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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Abstract

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.

About the authors

Irina I. Larina

Endocrinology Research Centre

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

науч. сотр. 

Russian Federation, Moscow

Anastasia S. Severina

Endocrinology Research Centre

Author for correspondence.
Email: ansev1@mail.ru
ORCID iD: 0000-0002-0296-4933

канд. мед. наук, вед. науч. сотр. 

Russian Federation, Moscow

Irina S. Maganeva

Endocrinology Research Centre

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

науч. сотр. 

Russian Federation, Moscow

Alina R. Ainetdinova

Endocrinology Research Centre

Email: ansev1@mail.ru

врач-кибернетик, науч. сотр. 

Russian Federation, Moscow

Anna K. Eremkina

Endocrinology Research Centre

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

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

Russian Federation, Moscow

Alina O. Gavrilova

Endocrinology Research Centre

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

клинический ординатор 

Russian Federation, Moscow

Minara S. 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

Russian Federation, Moscow

Ilya V. 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

Russian Federation, Moscow

Aleksey V. 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»

Russian Federation, Moscow; Moscow

Marina V. 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.

Russian Federation, Moscow

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Supplementary files

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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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