scholarly journals 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

2021 ◽  
Vol 93 (10) ◽  
pp. 1155-1163
Author(s):  
Irina I. Larina ◽  
Anastasia S. Severina ◽  
Irina S. Maganeva ◽  
Alina R. Ainetdinova ◽  
Anna K. Eremkina ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Advanced Glycation End Products ◽  
Metabolic Memory ◽  
Advanced Glycation ◽  
Significant Difference ◽  
Glycation End Products ◽  
End Products ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation

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 (p0.05; 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.

scholarly journals Сhronic kidney disease complications in patients with type 1 diabetes mellitus after simultaneous pancreas-kidney transplantation – potential role of oxidative stress and glycation end products

2020 ◽  
Vol 22 (5) ◽  
pp. 405-416
Author(s):  
Irina I. Larina ◽  
Anastasia S. Severina ◽  
Minara S. Shamkhalova ◽  
Daria N. Egorova ◽  
Larisa V. Nikankina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Memory ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation

BACKGROUND: Normoglycaemia in patients with diabetes mellitus type 1 (T1DM) after simultaneous pancreas-kidney transplantation (SPKT) is very interesting in regards to chronic kidney disease (CKD) complications dynamics depending of posttransplantation period and possible targets of potential treatment from the point of view metabolic memory AIM: To evaluate the relationship between oxidative stress indicators and advanced glycation end products and complications of end-stage renal disease (ESRD) in patients with T1DM аnd a long-term history of diabetes decompensation, who reached stable euglycemia after SPKT. MATERIALS AND METHODS: The study included 20 patients with compensation of carbohydrate metabolism after SPKT performed from November 2011 to September 2018. Assessment included examination of complications of ESRD (arterial hypertension, dyslipidemia, anemia, mineral and bone disorder) and analysis of "metabolic memory" markers: 3-nitrothyrosine (3-NT), superoxide dismutase (SOD), advanced glycation end products (AGE) and AGE receptor (RAGE). We performed follow-up examination of patients included in the early postoperative period (1st day/week) in 6-12 months after SPKT. RESULTS: All patients with DM1 duration for 22 [19; 28] years, diabetic nephropathy (DN) 8 [6; 14] years and duration of renal replacement therapy (dialysis) for 3 [1.5; 4] years reached euglycemia (HbA1c 5,5 [5,1; 5,8] %; С-peptide 3,2 [2,45; 3,63] ng/ml) after 6 month of surgical treatment. Despite of stable graft function (estimated glomerular filtration rate (eGFR) CKD-EPI 84 [69; 95] ml/min/1.73m2) 35% of patients still needed antihypertensive therapy, 40% needed treatment with recombinant human erythropoietin (RHuEPO) and 15% ferrotherapy. With vitamin D deficiency, observed in 80% of cases (13.3 [9.3; 18.5] ng/ml), 55% of patients had secondary hyperparathyroidism, 45% osteoporosis. The results of the correlation analysis revealed the association of the state of ESRD target organs with the studied "metabolic memory" markers: oxidative stress and AGE-RAGE system. CONCLUSIONS: SPKT as the way to achieve compensation of carbohydrate metabolism and uremia does not provide regress of diabetes and complications of ESRD. Analysis of "metabolic memory" markers indicate their direct contribution to the persistence of metabolic consequences of diabetic nephropathy (DN). Found trends need more long-lasting observation and enlargement of study groups.

scholarly journals Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
La Salete Martins ◽  
José C. Oliveira ◽  
José Ramón Vizcaíno ◽  
Isabel Fonseca ◽  
Carlos Gouveia ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Mean Values ◽  
Glycation End Products ◽  
End Products ◽  
Skin Biopsies ◽  
Pancreas Kidney Transplantation ◽  
Type 1 Diabetic Patients

Diabetes mellitus leads to increased Advanced Glycation End Products (AGE) production, which has been associated with secondary diabetic complications. Type 1 diabetic patients undergoing pancreas-kidney transplantation (SPKT) can restore normoglycemia and renal function, eventually decreasing AGE accumulation. We aimed to prospectively study AGE evolution after SPKT. Circulating AGE were assessed in 20 patients, at time 0 (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after successful SPKT. Global AGE and carboxymethyllysine (CML) were analyzed, as well as advanced oxidation protein products (AOPP). Skin biopsies were obtained at T0 and T12. Immunohistochemistry with anti-AGE antibody evaluated skin AGE deposition. AGE mean values were16.8±6.4 μg/mL at T0;17.1±3.8 μg/mL at T3;17.5±5.6 μg/mL at T6; and16.0±5.2 μg/mL at T12. CML mean values were0.94±0.36 ng/mL at T0;1.11±0.48 ng/mL at T3;0.99±0.42 ng/mL at T6; and0.78±0.38 ng/mL at T12. AOPP mean values were130.1±76.8 μMol/L at T0;137.3±110.6 μMol/L at T3;116.4±51.2 μMol/L at T6; and106.4±57.9 μMol/L at T12. CML variation was significant (P=0.022); AOPP variation was nearly significant (P=0.076). Skin biopsies evolved mostly from a cytoplasmic diffuse to a peripheral interkeratinocytic immunoreaction pattern; in 7 cases, a reduction in AGE immunoreaction intensity was evident at T12. In conclusion, glycoxidation markers decrease, plasmatic and on tissues, may start early after SPKT. Studies with prolonged follow-up may confirm these data.

P1157IMPACT OF MODE OF DIALYSIS ON COMPLICATIONS AFTER SIMULTANEOUS PANCREAS- KIDNEY TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Adoración Martinez ◽  
Manuel Lanuza ◽  
Diana Manzano ◽  
Francisca Lopez ◽  
Eulalia Carceles ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Transplantation ◽  
Postoperative Complications ◽  
Morbidity And Mortality ◽  
Dialysis Modality ◽  
Significant Difference ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Abdominal Infections ◽  
Simultaneous Pancreas Kidney Transplantation

Abstract Background and Aims Simultaneous pancreas-Kidney transplantation (SPKT) has established its position in treating patients with type 1diabetes and end-stage renal disease. Infections in the early post-transplantation period are one of the most significant causes of the high morbidity and mortality rates associated with SPKT. Pre-transplant dialysis modality may affect evolution and it has suspected that peritoneal dialysis (PD) is associated whit more surgical complications, especially intra-abdominal infections. The aim: evaluate whether pretransplant dialysis modality affects the risk for postoperative complications in SPKT transplant recipients Method retrospective and descriptive study of a series of patients who underwent SPKT from 2000 to 2018 in our hospital. We studied complication occurring during the first 3 months after transplantation Results From 2000 to 2019 we performed 38 SPKT in 22 men and 16 women. The mean age of the patients was 35.3(28-44) years. Of the 38 SPKT patients, 44.7% on hemodialysis before transplantation, 26.3% were on peritoneal dialysis and 28.9% had not received any substitutive renal therapy. Were similar regarding baseline characteristics. The complications of the post-transplant period are shown in graph 1. The most frequent complications were infectious in almost 2/3 of the patients and within them the intra-abdominal infections affected almost half, 18, of the patients. Were 3 thrombosis of the pancreas that caused the loss of the graft but none of the kidney. All early postoperative complications are compared in table 1.Whit no significant difference between groups of intraabdominal infection (p. 0.5) and graft thrombosis (p 0.7). There were also no differences in relaparotomy, acute rejection and delayed graft function During the follow-up 4 patients died, one case due to a heart attack while the other 3 in relation to intraabdominal infectious processes and need for reintervention Conclusion: Despite improvements in the outcomes of STKP infectious complications remain a significant cause of morbidity and mortality Peritoneal dialysis is not a risk factor postoperative complication after STPK

scholarly journals Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Qiushi Wang ◽  
Binlin Song ◽  
Shuai Jiang ◽  
Chen Liang ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Advanced Glycation End Products ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Metabolic Memory ◽  
Advanced Glycation ◽  
Open Probability ◽  
A6 Cells ◽  
Glycation End Products ◽  
End Products

Advanced glycation end-products (AGEs) are complex and heterogeneous compounds implicated in diabetes. Sodium reabsorption through the epithelial sodium channel (ENaC) at the distal nephron plays an important role in diabetic hypertension. Here, we report that H2S antagonizes AGEs-induced ENaC activation in A6 cells. ENaC open probability(PO)in A6 cells was significantly increased by exogenous AGEs and that this AGEs-induced ENaC activity was abolished by NaHS (a donor of H2S) and TEMPOL. Incubating A6 cells with the catalase inhibitor 3-aminotriazole (3-AT) mimicked the effects of AGEs on ENaC activity, but did not induce any additive effect. We found that the expression levels of catalase were significantly reduced by AGEs and both AGEs and 3-AT facilitated ROS uptake in A6 cells, which were significantly inhibited by NaHS. The specific PTEN and PI3K inhibitors, BPV(pic) and LY294002, influence ENaC activity in AGEs-pretreated A6 cells. Moreover, after removal of AGEs from AGEs-pretreated A6 cells for 72 hours, ENaCPOremained at a high level, suggesting that an AGEs-related “metabolic memory” may be involved in sodium homeostasis. Our data, for the first time, show that H2S prevents AGEs-induced ENaC activation by targeting the ROS/PI3K/PTEN pathway.

Pregnancy-Associated Plasma Protein A and Soluble Receptor for Advanced Glycation End Products after Kidney Transplantation

2007 ◽  
Vol 30 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Marta Kalousová ◽  
Kateřina Bartošová ◽  
Tomáš Zima ◽  
Jelena Skibová ◽  
Vladimír Teplan ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Plasma Protein ◽  
Advanced Glycation End Products ◽  
Protein A ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Evaluation of the AGE/sRAGE Axis in Patients with Multiple Myeloma

Antioxidants ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 55 ◽  
Author(s):  
Alessandro Allegra ◽  
Caterina Musolino ◽  
Elisabetta Pace ◽  
Vanessa Innao ◽  
Eleonora Di Salvo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Advanced Glycation End Products ◽  
Healthy Subjects ◽  
Advanced Glycation ◽  
Blood Samples ◽  
Significant Difference ◽  
Glycation End Products ◽  
End Products ◽  
Stress Influences

Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets.

scholarly journals Radiolabeling of [11C]FPS-ZM1, a receptor for advanced glycation end products-targeting positron emission tomography radiotracer, using a [11C]CO2-to-[11C]CO chemical conversion

2020 ◽  
Vol 12 (6) ◽  
pp. 511-521 ◽  
Author(s):  
Federico Luzi ◽  
Vilius Savickas ◽  
Carlotta Taddei ◽  
Stefan Hader ◽  
Nisha Singh ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Advanced Glycation End Products ◽  
Chemical Conversion ◽  
Emission Tomography ◽  
Advanced Glycation ◽  
Positron Emission ◽  
Significant Difference ◽  
Glycation End Products ◽  
End Products

Aim: The receptor for advanced glycation end products (RAGE) is a viable target for early Alzheimer’s disease (AD) diagnosis using positron emission tomography (PET) as RAGE overexpression precedes Aβ plaque formation. The development of a carbon-11 analog of FPS-ZM1 (N-benzyl-4-chloro-N-cyclohexylbenzamide, [11C]FPS-ZM1), possessing nanomolar affinity for RAGE, may enable the imaging of RAGE for early AD detection. Methodology & results: Herein we report an optimized [11C]CO2-to-[11C]CO chemical conversion for the synthesis of [11C]FPS-ZM1 and in vitro brain autoradiography. The [11C]CO2-to-[11C]CO conversion via 11C-silanecarboxylate derivatives was achieved with a 57% yield within 30 s from end of [11C]CO2 delivery. [11C]FPS-ZM1 was obtained with a decay-corrected isolated radiochemical yield of 9.5%. Conclusion: [11C]FPS-ZM1 distribution in brain tissues of wild-type versus transgenic AD model mice showed no statistically significant difference and high nondisplaceable binding.

scholarly journals Advanced glycation end products and their ratio to soluble receptor are associated with limitations in physical functioning only in women: results from the CARLA cohort

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Helen Ebert ◽  
Maria Elena Lacruz ◽  
Alexander Kluttig ◽  
Andreas Simm ◽  
Karin Halina Greiser ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Physical Functioning ◽  
Antihypertensive Drugs ◽  
Lipid Lowering ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Age Related ◽  
Significant Difference ◽  
Glycation End Products ◽  
End Products

Abstract Background Advanced glycation end products (AGEs), modifications of proteins or amino acids, are increasingly produced and accumulated with age-related diseases. Recent studies suggested that the ratio of AGEs and their soluble receptor (sRAGE) is a more accurate biomarker for age-related diseases than each separately. We aim to investigate whether this also applies for physical functioning in a broad age-spectrum. Methods AGE and sRAGE levels, and physical functioning (SF-12 questionnaire) of 967 men and 812 women (45–83 years) were measured in the CARLA study. We used ordinal logistic regression to examine associations between AGEs, sRAGE, and AGE/sRAGE ratio with physical functioning in sex- and age-stratified models. Results Higher levels of AGEs and AGE/sRAGE ratio were associated with lower physical functioning only in women, even after consideration of classical lifestyle and age-related factors (education, BMI, smoking, alcohol consumption, diet, creatinine clearance, diabetes mellitus, lipid lowering and antihypertensive drugs) (odds ratio (OR) =0.86, 95%confidence interval = 0.74–0.98 and OR = 0.86, 95%CI = 0.75–0.98 for AGEs and AGE/sRAGE ratio respectively). We could not demonstrate a significant difference across age. Conclusions We showed a sex-specific association between physical functioning and AGEs and AGE/sRAGE, but no stronger associations of the latter with physical functioning. Further investigation is needed in the pathophysiology of this association.

scholarly journals The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival

2021 ◽  
Vol 10 (8) ◽  
pp. 1632
Author(s):  
Hans-Michael Hau ◽  
Nora Jahn ◽  
Sebastian Rademacher ◽  
Elisabeth Sucher ◽  
Jonas Babel ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Function ◽  
Kidney Graft ◽  
Significant Difference ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Graft Implantation ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

Background/Objectives: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. Material and methods: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. Results: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3–17.1, p = 0.026) and five years (HR 3.7, 2.1–23.4, p = 0.040). Conclusion: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.

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