Detection of Activated Parietal Epithelial Cells on the Glomerular Tuft Distinguishes Early Focal Segmental Glomerulosclerosis from Minimal Change Disease

• DOI: 10.1016/j.ajpath.2014.08.007
• Publication Date: 2014-10-09T09:16:06Z
• Authors: Bart Smeets; Fabien Stucker; Jack Wetzels; Isabelle Brocheriou; Pierre Ronco; Hermann-Josef Gröne; Vivette D’Agati; Agnes B. Fogo; Toin H. van Kuppe...; Hans-Peter Fischer; Peter Boor; Jürgen Floege; Tammo Ostendorf; Marcus J. Moeller
• Keywords: Adult; Biopsy; Kidney Glomerulus; A Kinase Anchor Proteins; Cell Cycle Proteins; Kidney; Antibodies; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Claudin-1; Humans; Annexin A3; Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 11: Renal disorders RIHS: Radboud Institute for Health Sciences; Glomerulosclerosis, Focal Segmental; Podocytes; Nephrosis, Lipoid; Epithelial Cells; Middle Aged; Immunohistochemistry; 3. Good health; Hyaluronan Receptors; Microscopy, Fluorescence

In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of idiopathic nephrotic syndrome with no immune complexes can improve the sensitivity to detect sclerotic lesions compared with standard methods. Ninety-five renal biopsies were stained for claudin-1 (PEC marker), CD44 (activated PECs), and LKIV69 (PEC matrix); 38 had been diagnosed as early primary FSGS and 57 as minimal change disease. PEC markers were detected on the tuft in 87% of the biopsies of patients diagnosed as primary FSGS. PEC markers were detected in FSGS lesions from the earliest stages of disease. In minimal change disease, no PEC activation was observed by immunohistology. However, in 25% of biopsies originally diagnosed as minimal change disease the presence of small lesions indicative of a sclerosing process were detected, which were undetectable on standard periodic acid-Schiff staining, even though only a single histologic section for each PEC marker was evaluated. Staining for LKIV69 detected lesions with the highest sensitivity. Two novel PEC markers A-kinase anchor protein 12 and annexin A3 exhibited similar sensitivity. In summary, detection of PECs on the glomerular tuft by immunostaining improves the differentiation between minimal change disease and primary FSGS and may serve to guide clinical decision making.