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

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Thananda Trakarnvanich ◽  
Bancha Satirapoj ◽  
Swangjit Suraamornkul ◽  
Thanit Chirananthavat ◽  
Anoma Sanpatchayapong ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Vascular Calcification ◽  
Diabetic Kidney Disease ◽  
Controlled Trial ◽  
Kidney Injury ◽  
Dipeptidyl Peptidase ◽  
Control Group ◽  
Fatty Acid Binding ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4

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.

scholarly journals Effect of Dipeptidyl Peptidase- 4 (DPP-4) Inhibitor on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Nephropathy: A Randomized Controlled Trial

2021 ◽  
Author(s):  
Thananda Trakarnvanich ◽  
Bancha Satirapoj ◽  
Sawangjit Suraamornkul ◽  
Thanit Chiranantawat ◽  
Anoma Sanpatchayapong ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Vascular Calcification ◽  
Controlled Trial ◽  
Kidney Injury ◽  
Calcium Score ◽  
Coronary Calcification ◽  
Dipeptidyl Peptidase ◽  
Control Group ◽  
Fatty Acid Binding ◽  
Dipeptidyl Peptidase 4

Abstract 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 plan to evaluate the effects of a potent DPP4 inhibitor (gemigliptin) on these processes in diabetic nephropathy patients.Methods: This was a multicenter, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to a group treated with 50 mg gemigliptin daily with standard care of diabetes mellitus for 6 months. The changes in coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), vascular calcification and tubular renal injury markers 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 CAC score, CAVI, estimated GFR and proteinuria over the 6 months of the study did not significantly differ between the 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 to the control group. No serious adverse event was observed during the study.Conclusion: Our study shows that gemigliptin significantly improves renal tubular injury biomarkers and vascular calcification in patients with diabetic nephropathy; however, gemigliptin does not affect renal function or coronary calcification compared with the control. A larger and longer follow-up will be essential to determine these beneficial effects.Clinical trialsClinicalTrials.Gov Identifier: NCT04705506

FC 092EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY INJURY AND VASCULAR CALCIFICATION IN DIABETIC NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Thananda Trakarnvanich ◽  
Bancha Satirapoj ◽  
Swangjit Suraamornkul ◽  
Thanit Chiranantawat ◽  
Anoma Sanpatchayapong ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Vascular Calcification ◽  
Controlled Trial ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Calcium Score ◽  
Coronary Calcification ◽  
Control Group ◽  
Fatty Acid Binding ◽  
Dipeptidyl Peptidase 4

Abstract Background and Aims Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and contain pleiotropic actions on kidney injury, albuminuria and vascular inflammation especially in animal models. We plan to evaluate the efficacy of potent DPP4-inhibitors (gemigliptin) in response to these aspects in diabetic nephropathy patients. Method This is a multi-center, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to gemigliptin 50 mg daily and standard care of diabetes mellitus for 6 months. The changes of coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), markers of vascular calcification and markers of tubular renal injury were evaluated at baseline and 6 months. Results Overall 182 patients completed the study. Significantly reductions in hemoglobinA1C level were seen at month 6 with gemigliptin group (-0.67%) vs. control group (-0.15%; P=0.048). Changes of CAC score, CAVI, estimated GFR and proteinuria did not significantly difference in the both groups during 6 months of study. However, biomarkers of vascular calcification including serum bone alkaline phosphatase and biomarkers of kidney injury including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr improved significantly after gemigliptin treatment when compared to the control group. No serious adverse event was found during study. Conclusion Our study shows that gemigliptin has significant benefits on biomarkers of renal tubular injury and vascular calcification in patients with diabetic nephropathy, but gemigliptin does not affect on renal function and coronary calcification compared with control. The larger and longer follow-up will be essential to determine these beneficial effects.

scholarly journals Exercise Ameliorates Diabetic Kidney Disease in Type 2 Diabetic Fatty Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1754
Author(s):  
Itaru Monno ◽  
Yoshio Ogura ◽  
Jing Xu ◽  
Daisuke Koya ◽  
Munehiro Kitada
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Male Rats ◽  
Fatty Acid Binding ◽  
Diabetic Kidney ◽  
Beneficial Effects ◽  
Type 2 Diabetic

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar fatty (fa/fa) rats: WFRs) at 36 weeks of age. TET significantly suppressed the levels of albuminuria and urinary liver-type fatty-acid-binding protein (L-FABP), tubulointerstitial fibrosis, inflammation, and oxidative stress in the kidneys of WFRs. In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). In conclusion, TET ameliorates diabetes-induced kidney injury in type 2 diabetic fatty rats.

scholarly journals Dipeptidyl Peptidase-4 Inhibitors and Diabetic Kidney Disease: A Narrative Review

2021 ◽  
Author(s):  
Rodrigo Daza-Arnedo ◽  
Jorge-Eduardo Rico-Fontalvo ◽  
Nehomar Pájaro-Galvis ◽  
Víctor Leal-Martínez ◽  
Emilio Abuabara-Franco ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Narrative Review ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

DIPEPTIDYL-PEPTIDASE 4 INHIBITORS DID NOT IMPROVE RENAL ENDPOINTS IN ADVANCED DIABETIC KIDNEY DISEASE

2020 ◽  
Vol 26 (12) ◽  
pp. 1486-1496
Author(s):  
Edy Kornelius ◽  
Chien-Ning Huang ◽  
Shih-Chang Lo ◽  
Yu-Hsun Wang ◽  
Yi-Sun Yang
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
Urine Albumin ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Stage Renal Disease ◽  
End Stage

Objective: The efficacy of dipeptidyl-peptidase 4 inhibitors (DPP4is) in advanced diabetic kidney disease (DKD) is unknown. We investigated whether DPP4is confer renal protective benefits in DKD patients. Methods: We conducted a retrospective cohort study between 2012 and 2018 in Taiwan. We only included type 2 diabetes patients with estimated glomerular filtration rate (eGFR) between 30 and 90 mL/min/1.73 m2 and urine albumin to creatinine ratio between 300 and 5,000 mg/g. Patients with DPP4i prescriptions were selected as cases, while non-DPP4i users served as controls. We followed these patients until the presence of composite primary renal endpoints, which was defined by the earliest occur-rence of clinical renal outcomes. Results: A total of 522 patients were included in the analysis, comprising 273 patients with a DPP4i prescription who were selected as cases and 249 patients without DPP4i prescription who were assigned as controls. Median follow-up duration for DPP4i users and nonusers was 2.2 years and 3.4 years, respectively. At baseline, the mean glycated hemoglobin levels for DPP4i users and nonusers were 8.1% and 8.3%, respectively. Among patients with DPP4i prescriptions, there was no reduction in composite primary renal outcome, with a crude hazard ratio (HR) of 1.50 (95% confidence interval [CI], 0.95 to 2.36). Similar results were observed for the risk of persistent eGFR <15 mL/min/1.73 m2, with a HR of 1.68 (95% CI, 0.90 to 3.13), doubling of serum creatinine level, with a HR of 1.05 (95% CI, 0.15 to 7.45), and end-stage renal disease, with a HR of 0.87 (95% CI, 0.14 to 5.19). Conclusion: DPP4i prescription did not reduce the risk of composite renal endpoints in DKD patients. Abbreviations: BMI = body mass index; CI = confidence interval; CVOT = cardiovascular outcomes trial; DPP4i = dipeptidyl-peptidase 4 inhibitor; DKD = diabetic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HR = hazard ratio; SGLT2i = sodium-glucose cotransporter 2 inhibitor; T2D = type 2 diabetes; UACR = urine albumin to creatinine ratio

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