Bahadır ÖZTÜRK, Fikret AKYÜREK, Gülperi ÇELİK

Predictive role of methylarginines in renal failure

Aim: In this study, we aimed to investigate the role of methylarginines in renal failure and the process leading to failure. Acute RenalFailure (ARF) is defined as sudden onset, damage and loss of renal function. Chronic Kidney Disease (CKD) is generally definedas the presence of decreased renal function loss that persists for more than 3 months. Methylarginines are arginine derivativeswhich inhibit ischemia and vasoconstriction by inhibiting nitric oxide synthesis, causing ischemia and damage. Methylarginines aremetabolized mainly in the kidney. Their metabolism is in the form of direct excretion and enzymatic degradation.Material and Methods: The study was conducted from 2017 through 2018 in 89 patient (serum creatinine levels above 1.5 mg/dL) and 54 healthy control cases. Methylarginines were analyzed in positive mode from Turbo Ion Spray Electrospray (ESI) usingABSCIEX API 3200 High Performance Liquid Chromatography mass spectrometry (LC-MS / MS) instrument using C18 column. Ureaand creatinine were analyzed by Beckman Coulter AU5800 Series. Results were evaluated with SPSS system.Results: A significant difference was found in terms methylarginines urea and creatinine when patient and control groups compared.However, only creatinine and creatinine clearance values differences were found in patient groups in terms of acute and chronicrenal failure (respectively, p = 0.001 for creatinine and p = 0.028 for creatinine clearance).There was no difference in terms of otherparameters.Conclusions: Methylarginines can be considered as new and high potential biomarkers for evaluating renal function. However, it isnot considered to be adequate for show the prognosis of the disease.

PDF

___

1. Lempert KD, Kopp JB. Renal Failure Patients in Disasters. Disaster Med Public Health Prep 2019;13:782-90.
2. Liu X, Xu X, Shang R, et al. Asymmetric dimethylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease. Nitric Oxide 2018;78:113-20.
3. Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta 2015;438:350-7.
4. Fink HA, Ishani A, Taylor BC, et al. Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2012;156:570-81.
5. Mallamaci F, Tripepi G, Cutrupi S, et al. Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD. Kidney Int 2005;67:2330-7.
6. Kajimoto H, Kai H, Aoki H, et al. Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine. Kidney Int 2012;81:762-8.
7. Böger RH, Bode-Böger SM, Thiele W, et al. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1997;95:2068-74.
8. Emrich IE, Zawada AM, Martens-Lobenhoffer J, et al. Symmetric dimethylarginine (SDMA) outperforms asymmetric dimethylarginine (ADMA) and other methylarginines as predictor of renal and cardiovascular outcome in non-dialysis chronic kidney disease. Clin Res Cardio 2018;107:201-13.
9. Martens-Lobenhoffer J, Bode-Böger SM. Amino acid N-acetylation: metabolic elimination of symmetric dimethylarginine as symmetric N(α)- acetyldimethylarginine, determined in human plasma and urine by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2015;975:59-64.
10. Kielstein JT, Salpeter SR, Bode-Boeger SM, et al. Symmetric dimethylarginine (SDMA) as endogenous marker of renal function--a meta-analysis. Nephrol Dial Transplant 2006;21:2446-51.
11. Rysz J, Gluba-Brzózka A, Franczyk B, et al. Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome. Int J Mol Sci 2017;18.
12. Toth J, Racz A, Kaminski PM, et al. Asymmetrical dimethylarginine inhibits shear stress-induced nitric oxide release and dilation and elicits superoxidemediated increase in arteriolar tone. Hypertension 2007;49:563-8.
13. Bode-Böger SM, Scalera F, Kielstein JT, et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol 2006;17:1128-34.
14. Hanai K, Babazono T, Nyumura I, et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant 2009;24:1884-8.
15. Shafi T, Hostetter TH, Meyer TW, et al. Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients. Am J Kidney Dis 2017;70:48-58.
16. Willeit P, Freitag DF, Laukkanen JA, et al. Asymmetric dimethylarginine and cardiovascular risk: systematic review and meta-analysis of 22 prospective studies. J Am Heart Assoc 2015;4:e001833.
17. Xia Y, Dawson VL, Dawson TM, et al. Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitritemediated cellular injury. Proc Natl Acad Sci U S A 1996;93:6770-4.
18. Torino C, Pizzini P, Cutrupi S, et al. Vitamin D and methylarginines in chronic kidney disease (CKD). PLoS One 2017;12:e0185449.
19. Frenay AR, van den Berg E, de Borst MH, et al. Plasma ADMA associates with all-cause mortality in renal transplant recipients. Amino Acids. 2015;47:1941-9.
20. Sitar ME. Asymmetric Dimethylarginine and Its Relation As a Biomarker in Nephrologic Diseases. Biomark Insights 2016;11:131-37.
21. Said MY, Bollenbach A, Minović I, et al. Plasma ADMA, urinary ADMA excretion, and late mortality in renal transplant recipients. Amino Acids 2019;51:913-27.
22. Maas R, Mieth M, Titze SI, et al. Drugs linked to plasma homoarginine in chronic kidney disease patients-a cross-sectional analysis of the German Chronic Kidney Disease cohort. Nephrol Dial Transplant 2018.
23. Vanholder R, Pletinck A, Schepers E, et al. Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins (Basel) 2018;10.
24. Schepers E, Barreto DV, Liabeuf S, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease. Clin J Am Soc Nephrol 2011;6:2374-83.