Detecting Proteomic Indicators to Distinguish Diabetic Nephropathy from Hypertensive Nephrosclerosis by Integrating Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging with High-Mass Accuracy Mass Spectrometry
Open Access
- 14 February 2020
- journal article
- research article
- Published by S. Karger AG in Kidney and Blood Pressure Research
- Vol. 45 (2), 233-248
- https://doi.org/10.1159/000505187
Abstract
Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to end-stage renal disease. Patients are treated primarily through the management of cardiovascular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Methods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/Conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.Keywords
This publication has 38 references indexed in Scilit:
- Chronic kidney disease: global dimension and perspectivesThe Lancet, 2013
- Transcriptome Analysis of Human Diabetic Kidney DiseaseDiabetes, 2011
- A Glimpse of Various Pathogenetic Mechanisms of Diabetic NephropathyAnnual Review Of Pathology-Mechanisms Of Disease, 2011
- Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to PathophysiologyPLOS ONE, 2010
- Pgrmc1 (Progesterone Receptor Membrane Component 1) Associates with Epidermal Growth Factor Receptor and Regulates Erlotinib SensitivityJournal of Biological Chemistry, 2010
- Pathologic Classification of Diabetic NephropathyJournal of the American Society of Nephrology, 2010
- Urinary Proteomics in Diabetes and CKDJournal of the American Society of Nephrology, 2008
- Gene Expression Profiles of Multiple Breast Cancer Phenotypes and Response to Neoadjuvant ChemotherapyClinical Cancer Research, 2006
- Overexpression of the Cytochrome P450 Activator Hpr6 (Heme-1 Domain Protein/Human Progesterone Receptor) in TumorsTumor Biology, 2005
- Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64)Kidney International, 2003