Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease
Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/1/152 |
| _version_ | 1797625673062285312 |
|---|---|
| author | Naila Rabbani Antonysunil Adaikalakoteswari James R. Larkin Sianna Panagiotopoulos Richard J. MacIsaac Dennis K. Yue Gregory R. Fulcher Matthew A. Roberts Merlin Thomas Elif Ekinci Paul J. Thornalley |
| author_facet | Naila Rabbani Antonysunil Adaikalakoteswari James R. Larkin Sianna Panagiotopoulos Richard J. MacIsaac Dennis K. Yue Gregory R. Fulcher Matthew A. Roberts Merlin Thomas Elif Ekinci Paul J. Thornalley |
| author_sort | Naila Rabbani |
| collection | DOAJ |
| description | Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (<i>n</i> = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD. |
| first_indexed | 2024-03-11T09:59:37Z |
| format | Article |
| id | doaj.art-24670b4ce4864762984173f622ef70d4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:59:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24670b4ce4864762984173f622ef70d42023-11-16T15:30:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124115210.3390/ijms24010152Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney DiseaseNaila Rabbani0Antonysunil Adaikalakoteswari1James R. Larkin2Sianna Panagiotopoulos3Richard J. MacIsaac4Dennis K. Yue5Gregory R. Fulcher6Matthew A. Roberts7Merlin Thomas8Elif Ekinci9Paul J. Thornalley10Department of Basic Medical Science, College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarClinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UKClinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UKEndocrine Centre, Austin Health, The University of Melbourne, West Heidelberg, VIC 3084, AustraliaDepartment of Endocrinology & Diabetes, St Vincent’s Hospital Melbourne, Fitzroy, VIC 3065, AustraliaDiabetes Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, AustraliaDepartment of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, St Leonards, NSW 2065, AustraliaEastern Health Clinical School, Monash University, Box Hill, VIC 3128, AustraliaDepartment of Diabetes, Monash University, Melbourne, VIC 3004, AustraliaEndocrine Centre, Austin Health, The University of Melbourne, West Heidelberg, VIC 3084, AustraliaClinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UKAccumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (<i>n</i> = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.https://www.mdpi.com/1422-0067/24/1/152chronic kidney diseasediabetesglycationmethylglyoxalestimated glomerular filtration rate |
| spellingShingle | Naila Rabbani Antonysunil Adaikalakoteswari James R. Larkin Sianna Panagiotopoulos Richard J. MacIsaac Dennis K. Yue Gregory R. Fulcher Matthew A. Roberts Merlin Thomas Elif Ekinci Paul J. Thornalley Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease International Journal of Molecular Sciences chronic kidney disease diabetes glycation methylglyoxal estimated glomerular filtration rate |
| title | Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease |
| title_full | Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease |
| title_fullStr | Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease |
| title_full_unstemmed | Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease |
| title_short | Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease |
| title_sort | analysis of serum advanced glycation endproducts reveals methylglyoxal derived advanced glycation mg h1 free adduct is a risk marker in non diabetic and diabetic chronic kidney disease |
| topic | chronic kidney disease diabetes glycation methylglyoxal estimated glomerular filtration rate |
| url | https://www.mdpi.com/1422-0067/24/1/152 |
| work_keys_str_mv | AT nailarabbani analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT antonysuniladaikalakoteswari analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT jamesrlarkin analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT siannapanagiotopoulos analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT richardjmacisaac analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT denniskyue analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT gregoryrfulcher analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT matthewaroberts analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT merlinthomas analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT elifekinci analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease AT pauljthornalley analysisofserumadvancedglycationendproductsrevealsmethylglyoxalderivedadvancedglycationmgh1freeadductisariskmarkerinnondiabeticanddiabeticchronickidneydisease |