MMSL 2021, 90(4):165-171 | DOI: 10.31482/mmsl.2021.034
THE ROLE OF SYMMETRICAL AND ASYMMETRIC DIMETHYL-L-ARGININE AS BIOMARKERS IN DIALYSIS-DEPENDENT AKI PATIENTSOriginal article
- College of Pharmacy, University of Mosul, Mosul, Iraq
Introduction: Symmetrical and Asymmetric dimethyl-L-arginine were previously discovered in urine, the present study explored the link between acute kidney injury (AKI) and modulation in the level of these biomarkers.
Methods: Ninety volunteers were recruited in the current study, sixty of them were dialysis-dependent AKI patients, their ages ranged between 29-70 years, 13 were diabetic and 47 were non-diabetics patients. Thirty healthy subjects were recruited as a control group. Blood urea, serum creatinine, uric acid, glucose, lipid profile, albumin, hemoglobin, levels were measured using an automated analyzer (SK3002b). Asymmetric dimethyl-L-arginine (ADMA) and symmetric dimethyl-L-arginine (SDMA) serum concentrations were measured using ELISA.
Results: The findings of the current study demonstrated a significant decrease in hemoglobin and serum albumin levels alongside an increase in the serum creatinine, uric acid, and serum triglyceride (TG) in the patients when compared to the apparently healthy controls. Serum concentrations of ADMA and SDMA were significantly lower in healthy controls compared to the patients.
Conclusion: These data confirm the assumption which assumes that both, ADMA and SDMA serum levels are sensitive markers of reduced renal function and serum SDMA is more sensitive than ADMA in dialysis-dependent AKI patients.
Keywords: symmetric dimethyl-L-arginine; biomarker; dialysis; acute kidney injury; asymmetric dimethyl-L-arginine; dimethyl-L-arginine
Received: September 6, 2021; Revised: October 7, 2021; Accepted: October 11, 2021; Prepublished online: November 16, 2021; Published: December 3, 2021 Show citation
References
- Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book. Elsevier Health Sciences; 2017.
- Hoste EAJ, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-23.
Go to original source...
Go to PubMed...
- Jacob J, Dannenhoffer J, Rutter A. Acute Kidney Injury. Primary Care - Clinics in Office Practice. 2020;47(4):571-584.
Go to original source...
Go to PubMed...
- Zarbock A, Koyner JL, Hoste EAJ, et al. Update on perioperative acute kidney injury. Anesthesia and Analgesia. 2018;127(5):1236-1245.
Go to original source...
Go to PubMed...
- Tsigou E, Psallida V, Demponeras C, et al. Role of new biomarkers: Functional and structural damage. Critical Care Research and Practice. 2013;Article ID 361078.
Go to original source...
- Ralib AM, Pickering JW, Shaw GM, et al. Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. J Am Soc Nephrol. 2012;23(2):322-333.
Go to original source...
Go to PubMed...
- Abdulrazzaq G, Khalaf MM, Merkhan MM. Allopurinol therapy impairs lipid metabolism in patients with renal stone. Curr Top Pharmacol. 2020;24:105-12.
- Faisal IM, Merkhan MM, Almukhtar HM. Effect of chronic Allopurinol therapy on Thyroid function in patients with urate stones. J Adv Pharm Educ Res. 2020;10(4):4-7.
- Hend Y Younis, Imad A Thanoon, Nabeel N Fadhil, et al. Effect of zinc as an add on to metformin therapy on serum lipid profile and uric acid in type 2 diabetes mellitus patients. Current Topics in Pharmacology. 2021;25:53-59.
- Ahmad AA, Merkhan MM, Abdulrazzaq GM. Effect of Xanthine Oxidase Inhibition on Immunity Modulation in Human. Eur J Mol Clin Med. 2021;7(10):1307-16.
- Tutarel O, Denecke A, Bode-Böger SM, et al. Symmetrical dimethylarginine outperforms CKD-EPI and MDRD-derived eGFR for the assessment of renal function in patients with adult congenital heart disease. Kidney Blood Press Res. 2011;34(1):41-5.
Go to original source...
Go to PubMed...
- Hafiane A, Genest J. High density lipoproteins: Measurement techniques and potential biomarkers of cardiovascular risk. BBA Clinical. 2015 Jan 31;3:175-88.
Go to original source...
Go to PubMed...
- Teerlink T, Luo Z, Palm F, et al. Cellular ADMA: Regulation and action. Pharmacological Research. 2009;60(6):448-460.
Go to original source...
Go to PubMed...
- Rodionov RN, Martens-Lobenhoffer J, Brilloff S, 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;29:11.
Go to original source...
Go to PubMed...
- 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(8):2068-74.
Go to original source...
Go to PubMed...
- Bode-Böger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, et al. Symmetrical dimethylarginine: A new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol. 2006;17(4):1128-34.
Go to original source...
Go to PubMed...
- Kielstein JT, Bode-Böger SM, Frölich JC, et al. Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects. Circulation. 2003;107(14):1891-5.
Go to original source...
Go to PubMed...
- Schepers E, Barreto D V, Liabeuf S, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(10):2374-83.
Go to original source...
Go to PubMed...
- Rysz J, Gluba-Brzózka A, Franczyk B, et al. Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome. International Journal of Molecular Sciences. 2017;4;18(8):1702.
Go to original source...
Go to PubMed...
- 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(1):48-58.
Go to original source...
Go to PubMed...
- Ravani P, Tripepi G, Malberti F, et al. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: A competing risks modeling approach. J Am Soc Nephrol. 2005;16(8):2449-55.
Go to original source...
Go to PubMed...
- Busch M, Fleck C, Wolf G, et al. Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease - Possible candidates for paradoxical epidemiology? Amino Acids. 2006;30(3):225-32.
Go to original source...
Go to PubMed...
- Leone A, Moncada S, Vallance P, et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992;339(8793):572-5.
Go to original source...
Go to PubMed...
- Speer T, Rohrer L, Blyszczuk P, et al. Abnormal high-density lipoprotein induces endothelial dysfunction via activation of toll-like receptor-2. Immunity. 2013;38(4):754-68.
Go to original source...
Go to PubMed...
- Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacological Reviews. 1991;43(2):109-42.
Go to PubMed...
- 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(9):2446-51.
Go to original source...
Go to PubMed...
- Kielstein JT, Böger RH, Bode-Böger SM, et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol. 1999;10(3):594-600.
Go to original source...
Go to PubMed...
- Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int. 2000;58(3):1261-6.
Go to original source...
Go to PubMed...
- Nijveldt RJ, Van Leeuwen PAM, Van Guldener C, et al. Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans. Nephrol Dial Transplant. 2002;17(11):1999-2002.
Go to original source...
Go to PubMed...
- Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, N(G),N(G)-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem. 1989;264(17):10205-9.
Go to original source...
- Tousoulis D, Kampoli A-M, Tentolouris C, et al. The Role of Nitric Oxide on Endothelial Function. Curr Vasc Pharmacol. 2011;10(1):4-18.
Go to original source...
Go to PubMed...
- Fleck C, Schweitzer F, Karge E, et al. Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clinica Chimica Acta. 2003;336(1-2):1-12.
Go to original source...
Go to PubMed...
- Marescau B, Nagels G, Possemiers I, et al. Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency. Metabolism. 1997;46(9):1024-31.
Go to original source...
Go to PubMed...
- Kielstein JT, Böger RH, Bode-Böger SM, et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol. 2002;13(1):170-176.
Go to original source...
Go to PubMed...
- Leiper JM, Vallance P. The synthesis and metabolism of asymmetric dimethylarginine (ADMA). European Journal of Clinical Pharmacology. 2006;62:33-38.
Go to original source...
- MacAllister RJ, Rambausek MH, Vallance P, et al. Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure. Nephrol Dial Transplant. 1996;11(12):2449-52.
Go to original source...
Go to PubMed...
- Jofré R, Rodriguez-Benitez P, López-Gómez JM, et al. Inflammatory syndrome in patients on hemodialysis. Journal of the American Society of Nephrology. 2006;17(12 Suppl 3):S274-80.
Go to original source...
Go to PubMed...
- Zoccali C, Bode-Böger SM, Mallamaci F, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: A prospective study. Lancet. 2001;358(9299):2113-7.
Go to original source...
Go to PubMed...
- Valkonen VP, Päivä H, Salonen JT, et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet. 2001;358(9299):2127-8.
Go to original source...
Go to PubMed...
- Dückelmann C, Mittermayer F, Haider DG, et al. Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure. Arterioscler Thromb Vasc Biol. 2007;27(9):2037-42.
Go to original source...
Go to PubMed...
- Zoccali C, Benedetto FA, Maas R, et al. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol. 2002;13(2):490-496.
Go to original source...
Go to PubMed...