scholarly journals Chronic inflammation and progression of chronic kidney disease in patients with type 2 diabetes

2021 ◽  
pp. 36-43
Author(s):  
T. Mazur ◽  
N. Demikhova ◽  
T. Rudenko ◽  
A. Yurchenko ◽  
O. Yezhova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Chronic Inflammation ◽  
Diabetic Kidney Disease ◽  
Ckd Progression ◽  
Type 2 Dm ◽  
Tnf Α ◽  
Tgf Β1

Chronic inflammation, atherosclerosis, tubulointerstitial fibrosis, and vascular damage play a crucial role in the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (DM). However, specific biomarkers that can determine the progression of diabetic kidney disease, including patients with minimal albuminuria, remain undefined. The present study aimed to determine markers of chronic inflammation as indicators of CKD progression in patients with type 2 DM. Methods. 45 patients with type 2 DM and stage 1-3 CKD were involved in this cross-sectional observational study. Analysis of cellular mechanisms of CKD progression was performed on the concentrations of endothelin-1 (ET-1), fibronectin (FN), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta-1 (TGF-β1), and monocyte chemoattractant protein (MCP) -1) in the serum. Results. In patients with type 2 DM, an increasing trend in the majority of endothelial and proinflammatory mediators was found according to the CKD stages despite normal albuminuria. Conclusions. Concentrations of TNF-α, ET, TGF-β1 and MCP-1 can be used to assess the progression of CKD in patients with type 2 DM with normal albuminuria. Further researches are needed to determine early indicators of diabetic kidney disease progression.

scholarly journals Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers

2017 ◽  
Vol 10 ◽  
pp. 117864691769460 ◽  
Author(s):  
Subrata Debnath ◽  
Chakradhar Velagapudi ◽  
Laney Redus ◽  
Farook Thameem ◽  
Balakuntalam Kasinath ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Markers ◽  
Surrogate Marker ◽  
Inverse Association ◽  
Primary Case ◽  
Tnf Α ◽  
Associated Symptoms

Objective: Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD ( P < 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease ( P < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

scholarly journals Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone

2020 ◽  
Author(s):  
Rajiv Agarwal ◽  
Stefan D Anker ◽  
George Bakris ◽  
Gerasimos Filippatos ◽  
Bertram Pitt ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Diabetic Kidney Disease ◽  
Standard Of Care ◽  
Phase Iii ◽  
Diabetic Kidney ◽  
Mortality And Morbidity

Abstract Despite the standard of care, patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) progress to dialysis, are hospitalized for heart failure and die prematurely. Overactivation of the mineralocorticoid receptor (MR) causes inflammation and fibrosis that damages the kidney and heart. Finerenone, a nonsteroidal, selective MR antagonist, confers kidney and heart protection in both animal models and Phase II clinical studies; the effects on serum potassium and kidney function are minimal. Comprising the largest CKD outcomes program to date, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) are Phase III trials investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes from early to advanced CKD in T2D. By including echocardiograms and biomarkers, they extend our understanding of pathophysiology; by including quality of life measurements, they provide patient-centered outcomes; and by including understudied yet high-risk cardiorenal subpopulations, they have the potential to widen the scope of therapy in T2D with CKD. Trial registration number: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049)

Combined development of macrovascular and chronic kidney disease in type 2 diabetes associated with polymorphism of TNF-α gene

2016 ◽  
Vol 252 ◽  
pp. e143-e144
Author(s):  
O. Vikulova ◽  
N. Lebedeva ◽  
A. Zheleznyakova ◽  
A. Nikitin ◽  
M. Shamkhalova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tnf Α

scholarly journals Diabetic kidney disease: update on clinical management and non-glycaemic effects of newer medications for type 2 diabetes

2021 ◽  
Vol 12 ◽  
pp. 204201882110206
Author(s):  
Áine M. de Bhailís ◽  
Shazli Azmi ◽  
Philip A. Kalra
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Kidney ◽  
Renal Outcomes ◽  
First Choice ◽  
Treatment Of Diabetes

Type 2 diabetes is a leading cause of chronic kidney disease worldwide and continues to increase in prevalence. This in turn has significant implications for healthcare provision and the economy. In recent years there have been multiple advances in the glucose-lowering agents available for the treatment of diabetes, which not only modify the disease itself but also have important benefits in terms of the associated cardiovascular outcomes. The cardiovascular outcome trials of agents such as glucagon-like peptide-1 receptor agonists (GLP-RAs) and sodium glucose cotransporter 2 inhibitors (SGLT-2) have demonstrated significant benefits in reducing major adverse cardiovascular events, admissions for heart failure and in some cases mortality. Secondary analysis of these trials has also indicated significant renoprotective benefit. Canagliflozin and Renal Outcomes in Type 2 Diabetes Mellitus and Nephropathy (CREDENCE) a renal-specific trial, has shown major benefits with canagliflozin for renal outcomes in diabetic kidney disease, and similar trials with other SGLT-2 inhibitors are either underway or awaiting analysis. In this article we review current goals of treatment of diabetes and the implications of advancing renal impairment on choice of treatments. Areas discussed include the diagnosis of diabetic kidney disease and current treatment strategies for diabetic kidney disease ranging from lifestyle modifications to glycaemic control. This review focuses on the role of GLP-RAs and SGLT-2 inhibitors in treating those with diabetes and chronic kidney disease with some illustrative cases. It is clear that these agents should now be considered first choice in combination with metformin in those with diabetes and increased cardiovascular risk and/or reduced renal function, and in preference to other classes such as dipeptidyl peptidase-4 (DPP-4) inhibitors or sulphonylureas.

scholarly journals Effects of SGLT2 inhibitors on cardiovascular death and all-cause death in patients with type 2 diabetes and chronic kidney disease: an updated meta-analysis including the SCORED trial

2021 ◽  
Vol 12 ◽  
pp. 204201882110449
Author(s):  
Li-Min Zhao ◽  
Ze-Lin Zhan ◽  
Mei Qiu
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Ckd Progression ◽  
Meta Analyses

Background: The effects of sodium-glucose transporter 2 (SGLT2) inhibitors on cardiovascular death (CV death) and all-cause death (AC death) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are currently under intensive investigation. We intended to conduct an updated meta-analysis including the SCORED trial to evaluate the effects of SGLT2 inhibitors on death and cardiorenal events in this vulnerable population. Methods: Cardiorenal outcome trials of SGLT2 inhibitors were included. Primary outcomes were CV death and AC death, while secondary outcomes were hospitalization for heart failure (HHF), myocardial infarction (MI), CKD progression, cardiovascular death or hospitalization for heart failure (CV death or HHF), major adverse cardiovascular events (MACE), and stroke. Meta-analysis was conducted for each outcome. Results: Eight trials were included for meta-analysis. Compared with placebo, SGLT2 inhibitors significantly lowered the risk of CV death (HR = 0.86, 95% CI = 0.75–0.98), AC death (HR = 0.87, 95% CI = 0.79–0.96), HHF (HR = 0.64, 95% CI = 0.56–0.74), MI (HR = 0.76, 95% CI = 0.65–0.89), CKD progression (HR = 0.62, 95% CI = 0.54–0.72), and CV death or HHF (HR = 0.73, 95% CI = 0.67–0.80). No heterogeneity existed in the above meta-analyses (all I2 values = 0%), whereas moderate heterogeneity existed in the meta-analyses for MACE and stroke (I2 = 31.6% and 44.5%, respectively). Conclusions: Our findings suggest that SGLT2 inhibitors versus placebo significantly lower death, heart failure, renal failure, and MI events in patients with T2D and CKD. Head-to-head trials are needed to examine the possible differences in the effects of various gliflozins on MACE and stroke.

Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients

Biomarkers ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Shadia A. Fathy ◽  
Mohamed R. Mohamed ◽  
Mohamed A. M. Ali ◽  
Ashraf E. EL-Helaly ◽  
Abdulnabi T. Alattar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Genetic Variants ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals P1005LONG NONCODING RNAS MAY INTERVENE IN PODOCYTE INJURY AND PROXIMAL TUBULE DYSFUNCTION THROUGH MODULATING MIRNAS EXPRESSION IN EARLY DIABETIC KIDNEY DISEASE OF TYPE 2 DIABETES MELLITUS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ligia Petrica ◽  
FLORICA GADALEAN ◽  
ADRIAN VLAD ◽  
Mihaela Vlad ◽  
VICTOR DUMITRASCU ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Noncoding Rnas ◽  
Type 2 Dm ◽  
Lncrna Malat1 ◽  
Mirnas Expression

Abstract Background and Aims Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p&lt;0.0001; R2=0.727); urinary lncRNA NEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, and 29a (p&lt;0.0001; R2=0.702); urinary lncRNA MIAT correlated directly with miRNA93 and 29a, and eGFR (p&lt;0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, and 124 (p&lt;0.0001; R2=0.654); urinary lncRNA TUG1 correlated directly with eGFR, miRNA93 and 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, and 124 (p&lt;0.0001; R2=0.748). The results provided document upregulated lncRNA MALAT1 and NEAT1, as well as miRNA21 and 124. By contrast, lncRNA MIAT and TUG1, and miRNA93 and 29a were downregulated. Conclusion In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

scholarly journals Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease

2020 ◽  
Vol 8 (1) ◽  
pp. e000991 ◽  
Author(s):  
Laura Mayeda ◽  
Ronit Katz ◽  
Iram Ahmad ◽  
Nisha Bansal ◽  
Zona Batacchi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Peripheral Neuropathy ◽  
Kidney Disease ◽  
Glucose Monitoring ◽  
Type 2 Dm ◽  
Time In Range

​ObjectiveCompared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD.​Research design and methodsWe enrolled 105 people with type 2 DM treated with insulin or sulfonylurea, 81 participants with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) and 24 matched control participants with eGFR ≥60 mL/min/1.73 m2. Each participant wore a CGM for two 6-day periods. Calculated glycemic measures included TIR (glucose 70–180 mg/dL) and glucose management indicator (GMI). DPN symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire, with a positive MNSI score defined as ≥2 symptoms.​ResultsParticipants with CKD had a mean age of 68 years, diabetes duration 20 years, eGFR 38 mL/min/1.73 m2 and HbA1c 7.8%, 61 mmol/mol. Sixty-two participants reported ≥2 DPN symptoms, 51 (63%) with CKD and 11 (46%) controls. Less TIR and higher GMI were associated with higher risk of MNSI questionnaire score ≥2 (OR 1.25 (95% CI 1.02 to 1.52) per 10% lower TIR, and OR 1.79 (95% CI 1.05 to 3.04) per 1% higher GMI, adjusting for age, gender and race). Similar results were observed when analyses were restricted to participants with CKD. In contrast, there was no significant association of HbA1c with DPN symptoms.​ConclusionsSymptoms of DPN were common among participants with long-standing type 2 DM and CKD. Lower TIR and higher GMI were associated with DPN symptoms.

Interleukins and miRNAs intervene in the early stages of diabetic kidney disease in Type 2 diabetes mellitus patients

2019 ◽  
Vol 13 (18) ◽  
pp. 1577-1588 ◽  
Author(s):  
Ligia Petrica ◽  
Oana Milas ◽  
Mihaela Vlad ◽  
Adrian Vlad ◽  
Florica Gadalean ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Case Series ◽  
Diabetic Kidney ◽  
Type 2 Dm ◽  
Case Series Study

Aim: The involvement of proinflammatory interleukins (IL) in diabetic kidney disease of Type 2 diabetes mellitus (DM) patients was studied in relation to a particular miRNA profile. Materials & methods: A total of 117 patients with Type 2 DM and 11 controls were enrolled in a case series study. Serum and urinary ILs and miRNAs were assessed. Results: IL-1α correlated with miRNA21, 124, estimated glomerular filtration rate (eGFR) and negatively with miRNA125a and 192; IL-8 with miRNA21, 124, eGFR and negatively with miRNA125a, 126 and 146a; IL-18 with miRNA21, 124 and negatively with miRNA146a, 192, eGFR. Conclusion: There is an association between specific serum and urinary ILs and serum and urinary miRNAs profiles in the inflammatory response in Type 2 DM patients with diabetic kidney disease.

scholarly journals Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Takayuki Yamada ◽  
Mako Wakabayashi ◽  
Abhinav Bhalla ◽  
Nitin Chopra ◽  
Hirotaka Miyashita ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Renal Outcomes ◽  
Receptor Agonists ◽  
Type 2 Dm

Abstract Background Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients. Methods We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. Results Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75–0.96] and 0.68 [0.59–0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80–1.04] and 0.86 [0.72–1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78–1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63–0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69–0.95]), while exendin-4 analogues did not (RR 1.03 [0.88–1.20]). Conclusions In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

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