title: Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease.
abstract: 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.
authors.affiliation: Division of Nephrology and Clinical Immunology, Department of Internal Medicine II, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.affiliation: Department of Pathology, INSERM U702, Hôpital Tenon, Paris, France; Nephrology Service, University Hospitals of Geneva (HUG), Geneva, Switzerland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Stucker
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jack
authors.initials: J
authors.lastname: Wetzels
authors.affiliation: Department of Pathology, INSERM U702, Hôpital Tenon, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: Department of Pathology, INSERM U702, Hôpital Tenon, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York.
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.affiliation: Department of Biochemistry, NCMLS, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.affiliation: Q1 platform of the TRR57, Institute for Pathology, Sigmund-Freud-Straße 25, Bonn, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.affiliation: Q1 platform of the TRR57, Institute for Pathology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.affiliation: Division of Nephrology and Clinical Immunology, Department of Internal Medicine II, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Division of Nephrology and Clinical Immunology, Department of Internal Medicine II, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.affiliation: Division of Nephrology and Clinical Immunology, Department of Internal Medicine II, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: mmoeller@ukaachen.de.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Moeller
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism; D000328:Adult; D017318:Annexin A3 / Q000378:metabolism; D000906:Antibodies / Q000737:chemistry; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000175:diagnosis* / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D000906:Antibodies; C497483:CD44 protein, human; C568108:CLDN1 protein, human; D018797:Cell Cycle Proteins; D062445:Claudin-1; D018960:Hyaluronan Receptors; D017318:Annexin A3