微管蛋白β-4链失调。共聚焦显微镜证实ACTN4移位至肾小球基底膜（GBM）。
PIG是一种罕见的足细胞损伤，可单独存在而无基础疾病，或与各种疾病并发，尤其是SLE。足细胞细胞骨架蛋白ACTN4和微管蛋白β-4链失调，可能参与了PIG的发病机制。
