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Nephrol Dial Transplant (2002) 17: 1993-1998
© 2002 European Renal Association-European Dialysis and Transplant Association

Interstitial expression of {alpha}-SMA: an early marker of chronic renal allograft dysfunction

Chérif Badid1, Alexis Desmouliere2, Daniela Babici1, Aoumeur Hadj-Aissa1, Brigitte McGregor1, Nicole Lefrancois3, Jean Louis Touraine3 and Maurice Laville1,

1 Département de Néphrologie, Hôpital Edouard Herriot et EA 645, Laboratoire de Physiologie de l'Environnement, Faculté de Médecine Grange Blanche, Lyon, 2 GREF, INSERM 9917, Université Victor Segalen Bordeaux 2, Bordeaux and 3 Département de Transplantation et d'Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France

Background. Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using {alpha}-smooth-muscle actin ({alpha}-SMA) expression in time-zero biopsies predicts renal allograft dysfunction.

Methods. We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine {alpha}-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year.

Results. We found a significant correlation between interstitial {alpha}-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial {alpha}-SMA expression than non progressors (7.9±0.7 vs 4.3±0.4%), they showed only a tendency towards higher glomerular {alpha}-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between {alpha}-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF.

Conclusion. This study suggests that {alpha}-SMA evaluation in time-zero biopsies, especially the combination of {alpha}-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.

Keywords: chronic renal allograft dysfunction; cold ischaemic time; glomerular filtration rate; myofibroblast; {alpha}-smooth muscle actin

Correspondence and offprint requests to: Dr M. Laville, Département de Néphrologie, Hôpital Edouard Herriot, 5 place d'Arsonval 69437, Lyon Cedex 03, France. Email: maurice.laville{at}chu\|[hyphen]\|lyon.fr


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