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 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 Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiong-Fang Wu ◽  
Hao Kong ◽  
Zhen-Zhen Xu ◽  
Huai-Jin Li ◽  
Dong-Liang Mu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Partial Nephrectomy ◽  
Controlled Trial ◽  
Intervention Group ◽  
Kidney Injury ◽  
Control Group ◽  
Hemodynamic Management ◽  
Randomized Controlled ◽  
Renal Hilum ◽  
Pilot Randomized Controlled Trial

Abstract Background The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. Methods This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0–4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. Results From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28–1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. Conclusion For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. Trial registration Clinicaltrials.gov identifier: NCT02803372. Date of registration: June 6, 2016.

scholarly journals The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin

2018 ◽  
Vol 132 (4) ◽  
pp. 489-507 ◽  
Author(s):  
Keizo Kanasaki
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Renal Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Membrane Bound

Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

scholarly journals Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 87 ◽  
Author(s):  
Beata Jarmołowska ◽  
Marta Bukało ◽  
Ewa Fiedorowicz ◽  
Anna Cieślińska ◽  
Natalia Karolina Kordulewska ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Mononuclear Cells ◽  
Bovine Milk ◽  
Dipeptidyl Peptidase ◽  
Autism Spectrum ◽  
Control Group ◽  
Healthy Children ◽  
Dipeptidyl Peptidase 4 ◽  
Significant Difference

Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC 3.4.14.5) and it is exogenous substrate, β-casomorphin-7 (BCM7) in autism etiology. Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters. The inspiration for this study emanated from clinical experience of the daily diet role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.

scholarly journals Electrolytes supplementation can decrease the risk of nephrotoxicity in patients with solid tumors undergoing chemotherapy with cisplatin

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Omary M. S. Minzi ◽  
Tatu E. Lyimo ◽  
Francis F. Furia ◽  
Alphonce I. Marealle ◽  
Manase Kilonzi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Serum Creatinine ◽  
Solid Tumors ◽  
Normal Saline ◽  
Controlled Trial ◽  
Kidney Injury ◽  
Rank Test ◽  
Control Group ◽  
Relative Risks ◽  
Kaplan Meier

Abstract Background Cisplatin is an important drug in the treatment of various Cancers. However, this drug causes nephrotoxicity that is linked to electrolyte derangement. The aim of this study was to evaluate the effect of electrolyte supplementation in reducing kidney injury in patients receiving cisplatin-based regimen. Methods This was non-randomized interventional study conducted at Ocean Road Cancer Institute (ORCI) among patients with confirmed solid tumors. Patients who received cisplatin-based chemotherapy at a dose of ≥50 mg with intravenous normal saline supplemented with Magnesium, Calcium and Potassium (triple electrolyte supplementation) were compared with those who received cisplatin-based chemotherapy with normal saline alone. The patients were followed up for 4 weeks and serum creatinine was measured at every visit. Nephrotoxicity was defined as serum creatinine elevation > 1.5 times that at baseline. Results A total of 99 patients were recruited, whereby 49 patients (49.5%) received electrolyte supplementation (treatment group) and 50 patients (51.5%) did not receive electrolyte supplementation (control group). The incidence risk of nephrotoxicity was 20.41% (n = 10) in the treatment group and 54% (n = 27) in the control group. Patients in the control group were 2.6 times more likely to experience nephrotoxicity as compared to treatment group [Relative Risks (RR); 2.6, 95%CI; 1.5–4.9, P < 0.0001]. The most common malignancy was cervical cancer, n = 43 (87.8%) in treatment group and n = 45 (90.0%) in the control group (P = 0.590). The Kaplan-Meier analysis and the log-rank test revealed that electrolytes supplementation was associated with extended survival with less nephrotoxicity incidences [P = 0.0004; Hazard ratio (HR) 0.3149; 95% CI 0.165 to 0.6011]. Conclusions Electrolytes supplementation decreases the risk of nephrotoxicity after chemotherapy with cisplatin. A randomized controlled trial with a larger sample size is recommended to evaluate the robustness of these findings.

scholarly journals Stromal cell–derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy

2016 ◽  
Vol 90 (4) ◽  
pp. 783-796 ◽  
Author(s):  
Satoru Takashima ◽  
Hiroki Fujita ◽  
Hiromi Fujishima ◽  
Tatsunori Shimizu ◽  
Takehiro Sato ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Stromal Cell ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Stromal Cell Derived Factor
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