KIDNEY PARENCHYMA METABOLITES AS PROGNOSTIC BIOMARKERS FOR LONG-TERM KIDNEY FUNCTION AFTER NEPHRECTOMY FOR RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP08)1 Apr 2020MP08-18 KIDNEY PARENCHYMA METABOLITES AS PROGNOSTIC BIOMARKERS FOR LONG-TERM KIDNEY FUNCTION AFTER NEPHRECTOMY FOR RENAL CELL CARCINOMA Barak Rosenzweig*, Pedro Recabal, Caroline Gluck, Jonathan A Coleman, Katalin Susztak, A. Ari Hakimi, Edgar A Jaimes, and Robert H Weiss Barak Rosenzweig*Barak Rosenzweig* More articles by this author , Pedro RecabalPedro Recabal More articles by this author , Caroline GluckCaroline Gluck More articles by this author , Jonathan A ColemanJonathan A Coleman More articles by this author , Katalin SusztakKatalin Susztak More articles by this author , A. Ari HakimiA. Ari Hakimi More articles by this author , Edgar A JaimesEdgar A Jaimes More articles by this author , and Robert H WeissRobert H Weiss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000828.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nephrectomy, the standard of care for localized renal cell carcinoma (RCC), may lead to kidney function loss. To identify prognostic biomarkers of postoperative renal function using metabolomics. METHODS: Metabolomics data from benign kidney parenchyma were collected prospectively from 138 patients with RCC who underwent nephrectomy at a single institution. The primary endpoint was the difference between the postoperative and preoperative estimated glomerular filtration rate divided by the elapsed time (eGFR slope). eGFR slope was calculated approximately two years post-nephrectomy (GFR1), and at last follow-up (GFR2). A multivariate regularized regression model identified clinical characteristics and abundance of metabolites in baseline benign kidney parenchyma that were significantly associated with eGFR slope. Unique metabolite signatures of eGFR slope were analyzed by older age, nephrectomy type, and preoperative eGFR. Findings were validated by associating gene expression data with eGFR slope in an independent cohort (n=58). RESULTS: Data were compiled on 78 patients (median age 62.6 years, 65.4% males). The mean follow-up was 25±3.4 months for GFR1 and 69.5±23.5 months for GFR2, and 17 (22%) and 32 (41%) patients showed eGFR recovery, respectively. Nephrectomy type, blood lipids, gender, and 23 metabolites from benign parenchyma (18 identified) were significantly associated with eGFR slope. Specifically, abundance of 1-arachidonoylglycerophosphoethanolamine, a fat metabolism-related metabolite, was positively associated with eGFR slope, as was gene expression of the enzymes in its pathway (fig.1). Subgroup analysis identified unique “metabolite signatures” by older age, nephrectomy type, and preoperative eGFR. CONCLUSIONS: Nephrectomy type, gender, blood lipids, and benign parenchyma metabolites at nephrectomy were associated with long-term kidney function. Some of these metabolites have been previously described in kidney disease-related processes, vouching for their validity in the present setting. On further study, these metabolites may be useful as potential biomarkers and to identify novel therapeutic targets for malignancy-associated renal disease. Source of Funding: NIDDK: U01 DK103225 & P30 CA008748 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e113-e113 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Barak Rosenzweig* More articles by this author Pedro Recabal More articles by this author Caroline Gluck More articles by this author Jonathan A Coleman More articles by this author Katalin Susztak More articles by this author A. Ari Hakimi More articles by this author Edgar A Jaimes More articles by this author Robert H Weiss More articles by this author Expand All Advertisement PDF downloadLoading ...