title: Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments.
abstract: 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 were 16.8 ± 6.4 μg/mL at T0; 17.1 ± 3.8 μg/mL at T3; 17.5 ± 5.6 μg/mL at T6; and 16.0 ± 5.2 μg/mL at T12. CML mean values were 0.94 ± 0.36 ng/mL at T0; 1.11 ± 0.48 ng/mL at T3; 0.99 ± 0.42 ng/mL at T6; and 0.78 ± 0.38 ng/mL at T12. AOPP mean values were 130.1 ± 76.8 μMol/L at T0; 137.3 ± 110.6 μMol/L at T3; 116.4 ± 51.2 μMol/L at T6; and 106.4 ± 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.
authors.affiliation: Nephrology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar and University Hospital de Santo António, University of Porto, Porto, Portugal; Transplantation Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: La Salete
authors.identifier: 0000-0002-6110-2102
authors.initials: LS
authors.lastname: Martins
authors.affiliation: Clinical Pathology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: José C
authors.initials: JC
authors.lastname: Oliveira
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar and University Hospital de Santo António, University of Porto, Porto, Portugal; Surgical Pathology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Vizcaíno
authors.affiliation: Nephrology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar and University Hospital de Santo António, University of Porto, Porto, Portugal.
authors.forename: Isabel
authors.identifier: 0000-0001-8984-1751
authors.initials: I
authors.lastname: Fonseca
authors.affiliation: Surgical Pathology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gouveia
authors.affiliation: Transplantation Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal; Surgery Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Donzília
authors.initials: D
authors.lastname: Silva
authors.affiliation: Nephrology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar and University Hospital de Santo António, University of Porto, Porto, Portugal; Transplantation Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: António C
authors.initials: AC
authors.lastname: Henriques
authors.affiliation: Cellular and Molecular Nephrology Laboratory, Division of Nephrology, University of São Paulo, São Paulo, Brazil.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Noronha
authors.affiliation: Nephrology Department, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar and University Hospital de Santo António, University of Porto, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Rodrigues
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000009:adverse effects*; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000737:chemistry; D016035:Pancreas Transplantation / Q000009:adverse effects*; D011446:Prospective Studies; D011506:Proteins / Q000737:chemistry; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D017127:Glycation End Products, Advanced; D011506:Proteins; C048496:N(6)-carboxymethyllysine; D008239:Lysine; D010100:Oxygen