title: Glomerular endothelial cell injury and focal segmental glomerulosclerosis lesion in idiopathic membranous nephropathy.
abstract: BACKGROUND
  Focal segmental glomerulosclerosis (FSGS) lesions have often been discussed as a negative predictor in idopathic membranous nephropathy (MN). The mechanism of the development of FSGS lesion in MN is still uncertain.
  
  
  METHODS
  From 250 cases of MN, 26 cases contained FSGS lesion. We compared the clinicopathological characteristics between MN cases with FSGS lesion [MN-FSGS(+)] and MN without FSGS lesion [MN-FSGS(-)], matched for gender, age, stage of MN.
  
  
  RESULTS
  The glomerular filtration rate (eGFR) was significantly lower in MN-FSGS(+) cases compared to MN-FSGS(-), although nephrotic syndrome, hematuria, and systolic blood pressure levels were not significantly different between the two groups. Pathologically, glomeruli in MN-FSGS(+) cases showed narrowing and loss of glomerular capillaries with separating from GBM or disappearance of CD34+ endothelial cells, and accumulation of extracellular matrix (ECM) in capillary walls, indicating the development of glomerular capillary injury. These findings of endothelial injury were seen even in MN-FSGS(-) cases, but they were more prominent in MN-FSGS(+) than MN-FSGS(-) by computer assessed morphometric analysis. In MN-FSGS(+) cases, 44 out of 534 glomeruli (8.2%) contained FSGS lesions (n = 31, NOS lesion; n = 13, perihilar lesion). Significant thickness of GBM with ECM accumulation was evident in MN-FSGS(+) cases. Podocyte injury with effacement of foot processes was also noted, but the expression of VEGF on podocytes was not different between the two groups, which suggests that the significant thickness of capillary walls may influence the function of VEGF from podocyte resulting in the glomerular capillary injury that contribute to the development of FSGS lesion in MN.
  
  
  CONCLUSIONS
  Glomerular capillary injury was seen in all MN cases. Furthermore, the prominent injuries of glomerular capillaries may be associated with the deterioration of eGFR and the formation of FSGS lesions in MN.
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Megumi
authors: M
authors: Morita
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Akiko
authors: A
authors: Mii
authors: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors: Akira
authors: A
authors: Shimizu
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Fumihiko
authors: F
authors: Yasuda
authors: Department of Nephrology, George Washington University Medical Center, Washington, District of Columbia, United States of America.
authors: Jun
authors: J
authors: Shoji
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Yukinari
authors: Y
authors: Masuda
authors: Division of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan.
authors: Ryuji
authors: R
authors: Ohashi
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Kiyotaka
authors: K
authors: Nagahama
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Tomohiro
authors: T
authors: Kaneko
authors: Department of Nephrology, Nippon Medical School, Tokyo, Japan.
authors: Shuichi
authors: S
authors: Tsuruoka
mesh_terms: D000368:Aged; D001706:Biopsy; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D015433:Glomerulonephritis, Membranous / Q000378:metabolism / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000293:injuries / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A