Evaluation of amino acid clearances in post-transplant kidney patients stratified by eGFR

Year 2024, Volume: 28 Issue: 4, 1265 - 1274, 28.06.2025

Ihsan Yozgat Neslihan Yildirim Saral Soner Duman , Bulent Oktay , Mustafa Serteser

Abstract

The human kidney has a prominent role in the metabolism of amino acids and the control of plasma concentrations. Treatment modalities, such as kidney transplantation, hemodialysis, etc., may alter amino acid concentrations. In the present study, we aimed to evaluate the effect of kidney transplantation on the amino acid profile and the relationship between creatinine clearance and amino acid clearances in post-transplant kidney patients. Serum and urine samples were obtained from 133 patients after kidney transplantation. Patients were divided into three groups based on eGFR. Amino acid profiles were performed by liquid chromatography coupled with tandem mass spectrometry, and clearances were calculated using the 24-hour creatinine clearance formula. The amino acid clearances between the studied groups differed significantly in 10 of the 27 amino acids. While 1-methyl-l-histidine, 3-methyl-l- histidine, Arginine, Cystine, Ethanolamine, Glycine, L-Histidine, Isoleucine, and Taurine significantly showed an upward trend, L-Proline especially revealed a downward trend. Amino acid clearances that showed the strongest correlation with creatinine clearance were 1-methyl-l-histidine, 3-methyl-l-histidine, and ethanolamine. However, Arginine and L-proline had a weak positive and negative linear relationship, respectively. This study showed that amino acid clearances varied in kidney transplant patients among the studied groups. Increased or decreased amino acid clearances are affected by the progression of renal dysfunction. These results give insight into kidney transplantation- associated modifications of amino acid metabolism.

Keywords

Amino acids , kidney transplantation , amino acid clearance , estimated glomerular filtration rate , creatinine clearance.

References

• [1] Jager KJ, Kovesdy C, Langham R, Rosenberg M, Jha V, Zoccali C. A single number for advocacy and communication—worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019; 96(5):1048–1050. https://doi.org/10.1016/j.kint.2019.07.012
• [2] Bikbov B, Purcell CA, Levey AS, Smith M, Abdoli A, Abebe M, Adebayo OM, Afarideh M, Agarwal SK, Agudelo-Botero M, Ahmadian E, Al-Aly Z, Alipour V, Almasi-Hashiani A, Al-Raddadi RM, Alvis-Guzman N, Amini S, Andrei T, Andrei CL, Andualem Z, Anjomshoa M, Arabloo J, Ashagre AF, Asmelash D, Ataro Z, Atout MM d. W, Ayanore MA, Badawi A, Bakhtiari A, Ballew SH, Balouchi A, Banach M, Barquera S, Basu S, Bayih MT, Bedi N, Bello AK, Bensenor IM, Bijani A, Boloor A, Borzì AM, Cámera LA, Carrero JJ, Carvalho F, Castro F, Catalá-López F, Chang AR, Chin KL, Chung SC, Cirillo M, Cousin E, Dandona L, Dandona R, Daryani A. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2020; 395(10225):709–733. https://doi.org/10.1016/S0140-6736(20)30045-3
• [3] Abubakar II, TIillmann T, Banerjee A. Europe PMC Funders Group GlobMENDONÇA, M. F. S. Incidência De Transtorno Mental Comum E Violência Por Parceiro Íntimo. 2015. p. 1–8. al , regional , anMENDONÇA, M. F. S. Incidência De Transtorno Mental Comum E Violência Por Parceiro Íntimo. 2015. p. 1–8. Lancet (London, England). 2015; 385(9963):117–171. https://doi.org/10.1016/S0140-6736(14)61682-2.Global
• [4] Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl. 2022; 12(1):7–11. https://doi.org/10.1016/j.kisu.2021.11.003
• [5] Pitts RF. Symposium on acid-base homeostasis. Control of renal production of ammonia. Kidney Int. 1972; 1(5):297–305. https://doi.org/10.1038/ki.1972.42
• [6] Maloy S. Amino Acids. Elsevier Inc., 2013; 1(5):54–56. https://doi.org/10.1016/B978-0-12-374984-0.00051-6
• [7] Makrides V, Camargo SMR, Verrey F. Transport of amino acids in the kidney. Comprehens Physiol. 2014; 4(1):367–403. https://doi.org/10.1002/cphy.c130028
• [8] Lee H, Jang HB, Yoo MG, Park SI, Lee HJ. Amino acid metabolites associated with chronic kidney disease: An eight-year follow-up korean epidemiology study. Biomedicines. 2020; 8(7):222. https://doi.org/10.3390/BIOMEDICINES8070222
• [9] Schnackenberg LK, Sun J, Bhattacharyya S, Gill P, James LP, Beger RD. Metabolomics analysis of urine samples from children after acetaminophen overdose. Metabolites. 2017; 7(3). https://doi.org/10.3390/metabo7030046 doi:10.3390/metabo7030046
• [10] Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D. Histidine: A systematic review on metabolism and physiological effects in human and different animal species. Nutrients. 2020;12(5):1414. https://doi.org/10.3390/nu12051414
• [11] Watanabe M, Suliman ME, Qureshi AR, Garcia-Lopez E, Bárány P, Heimbürger O, Stenvinkel P, Lindholm B. Consequences of low plasma histidine in chronic kidney disease patients: Associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr. 2008; 87(6):1860–1866. https://doi.org/10.1093/ajcn/87.6.1860
• [12] Schuller-Levis GB, Park E. Taurine: New implications for an old amino acid. FEMS Microbiol Lett. 2003; 226(2):195–202. https://doi.org/10.1016/S0378-1097(03)00611-6
• [13] Huxtable RJ. Actions of taurine. Physiol Rev. 1992; 72(1):101–163. https://doi.org/10.1152/physrev.1992.72.1.101
• [14] Chesney RW, Han X, Patters AB. Taurine and the renal system. J Biomed Sci. 2010; 17(SUPPL. 1):1–10. https://doi.org/10.1186/1423-0127-17-S1-S4
• [15] Said MY, Post A, Minović I, van Londen M, van Goor H, Postmus D, Heiner-Fokkema MR, van den Berg E, Pasch A, Navis G, Bakker SJL. Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study. Transplant Int. 2020; 33(7):752–761. https://doi.org/10.1111/tri.13600
• [16] Popolo A, Adesso S, Pinto A, Autore G, Marzocco S. L-Arginine and its metabolites in kidney and cardiovascular disease. Amino Acids. 2014; 46(10):2271–2286. https://doi.org/10.1007/s00726-014-1825-9
• [17] Saito R, Hirayama A, Akiba A, Kamei Y, Kato Y, Ikeda S, Kwan B, Pu M, Natarajan L, Shinjo H, Akiyama S, Tomita M, Soga T, Maruyama S. Urinary metabolome analyses of patients with acute kidney injury using capillary electrophoresis-mass spectrometry. Metabolites. 2021; 11(10):671. https://doi.org/10.3390/metabo11100671 doi:10.3390/metabo11100671
• [18] Podkowińska A, Formanowicz D. Chronic kidney disease as oxidative stress-and inflammatory-mediated cardiovascular disease. Antioxidants. 2020; 9(8):752. https://doi.org/10.3390/antiox9080752
• [19] Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, Warady BA. Chronic ınflammation in chronic kidney disease progression: Role of Nrf2. Kidney Int Rep. 2021; 6(7):1775–1787. https://doi.org/10.1016/j.ekir.2021.04.023.
• [20] Combs JA, Denicola GM. The non-essential amino acid cysteine becomes essential for tumor proliferation and survival. Cancers. 2019; 11(5):678. https://doi.org/10.3390/cancers11050678
• [21] Correia MJ, Pimpão AB, Fernandes DGF, Morello J, Sequeira CO, Calado J, Antunes AMM, Almeida MS, Branco P, Monteiro EC, Vicente JB, Serpa J, Pereira SA. Cysteine as a multifaceted player in kidney, the cysteine-related thiolome and ıts ımplications for precision medicine. Molecules. 2022; 27(4):1416. https://doi.org/10.3390/molecules27041416 doi:10.3390/molecules27041416