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.

scholarly journals MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

scholarly journals GLP-1 receptor agonists in diabetic kidney disease: from the patient-side to the bench-side

2018 ◽  
Vol 315 (6) ◽  
pp. F1519-F1525 ◽  
Author(s):  
Brad P. Dieter ◽  
Radica Z. Alicic ◽  
Katherine R. Tuttle
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Renin Angiotensin System ◽  
Diabetic Kidney ◽  
Receptor Agonists ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1 ◽  
Patient Side ◽  
End Stage

Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Since the development of renin-angiotensin system inhibition nearly three decades ago, no new therapeutic agents have received regulatory approval for treatment of DKD. Glucagon-like peptide-1 (GLP-1) receptor agonists, a class of newer antihyperglycemic agents, have shown promise for prevention of DKD onset and progression. This perspective summarizes clinical and experimental observations to give insight into biological mechanisms beyond glycemic control, such as natriuresis and anti-inflammatory actions, for preservation of kidney function in patients with diabetes.

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 &lt; 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 &lt; 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 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 Association between PTX3 and PVT1 genetic polymorphisms and the risk of diabetic kidney disease in type 2 diabetic patients

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Sindhu Varghese ◽  
Gowtham Kumar Subburaj
Keyword(s):  
Kidney Disease ◽  
Genetic Polymorphisms ◽  
Diabetic Kidney Disease ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Diabetic Kidney ◽  
Increased Risk ◽  
Type 2 Diabetic

Abstract Background Very few studies have investigated the role of PTX3 and PVT1 genetic polymorphisms and their association in the progression of diabetic kidney diseases. Diabetic kidney disease (DKD) is a prominent reason of end-stage renal disease and also known to be involved in the high mortality rate of cardiovascular diseases. The current study has examined the role of PTX3 and PVT1 genetic polymorphisms in the development of diabetic kidney disease in type 2 diabetic patients. Results A significant difference between the genotypes and alleles of the rs2305619 polymorphism was observed in the diabetic patients with DKD when compared with the control group. The frequency of GG genotype was observed to be high in diabetic patients with DKD when compared to the other two groups. This specified that diabetic patients with GG genotype are at an increased risk to develop DKD. However, PVT1 (G/A) polymorphism did not show any association in the allele and genotypic frequencies with DKD when compared with T2DM and controls. Conclusion Our results propose a major influence of GG genotype of rs2305619 polymorphism to be significantly linked with an increased risk of DKD in type 2 diabetic patients.

scholarly journals Prevalence and risk factors of diabetic kidney disease in north eastern Nigeria

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Ijuptil Chiroma ◽  
Mohammad Maina Sulaiman ◽  
Bilkisu Mohammed Mubi ◽  
Akilahyel Auta Ndahi ◽  
Ahidiyu Anaryu Mamza ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Stage Iv ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
North Eastern ◽  
Male Sex ◽  
Stage Renal Disease

Diabetic Kidney Disease (DKD) is a leading cause of chronic kidney disease and end stage renal disease. In northeastern Nigeria the epidemiology and risk factors have not been fully studied. This study aimed at evaluating the prevalence and risk factors of DKD in Maiduguri, north eastern Nigeria. The study population consisted of adult diabetic patients recruited consecutively at the diabetic clinic of University of Maiduguri Teaching Hospital Maiduguri. Socio-demographic variables including age, sex, weight, BMI, as well as laboratory parameters, were obtained from each patient. Glomerular filtration rate was derived from CKD-EPI formula using serum creatinine. Two hundred and sixty-one diabetic patients were recruited. The prevalence of DKD among them was 42.9%. Classification based on eGFRshowed that 35(13.4%) patients had hyperfiltration; 48 (18.4%) stage I; 66 (25.3%) stage II; 68 (26.1%) stage III; 36 (13.8%) stage IV; 8 (3.1%) stage V. One hundred and seventeen (44.8%) had proteinuria. Low eGFR <60ml/1.73M2 was associated with age >50 years (r=1.039, p=0.011); male sex (r=-0.899, p=0.008); hyperuricaemia (r=1.010, p=0.000); low PCV (r=1.276, p=0.000); HbA1C (r=1.127, p=0.030); proteinuria (r=2.011, p=0.004).This study has shown that chronic kidney disease is common among diabetic patients in northeastern Nigeria. Age, male sex, hyperuricaemia, low PCV, high HbA1C levels and proteinuria were found to be associated with development of DKD.

scholarly journals Roles of mTOR in Diabetic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 321
Author(s):  
Mako Yasuda-Yamahara ◽  
Shinji Kume ◽  
Hiroshi Maegawa
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cell Injury ◽  
Nutrient Sensing ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Number Of Patients ◽  
New Treatment ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.

scholarly journals The Podocyte in Diabetic Kidney Disease

2009 ◽  
Vol 9 ◽  
pp. 1127-1139 ◽  
Author(s):  
Erin Stitt-Cavanagh ◽  
Laura MacLoed ◽  
Chris R.J. Kennedy
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Peroxisome Proliferator ◽  
Diabetic Kidney ◽  
Cellular Hypertrophy ◽  
Treatment And Prevention ◽  
Filtration Barrier ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Approaching epidemic levels, diabetic kidney disease (DKD) is now the leading cause of end-stage renal disease (ESRD). Microalbuminuria is an early clinical marker of DKD that results from damage to the glomerular filtration barrier at the level of the highly differentiated glomerular podocyte cells. Injury to these epithelial cells, podocytopathies, includes cellular hypertrophy, foot process effacement, detachment from the glomerular basement membrane, and apoptosis. Here we review the role of a number of recently identified factors that contribute to podocytopathies in DKD. These factors include members of the renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) types 1 and 2, prorenin and its receptor, reactive oxygen species (ROS), prostanoids, peroxisome proliferator-activated receptors (PPAR), advanced glycation end-products (AGEs) and their receptors (RAGE), adiponectin, and microRNAs. As the number of therapeutic options that slow, but do not halt, the progression of DKD to ESRD remains limited, a more comprehensive understanding of the signaling events that contribute to this increasingly prevalent disease may identify novel avenues for treatment and prevention.

scholarly journals Interprofessional medication adherence programme for patients with diabetic kidney disease: a mixed randomized controlled and qualitative trial protocol (PANDIA-IRIS) (Preprint)

2020 ◽  
Author(s):  
Carole Bandiera ◽  
Jennifer Dotta-Celio ◽  
Isabella Locatelli ◽  
Dina Nobre ◽  
Grégoire Wuerzner ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Kidney Disease ◽  
Clinical Outcomes ◽  
Health Care Providers ◽  
Diabetic Kidney Disease ◽  
Clinical Success ◽  
Diabetic Patients ◽  
Care Providers ◽  
Diabetic Kidney ◽  
The Impact

BACKGROUND Despite effective treatments, more than 30% of diabetic patients will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programmes are crucial. The PANDIA-IRIS (« patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l’adhésion thérapeutique ») study is based on a routine medication adherence programme led by pharmacists. OBJECTIVE The aim of this study is to define the impact of the duration of this medication adherence programme on long-term adherence and the clinical outcomes in DKD patients. METHODS The monocentric adherence programme consists of short, repeated motivational interviews focused on patients’ medication behaviour combined with the use of electronic monitors (EM) that record each daily opening. In total, 72 patients are randomized 1:1 in two parallel arms; the adherence programme will last 6 months in the first arm versus 12 months in the second. After the intervention phases, patients continue using their EM for a total of 24 months, but without receiving feedback. EM and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation (GEE) multimodelling respectively. The evolution of the ADVANCE and UKPDS clinical scores based on medication adherence will be analysed with GEE models. Patients’ satisfaction with the study will be assessed through qualitative interviews, which will be transcribed verbatim, coded and analysed for main themes. RESULTS The study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, two amendments to the protocol have been approved in June 2017 and October 2019. Patients’ recruitment began in April 2016 and ended in October 2020. In total, 73 patients have been included. Data collection is ongoing, and data analysis is planned for 2022. CONCLUSIONS The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence programme on adherence and clinical outcomes of patients with diabetic kidney disease. Monitoring medication adherence during the post-intervention phase is innovative and will shed light on the duration of the intervention on medication adherence. CLINICALTRIAL The study has been registered at clinicaltrials.gov (n°NCT04190251_PANDIA IRIS).

Sign in / Sign up

Export Citation Format

Share Document