Metabolomic Alterations Associated with Cause of CKD

Clinical journal of the American Society of Nephrology: CJASN

Morgan E. Grams¹ 

[1] *Division of Nephrology, Department of Medicine, and..†Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;‖Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts..‖Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts..‖Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts..‖Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts..†Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;†Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

关键词: MDRD Study;    Metabolomic profiling;    metabolites;    glomerular filtration rate;    Kynurenic Acid;    homocitrulline;    blood pressure;    Body Mass Index;    Random Allocation;    Tandem Mass Spectrometry;    kidney;    Renal Insufficiency, Chronic;    proteinuria;    Citrulline;    Polycystic Kidney Diseases;    Diet;    Prognosis;    Demography;    Sulfates;    Hippurates;    Chromatography, Liquid;    Dietary Proteins;    Male;   

DOI  :  10.2215/CJN.02560317

学科分类：泌尿医学

来源: American Society of Nephrology

【 摘 要 】

Background and objectives Causes of CKD differ in prognosis and treatment. Metabolomic indicators of CKD cause may provide clues regarding the different physiologic processes underlying CKD development and progression.Design, setting, participants & measurements Metabolites were quantified from serum samples of participants in the Modification of Diet in Renal Disease (MDRD) Study, a randomized controlled trial of dietary protein restriction and BP control, using untargeted reverse phase ultraperformance liquid chromatography tandem mass spectrometry quantification. Known, nondrug metabolites (n=687) were log-transformed and analyzed to discover associations with CKD cause (polycystic kidney disease, glomerular disease, and other cause). Discovery was performed in Study B, a substudy of MDRD with low GFR (n=166), and replication was performed in Study A, a substudy of MDRD with higher GFR (n=423).Results Overall in MDRD, average participant age was 51 years and 61% were men. In the discovery study (Study B), 29% of participants had polycystic kidney disease, 28% had glomerular disease, and 43% had CKD of another cause; in the replication study (Study A), the percentages were 28%, 24%, and 48%, respectively. In the discovery analysis, adjusted for demographics, randomization group, body mass index, hypertensive medications, measured GFR, log-transformed proteinuria, and estimated protein intake, seven metabolites (16-hydroxypalmitate, kynurenate, homovanillate sulfate, N2,N2-dimethylguanosine, hippurate, homocitrulline, and 1,5-anhydroglucitol) were associated with CKD cause after correction for multiple comparisons (P<0.0008). Five of these metabolite associations (16-hydroxypalmitate, kynurenate, homovanillate sulfate, N2,N2-dimethylguanosine, and hippurate) were replicated in Study A (P<0.007), with all replicated metabolites exhibiting higher levels in polycystic kidney disease and lower levels in glomerular disease compared with CKD of other causes.Conclusions Metabolomic profiling identified several metabolites strongly associated with cause of CKD.

【 授权许可】

CC BY