Novel Label-Free Chemical Imaging for the Identification of Biomarkers of Diabetic Nephropathy Recurrence
thesisposted on 28.10.2014, 00:00 by Vishal K. Varma
The main treatment for end-stage renal disease is kidney transplantation, however close monitoring of post-transplant biopsies is required to identify subclinical complications. We identified biochemical markers using Chemical imaging that were associated with recurrent diabetic nephropathy. Chemical Imaging is an emerging approach to obtain images of the biochemical composition of tissue biopsies in a label-free fashion. A pilot study focused on identifying 8 patients with no evidence of diabetic nephropathy and 8 patients with advanced diabetic nephropathy. Serial sections were acquired and stained with PAS or imaged using chemical imaging. IR spectra were extracted to identify biomarkers associated with diabetic nephropathy progression. A second follow up study was performed with 5 patients with histological evidence of diabetic nephropathy (subtle to advanced), and 8 patients with no histological evidence of diabetic nephropathy. These first two studies involved native kidney tissues obtained through nephrectomies as well as biopsies. And lastly, a third study identified three renal transplant patients who underwent very rapid recurrent diabetic nephropathy and two patients with no evidence of diabetic nephropathy after two years. Biomarkers were identified that were changed in renal structures associated with the progression of diabetic nephropathy, including increased levels of glycation. The study also aimed to correlate clinical and histological parameters with signature we obtain from this technique. These biomarkers were found to be increasing in the cohort of transplant patients that underwent rapid diabetic nephropathy recurrence. In addition, the early biopsies from the patients that underwent later diabetic nephropathy progression were biochemically different from the non-progressive patients, suggesting that chemical imaging may identify pre-histological biomarkers that will predict outcome. We have identified a number of biomarkers that are associated with the advancement of diabetic nephropathy and that we can track the early recurrence of diabetic nephropathy in surveillance biopsies.