Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Clin J Am Soc Nephrol. 2012 Nov;7(11):1852-8. doi: 10.2215/CJN.10571011. Epub 2012 Aug 23.
Podocyte loss is key in glomerulosclerosis. Activated parietal epithelial cells are proposed to contribute to pathogenesis of glomerulosclerosis and may serve as stem cells that can transition to podocytes. CD44 is a marker for activated parietal epithelial cells. This study investigated whether activated parietal epithelial cells are increased in early recurrent FSGS in transplant compared with minimal change disease.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CD44 staining in renal allograft biopsies from 12 patients with recurrent FSGS was performed and compared with native kidneys with minimal change disease or FSGS and normal control native and transplant kidneys without FSGS. CD44+ epithelial cells along Bowman's capsule in the parietal epithelial cell location and over the glomerular tuft in the visceral epithelial cell location were assessed.
Cases with early recurrent FSGS manifesting only foot process effacement showed significantly increased CD44+ visceral epithelial cells involving 29.0% versus 2.6% of glomeruli in minimal change disease and 0% in non-FSGS transplants. Parietal location CD44 positivity also was numerically increased in recurrent FSGS. In later transplant biopsies, glomeruli with segmental lesions had more CD44+ visceral epithelial cells than glomeruli without lesions.
Parietal epithelial cell activation marker is significantly increased in evolving FSGS versus minimal change disease, and this increase may distinguish early FSGS from minimal change disease. Whether parietal epithelial cell activation contributes to pathogenesis of sclerosis in idiopathic FSGS or is a regenerative/repair response to replace injured podocytes awaits additional study.
足细胞丢失是肾小球硬化的关键。活化的壁细胞上皮细胞被认为参与了肾小球硬化的发病机制，并且可能作为干细胞向足细胞转化。CD44 是活化的壁细胞上皮细胞的标志物。本研究旨在探讨与微小病变性肾病相比，移植后早期复发性 FSGS 中活化的壁细胞上皮细胞是否增加。
设计、地点、参与者和测量方法：对 12 例复发性 FSGS 移植肾活检标本进行 CD44 染色，并与微小病变性肾病或 FSGS 及正常对照的原肾和无 FSGS 的移植肾进行比较。评估位于壁细胞上皮细胞位置的沿鲍曼囊的 CD44+上皮细胞和位于脏层上皮细胞位置的覆盖在肾小球足突上的 CD44+上皮细胞。
仅表现为足突融合的早期复发性 FSGS 病例显示 CD44+脏层上皮细胞显著增加，占微小病变性肾病肾小球的 29.0%，而 FSGS 移植肾为 0%，非 FSGS 移植肾为 2.6%。复发性 FSGS 中壁细胞位置的 CD44 阳性也呈数值增加。在后期移植活检中，有节段性病变的肾小球比无病变的肾小球有更多的 CD44+脏层上皮细胞。
与微小病变性肾病相比，进展性 FSGS 中壁细胞上皮细胞激活标志物显著增加，这种增加可能有助于将早期 FSGS 与微小病变性肾病区分开来。壁细胞上皮细胞的激活是否有助于特发性 FSGS 的硬化发病机制，或者是否是对受损足细胞的再生/修复反应，还需要进一步的研究。
