Novel Urinary Biomarkers of Interstitial Fibrosis/Tubular Atrophy Progression in Kidney Transplantation
thesisposted on 2016-07-01, 00:00 authored by Sanjeev Akkina
Interstitial Fibrosis/Tubular Atrophy (IF/TA) is a common problem in kidney transplantation that ultimately leads to allograft failure. There are no early non-invasive biomarkers of IF/TA available that can be used to identify early IF/TA where interventions can be implemented to prevent irreversible injury. The object of this work is to identify novel biomarkers of IF/TA in the urine of kidney transplant recipients using proteomic methods. Mass spectrometry with isobaric tagging with iTRAQ labeling was used to quantify protein abundance in urine samples. We used individuals from two separate cohorts to identify these biomarkers. The discovery phase of the study used a cross-sectional cohort to identify candidate biomarkers of IF/TA. The validation phase used the prospective cohort to see which of the candidate biomarkers could predict progression of IF/TA. From a sample size of 24 in the cross-sectional cohort, we identified 55 candidate biomarkers that were upregulated in at least of the 1 of the fibrosis comparisons (none-mild, none-moderate/severe, mild-moderate/severe). In the validation cohort, 4 of these biomarkers were able to differentiate progressors versus non-progressors of IF/TA. These biomarkers include alpha-1-acid glycoprotein, alpha-2-macroglobulin, apolipoprotein A-IV, apolipoprotein C-III, immunoglobulin J chain, pigment epithelium-derived factor, profilin-1, and retinol binding protein 4. Using proteomic methods, we identified 4 novel urinary biomarkers of IF/TA in kidney transplant recipients. Further studies are needed to confirm these findings and assess the clinical utility of these biomarkers in transplantation.