scholarly journals Roles of Gut Microbial Metabolites in Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Fang ◽  
Na Liu ◽  
Binjie Zheng ◽  
Fei Guo ◽  
Xiangchang Zeng ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Microbial Metabolites ◽  
Therapeutic Approaches ◽  
Diabetic Kidney ◽  
Global Challenge ◽  
Physiological Processes ◽  
Health And Disease

Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.

scholarly journals Mitophagy in Diabetic Kidney Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaofeng Zhang ◽  
Jing Feng ◽  
Xia Li ◽  
Dan Wu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Therapeutic Approaches ◽  
End Stage Kidney Disease ◽  
Common Cause ◽  
Diabetic Kidney ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
End Stage

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease worldwide and is the main microvascular complication of diabetes. The increasing prevalence of diabetes has increased the need for effective treatment of DKD and identification of new therapeutic targets for better clinical management. Mitophagy is a highly conserved process that selectively removes damaged or unnecessary mitochondria via the autophagic machinery. Given the important role of mitophagy in the increased risk of DKD, especially with the recent surge in COVID-19-associated diabetic complications, in this review, we provide compelling evidence for maintaining homeostasis in the glomeruli and tubules and its underlying mechanisms, and offer new insights into potential therapeutic approaches for treatment of DKD.

scholarly journals Role of Nox2 in diabetic kidney disease

2013 ◽  
Vol 304 (7) ◽  
pp. F840-F848 ◽  
Author(s):  
Young-Hyun You ◽  
Shinichi Okada ◽  
San Ly ◽  
Karin Jandeleit-Dahm ◽  
David Barit ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Macrophage Infiltration ◽  
Diabetic Kidney

NADPH oxidase (Nox) isoforms have been implicated in contributing to diabetic microvascular complications, but the functional role of individual isoforms in diabetic kidney are unclear. Nox2, in particular, is highly expressed in phagocytes and may play a key inflammatory role in diabetic kidney disease. To determine the role of Nox2, we evaluated kidney function and pathology in wild-type (WT; C57BL/6) and Nox2 knockout (KO) mice with type 1 diabetes. Diabetes was induced in male Nox2 KO and WT mice with a multiple low-dose streptozotocin protocol. Groups were studied for kidney disease after 8 and 20 wk of diabetes. Hyperglycemia and body weights were similar in WT and Nox2 KO diabetic mice. All functional and structural features of early and later stage diabetic kidney disease (albuminuria, mesangial matrix, tubulointerstitial disease, and gene expression of matrix and transforming growth factor-β) were similar in both diabetic groups compared with their respective nondiabetic groups, except for reduction of macrophage infiltration and monocyte chemoattractant protein-1 in the diabetic Nox2 KO mice. Systolic blood pressure by telemetry was surprisingly increased in Nox2 KO mice; however, the systolic blood pressure was reduced in the diabetic WT and Nox2 KO mice by tail-cuff. Interestingly, diabetic Nox2 KO mice had marked upregulation of renal Nox4 at both the glomerular and cortical levels. The present results demonstrate that lack of Nox2 does not protect against diabetic kidney disease in type 1 diabetes, despite a reduction in macrophage infiltration. The lack of renoprotection may be due to upregulation of renal Nox4.

scholarly journals Diabetic Kidney Disease in Childhood and Adolescence: Conventional and Novel Renoprotective Strategies

2020 ◽  
pp. 68-77
Author(s):  
Samuel N Uwaezuoke ◽  
Adaeze C Ayuk
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Clinical Syndrome ◽  
Clinical Staging ◽  
Childhood And Adolescence ◽  
Diabetic Kidney ◽  
Haemodynamic Changes ◽  
End Stage

Diabetic kidney disease (DKD) is defined as a clinical syndrome consisting of persistent macroalbuminuria, progressive decline in glomerular filtration rate (GFR), hypertension, increased cardiovascular disease events, and the associated mortality of these conditions. The disease evolves from the microvascular complications of poorly controlled Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). The pathogenic pathways comprise renal haemodynamic changes, ischaemia and inflammation, and overactive renin–angiotensin–aldosterone system (RAAS), through which several events cascade down from hyperglycaemia to renal fibrosis. Conventional and novel renoprotective strategies target modifiable DKD risk factors and specific stages of the pathogenic pathways, respectively. Although these strategies may slow DKD progression to end-stage kidney disease (ESKD), novel drugs are still undergoing trials for validation in human participants. This narrative review appraises these renoprotective strategies and highlights the current clinical staging and pathogenesis of the disease.

Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study

2018 ◽  
Vol 72 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Zahra Aryan ◽  
Alireza Ghajar ◽  
Sara Faghihi-Kashani ◽  
Mohsen Afarideh ◽  
Manouchehr Nakhjavani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
High Sensitivity ◽  
Population Based ◽  
End Points ◽  
Diabetic Kidney ◽  
Reactive Protein ◽  
Hs Crp ◽  
Traditional Risk Factors

Background/Aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024–1.032) for CHD, 1.025 (1.021–1.029) for diabetic neuropathy, 1.037 (1.030–1.043) for diabetic retinopathy, and 1.035 (1.027–1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D.

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 Role of TGF-alpha in the progression of diabetic kidney disease

2017 ◽  
Vol 312 (6) ◽  
pp. F951-F962 ◽  
Author(s):  
Josef G. Heuer ◽  
Shannon M. Harlan ◽  
Derek D. Yang ◽  
Dianna L. Jaqua ◽  
Jeffrey S. Boyles ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Neutralizing Antibodies ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Neutralizing Antibody ◽  
Diabetic Kidney

Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease.

The Role of Insulin-like Growth Factors in Diabetic Kidney Disease

1993 ◽  
Vol 22 (5) ◽  
pp. 722-726 ◽  
Author(s):  
Derek LeRoith ◽  
Haim Werner ◽  
Moshe Phillip ◽  
Charles T. Roberts
Keyword(s):  
Growth Factors ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Insulin Like Growth Factors
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