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Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction
Chérif Badid1, Alexis Desmouliere, Daniela Babici
1Département de Néphrologie, Hôpital Edouard Herriot et EA 645, Laboratoire de Physiologie de l'Environnement, Faculté de Médecine Grange Blanche, 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.
Insights
Early detection of alpha-smooth-muscle actin (alpha-SMA) in kidney transplant biopsies can predict graft dysfunction. Combining alpha-SMA expression with interstitial fibrosis offers strong predictive value for chronic renal allograft issues.
Area of Science:
- Nephrology
- Transplantation immunology
- Pathology
Background:
- Myofibroblast infiltration is linked to declining kidney function in chronic kidney diseases.
- Alpha-smooth-muscle actin (alpha-SMA) is a marker for myofibroblasts.
Purpose of the Study:
- To determine if early detection of alpha-SMA expression in time-zero biopsies predicts renal allograft dysfunction.
- To assess the predictive value of alpha-SMA for renal graft survival.
Main Methods:
- 38 renal transplant patients' time-zero biopsies were analyzed for alpha-SMA expression using immunohistochemistry.
- Glomerular filtration rate (GFR) was monitored for 3 years post-transplant.
- Correlation analysis was performed between alpha-SMA levels and GFR variation, considering factors like cold ischemic time and acute rejections.
Main Results:
- A significant correlation was found between interstitial alpha-SMA expression and GFR evolution (r=0.60, P<0.001).
- Patients with declining GFR (progressors) showed higher interstitial alpha-SMA expression compared to non-progressors.
- Interstitial fibrosis in time-zero biopsies was also more prevalent in progressors.
Conclusions:
- Alpha-SMA evaluation in time-zero biopsies can predict chronic renal allograft dysfunction.
- The combination of alpha-SMA expression and interstitial fibrosis provides a strong predictive marker for graft dysfunction.