Skip to content
2000
image of Total Anti-oxidant Capacity and Immunosuppressive Drug Blood Levels after Kidney Transplantation: A Patent Perspective

Abstract

Background

It is well known that acute or chronic kidney injury could be due to free radicals and pro-oxidants. This investigation aimed to monitor tacrolimus or cyclosporine blood trough levels and anti-oxidant capacity after kidney transplantation. Methods: There was no intervention in the routine management of transplant recipients. The sample size (n=70) included healthy individuals and kidney-transplanted recipients (n=25 on tacrolimus and n=10 on cyclosporine). The study population was matched for age. The attained information was examined by using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was considered as ≤ 0.05.

Results

In healthy individuals, the mean ± SD for the capacity of antioxidants was 91.9 ± 16.6 (u/ml), which was significantly higher when compared to the mean value of 28.5 ± 22.6 (u/ml) versus 24.7 ± 25.5 (u/ml), kidney recipients with tacrolimus versus cyclosporine ( ≤ 0.04) as immunosuppressive drugs. The mean value of tacrolimus levels was 14.6 ± 6.4 (ng/ml). The correlation between tacrolimus and cyclosporine trough levels and anti-oxidant capacity was 0.19 ( ≤ 0.14). There were no significant differences regarding age in cases and controls ( ≤ 42).

Conclusion

This study showed that the capacity of anti-oxidants in kidney transplant recipients, those on tacrolimus or cyclosporine, might be lower than in healthy individuals. Subsequent investigations are recommended to delve into the therapeutic consequences of the influence of antioxidant therapies on the clinical outcomes of transplanted recipients.

Loading

Article metrics loading...

/content/journals/raiad/10.2174/0127722708319486241202113259
2024-12-10
2025-01-20
Loading full text...

Full text loading...

References

  1. Manns B. Hemmelgarn B. Tonelli M. Au F. So H. Weaver R. Quinn A.E. Klarenbach S. The cost of care for people with chronic kidney disease. Can. J. Kidney Health Dis. 2019 6 2054358119835521 10.1177/2054358119835521
    [Google Scholar]
  2. Collister D. Pannu N. Ye F. James M. Hemmelgarn B. Chui B. Manns B. Klarenbach S. Health care costs associated with AKI. Clin. J. Am. Soc. Nephrol. 2017 12 11 1733 1743 10.2215/CJN.00950117
    [Google Scholar]
  3. Daenen K. Andries A. Mekahli D. Van Schepdael A. Jouret F. Bammens B. Oxidative stress in chronic kidney disease. Pediatr. Nephrol. 2019 34 6 975 991 10.1007/s00467‑018‑4005‑4
    [Google Scholar]
  4. Tabriziani H. Lipkowitz M.S. Vuong N. Chronic kidney disease, kidney transplantation and oxidative stress: a new look to successful kidney transplantation. Clin. Kidney J. 2018 11 1 130 135 10.1093/ckj/sfx091
    [Google Scholar]
  5. Rajbala A. Sane A.S. Shah P.R. Mishra V.V. Patel S.M. Shah S.A. Shah V.R. Trivedi H.L. Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system. Panminerva Med. 1999 41 1 31 34
    [Google Scholar]
  6. Dennis J. Witting P. Protective Role for Antioxidants in Acute Kidney Disease. Nutrients 2017 9 7 718 10.3390/nu9070718
    [Google Scholar]
  7. Gyurászová M. Gurecká R. Bábíčková J. Tóthová Ľ. Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Oxid. Med. Cell. Longev. 2020 2020 1 11 10.1155/2020/5478708
    [Google Scholar]
  8. Basile D.P. Anderson M.D. Sutton T.A. Pathophysiology of acute kidney injury. Compr. Physiol. 2012 2 2 1303 1353 10.1002/cphy.c110041
    [Google Scholar]
  9. Fonseca I Evidence-based practice, step by step: searching for the evidence. Am J Nurs. 2014 110 5 41 7 10.1097/01
    [Google Scholar]
  10. Nafar M Oxidative stress in kidney transplantation: Causes, consequences, and potential treatment. Iran J Kidney Dis. 2011 5 6 357 72
    [Google Scholar]
  11. Chrzanowska M. Kamińska J. Głyda M. Duda G. Makowska E. Antioxidant capacity in renal transplant patients. Pharmazie 2010
    [Google Scholar]
  12. Tariq M. Morais C. Sobki S. Al Sulaiman M. Al Khader A. N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol. Dial. Transplant. 1999 14 4 923 929 10.1093/ndt/14.4.923
    [Google Scholar]
  13. Manrique J. Errasti P. Lavilla J. Rossich E. Hernandez A. Pujante D. Garcia-Fernández N. Purroy A. Treatment of hyperhomocysteinemia after renal transplantation. Transplant. Proc. 2003 35 5 1742 1744 10.1016/S0041‑1345(03)00628‑6
    [Google Scholar]
  14. Vural A. Yilmaz M.I. Caglar K. Aydin A. Sonmez A. Eyileten T. Acikel C. Gulec B. Kozak O. Oner K. Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine A and tacrolimus-based regimens. Am. J. Nephrol. 2005 25 3 250 255 10.1159/000086079
    [Google Scholar]
  15. Cofan F. Cofan M. Campos B. Guerra R. Campistol J.M. Oppenheimer F. Effect of calcineurin inhibitors on low-density lipoprotein oxidation. Transplant. Proc. 2005 37 9 3791 3793 10.1016/j.transproceed.2005.10.068
    [Google Scholar]
  16. Perrea DN Moulakakis KG Poulakou MV Vlachos IS Papachristodoulou A Kostakis AI Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function. Int Urol Nephrol. 2006 38 2 343 8 10.1007/s11255‑006‑0054‑x
    [Google Scholar]
  17. Mazdak H Tolou Ghamari Z Gholampour M. Bladder cancer: total antioxidant capacity and pharmacotherapy with vitamin-E. Int Urol Nephrol. 2020 52 7 1255 1260 10.1007/s11255‑020‑02411‑3
    [Google Scholar]
  18. Tolou-Ghamari Z. Mortazavi M. Palizban A.A. Najafi M.R. The investigation of correlation between Iminoral concentration and neurotoxic levels after kidney transplantation. Adv. Biomed. Res. 2015 4 1 59 10.4103/2277‑9175.151876
    [Google Scholar]
  19. Tadayon F. Shariati A. Tolou-Ghamari Z. Type of vascular anastomosis and early outcome after kidney transplantation. Urologiia 2021
    [Google Scholar]
  20. Kurutas E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr. J. 2015 15 1 71 10.1186/s12937‑016‑0186‑5
    [Google Scholar]
  21. Tolou-Ghamari Z. Tacrolimus and cyclosporin pharmacotherapy, detection methods, cytochrome p450 enzymes after heart transplantation. Cardiovasc. Hematol. Agents Med. Chem. 2024 22 2 106 113 10.2174/1871525721666230726150021
    [Google Scholar]
  22. Tolou Ghamari Z. Palizban A.A. Tacrolimus Pharmacotherapy: Infectious Complications and Toxicity in Organ Transplant Recipients; An Updated Review. Curr. Drug Res. Rev. 2023 10.2174/0125899775259326231212073240
    [Google Scholar]
  23. Tolou-Ghamari Z. Palizban A.A. Michael Tredger J. Clinical monitoring of tacrolimus after liver transplantation using pentamer formation assay and microparticle enzyme immunoassay. Drugs R D. 2004 5 1 17 22 10.2165/00126839‑200405010‑00003
    [Google Scholar]
  24. Tolou-Ghamari Z. Wendon J. Tredger J.M. In vitro pentamer formation as a biomarker of tacrolimus-related immunosuppressive activity after liver transplantation. Clin. Chem. Lab. Med. 2000 38 11 1209 1211 10.1515/CCLM.2000.190
    [Google Scholar]
  25. Tolou-Ghamari Z. Palizban A.A. Laboratory Monitoring of Cyclosporine Pre-Dose Concentration (C 0) after Kidney Transplantation in Isfahan. IJMS 2003 28 2 81 85
    [Google Scholar]
  26. Carcy R. Cougnon M. Poet M. Durandy M. Sicard A. Counillon L. Blondeau N. Hauet T. Tauc M. Pisani D.F. Targeting oxidative stress, a crucial challenge in renal transplantation outcome. Free Radic. Biol. Med. 2021 169 258 270 10.1016/j.freeradbiomed.2021.04.023
    [Google Scholar]
  27. Mittal M. Siddiqui M.R. Tran K. Reddy S.P. Malik A.B. Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox Signal. 2014 20 7 1126 1167 10.1089/ars.2012.5149
    [Google Scholar]
  28. Cau S.B.A. Carneiro F.S. Tostes R.C. Differential modulation of nitric oxide synthases in aging: therapeutic opportunities. Front. Physiol. 2012 3 218 10.3389/fphys.2012.00218
    [Google Scholar]
  29. Kwiatkowska M. Oldakowska-Jedynak U. Wojtaszek E. Glogowski T. Malyszko J. Potential Effects of Immunosuppression on Oxidative Stress and Atherosclerosis in Kidney Transplant Recipients. Oxid. Med. Cell. Longev. 2021 2021 1 6660846 10.1155/2021/6660846
    [Google Scholar]
  30. Thongprayoon C. Hansrivijit P. Kovvuru K. Kanduri S.R. Bathini T. Pivovarova A. Smith J.R. Cheungpasitporn W. Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients. J. Clin. Med. 2020 9 7 2193 10.3390/jcm9072193
    [Google Scholar]
  31. Tolou-Ghamari Z. Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation. J. Nephropathol. 2012 1 1 23 30 10.5812/jnp.6
    [Google Scholar]
  32. Elsamanoudy A.Z. El-Bassossy H.M. Hassanien M.A. Bima A. Ghoneim F.M. Renal oxidative stress and inflammatory response in perinatal Cyclosporine-A exposed rat progeny and its relation to gender. J. Microsc. Ultrastruct. 2019 7 1 44 49 10.4103/JMAU.JMAU_52_18
    [Google Scholar]
  33. Abd-Eldayem A.M. Makram S.M. Messiha B.A.S. Abd-Elhafeez H.H. Abdel-Reheim M.A. Cyclosporine-induced kidney damage was halted by sitagliptin and hesperidin via increasing Nrf2 and suppressing TNF-α, NF-κB, and Bax. Sci. Rep. 2024 14 1 7434 10.1038/s41598‑024‑57300‑x
    [Google Scholar]
  34. Liu C. Zhu P. Fujino M. Isaka Y. Ito H. Takahashi K. Nakajima M. Tanaka T. Zhuang J. Li X.K. 5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy. Biochem. Biophys. Res. Commun. 2019 508 2 583 589 10.1016/j.bbrc.2018.11.175
    [Google Scholar]
  35. Lu Y. Li C.F. Ping N.N. Sun Y.Y. Wang Z. Zhao G.X. Yuan S.H. Zibrila A.I. Soong L. Liu J.J. Hydrogen‐rich water alleviates cyclosporine A‐induced nephrotoxicity via the Keap1/Nrf2 signaling pathway. J. Biochem. Mol. Toxicol. 2020 34 5 e22467 10.1002/jbt.22467
    [Google Scholar]
  36. Al-Massarani G. Vacher-Coponat H. Paul P. Widemann A. Arnaud L. Loundou A. Robert S. Berland Y. Dignat-George F. Camoin-Jau L. Impact of immunosuppressive treatment on endothelial biomarkers after kidney transplantation. Am. J. Transplant. 2008 8 11 2360 2367 [x.]. 10.1111/j.1600‑6143.2008.02399.x
    [Google Scholar]
  37. Tolou-Ghamari Z. Monitoring tacrolimus after liver transplantation; consideration of alternative techniques and the influence of clinical status. London King’s College 1999
    [Google Scholar]
  38. Tolou-Ghamari Z. Palizban A. Gharavi M. Cyclosporin trough concentration-rejection relationship after kidney transplantation. Indian J. Pharmacol. 2003 35 6 395 396
    [Google Scholar]
  39. Tolou-Ghamari Z Sanei B. Prograf Concentrations in Liver Transplantation: Correlation with Headache and Other Neurotoxic Complications? Thrita. 2016 5 1
    [Google Scholar]
  40. Tolou-Ghamari Z. Monitoring heart transplant recipients in order to investigate immunosuppressive drug absorption using pharmacokinetics parameters and its’ correlation with nephrotoxicity. AJECR 2019 6 4
    [Google Scholar]
  41. Tolou-Ghamari Z. Palizban A.A. Tredger J.M. Modelling tacrolimus AUC in acute and chronic liver disease immediately after transplant. Transplantationsmedizin. Organ der Deutschen Transplantationsgesellschaft 2004 16 2 109 111
    [Google Scholar]
  42. Tolou-Ghamari Z. Palizban A.A. Wendon J. Tredger J.M. Pharmacokinetics of tacrolimus immediately after liver transplantation. Transplantationsmedizin. Organ der Deutschen Transplantationsgesellschaft 2004 16 2 112 116
    [Google Scholar]
  43. Ammar M. Yaich S. Hakim A. Ghozzi H. Sahnoun Z. Ben Hmida M. Zghal K. Ben Mahmoud L. Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients. Ren. Fail. 2024 46 1 2313863 10.1080/0886022X.2024.2313863
    [Google Scholar]
  44. Frijhoff J. Winyard P.G. Zarkovic N. Davies S.S. Stocker R. Cheng D. Knight A.R. Taylor E.L. Oettrich J. Ruskovska T. Gasparovic A.C. Cuadrado A. Weber D. Poulsen H.E. Grune T. Schmidt H.H.H.W. Ghezzi P. Clinical relevance of biomarkers of oxidative stress. Antioxid. Redox Signal. 2015 23 14 1144 1170 10.1089/ars.2015.6317
    [Google Scholar]
  45. Stefanović N.Z. Cvetković T.P. Jevtović-Stoimenov T.M. Zvezdanović-Čelebić L.V. Stojanović D.R. Ignjatović A.M. Živković N.D. Veličković-Radovanović R.M. Potential role of tacrolimus in erythrocytes’ antioxidative capacity in long-term period after renal transplantation. Eur. J. Pharm. Sci. 2015 70 132 139 10.1016/j.ejps.2015.01.013
    [Google Scholar]
  46. de Cal M. Silva S. Cruz D. Basso F. Corradi V. Lentini P. Nalesso F. Dissegna D. Goepel V. Chiaramonte S. Ronco C. Oxidative stress and ‘monocyte reprogramming’ after kidney transplant: a longitudinal study. Blood Purif. 2008 26 1 105 110 10.1159/000110575
    [Google Scholar]
  47. Joncquel M. Labasque J. Demaret J. Bout M.A. Hamroun A. Hennart B. Tronchon M. Defevre M. Kim I. Kerckhove A. George L. Gilleron M. Dessein A.F. Zerimech F. Grzych G. Targeted Metabolomics Analysis Suggests That Tacrolimus Alters Protection against Oxidative Stress. Antioxidants 2023 12 7 1412 10.3390/antiox12071412
    [Google Scholar]
  48. Kidokoro K. Satoh M. Nagasu H. Sakuta T. Kuwabara A. Yorimitsu D. Nishi Y. Tomita N. Sasaki T. Kashihara N. Tacrolimus induces glomerular injury via endothelial dysfunction caused by reactive oxygen species and inflammatory change. Kidney Blood Press. Res. 2012 35 6 549 557 10.1159/000339494
    [Google Scholar]
  49. Stumpf J. Budde K. Witzke O. Sommerer C. Vogel T. Schenker P. Woitas R.P. Opgenoorth M. Trips E. Schrezenmeier E. Hugo C. Girndt M. Wolf G. Kurschat C. Lopau K. Lutz J. Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation: results from a prospective randomized controlled non-inferiority trial (Slow & Low study). EClinicalMedicine 2024 67 102381 10.1016/j.eclinm.2023.102381
    [Google Scholar]
  50. Deng S. Jin T. Zhang L. Bu H. Zhang P. Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Mol. Med. Rep. 2016 14 5 4124 4134 10.3892/mmr.2016.5735
    [Google Scholar]
  51. Jiang Y.J. Cui S. Luo K. Ding J. Nan Q.Y. Piao S.G. Xuan M.Y. Zheng H.L. Jin Y.J. Jin J.Z. Lee J.P. Chung B.H. Choi B.S. Yang C.W. Li C. Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.) 2021 36 6 1437 1449 10.3904/kjim.2021.326
    [Google Scholar]
  52. Moreno J.M. Ruiz M.C. Ruiz N. Gomez I. Vargas F. Asensio C. Osuna A. Modulation factors of oxidative status in stable renal transplantation. Transplant. Proc. 2005 37 3 1428 1430 10.1016/j.transproceed.2005.02.037
    [Google Scholar]
  53. Tolou-Ghamari Z. Nosocomial Urinary Tract Infections in a Tertiary Hospital; Preliminary Study of Antibiotics Susceptibility Testing and Pathogen Types. Antiinfect. Agents 2024 22 2 e251023222696 10.2174/0122113525258170231016081424
    [Google Scholar]
  54. Tolou-Ghamari Z. Investigation of Nosocomial Urianary Tract Infections Post transplanatation, Main Pathogens, and Sensitivity Tests. Curr. Drug Ther. 2023 10.2174/0115748855271275231115064229
    [Google Scholar]
  55. Tolou-Ghamari Z. Preliminary Study of Antibiotics Susceptibility Testing and Pathogens Associated with Nosocomial Infections in a Tertiary Hospital. Antiinfect. Agents 2024 22 2 e271023222865 10.2174/0122113525259607231020063637
    [Google Scholar]
  56. Rodrigues-Diez R. González-Guerrero C. Ocaña-Salceda C. Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling. Sci Rep. 2016 6 27915 10.1038/srep27915
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708319486241202113259
Loading
/content/journals/raiad/10.2174/0127722708319486241202113259
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: cyclosporine ; tacrolimus ; kidney ; recipient ; Anti-oxidant capacity ; transplantation
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test