title: Early interstitial accumulation of collagen type I discriminates chronic rejection from chronic cyclosporine nephrotoxicity.
abstract: Little is known regarding the composition of the interstitial extracellular matrix of kidney allografts with deteriorating function. Collagen I, III, and IV, the collagen IV alpha3 chain, and the laminin beta2 chain were investigated in biopsies of allografted kidneys with chronic cyclosporine A nephrotoxicity (CsAT) (n = 17), chronic rejection (CR) (n = 12), or chronic allograft nephropathy (CAN) (n = 19). alpha-Smooth muscle actin expression was also examined. Normal native kidneys were used as control samples (n = 11). Biopsy samples were studied with routine light microscopy and immunostaining. The mean interstitial fibrosis scores were significantly higher for the CR and CAN groups, compared with the chronic CsAT group. The cortical tubulointerstitial areas of the CR and CAN groups, but not the chronic CsAT group, contained more collagen I than did normal control samples. Differences were noted even in biopsies with mild fibrosis. Accumulation of collagen III, IV, and IV alpha3 was increased in all patient groups. Collagen III accumulation was greater in the CR and CAN groups than in the chronic CsAT group. Receiver-operating characteristic curve analysis demonstrated that collagen I staining had the best discriminatory value in differentiating CR from chronic CsAT, with a sensitivity of 63% and a specificity of 94% at a cutoff value of 19%. Laminin beta2 staining did not differentiate CR from CsAT. Increased alpha-smooth muscle actin staining did not differ among the three groups. It was concluded that, during chronic CsAT, collagen III and IV were preferentially accumulated in the tubulointerstitium. Early increases in the deposition of collagen I, with collagen III and IV, were more specific for CR. CR seems to elicit a more pronounced fibrotic response than does chronic CsAT.
authors.affiliation: Departments of Nephrology and Pathology, Leiden University Medical Center, Leiden, The Netherlands. RNR@euronet.nl
authors.forename: Rene C
authors.initials: RC
authors.lastname: Bakker
authors.forename: Klaas
authors.initials: K
authors.lastname: Koop
authors.forename: Yvo W
authors.initials: YW
authors.lastname: Sijpkens
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.forename: Emile
authors.initials: E
authors.lastname: De Heer
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: Leendert C
authors.initials: LC
authors.lastname: Paul
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D024042:Collagen Type I / Q000378:metabolism*; D016572:Cyclosporine / Q000009:adverse effects* / Q000633:toxicity*; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D006084:Graft Rejection; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000473:pathology; D016030:Kidney Transplantation; D007797:Laminin / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D012372:ROC Curve; D013997:Time Factors
chemical_list: D000199:Actins; D024042:Collagen Type I; D007166:Immunosuppressive Agents; D007797:Laminin; C058783:laminin beta2; D016572:Cyclosporine