Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial

Introduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients wit...

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Main Authors: Thananda Trakarnvanich, Bancha Satirapoj, Swangjit Suraamornkul, Thanit Chirananthavat, Anoma Sanpatchayapong, Torpong Claimon
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2021/7382620
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author Thananda Trakarnvanich
Bancha Satirapoj
Swangjit Suraamornkul
Thanit Chirananthavat
Anoma Sanpatchayapong
Torpong Claimon
author_facet Thananda Trakarnvanich
Bancha Satirapoj
Swangjit Suraamornkul
Thanit Chirananthavat
Anoma Sanpatchayapong
Torpong Claimon
author_sort Thananda Trakarnvanich
collection DOAJ
description Introduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD). Methods. This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months. Results. In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study. Conclusion. Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.
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spelling doaj-art-37194a6058fc44a88ec6861da6abdb822025-02-03T01:25:07ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/73826207382620Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled TrialThananda Trakarnvanich0Bancha Satirapoj1Swangjit Suraamornkul2Thanit Chirananthavat3Anoma Sanpatchayapong4Torpong Claimon5Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, ThailandFaculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandDepartment of Medicine, Police General Hospital, Bangkok, ThailandFaculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandFaculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandIntroduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD). Methods. This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months. Results. In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study. Conclusion. Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.http://dx.doi.org/10.1155/2021/7382620
spellingShingle Thananda Trakarnvanich
Bancha Satirapoj
Swangjit Suraamornkul
Thanit Chirananthavat
Anoma Sanpatchayapong
Torpong Claimon
Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
Journal of Diabetes Research
title Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
title_full Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
title_fullStr Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
title_full_unstemmed Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
title_short Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
title_sort effect of dipeptidyl peptidase 4 dpp 4 inhibition on biomarkers of kidney injury and vascular calcification in diabetic kidney disease a randomized controlled trial
url http://dx.doi.org/10.1155/2021/7382620
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