The components of arginine and methylarginine metabolism are indicative of altered kidney function in intrauterine growth-restricted neonates.
Journal
Journal of hypertension
ISSN: 1473-5598
Titre abrégé: J Hypertens
Pays: Netherlands
ID NLM: 8306882
Informations de publication
Date de publication:
07 Aug 2024
07 Aug 2024
Historique:
medline:
7
8
2024
pubmed:
7
8
2024
entrez:
7
8
2024
Statut:
aheadofprint
Résumé
Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates. Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method. After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates. Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates.
Sections du résumé
BACKGROUND
BACKGROUND
Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates.
METHODS
METHODS
Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method.
RESULTS
RESULTS
After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates.
CONCLUSION
CONCLUSIONS
Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates.
Identifiants
pubmed: 39108098
doi: 10.1097/HJH.0000000000003818
pii: 00004872-990000000-00515
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Références
Gordijn SJ, Beune M, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol 2016; 48:333–339.
Nawathe A, Lees C. Early onset fetal growth restriction. Best Pract Res Clin Obstet Gynaecol 2017; 38:24–37.
Peipert JF, Donnenfeld AE. Oligohydramnios: a review. Obstet Gynecol Surv 1991; 46:325–339.
Intrauterine growth restriction. Guideline of the German Society of Gynecology and Obstetrics October 2016.
Nardozza LM, Caetano AC, Zamarian AC, Mazzola JB, Silva CP, Marcal VM, et al. Fetal growth restriction: current knowledge. Arch Gynecol Obstet 2017; 295:1061–1077.
Mayer C, Joseph KS. Fetal growth: a review of terms, concepts and issues relevant to obstetrics. Ultrasound Obstet Gynecol 2013; 41:136–145.
Wollmann HA. Intrauterine growth restriction: definition and etiology. Horm Res 1998; 49: (Suppl 2): 1–6.
Usha K, Sarita B. Placental insufficiency and fetal growth restriction. J Obstet Gynecol 2011; 61:505–511.
Sutherland MR, Black MJ. The impact of intrauterine growth restriction and prematurity on nephron endowment. Nat Rev Nephrol 2023; 19:218–228.
Dotsch J, Plank C. [Intrauterine growth restriction and renal function–a long-term problem?]. Gynakol Geburtshilfliche Rundsch 2009; 49:8–12.
Zohdi V, Sutherland MR, Lim K, Gubhaju L, Zimanyi MA, Black MJ. Low birth weight due to intrauterine growth restriction and/or preterm birth: effects on nephron number and long-term renal health. Int J Nephrol 2012; 2012:136942.
White SL, Perkovic V, Cass A, Chang CL, Poulter NR, Spector T, et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis 2009; 54:248–261.
Hallan S, Euser AM, Irgens LM, Finken MJ, Holmen J, Dekker FW. Effect of intrauterine growth restriction on kidney function at young adult age: the Nord Trondelag Health (HUNT 2) Study. Am J Kidney Dis 2008; 51:10–20.
Devaskar SU, Chu A. Intrauterine growth restriction: hungry for an answer. Physiology (Bethesda) 2016; 31:131–146.
Vallance P, Chan N. Endothelial function and nitric oxide: clinical relevance. Heart 2001; 85:342–350.
Rinde NB, Enoksen IT, Melsom T, Fuskevag OM, Eriksen BO, Norvik JV. Nitric oxide precursors and dimethylarginines as risk markers for accelerated measured GFR decline in the general population. Kidney Int Rep 2023; 8:818–826.
Jarzebska N, Mangoni AA, Martens-Lobenhoffer J, Bode-Boger SM, Rodionov RN. The second life of methylarginines as cardiovascular targets. Int J Mol Sci 2019; 20:4592.
Oliva-Damaso E, Oliva-Damaso N, Rodriguez-Esparragon F, Payan J, Baamonde-Laborda E, Gonzalez-Cabrera F, et al. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines in chronic kidney disease: a clinical approach. Int J Mol Sci 2019; 20:3668.
Emrich IE, Zawada AM, Martens-Lobenhoffer J, Fliser D, Wagenpfeil S, Heine GH, Bode-Boger SM. Symmetric dimethylarginine (SDMA) outperforms asymmetric dimethylarginine (ADMA) and other methylarginines as predictor of renal and cardiovascular outcome in nondialysis chronic kidney disease. Clin Res Cardiol 2018; 107:201–213.
Rodionov RN, Martens-Lobenhoffer J, Brilloff S, Hohenstein B, Jarzebska N, Jabs N, et al. Role of alanine:glyoxylate aminotransferase 2 in metabolism of asymmetric dimethylarginine in the settings of asymmetric dimethylarginine overload and bilateral nephrectomy. Nephrol Dial Transplant 2014; 29:2035–2042.
Böger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, et al. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation 2009; 119:1592–1600.
Martens-Lobenhoffer J, Emrich IE, Zawada AM, Fliser D, Wagenpfeil S, Heine GH, Bode-Boger SM. L-Homoarginine and its AGXT2-metabolite GOCA in chronic kidney disease as markers for clinical status and prognosis. Amino Acids 2018; 50:1347–1356.
Ravani P, Maas R, Malberti F, Pecchini P, Mieth M, Quinn R, et al. Homoarginine and mortality in predialysis chronic kidney disease (CKD) patients. PLoS One 2013; 8:e72694.
Heuchel KM, Ebach F, Alsat EA, Reutter H, Mueller A, Hilger AC. Blood pressure and kidney function in neonates and young infants with intrauterine growth restriction. Pediatr Nephrol 2023; 38:1223–1232.
Voigt M, Rochow N, Schneider KTM, Hagenah HP, Scholz R, Hesse V, et al. Neue Perzentilwerte für die Körpermaße neugeborener Einlinge: Ergebnisse der deutschen Perinatalerhebung der Jahre 2007–2011 unter Beteiligung aller 16 Bundesländer [New percentile values for the body measurements of newborn infants: results of the results of the German perinatal survey of the years 2007–2011 with the participation all 16 federal states]. Z Geburtshilfe Neonatol 2014; 218:210–217.
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20:629–637.
Schlosser P, Scherer N, Grundner-Culemann F, Monteiro-Martins S, Haug S, Steinbrenner I, et al. Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. Nat Genet 2023; 55:995–1008.
FDA. M10 bioanalytical method validation and study sample analysis: guidance for industry. 2022.
Bonnitcha P, Sullivan D, Fitzpatrick M, Ireland A, Nguyen VL, Koay YC, O'Sullivan J. Design and validation of an LC-MS/MS method for simultaneous quantification of asymmetric dimethylguanidino valeric acid, asymmetric dimethylarginine and symmetric dimethylarginine in human plasma. Pathology 2022; 54:591–598.
de Boo HA, van Zijl PL, Lafeber HN, Harding JE. Urea production and arginine metabolism are reduced in the growth restricted ovine fetus. Animal 2007; 1:699–707.
Jarzebska N, Georgi S, Jabs N, Brilloff S, Maas R, Rodionov RN, et al. Kidney and liver are the main organs of expression of a key metabolic enzyme alanine:glyoxylate aminotransferase 2 in humans. Atheroscler Suppl 2019; 40:106–112.
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed Fel Z, Davies N, Sharma V, et al. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. J Hepatol 2015; 62:325–331.
Martens-Lobenhoffer J, Bode-Boger SM. Amino acid N-acetylation: metabolic elimination of symmetric dimethylarginine as symmetric N(alpha)-acetyldimethylarginine, determined in human plasma and urine by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 975:59–64.
Martens-Lobenhoffer J, Rodionov RN, Bode-Boger SM. Determination of asymmetric Nalpha-acetyldimethylarginine in humans: a phase II metabolite of asymmetric dimethylarginine. Anal Biochem 2014; 452:25–30.
Kanbay M, Copur S, Yildiz AB, Covic A, Covic A, Ciceri P, et al. Intrauterine life to adulthood: a potential risk factor for chronic kidney disease. Nephrol Dial Transplant 2023; 38:2675–2684.
Drechsler C, Kollerits B, Meinitzer A, Marz W, Ritz E, Konig P, et al. Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study. PLoS One 2013; 8:e63560.