Usefulness of morphometric image analysis with Sirius Red to assess interstitial fibrosis after renal transplantation from uncontrolled circulatory death donors

Myriam Dao,Charlotte Mussini,Hélène François,Christelle Pouliquen,Alyette Duquesne,Katia Posseme,Sophie Ferlicot,Antoine Durrbach,Catherine Guettier

doi:10.1038/s41598-020-63749-3

Abstract

Early interstitial fibrosis (IF) correlates with long-term renal graft dysfunction, highlighting the need for accurate quantification of IF. However, the currently used Banff classification exhibits some limitations. The aim of our study was to precisely describe the progression of IF after renal transplantation using a new morphometric image analysis method relying of Sirius Red staining. The morphometric analysis we developed showed high inter-observer and intra-observer reproducibility, with ICC [95% IC] of respectively 0.75 [0.67–0.81] (n = 151) and 0.88 [0.72–0.95] (n = 21). We used this method to assess IF (mIF) during the first year after the kidney transplantation from 66 uncontrolled donors after circulatory death (uDCD). Both mIF and interstitial fibrosis (ci) according to the Banff classification significantly increased the first three months after transplantation. From M3 to M12, mIF significantly increased whereas Banff classification failed to highlight increase of ci. Moreover, mIF at M12 (p = 0.005) correlated with mean time to graft function recovery and was significantly associated with increase of creatininemia at M12 and at last follow-up. To conclude, the new morphometric image analysis method we developed, using a routine and cheap staining, may provide valuable tool to assess IF and thus to evaluate new sources of grafts.

Highlights

Interstitial fibrosis (IF) correlates with long-term renal graft dysfunction, highlighting the need for accurate quantification of interstitial fibrosis (IF)
The aim of the study was to assess the initial progression of interstitial fibrosis and tubular atrophy in kidney grafts from uncontrolled donors after circulatory death (uDCD) formerly classified as “Maastricht II” non heart beating donors, using a new image analysis method based on Sirius Red staining
We compared morphometric quantification of interstitial fibrosis and semi-quantitative analysis performed by an expert pathologist (SF) according to Banff criteria (Fig. 1E)

Summary

Introduction

Interstitial fibrosis (IF) correlates with long-term renal graft dysfunction, highlighting the need for accurate quantification of IF. The only reliable method to assess IF/TA is the histological evaluation of a graft biopsy[30,31] which allows to determine specific lesions and pathogenic processes affecting the graft[22,23] It is well-known that early IF correlates with long-term graft dysfunction[32,33,34], highlighting the need for accurate quantification of IF to better identify patients requiring specific therapeutic interventions and to determine the efficacity of such interventions. The aim of the study was to assess the initial progression of interstitial fibrosis and tubular atrophy in kidney grafts from uDCD formerly classified as “Maastricht II” non heart beating donors, using a new image analysis method based on Sirius Red staining

Objectives

Methods

Results

Conclusion