Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation

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Aim. To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism.

Materials and methods. The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels.

Results. All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p<0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51).

Conclusion. The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.

作者简介

Irina Larina

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0001-6783-4200

науч. сотр. 

俄罗斯联邦, Moscow

Anastasia Severina

Endocrinology Research Centre

编辑信件的主要联系方式.
Email: ansev1@mail.ru
ORCID iD: 0000-0002-0296-4933

канд. мед. наук, вед. науч. сотр. 

俄罗斯联邦, Moscow

Irina Maganeva

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0002-0067-3622

науч. сотр. 

俄罗斯联邦, Moscow

Alina Ainetdinova

Endocrinology Research Centre

Email: ansev1@mail.ru

врач-кибернетик, науч. сотр. 

俄罗斯联邦, Moscow

Anna Eremkina

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0001-6667-062X

канд. мед. наук, зав. отд. патологии околощитовидных желез 

俄罗斯联邦, Moscow

Alina Gavrilova

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0001-8148-8180

клинический ординатор 

俄罗斯联邦, Moscow

Minara Shamhalova

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0002-3433-0142

д-р мед. наук, зав. отд. диабетической болезни почек и посттрансплантационной реабилитации

俄罗斯联邦, Moscow

Ilya Dmitriev

Sklifosovsky Research Institute of Emergency Medicine

Email: ansev1@mail.ru
ORCID iD: 0000-0002-5731-3310

канд. мед. наук, зав. отд. трансплантации почки и поджелудочной железы

俄罗斯联邦, Moscow

Aleksey Pinchuk

Sklifosovsky Research Institute of Emergency Medicine; Research Institute of Healthсare Organization and Medical Management

Email: ansev1@mail.ru
ORCID iD: 0000-0001-9019-9567

д-р мед. наук, зав. научным отд. трансплантации почки и поджелудочной железы ГБУЗ «НИИ СП им. Н.В. Склифосовского», зав. ОМО по трансплантологии ГБУ «НИИ организации здравоохранения и медицинского менеджмента»

俄罗斯联邦, Moscow; Moscow

Marina Shestakova

Endocrinology Research Centre

Email: ansev1@mail.ru
ORCID iD: 0000-0002-5057-127X

акад. РАН, д-р мед. наук, проф., зав. каф. диабетологии и диетологии, дир. Института диабета, зам. дир.

俄罗斯联邦, Moscow

参考

  1. Ortiz F, Harjutsalo V, Helanterä I, et al. Long-term mortality after kidney transplantation in a nationwide cohort of patients with type 1 diabetes in Finland. Diabetes Care. 2019;42:55-61. doi: 10.2337/dc18-1029
  2. Bahar SG, Devulapally P. Pancreas Transplantation. 2020. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2021.
  3. Готье С.В., Хомяков С.М. Донорство и трансплантация органов в Российской Федерации в 2019 году. XII сообщение регистра Российского трансплантологического общества. Вестник трансплантологии и искусственных органов. 2020;22(2):8-34 [Gautier SV, Khomyakov SM. Organ donation and transplantation in the Russian Federation in 2019. 12th report from the Registry of the Russian Transplant Society. Vestnik transplantologii i iskusstvennykh organov. 2020;22(2):8-34 (in Russian)]. doi: 10.15825/1995-1191-2020-2-8-34
  4. Столяревич Е.С., Томилина Н.А. Поздняя дисфункция трансплантированной почки: морфологическая структура, критерии диагностики. Трансплантология. 2009;1:19-31 [Stolyarevich ES, Tomilina NA. Late grafted kidney dysfunction: morphological structure, criteria for diagnosis. Transplantologiia. 2009;1:19-31 (in Russian)]. doi: 10.23873/2074-0506-2009-0-1-19-31
  5. Глазунова А.М., Арутюнова М.С., Тарасов Е.В., и др. Влияние сочетанной трансплантации почки и поджелудочной железы на динамику поздних осложнений у больных сахарным диабетом 1-го типа. Сахарный диабет. 2015;18(2):69-78 [Glazunova AM, Arutyunova MS, Tarasov EV, et al. Late Diabetic Complications in Patients with Type 1 Diabetes who Received Simultaneous Pancreas-Kidney Transplantation. Sakharnyi diabet. 2015;18(2):69-78 (in Russian)]. doi: 10.14341/DM2015269-78
  6. Fioretto P, Steffes MW, Sutherland DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med. 1998;339(2):69-75. doi: 10.1056/NEJM199807093390202
  7. Browne S, Gill J, Dong J, et al. The impact of pancreas transplantation on kidney allograft survival. Am J Transplant. 2011;11(9):1951-8. doi: 10.1111/j.1600-6143.2011.03627.x
  8. Yamagishi S, Nakamura N, Suematsu M, et al. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes. Mol Med. 2015;21 Suppl. 1(Suppl. 1):S32-40. doi: 10.2119/molmed.2015.00067
  9. Spadella CT, Machado JL, Lerco MM, et al. Pancreas transplantation prevents cellular oxidative stress in kidneys of alloxan-induced diabetic rats. Transplant Proc. 2008;40(2):524-8. doi: 10.1016/j.transproceed.2008.01.050
  10. Dozio E, Vettoretti S, Caldiroli L, et al. Advanced Glycation End Products (AGE) and Soluble Forms of AGE Receptor: Emerging Role as Mortality Risk Factors in CKD. Biomedicines. 2020;8(12):638. doi: 10.3390/biomedicines8120638
  11. Ветчинникова О.Н. Трансплантация почки и костная болезнь: факторы риска развития, диагностика. Вестник трансплантологии и искусственных органов. 2017;19(1):111-21 [Vetchinnikova ON. Kidney transplantation and bone disease: risk factors of development and diagnostics. Vestnik transplantologii i iskusstvennykh organov. 2017;19(1):111-21 (in Russian)]. doi: 10.15825/1995-1191-2017-1-111-121
  12. Jenssen TG, Lindahl JPH, Reinholdt F, et al. Simultaneous kidney and pancreas transplantation, compared to hyperglycaemia, improves longterm (>8 yrs) outcome in the transplanted kidney. Diabetologia Clinical and Experimental. Diabetologia. 2011;54:2417-20.
  13. Matas AJ, Gillingham KJ, Humar A, et al. 2202 kidney transplant recipients with 10 years of graft function: what happens next? Am J Transplant. 2008;8(11):2410-9. doi: 10.1111/j.1600-6143.2008.02414.x
  14. Bhalla V, Nast CC, Stollenwerk N, et al. Recurrent and de novo diabetic nephropathy in renal allografts. Transplantation. 2003;75(1):66-71. doi: 10.1097/00007890-200301150-00012
  15. Shin S, Jung CH, Choi JY, et al. Long-term effects of pancreas transplant alone on nephropathy in type 1 diabetic patients with optimal renal function. PLoS One. 2018;13(1):e0191421. doi: 10.1371/journal.pone.0191421
  16. Lindahl JP, Reinholt FP, Eide IA, et al. In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves longterm kidney graft ultrastructure and function better than transplantation of kidney alone. Diabetologia. 2014;57(11):2357-65. doi: 10.1007/s00125-014-3353-2
  17. Reine TM, Kolseth IB, Meen AJ, et al. Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation. Diabetes Res Clin Pract. 2015;107(1):46-53. doi: 10.1016/j.diabres.2014.10.006
  18. Rabbani N, Thornalley PJ. Advanced glycation end products in the pathogenesis of chronic kidney disease. Kidney Int. 2018;93:803-13. doi: 10.1016/j.kint.2017.11.034
  19. Shimoike T, Inoguchi T, Umeda F, et al. The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy. Metabolism. 2000;49:1030-5. doi: 10.1053/meta.2000.7738
  20. Nazratun N, Mahmood AA, Kuppusamy UR, et al. Diabetes mellitus exacerbates advanced glycation end product accumulation in the veins of end-stage renal failure patients. Vasc Med. 2006;11:245-50. doi: 10.1177/1358863x06072202
  21. Martins LS, Oliveira JC, Vizcaíno JR, et al. Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments. Oxid Med Cell Longev. 2016;2016:2189582. doi: 10.1155/2016/2189582
  22. Yan SF, Ramasamy R, Schmidt AM. Receptor for AGE (RAGE) and its ligands-cast into leading roles in diabetes and the inflammatory response. J Mol Med (Berl). 2009;87(3):235-47. doi: 10.1007/s00109-009-0439-2
  23. Heier M, Margeirsdottir HD, Gaarder M, et al. Soluble RAGE and atherosclerosis in youth with type 1 diabetes: A 5-year follow-up study. Cardiovasc Diabetol. 2015;14:126. doi: 10.1186/s12933-015-0292-2
  24. Thomas MC, Woodward M, Neal B, et al; ADVANCE Collaborative Group. Relationship between levels of advanced glycation end products and their soluble receptor and adverse outcomes in adults with type 2 diabetes. Diabetes Care. 2015;38:1891-7. doi: 10.2337/dc15-0925
  25. Koyama H, Nishizawa Y. AGEs/RAGE in CKD: irreversible metabolic memory road toward CVD? Eur J Clin Invest. 2010;40(7):623-35. doi: 10.1111/j.1365-2362.2010.02298.x
  26. Whaley-Connell A, Sowers JR. Oxidative stress in the cardiorenal metabolic syndrome. Curr Hypertens Rep. 2012;14(4):360-5. doi: 10.1007/s11906-012-0279-2
  27. Ceriello A, Ihnat MA, Thorpe JE. Clinical review 2: The "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications? J Clin Endocrinol Metab. 2009;94(2):410-5. doi: 10.1210/jc.2008-1824
  28. Kowluru RA, Abbas SN, Odenbach S. Reversal of hyperglycemia and diabetic nephropathy: effect of reinstitution of good metabolic control on oxidative stress in the kidney of diabetic rats. J Diabetes Complications. 2004;18(5):282-8. doi: 10.1016/j.jdiacomp.2004.03.002
  29. Егшатян Л.В., Мокрышева Н.Г. Эктопическая кальцификация при хронической болезни почек. Часть 1. Классификация и патогенез. Нефрология. 2017;21(4):30-9 [Egshatyan LV, Mokrysheva NG. Ectopic calcification in chronic kidney disease. Part 1. Classification and pathogenesis. Nefrologiia. 2017;21(4):30-9 (in Russian)]. doi: 10.24884/1561-6274-2017-21-4-30-39
  30. Vangala C, Pan J, Cotton RT, Ramanathan V. Mineral and Bone Disorders After Kidney Transplantation. Front Med (Lausanne). 2018;5:211. doi: 10.3389/fmed.2018.00211

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2. Fig. 1. Values of the estimated glomerular filtration rate in the examined groups of patients.

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3. Fig. 2. Glycation end-products levels and the glycation end-products receptor levels.

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4. Fig. 3. Correlation analysis for the relationship between glycation end-products and the glycation end-products receptor and indicators of renal graft function and HbA1c levels.

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5. Fig. 4. Correlation between hypertension duration and the glycation end-products receptor levels.

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6. Fig. 5. Correlation between osteoprotegerin and 3-NT levels.

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