{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:18Z","timestamp":1760060778823,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development (NICHD)","award":["R01HD070511"],"award-info":[{"award-number":["R01HD070511"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>End-stage kidney disease is preferably treated by kidney transplantation. The function of the allograft often determines kidney-controlled processes and requires long-term monitoring. Kidneys are organs with a very high metabolic rate, and, thus, a metabolomics approach is suitable to observe systemic metabolic changes that are related to graft adaptation. To understand these ongoing changes in post-transplant pediatric patients, we applied a targeted liquid chromatography\/tandem mass spectrometry-based metabolomics approach. Time-dependent changes of 140 metabolites in plasma samples prospectively collected from 23 pediatric kidney graft recipients receiving tacrolimus-based immunosuppression were monitored over the first 4 years after transplantation and compared to levels prior to transplantation. Furthermore, by comparing the pre-transplant metabolite levels to those measured in healthy children, we were able to obtain insights into the pathways associated with kidney failure. Arginine biosynthesis, alanine, aspartate, glutamine, and glutamate metabolism, taurine and tryptophan metabolism were the most affected pathways that separate the pediatric patients with and without kidney failure. Accumulation of uremic toxins such as various tryptophan\/kynurenine and tryptophan\/indole metabolism pathway intermediates, and betaine and methionine cycle metabolites was evident in patients with restricted kidney function. Furthermore, reduced nicotinamide production, insufficient hydroxylation of phenylalanine to tyrosine, lowered cysteine, arginine, glutamine, taurine, and overall amino acid utilization, as well as diminished levels of protective antioxidants such as glutathione and vitamins B6 and C, were all the result of progressive kidney failure leading to transplantation. Importantly, following kidney transplantation and recovery of kidney function, the levels of most of the previously described metabolites normalized toward the levels observed in healthy participants. The here identified metabolic patterns could be used as markers to monitor the progression of pediatric chronic kidney disease patients towards kidney failure, and assuming their direct association with kidney function, they could serve as markers of successful graft adaptation.<\/jats:p>","DOI":"10.3390\/ijms26189190","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"9190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monitoring of Allograft Adaptation After Kidney Transplantation in Pediatric Patients by Targeted Plasma Metabolomics"],"prefix":"10.3390","volume":"26","author":[{"given":"Jelena","family":"Klawitter","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA"},{"name":"Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-3843","authenticated-orcid":false,"given":"Bruce E.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Shillingburg","sequence":"additional","affiliation":[{"name":"Emergency Department, University of Tennessee Medical Center, Knoxville, TN 37920, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-4820","authenticated-orcid":false,"given":"Jost","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Touraj","family":"Shokati","sequence":"additional","affiliation":[{"name":"HepQuant, LLC, Denver, CO 80237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0460-2477","authenticated-orcid":false,"given":"Melissa A.","family":"Cadnapaphornchai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Galinkin","sequence":"additional","affiliation":[{"name":"US Anesthesia Partners of Colorado, Greenwood Village, CO 80111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3476-9956","authenticated-orcid":false,"given":"Joshua M.","family":"Thurman","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7297-147X","authenticated-orcid":false,"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJM199408113310606","article-title":"Renal transplantation","volume":"331","author":"Suthanthiran","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(79)92440-1","article-title":"Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers","volume":"2","author":"Calne","year":"1979","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0140-6736(89)91014-3","article-title":"FK 506 for liver, kidney, and pancreas transplantation","volume":"2","author":"Starzl","year":"1989","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/ajt.16502","article-title":"OPTN\/SRTR 2019 Annual Data Report: Kidney","volume":"21","author":"Hart","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/j.1600-6143.2004.00515.x","article-title":"Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies?","volume":"4","author":"Schold","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1600-6143.2004.00332.x","article-title":"Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era","volume":"4","author":"Schold","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1053\/j.ajkd.2010.04.010","article-title":"KDOQI US commentary on the 2009 KDIGO clinical practice guideline for the care of kidney transplant recipients","volume":"56","author":"Bia","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ki.2009.377","article-title":"KDIGO clinical practice guideline for the care of kidney transplant recipients: A summary","volume":"77","author":"Kasiske","year":"2010","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1111\/j.1600-6143.2009.02834.x","article-title":"Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients","volume":"9","author":"Eckardt","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1046\/j.1523-1755.2001.00030.x","article-title":"International variation in the interpretation of renal transplant biopsies: Report of the CERTPAP Project","volume":"60","author":"Furness","year":"2001","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/MNH.0000000000000648","article-title":"Are borderline changes real rejection? Current viewpoints","volume":"29","author":"Park","year":"2020","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1111\/j.1600-6143.2005.00988.x","article-title":"Safety and adequacy of renal transplant protocol biopsies","volume":"5","author":"Schwarz","year":"2005","journal-title":"Am. J. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s11306-018-1419-8","article-title":"Identification of a urine metabolite constellation characteristic for kidney allograft rejection","volume":"14","author":"Banas","year":"2018","journal-title":"Metabolomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1089\/omi.2019.0158","article-title":"A Noninvasive Urine Metabolome panel as potential biomarkers for diagnosis of t cell-mediated renal transplant rejection","volume":"24","author":"Kalantari","year":"2020","journal-title":"OMICS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/TP.0b013e3181edd69a","article-title":"Metabonomic analysis of serum metabolites in kidney transplant recipients with cyclosporine A- or tacrolimus-based immunosuppression","volume":"90","author":"Kim","year":"2010","journal-title":"Transplantation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.transproceed.2017.03.055","article-title":"Metabolomics study for identification of potential biomarkers of long-term survival in kidney transplantation recipients","volume":"49","author":"Lee","year":"2017","journal-title":"Transplant. Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000125935","article-title":"Metabolomics: A complementary tool in renal transplantation","volume":"160","author":"Wishart","year":"2008","journal-title":"Contrib. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1016\/j.ajt.2024.01.012","article-title":"OPTN\/SRTR 2022 Annual Data Report: Kidney","volume":"24","author":"Lentine","year":"2024","journal-title":"Am. J. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1021\/pr300900b","article-title":"Hippurate: The natural history of a mammalian-microbial cometabolite","volume":"12","author":"Lees","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.biochi.2017.05.010","article-title":"Exploring binding characteristics and the related competition of different protein-bound uremic toxins","volume":"139","author":"Deltombe","year":"2017","journal-title":"Biochimie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1681\/ASN.2021030336","article-title":"Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease","volume":"32","author":"Mair","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Stanimirova, I., Banasik, M., Zabek, A., Dawiskiba, T., Koscielska-Kasprzak, K., Wojtowicz, W., Krajewska, M., Janczak, D., and Mlynarz, P. (2020). Serum metabolomics approach to monitor the changes in metabolite profiles following renal transplantation. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-74245-z"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sun, B., Wang, X., Liu, X., Wang, L., Ren, F., Wang, X., and Leng, X. (2020). Hippuric acid promotes renal fibrosis by disrupting redox homeostasis via facilitation of NRF2-KEAP1-CUL3 interactions in chronic kidney disease. Antioxidants, 9.","DOI":"10.3390\/antiox9090783"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1258\/0004563011900713","article-title":"Effects of renal sorbitol accumulation on urinary excretion of enzymes in hyperglycaemic rats","volume":"38","author":"Ishii","year":"2001","journal-title":"Ann. Clin. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cca.2015.04.005","article-title":"A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine","volume":"446","author":"Klepacki","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.lfs.2010.08.003","article-title":"Enzymes involved in osmolyte synthesis: How does oxidative stress affect osmoregulation in renal cells?","volume":"87","year":"2010","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"c38","DOI":"10.1159\/000245068","article-title":"Vitamin B6 metabolism in chronic kidney disease--relation to transsulfuration, advanced glycation and cardiovascular disease","volume":"114","author":"Busch","year":"2010","journal-title":"Nephron Clin. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/ajcn\/75.1.57","article-title":"Elevated plasma 4-pyridoxic acid in renal insufficiency","volume":"75","author":"Coburn","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3904\/kjim.1986.1.1.86","article-title":"2,3-diphosphoglyceric acid changes in uremia and during hemodialysis","volume":"1","author":"Kang","year":"1986","journal-title":"Korean J. Intern. Med."},{"key":"ref_30","first-page":"207","article-title":"An increase in bile acids in the serum of patients with chronic kidney failure","volume":"86","author":"Balestri","year":"1995","journal-title":"Minerva Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e7145","DOI":"10.7717\/peerj.7145","article-title":"Targeted metabolomics study of serum bile acid profile in patients with end-stage renal disease undergoing hemodialysis","volume":"7","author":"Li","year":"2019","journal-title":"PeerJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1023\/A:1020575001944","article-title":"Chronic renal failure-induced changes in serum and urine bile acid profiles","volume":"47","author":"Jimenez","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"F130","DOI":"10.1152\/ajprenal.00114.2013","article-title":"Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters","volume":"306","author":"Gai","year":"2014","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s11255-014-0901-0","article-title":"Mechanism underlying an elevated serum bile acid level in chronic renal failure patients","volume":"47","author":"Chu","year":"2015","journal-title":"Int. Urol. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jnutbio.2013.11.010","article-title":"Betaine supplementation protects against high-fructose-induced renal injury in rats","volume":"25","author":"Fan","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1046\/j.1523-1755.2002.00199.x","article-title":"Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure","volume":"61","author":"McGregor","year":"2002","journal-title":"Kidney Int."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bassi, R., Niewczas, M.A., Biancone, L., Bussolino, S., Merugumala, S., Tezza, S., D\u2019Addio, F., Ben Nasr, M., Valderrama-Vasquez, A., and Usuelli, V. (2017). Metabolomic Profiling in Individuals with a Failing Kidney Allograft. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169077"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1365-2796.1989.tb01378.x","article-title":"Sulphur amino acids in plasma and muscle in patients with chronic renal failure: Evidence for taurine depletion","volume":"226","author":"Bergstrom","year":"1989","journal-title":"J. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1178646920954882","DOI":"10.1177\/1178646920954882","article-title":"Kynurenine Pathway in Chronic Kidney Disease: What\u2019s Old, What\u2019s New, and What\u2019s Next?","volume":"13","author":"Mor","year":"2020","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s43440-021-00329-w","article-title":"Kynurenine pathway in kidney diseases","volume":"74","author":"Zakrocka","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.atherosclerosis.2008.08.014","article-title":"The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease","volume":"204","author":"Pawlak","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/0886022X.2016.1209389","article-title":"Serum indoleamine 2,3 dioxygenase and tryptophan and kynurenine ratio using the UPLC-MS\/MS method, in patients undergoing peritoneal dialysis, hemodialysis, and kidney transplantation","volume":"38","author":"Yilmaz","year":"2016","journal-title":"Ren. Fail."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1016\/j.clnu.2018.11.029","article-title":"Clinical association between the metabolite of healthy gut microbiota, 3-indolepropionic acid and chronic kidney disease","volume":"38","author":"Sun","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tourountzis, T., Lioulios, G., Fylaktou, A., Moysidou, E., Papagianni, A., and Stangou, M. (2022). Microbiome in Chronic Kidney Disease. Life, 12.","DOI":"10.3390\/life12101513"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Snauwaert, E., Holvoet, E., Van Biesen, W., Raes, A., Glorieux, G., Vande Walle, J., Roels, S., Vanholder, R., Askiti, V., and Azukaitis, K. (2019). Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins, 11.","DOI":"10.3390\/toxins11040235"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Castillo-Rodriguez, E., Fernandez-Prado, R., Esteras, R., Perez-Gomez, M.V., Gracia-Iguacel, C., Fernandez-Fernandez, B., Kanbay, M., Tejedor, A., Lazaro, A., and Ruiz-Ortega, M. (2018). Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression. Toxins, 10.","DOI":"10.3390\/toxins10070300"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ndt\/gfq818","article-title":"The gut-kidney axis: Indoxyl sulfate, p-cresyl sulfate and CKD progression","volume":"26","author":"Meijers","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Kim, H.E., Park, J.I., Cho, H., Kwak, M.J., Kim, B.Y., Yang, S.H., Lee, J.P., Kim, D.K., and Joo, K.W. (2020). The association between gut microbiota and uremia of chronic kidney disease. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060907"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1097\/MNH.0000000000000275","article-title":"Biomarkers for predicting outcomes in chronic kidney disease","volume":"25","author":"Tummalapalli","year":"2016","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/ndt\/gfq580","article-title":"p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease","volume":"26","author":"Wu","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Vaziri, N.D., Liu, S.M., Lau, W.L., Khazaeli, M., Nazertehrani, S., Farzaneh, S.H., Kieffer, D.A., Adams, S.H., and Martin, R.J. (2014). High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114881"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biochi.2023.05.001","article-title":"Effects of resveratrol on inflammation and oxidative stress induced by the uremic toxin indoxyl sulfate in Murine macrophage-like RAW 264.7","volume":"213","author":"Alvarenga","year":"2023","journal-title":"Biochimie"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Saranya, G.R., and Viswanathan, P. (2023). Gut microbiota dysbiosis in AKI to CKD transition. Biomed. Pharmacother., 161.","DOI":"10.1016\/j.biopha.2023.114447"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1073\/pnas.97.3.1242","article-title":"The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney","volume":"97","author":"Moller","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Riccio, S., Valentino, M.S., Passaro, A.P., Izzo, M., Guarino, S., Miraglia Del Giudice, E., Marzuillo, P., and Di Sessa, A. (2022). new insights from metabolomics in pediatric renal diseases. Children, 9.","DOI":"10.3390\/children9010118"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16196","DOI":"10.1172\/jci.insight.161696","article-title":"Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study","volume":"7","author":"Wen","year":"2022","journal-title":"JCI Insight"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.ekir.2018.02.001","article-title":"Association between newborn metabolic profiles and pediatric kidney disease","volume":"3","author":"Sood","year":"2018","journal-title":"Kidney Int. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1056\/NEJM199804093381507","article-title":"Homocysteine and atherothrombosis","volume":"338","author":"Welch","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1034\/j.1600-6143.2002.20404.x","article-title":"Hyperhomocysteinemia in renal transplant recipients","volume":"2","author":"Friedman","year":"2002","journal-title":"Am. J. Transplant."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/ndt\/gfq404","article-title":"Methylation cycle, arginine-creatine pathway and asymmetric dimethylarginine in paediatric renal transplant","volume":"26","author":"Andrade","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1203\/PDR.0b013e318176180e","article-title":"The arginine-creatine pathway is disturbed in children and adolescents with renal transplants","volume":"64","author":"Andrade","year":"2008","journal-title":"Pediatr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Arumugam, M.K., Paal, M.C., Donohue, T.M., Ganesan, M., Osna, N.A., and Kharbanda, K.K. (2021). Beneficial effects of betaine: A comprehensive review. Biology, 10.","DOI":"10.3390\/biology10060456"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhao, G., He, F., Wu, C., Li, P., Li, N., Deng, J., Zhu, G., Ren, W., and Peng, Y. (2018). Betaine in inflammation: Mechanistic aspects and applications. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01070"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e440","DOI":"10.1111\/dme.12028","article-title":"The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: A randomized crossover trial in uraemic patients","volume":"29","author":"Ozbay","year":"2012","journal-title":"Diabet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ijsu.2017.12.037","article-title":"Higher tacrolimus blood concentration is related to increased risk of post-transplantation diabetes mellitus after living donor liver transplantation","volume":"51","author":"Song","year":"2018","journal-title":"Int. J. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/ndt\/gfm544","article-title":"Glucose metabolism before and after conversion from cyclosporine microemulsion to tacrolimus in stable renal recipients","volume":"23","author":"Gelens","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1016\/j.transproceed.2012.09.053","article-title":"New-onset diabetes after transplantation: Drug-related risk factors","volume":"44","author":"Santos","year":"2012","journal-title":"Transplant. Proc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1097\/01.TP.0000084295.67371.11","article-title":"Diabetes mellitus after transplant: Relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy","volume":"76","author":"Sato","year":"2003","journal-title":"Transplantation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6542346","DOI":"10.1155\/2020\/6542346","article-title":"Exploring the mechanism of skeletal muscle in a tacrolimus-induced posttransplantation diabetes mellitus model on gene expression profiles","volume":"2020","author":"Zheng","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Joncquel, M., Labasque, J., Demaret, J., Bout, M.A., Hamroun, A., Hennart, B., Tronchon, M., Defevre, M., Kim, I., and Kerckhove, A. (2023). Targeted metabolomics analysis suggests that tacrolimus alters protection against oxidative stress. Antioxidants, 12.","DOI":"10.3390\/antiox12071412"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1159\/000519811","article-title":"The kynurenine pathway in acute kidney injury and chronic kidney disease","volume":"52","author":"Wee","year":"2021","journal-title":"Am. J. Nephrol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3945\/ajcn.117.164012","article-title":"Functional vitamin B6 status and long-term mortality in renal transplant recipients","volume":"106","author":"Minovic","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wagner-Golbs, A., Neuber, S., Kamlage, B., Christiansen, N., Bethan, B., Rennefahrt, U., Schatz, P., and Lind, L. (2019). Effects of long-term storage at \u221280 degrees c on the human plasma metabolome. Metabolites, 9.","DOI":"10.3390\/metabo9050099"},{"key":"ref_75","first-page":"S151","article-title":"Measurement of glomerular filtration rate","volume":"63","author":"Gaspari","year":"1997","journal-title":"Kidney Int. Suppl."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD","volume":"20","author":"Schwartz","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e010711","DOI":"10.1161\/JAHA.118.010711","article-title":"Metabolomic fingerprinting of infants undergoing cardiopulmonary bypass: Changes in metabolic pathways and association with mortality and cardiac intensive care unit length of stay","volume":"7","author":"Davidson","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"F20","DOI":"10.1152\/ajprenal.00039.2022","article-title":"Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury","volume":"323","author":"Davidson","year":"2022","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nprot.2012.024","article-title":"A positive\/negative ion-switching, targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue","volume":"7","author":"Yuan","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","article-title":"Using MetaboAnalyst 5.0 for LC-HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data","volume":"17","author":"Pang","year":"2022","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:19Z","timestamp":1760035579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,20]]},"references-count":80,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189190"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189190","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,20]]}}}