Background

The main treatment for end-stage renal disease is kidney transplantation, however close monitoring of post-transplant biopsies is required to identify subclinical complications. In this study, we focused on identifying biochemical markers associated with change in interstitial fibrosis in transplant patients using chemical imaging. Chemical Imaging is an emerging approach to obtain images of the biochemical composition of tissue biopsies in a label-free fashion.

Design

A pilot study focused on identifying 5 patients with no progression of interstitial fibrosis and 5 patients with increase in interstitial fibrosis over time. Serial sections were acquired and stained for detection of fibrosis with trichrome stain or imaged using chemical imaging. Infrared spectra were extracted to identify biomarkers associated with interstitial fibrosis progression. Each patient had an early time point biopsy and a late time point biopsy. The early and late protocol biopsies between each group was compared using chemical information extracted from areas of fibrosis of each biopsy.

Results

Biomarkers were identified that were changed in regions of interstitial fibrosis associated with progression in sequential biopsies. Using multivariable analysis techniques on the chemical data collected, we were able to segregate the late biopsies into cases that would have progressive increase in fibrosis from those did not show significant alteration in fibrosis. The biochemical signatures between the late biopsies from “rapid progressors” and “non progressors” cohorts were distinct suggesting different underlying biochemical reactions in the two groups. In addition, early biopsies from the patients who later developed increased fibrosis were biochemically different from those who did not, suggesting that chemical imaging may identify pre-histological biomarkers that will predict outcome.

Conclusion

We have identified a number of biochemical markers that are associated with the advancement of interstitial fibrosis, a component of chronic rejection, and that we can distinguish between the late and early cases for each group using the biochemical information. In addition, we have highlighted a 'biochemical-signature' that may be predictive of the later interstitial fibrosis, using baseline biopsies. Additional cases should allow us to validate these preliminary findings.

CITATION INFORMATION: Varma V, Kajdacsy-Balla A, Akkina S, Setty S, Walsh M. Identification of Biomarkers for Progressive Fibrosis in Renal Transplant Patients Using Novel Chemical Imaging Approaches. Am J Transplant. 2016;16 (suppl 3).

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