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One potential mechanism underlying cellular dysfunction contributing to kidney disease is aberrant protein post\u2010translational modifications. Lysine acetylation is associated with cellular metabolic flux and is thought to be altered in patients with diabetes and dysfunctional renal metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Design<\/jats:title><jats:p>A novel extraction and LC\u2010MS\/MS approach was adapted to quantify sites of lysine acetylation from formalin\u2010fixed paraffin\u2010embedded (FFPE) kidney tissue and from patients with DKD and non\u2010diabetic donors (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 and <jats:italic>n<\/jats:italic>\u00a0=\u00a07, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of FFPE tissues identified 840 total proteins, with 225 of those significantly changing in patients with DKD. Acetylomic analysis quantified 289 acetylated peptides, with 69 of those significantly changing. Pathways impacted in DKD patients revealed numerous metabolic pathways, specifically mitochondrial function, oxidative phosphorylation, and sirtuin signaling. Differential protein acetylation in DKD patients impacted sirtuin signaling, valine, leucine, and isoleucine degradation, lactate metabolism, oxidative phosphorylation, and ketogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>A quantitative acetylomics platform was developed for protein biomarker discovery in formalin\u2010fixed and paraffin\u2010embedded biopsies of kidney transplant patients suffering from DKD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.202400018","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T10:09:45Z","timestamp":1719223785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Quantifying Protein Acetylation in Diabetic Nephropathy from Formalin\u2010Fixed Paraffin\u2010Embedded Tissue"],"prefix":"10.1002","volume":"18","author":[{"given":"Stefanie K.","family":"Schwab","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Harris","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Michel","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney D.","family":"McGinnis","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rooban B.","family":"Nahomi","sequence":"additional","affiliation":[{"name":"Sue Anschutz\u2010Rodgers Eye Center and Department of Ophthalmology University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Assiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Reisdorph","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kammi","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Chicago Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-1400","authenticated-orcid":false,"given":"David J.","family":"Orlicky","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Levi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular &amp; Cellular Biology Georgetown University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram H.","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Sue Anschutz\u2010Rodgers Eye Center and Department of Ophthalmology University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1499-6174","authenticated-orcid":false,"given":"Kristofer S.","family":"Fritz","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.184"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010018\u20100001\u2010y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31694-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051123"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2015.02.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.580167"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.580171"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187752"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20101770"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014\u2010022\u201009346\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5420"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201100550"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102792"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2021.11.005"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.11.159"},{"issue":"092","key":"e_1_2_9_20_1","article-title":"Efficacy of n\u2010Heptane as a Xylene Substitute in Routine Histopathology","volume":"5","author":"Shrivastava A. 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