scholarly journals Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis

2020 ◽  
Vol 13 (4) ◽  
pp. 666-673
Author(s):  
Annalisa Terranegra ◽  
Teresa Arcidiacono ◽  
Lorenza Macrina ◽  
Caterina Brasacchio ◽  
Francesca Pivari ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Gene Ontology ◽  
Kidney Disease ◽  
Genetic Markers ◽  
Genetic Variants ◽  
Fixation Index ◽  
Gene Ontology Analysis ◽  
Cox Regression Analysis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background Chronic kidney disease (CKD) patients under hemodialysis show a higher risk of cardiovascular (CV) mortality and morbidity than the general population. This study aims to identify genetic markers that could explain the increased CV risk in hemodialysis. Methods A total of 245 CKD patients under hemodialysis were recruited and followed up for 5 years to record CV events. Genetic analysis was performed using single-nucleotide polymorphisms (SNPs) genotyping by Infinium Expanded Multi-Ethnic Genotyping Array (Illumina, San Diego, CA, USA) comparing patients with and without a history of CV events [161 cardiovascular diseases (CVDs) and 84 no CVDs]. The fixation index (Fst) measure was used to identify the most differentiated SNPs, and gene ontology analysis [Protein Analysis THrough Evolutionary Relationships (PANTHER) and Ingenuity Pathway Analysis (IPA)] was applied to define the biological/pathological roles of the associated SNPs. Partitioning tree analysis interrogated the genotype–phenotype relationship between discovered genetic variants and CV phenotypes. Cox regression analysis measured the effect of these SNPs on new CV events during the follow-up (FU). Results Fst analysis identified 3218 SNPs that were significantly different between CVD and no CVD. Gene ontology analysis identified two of these SNPs as involved in cardiovascular disease pathways (Ingenuity Pathway) and heart development (Panther) and belonging to 2 different genes: Glucagon-like peptide-1 receptor (GLP1R) and Sarcoglycan delta (SGCD). The phenotype–genotype analysis found a higher percentage of CVD patients carrying the GLP1R rs10305445 allele A (P = 0.03) and lower percentages of CVD patients carrying the SGCD rs145292439 allele A (P = 0.038). Moreover, SGCD rs145292439 was associated with higher levels of high-density lipoprotein (P = 0.015). Cox analysis confirmed the increased frequency of CV events during the 5-year FU in patients carrying GLP1R rs1035445 allele A but it did not show any significant association with SGCD rs145292439. Conclusions This study identified GLP1R rs10305445 and SCGD rs145292439 as potential genetic markers that may explain the higher risk of CVD in hemodialysis patients.

scholarly journals Renal Tubular Glucagon-Like Peptide-1 Receptor Expression Is Increased in Early Sepsis but Reduced in Chronic Kidney Disease and Sepsis-Induced Kidney Injury

2019 ◽  
Vol 20 (23) ◽  
pp. 6024
Author(s):  
Jae Hyun Choi ◽  
Seung Jung Kim ◽  
Soon Kil Kwon ◽  
Hye-Young Kim ◽  
Hyunjung Jeon
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Receptor Expression ◽  
Sepsis Group ◽  
Renal Tubules ◽  
Cecal Perforation ◽  
Glucagon Like Peptide ◽  
Early Sepsis ◽  
Glucagon Like Peptide 1

Acute kidney injury (AKI) is common in patients with sepsis and causes renal ischemia. Glucagon-like peptide-1 (GLP-1) protects the vascular system and the kidney, and GLP-1 receptor (GLP-1R) is expressed in the kidney. Renal GLP-1R activity is decreased in chronic kidney disease (CKD), but is increased by the inflammatory response; however, the effect of AKI on GLP-1R expression is unknown. We investigated the role of GLP-1 by assessing GLP-1R expression in the renal cortex in animals with AKI-related sepsis, CKD, and CKD-with-sepsis. We generated a model of CKD by 5/6 nephrectomy, and sepsis induced by cecal perforation, in male Sprague–Dawley rats. We compared renal GLP-1R expression at 3, 6, 12, 24, and 72 h after cecal perforation, and in CKD and CKD-with-sepsis. We performed blood and urine tests, western blotting (WB), and immunohistochemistry (IHC) to assay GLP-1R expression in renal tubules. The CKD-with-sepsis group showed the lowest kidney function, urine volume, and serum glucose and albumin levels. GLP-1R expression in renal tubules was decreased at 3 h, increased at 24 h, and decreased at 72 h after sepsis induction. GLP-1R expression was decreased at 8 weeks after CKD and was lowest in the CKD-with-sepsis group. The WB results were verified against those obtained by IHC. GLP-1R expression in renal tubules is increased in early sepsis, which may explain the protective effect of endogenous GLP-1 against sepsis-related inflammation.

scholarly journals The effect of modern hypoglycemic therapy on the course of chronic kidney disease in patients with type 2 diabetes mellitus

2021 ◽  
Vol 17 (8) ◽  
pp. 624-632
Author(s):  
V.I. Katerenchuk
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Sodium Glucose Cotransporter ◽  
Combined Use ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The article presents the literature review of the possibilities of modern antidiabetic therapy in the prevention of chronic kidney disease in patients with type 2 diabetes mellitus. The mechanisms of development and features of kidney disease in type 2 diabetes mellitus are described. The results of most recent clinical trials for studying the possibility of nephroprotection with new groups of hypoglycemic agents are reviewed: dipeptidyl peptidase-4 inhi-bitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors. The advantages of usage and the nephroprotective effects of agonists of glucagon-like peptide-1 receptors and sodium-glucose loop cotransporter-2 inhibitors are determined. Particular attention is paid to the nephroprotective effect of sodium-glucose loop co-transporter inhibitors as the only class of drugs that have demonstrated a reduction in the rate of decrease in glomerular filtration rate in patients with diabetes. The expediency of further study of the efficacy of the combined use of sodium-glucose cotransporter-2 inhibitors and agonists of glucagon-like peptide-1 receptors in diabetic chronic kidney disease is indicated. For a long time, approaches to the treatment of diabetic kidney disease did not differ for patients with type 1 and type 2 diabetes. The stu­dies of recent years have shown that new hypoglycemic drugs can not only lower blood glucose levels but also have a beneficial effect on renal function. The mechanisms of nephroprotective effects have not been fully studied, but it is clear that they are beyond the scope of improved glycemic control. The possibility of the nephroprotective effect of these drugs on a glomerular filtration rate in the range of 30–15 ml/min/1.73 m2 and below remains unexplored. The effect of the combined use of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors is also unclear: will this combination predominate over monotherapy, and, if so, to what extent?

scholarly journals The Comparison of the Kidney Effects of Dipeptidyl Peptidase 4 Inhibitors and Glucagon-Like Peptide 1 Agonist-Administered Concomitant with Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients with Type Diabetes Mellitus and Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Kazuo Kobayashi ◽  
Masao Toyoda ◽  
Nobuo Hatori ◽  
Kazuyoshi Sato ◽  
Masaaki Miyakawa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Japanese Patients ◽  
Dipeptidyl Peptidase ◽  
Concomitant Treatment ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background and Aim. Strong evidence exists supporting the utility of sodium glucose cotransporter inhibitors (SGLT2is) for treating not only cardiovascular events but also renal events. We previously reported that SGLT2is improved the urine albumin-to-creatine ratio (ACR) in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Only 8% of patients were treated with SGLT2is alone, and more than 70% of them additionally received incretin-related agents, such as dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide 1 agonist (GLP1Ra). Both agents reduce the plasma glucose level with an incretin effect, but the differences in the renoprotective effects between these agents are poorly understood. Methods. We retrospectively constructed database of 763 Japanese patients with T2DM and CKD who received sSGLT2is for more than 1 year. Among these SGLT2i-treated patients, 338 were receiving concomitant DPP4i (DPP4i group), and 99 were receiving concomitant GLP1Ra (GLP1Ra group). The two groups were compared using the propensity score matching method. Results. In the matched model including 86 cases per group, the decrease in the logarithmic value of the ACR and rate of reduction in the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) of the GLP1Ra group showed no significant difference from those in the DPP4i group ( − 0.12 ± 0.48 vs. − 0.13 ± 0.45 and − 2.3 ± 18.5 vs. − 6.2 ± 13.8 , respectively, P = 0.10 ). However, the incidence of a >6.4% decrease in the eGFR was significantly lower in the GLP1Ra group than in the DPP4i group (35% vs. 52%, respectively, P = 0.03 ). The level of hemoglobin A1c (mmol/mol) after SGLT2i treatment was significantly lower in the DPP4i group than in the GLP1Ra group in the matched model ( 58.3 ± 11.8 and 62.7 ± 14.8 , respectively, P = 0.02 ). Conclusion. Among the SGLT2i-treated patients with T2DM and CKD, concomitant treatment with GLP1Ra has a marked improving effect on the change in the eGFR.

scholarly journals Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease

2017 ◽  
Vol 313 (2) ◽  
pp. R149-R157 ◽  
Author(s):  
Gao-Jue Wu ◽  
Xu-Dong Cai ◽  
Jie Xing ◽  
Guang-Hui Zhong ◽  
Jiande D. Z. Chen
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Slow Waves ◽  
Gastric Slow Waves ◽  
Gi Symptoms ◽  
Dyspeptic Symptoms ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Upper Gastrointestinal

Patients with chronic kidney disease (CKD) commonly complain upper gastrointestinal (GI) symptoms, especially anorexia. Hemodialysis (HD) has been noted to improve GI symptoms; however, the underlying mechanisms are unclear. This study was designed 1) to study effects of HD on GI symptoms and gastric slow waves; and 2) to investigate possible roles of ghrelin and glucagon-like peptide-1 (GLP-1): the study recruited 13 healthy controls, 20 CKD patients without HD (CKD group), and 18 CKD patients with HD (HD group). Dyspeptic symptoms, autonomic functions, gastric slow waves, and plasma level of ghrelin and GLP-1 were analyzed. First, the CKD patients with HD showed markedly lower scores of anorexia (0.6 ± 0.2 vs. 3.2 ± 0.4, P < 0.001) compared with patients without HD. Second, the CKD group but not HD group showed a significant reduction (25.6%) in the percentage of normal gastric slow waves, compared with controls. Third, the CKD group exhibited a significantly lower ghrelin level compared with the HD group (26.8 ± 0.9 vs. 34.1 ± 2.3 ng/l, P < 0.02) and a higher GLP-1 level (29.4 ± 2.8 vs. 20.0 ± 2.1 pmol/l, P < 0.05) compared with controls. Moreover, the percentage of normal slow waves was positively correlated with ghrelin ( r = 0.385, P = 0.019) but negatively correlated with GLP-1 ( r = −0.558, P < 0.001) in all CKD patients. Hemodialysis improves upper GI symptoms and gastric slow waves in CKD patients. An increase in ghrelin and a decrease in GLP-1 might be involved in the HD-induced improvement in gastric slow waves.

scholarly journals Impact of antithrombotic therapy in the prognosis of atrial fibrillation patients with advanced chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.M Andreu Cayuelas ◽  
S Raposeiras-Roubin ◽  
E Fortuny Frau ◽  
A Garcia Del Egido ◽  
J Seller-Moya ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antithrombotic Therapy ◽  
Anticoagulation Therapy ◽  
Bleeding Event ◽  
Funding Source ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Cox Regression Analysis

Abstract Introduction Chronic kidney disease (CKD) is associated with an elevated thromboembolic and bleeding risk in atrial fibrillation (AF) patients, so the decision of antithrombotic therapy is a challenge. Purpose To analyze mortality, embolic and bleeding events in patients with advanced CKD and AF. Methods Multicentric retrospective registry on patients with AF and advanced CKD (CKD-EPI &lt;30 mL/min/1.73 m2). For death, multivariable Cox regression analysis was developed. For embolic and bleeding events, competing-risks regression based on Fine and Gray's proportional subhazards model was performed, being death the competing event Results We analysed 405 patients with advanced CKD and newly diagnosed AF. 57 patients were not treated with antithrombotic therapy (14.1%), 80 only with antiplatelet/s (19.8%), 211 only with anticoagulation (52.1%), and 57 with anticoagulant plus antiplatelet/s (14.1%). During a follow-up of 4.6±2.5 years, 205 died (50.6%), 34 had embolic events (8.4%) and 85 had bleeding outcomes (21.0%). Bleeding event rate was significantly lower in patients without antithrombotic therapy (Figure). After multivariate analysis, anticoagulant treatment was associated with higher bleeding rates, without differences in mortality or embolic events (Table). Conclusion Anticoagulation therapy was associated with a significant increase in bleeding events in patients with advanced CKD and newly diagnosed AF. None of the antithrombotic therapy regimens resulted in lower embolic events rate neither benefit in mortality. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unconditional grant from BMS-Pfizer

scholarly journals Association of chronic kidney disease with mortality risk in patients with lung cancer: a nationwide Taiwan population-based cohort study

BMJ Open ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. e019661 ◽  
Author(s):  
Yu-Feng Wei ◽  
Jung-Yueh Chen ◽  
Ho-Shen Lee ◽  
Jiun-Ting Wu ◽  
Chi-Kuei Hsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Renal Disease ◽  
Mortality Risk ◽  
Population Based ◽  
Research Database ◽  
Cox Regression Analysis ◽  
Increased Risk

ObjectiveOur population-based research aimed to clarify the association between chronic kidney disease (CKD) and mortality risk in patients with lung cancer.DesignRetrospective cohort studySettingNational health insurance research database in TaiwanParticipantsAll (n=1 37 077) Taiwanese residents who were diagnosed with lung cancer between 1997 and 2012 were identified. Eligible patients with baseline CKD (n=2269) were matched with controls (1:4, n=9076) without renal disease according to age, sex and the index day of lung cancer diagnosis.MethodsThe cumulative incidence of death was calculated by the Kaplan-Meier method, and the risk determinants were explored by the Cox proportional hazards model.ResultsMortality occurred in 1866 (82.24%) and 7135 (78.61%) patients with and without CKD, respectively (P=0.0001). The cumulative incidences of mortality in patients with and without chronic renal disease were 72.8% vs 61.6% at 1 year, 82.0% vs 76.6% at 2 years and 88.9% vs 87.2% at 5 years, respectively. After adjusting for multiple confounding factors including age and comorbidities, Cox regression analysis revealed that CKD was associated with an increased risk of mortality (adjusted HR 1.38; 95% CI 1.29 to 1.47). Stratified analysis further showed that the association was consistent across patient subgroups.ConclusionComorbidity associated with CKD is a risk factor for mortality in patients with lung cancer.

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