title: Endoplasmic Reticulum Stress Predicts Clinical Response to Cyclosporine Treatment in Primary Membranous Nephropathy.
abstract: Little is known about the endoplasmic reticulum stress (ERS) marker glucose regulated protein 78 (GRP78) and calcineurin in the kidney in primary membranous nephropathy (PMN) and if they could predict post-cyclosporine treatment outcome.
  
  
  
  This is a retrospective study using a dataset of biopsy-confirmed PMN from Peking Union Medical College Hospital from 1996 to 2014. Seventy-six adult patients treated with cyclosporine as primary immunosuppression for at least 6 months were studied. Immunohistochemistry was used to detect GRP78 and calcineurin in the kidney. Serum calcineurin was assayed by ELISA. Patients were grouped into no-remission (NR, n = 17), partial remission (PR, n = 39), or complete remission (CR, n = 20) at the end of 6 months of treatment.
  
  
  
  There was no difference of initial dose of cyclosporine among NR, PR, and CR groups. Kidney calcineurin expression in PMN was significantly increased compared to that in controls (p < 0.0083). The glomerular GRP78 in NR PMN was higher than that in control, CR and PR patients (p < 0.0083). Kidney calcineurin expression and GRP78 expression was positively correlated. However, there were no differences in either serum calcineurin levels or kidney calcineurin expressions among NR, PR or CR groups. There was a negative correlation between serum calcineurin activity and whole kidney calcineurin expression (p = 0.034) or glomerular calcineurin expression (p = 0.007). Neither kidney calcineurin nor GRP78 expression was correlated with proteinuria.
  
  
  
  ERS marker GRP78 in the glomeruli but not serum or kidney calcineurin expression could be a useful marker in PMN to negatively predict the response to cyclosporine treatment at the sixth month.
authors.affiliation: Division of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Tao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yubing
authors.initials: Y
authors.lastname: Wen
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Limeng
authors.initials: L
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Mingxi
authors.initials: M
authors.lastname: Li
authors.forename: Xuewang
authors.initials: X
authors.lastname: Li
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lafayette
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000097:blood; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D065095:Calcineurin Inhibitors; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D016572:Cyclosporine; D019703:Calcineurin