Parietal epithelial cell activation marker in early recurrence of FSGS in the transplant

Abstract

Background and objectives: 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.

Results: 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.

Conclusions: 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.

Figure 1.

CD44 in early recurrent FSGS. Significantly increased CD44 staining in visceral epithelial cell location in early recurrent FSGS with extensive foot process effacement only and no segmental sclerosis (A) compared with minimal CD44 staining in visceral location in a case of native kidney minimal change disease (B; anti-CD44 stain). Original magnification, ×400.

Figure 2.

CD44 in established FSGS. In cases with established segmental sclerosis, glomeruli with lesions (A; right glomerulus) showed more visceral epithelial cell location CD44 staining than non-sclerosed glomeruli (A; left glomerulus). Parietal epithelial cells stained for CD44 equally in glomeruli with (B) or without (A; left glomerulus) segmental sclerosis (anti-CD44 stain). Original magnification, ×200 in A; ×400 in B.

Figure 3.

CD44 staining in both podocyte and parietal location in a glomerulus without segmental lesion in a biopsy with FSGS (anti-CD44 stain). Original magnification, ×200.

Figure 4.

Cellular bridges in recurrent FSGS. Glomeruli in two cases (A and B) of recurrent FSGS in the transplant with cellular bridges with CD44+ cells along these adhesions (anti-CD44 stain). Original magnification, ×3800 in A; ×3400 in B.

Figure 5.

Specific identification of CD44 staining in glomerular epithelial cells was done by anatomic location and aided by CD45 staining on adjacent sections to identify leukocyte staining. In a case of rejection, intraglomerular (within capillary lumens) and interstitial leukocytes were stained for CD44 and CD45 (A and B). In a case of FSGS recurrence in the transplant, activated parietal epithelial cells along the inside of Bowman’s capsule were stained with CD44 (C) but not CD45 (D). Interstitial leukocytes were stained with both CD44 and CD45 (C and D). A and C, anti-CD44; B and D, anti-CD45 (same glomeruli from each case in adjacent sections). Original magnification, ×200.