scholarly journals Role of incretin based therapies in the treatment of diabetic kidney disease

2018 ◽  
Vol 21 (5) ◽  
pp. 395-398 ◽  
Author(s):  
Paola Fioretto ◽  
Andrea Frascati
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
The Metabolic Syndrome ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Glucagon Like Peptide 1 ◽  
Stage Renal Disease

Diabetic kidney disease (DKD), a serious microvascular complication of diabetes mellitus is a leading cause of end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Despite advancements in blood glucose and blood pressure (BP) control, ~20% to 40% of patients with diabetes mellitus develop DKD. Intensive glycaemic and BP control positively influence decline in estimated glomerular filtration rate and albuminuria, thereby delaying the onset and progression of diabetic nephropathy. Incretin based therapies namely glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used glucose lowering agents and have shown favorable renal outcomes in DKD. This article discusses the extra-glycaemic properties of incretin based therapies and their renoprotective effects on components of the metabolic syndrome, including obesity, hypertension and dyslipidaemia; reduction in oxidative stress and inflammation; and increase in natriuresis.

scholarly journals Renal Effects of DPP-4 Inhibitors: A Focus on Microalbuminuria

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Martin Haluzík ◽  
Jan Frolík ◽  
Ivan Rychlík
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cardiovascular Complications ◽  
Special Focus ◽  
Renal Effects ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

Incretin-based therapies represent one of the most promising options in type 2 diabetes treatment owing to their good effectiveness with low risk of hypoglycemia and no weight gain. Other numerous potential beneficial effects of incretin-based therapies have been suggested based mostly on experimental and small clinical studies including its beta-cell- and vasculo-protective actions. One of the recently emerged interesting features of dipeptidyl peptidase-4 (DPP-4) inhibitors is its possible protective effect on the diabetic kidney disease. Here, we review the renal effects of DPP-4 inhibitors with special focus on its influence on the onset and progression of microalbuminuria, as presence of microalbuminuria represents an important early sign of kidney damage and is also associated with increased risk of hypoglycemia and cardiovascular complications. Mechanisms underlying possible nephroprotective properties of DPP-4 inhibitors include reduction of oxidative stress and inflammation and improvement of endothelial dysfunction. Effects of DPP-4 inhibitors may be both glucagon-like peptide-1 (GLP-1) dependent and independent. Ongoing prospective studies focused on the nephroprotective effects of DPP-4 inhibitors will further clarify its possible role in the prevention/attenuation of diabetic kidney disease beyond its glucose lowering properties.

scholarly journals Susceptibility of ApoB and PCSK9 Genetic Polymorphisms to Diabetic Kidney Disease Among Chinese Diabetic Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Liang Ma ◽  
Shaoting Wang ◽  
Hailing Zhao ◽  
Meijie Yu ◽  
Xiangling Deng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Chinese Patients ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Increased Risk

This study aimed to investigate the susceptibility of 8 polymorphisms in ApoB and PCSK9 genes to diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus. This is a case-control association study, including 575 DKD cases and 653 controls. Genotypes were determined using ligase detection reaction method, and data are analyzed using STATA software. The genotype distributions of rs1042034 and rs12720838 differed significantly between the two groups (P < 0.001 and P = 0.008, respectively). After adjusting for confounding factors, the mutations of rs1042034 and rs12720838 were associated with the significantly increased risk of DKD. For instance, carriers of rs1042034 T allele (CT and TT genotypes) were 1.07 times more likely to have DKD than carriers of rs1042034 CC genotype [odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.03–1.10, P < 0.001]. Further, haplotype T-A-G-T in ApoB gene was overrepresented in cases (18.10%) compared with controls (12.76%) (PSimulated = 0.045), and haplotype T-A-G-T was associated with a 33% increased risk of DKD (OR = 1.33, 95% CI: 1.04, 1.70). In further haplotype-phenotype analysis, significant association was only noted for hypertension and omnibus haplotypes in ApoB gene (PSimulated = 0.001). Our findings indicate that ApoB gene is a candidate gene for DKD in Chinese patients with type 2 diabetes mellitus.

scholarly journals Inflammatory Cytokines in Diabetic Kidney Disease: Pathophysiologic and Therapeutic Implications

2021 ◽  
Vol 7 ◽  
Author(s):  
Javier Donate-Correa ◽  
Carla M. Ferri ◽  
Fátima Sánchez-Quintana ◽  
Atteneri Pérez-Castro ◽  
Ainhoa González-Luis ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Therapeutic Implications ◽  
Cardiovascular Morbidity And Mortality ◽  
Patients With Diabetes ◽  
Traditional Risk Factors ◽  
Stage Renal Disease ◽  
End Stage ◽  
Underlying Processes

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and a main contributing factor for cardiovascular morbidity and mortality in patients with diabetes mellitus. Strategies employed to delay the progression of this pathology focus on the control of traditional risk factors, such as hyperglycemia, and elevated blood pressure. Although the intimate mechanisms involved in the onset and progression of DKD remain incompletely understood, inflammation is currently recognized as one of the main underlying processes. Untangling the mechanisms involved in the appearing of a harmful inflammatory response in the diabetic patient is crucial for the development of new therapeutic strategies. In this review, we focus on the inflammation-related pathogenic mechanisms involved in DKD and in the therapeutic utility of new anti-inflammatory strategies.

scholarly journals Association Between miR-30a/SNAI1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease

2020 ◽  
Author(s):  
CaiLian Yang ◽  
Tao Tong ◽  
MingFang Sun ◽  
Bo Zhou
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Disease Risk ◽  
Multiple Logistic Regression Analysis ◽  
Diabetic Kidney ◽  
Increased Risk

Abstract Background: Diabetic kidney disease is a leading cause of end-stage kidney disease worldwide, its incidence is still increasing and the precise mechanism is not yet fully understood.This study aimed to investigate the possible association of miR-30a and its potential target gene, SNAI1, polymorphisms with diabetic kidney disease in patients with type 2 diabetes mellitus. Methods: This case-control is study included 240 type 2 diabetes mellitus patients with diabetic kidney disease and 280 patients without diabetic kidney disease. Genotyping of miR-30a and SNAI1 polymorphisms were performed by allelic discrimination assay with Taq-Man-MGB probes. Result: The results demonstrated that the CC genotype of rs2222722 in miR-30a was associated with an increased risk of diabetic kidney disease in Chinese type 2 diabetes mellitus patients (OR = 2.81, 95% CI 1.58-4.97, p < 0.001). Stratified analyses revealed that the miR-30a CC genotype was strongly associated with an increased risk of diabetic kidney disease in subjects who were young (< 65 years), male, and had a low body mass index, as well as those with poor glycemic control. What’s more, CC genotype carriers were more likely to exhibit decreased estimated glomerular filtration rate levels and urinary protein production. In addition, the GG genotype of SNAI1 was also associated with the development of diabetic kidney disease, and the risk was 1.73 times higher than that in AA+AG genotype carriers (95% CI 1.01-2.96, p = 0.046). Multiple logistic regression analysis showed that the miR-30a CC and SNAI1 GG genotypes were indispensable and dangerous contributing factors to the development of diabetic kidney disease. Conclusion: The CC genotype of miR-30a rs2222722 and GG genotype of SNAI1 rs1543442 might be associated with diabetic kidney disease risk in Chinese type 2 diabetes mellitus patients.

scholarly journals Evaluation of urinary biomarkers for prediction of diabetic kidney disease: a propensity score matching analysis

2019 ◽  
Vol 10 ◽  
pp. 204201881989111
Author(s):  
Yongzhang Qin ◽  
Shuang Zhang ◽  
Xiaofang Shen ◽  
Shunming Zhang ◽  
Jingyu Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Diabetic Kidney Disease ◽  
Urinary Biomarkers ◽  
Retinol Binding Protein ◽  
Cross Sectional ◽  
Diabetic Kidney ◽  
Increased Risk

Background: The aim of this study was to evaluate the diagnostic value of six urinary biomarkers for prediction of diabetic kidney disease (DKD). Methods: The cross-sectional study recruited 1053 hospitalized patients with type 2 diabetes mellitus (T2DM), who were categorized into the diabetes mellitus (DM) with normoalbuminuria (NA) group ( n = 753) and DKD group ( n = 300) according to 24-h urinary albumin excretion rate (24-h UAE). Data on the levels of six studied urinary biomarkers [transferrin (TF), immunoglobulin G (IgG), retinol-binding protein (RBP), β-galactosidase (GAL), N-acetyl-beta-glucosaminidase (NAG), and β2-microglobulin (β2MG)] were obtained. The propensity score matching (PSM) method was applied to eliminate the influences of confounding variables. Results: Patients with DKD had higher levels of all six urinary biomarkers. All indicators demonstrated significantly increased risk of DKD, except for GAL and β2MG. Single RBP yielded the greatest area under the curve (AUC) value of 0.920 compared with the other five markers, followed by TF (0.867) and IgG (0.867). However, GAL, NAG, and β2MG were shown to have a weak prognostic ability. The diagnostic values of the different combinations were not superior to the single RBP. Conclusions: RBP, TF, and IgG could be used as reliable or good predictors of DKD. The combined use of these biomarkers did not improve DKD detection.

scholarly journals Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Athanasios Roumeliotis ◽  
Stefanos Roumeliotis ◽  
Fotis Tsetsos ◽  
Marianthi Georgitsi ◽  
Panagiotis I. Georgianos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetes Mellitus Type 2 ◽  
Diabetic Kidney Disease ◽  
Diabetes Mellitus Type ◽  
Nucleotide Polymorphisms ◽  
Diabetic Kidney ◽  
Increased Risk

Diabetic type 2 patients compared to nondiabetic patients exhibit an increased risk of developing diabetic kidney disease (DKD), the leading cause of end-stage renal disease. Hyperglycemia, hypertension, oxidative stress (OS), and genetic background are some of the mechanisms and pathways implicated in DKD pathogenesis. However, data on OS pathway susceptibility genes show limited success and conflicting or inconclusive results. Our study is aimed at exploring OS pathway genes and variants which could be associated with DKD. We recruited 121 diabetes mellitus type 2 (DM2) patients with DKD (cases) and 220 DM2, non-DKD patients (control) of Greek origin and performed a case-control association study using genome-wide association data. PLINK and EIGENSOFT were used to analyze the data. Our results indicate 43 single nucleotide polymorphisms with their 21 corresponding genes on the OS pathway possibly contributing or protecting from DKD: SPP1, TPO, TTN, SGO2, NOS3, PDLIM1, CLU, CCS, GPX4, TXNRD2, EPHX2, MTL5, EPX, GPX3, ALOX12, IPCEF1, GSTA, OXR1, GPX6, AOX1, and PRNP. Therefore, a genetic OS background might underlie the complex pathogenesis of DKD in DM2 patients.

scholarly journals Incretins in the Therapy of Diabetic Kidney Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12312
Author(s):  
Agnieszka Przezak ◽  
Weronika Bielka ◽  
Andrzej Pawlik
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Oral Glucose ◽  
Antidiabetic Drug ◽  
Diabetic Kidney ◽  
Dipeptidyl Peptidase 4 ◽  
Drug Classes ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes

Diabetic kidney disease is a microvascular complication that occurs in patients with diabetes. It is strongly associated with increased risk of kidney replacement therapy and all-cause mortality. Incretins are peptide hormones derived from the gastrointestinal tract, that besides causing enhancement of insulin secretion after oral glucose intake, participate in many other metabolic processes. Antidiabetic drug classes, such as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide receptor agonists, which way of action is based on incretins facility, not only show glucose-lowering properties but also have nephroprotective functions. The aim of this article is to present the latest information about incretin-based therapy and its influence on diabetic kidney disease appearance and progression, point its potential mechanisms of kidney protection and focus on future therapeutic possibilities bound with these two antidiabetic drug classes.

scholarly journals GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

2020 ◽  
Vol 9 (4) ◽  
pp. 947 ◽  
Author(s):  
José Luis Górriz ◽  
María José Soler ◽  
Juan F. Navarro-González ◽  
Clara García-Carro ◽  
María Jesús Puchades ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Glycemic Control ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Receptor Agonists ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
The Impact

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

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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