Update on diagnosis, pathophysiology, and management of diabetic kidney disease

Sugahara, Mai; Pak, Wai Lun Will; Tanaka, Tetsuhiro; Tang, Sydney C. W.; Nangaku, Masaomi

doi:10.1111/nep.13860

Cited by 76 publications

(84 citation statements)

References 116 publications

(122 reference statements)

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“…The pathogenesis of DKD is complex, and multiple pathways involve several years before clinical diagnosis of DKD. The pro-inflammatory and pro-fibrotic processes during DKD development and progression result from metabolic alterations, hyperfiltration, reactive oxidative stress (ROS), immune and inflammation activation, and subsequent fibrosis [11][12][13][14][15]. DKD usually is classified as a non-inflammatory glomerular disease; however, genome-wide transcriptome analysis studies consistently indicate the strong presence of inflammatory signaling pathways [16].…”

Section: The Role Of Inflammation In the Patho-physiology Of Dkdmentioning

confidence: 99%

The role of inflammation in diabetic kidney disease

Jung

Moon

2021

Korean J Intern Med

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Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease for over 20 years. Yet, over these two decades, the clinical approach to this condition has not much improved beyond the administration of glucose-lowering agents, renin-angiotensin-aldosterone system blockers for blood pressure control, and lipid-lowering agents. The proportion of diabetic patients who develop DKD and progress to end-stage renal disease has remained nearly the same. This unmet need for DKD treatment is caused by the complex pathophysiology of DKD, and the difficulty of translating treatment from bench to bed, which further adds to the growing argument that DKD is not a homogeneous disease. To better capture the full spectrum of DKD in our design of treatment regimens, we need improved diagnostic tools that can better distinguish the subgroups within the condition. For instance, DKD is typically placed in the broad category of a non-inflammatory kidney disease. However, genome-wide transcriptome analysis studies consistently indicate the inflammatory signaling pathway activation in DKD. This review will utilize human data in discussing the potential for redefining the role of inflammation in DKD. We also comment on the therapeutic potential of targeted anti-inflammatory therapy for DKD.

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Section: The Role Of Inflammation In the Patho-physiology Of Dkdmentioning

confidence: 99%

The role of inflammation in diabetic kidney disease

Jung

Moon

2021

Korean J Intern Med

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“…Reportedly, liraglutide suppresses autophagy in human kidney-2 cells and diabetic rat kidneys [ 117 ]. In experimental models, however, GLP-1 appears to regulate autophagy flux positively through the AMPK-mTOR signaling pathway [ 117 , 118 , 119 , 120 ]. In addition, GLP1 receptor agonists can also contribute to the restoration of autophagy balance in kidney tissues through the reduction of glycemia, inflammation, and oxidative stress [ 118 , 119 ].…”

Section: Potential Implications For the Pharmacological Treatment And Prevention Of Dkd Focus On New Antidiabetic Agentsmentioning

confidence: 99%

Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions

Gonzalez

Negueruela

Santamarina

et al. 2021

Cells

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Diabetic kidney disease (DKD) is a frequent, potentially devastating complication of diabetes mellitus. Several factors are involved in its pathophysiology. At a cellular level, diabetic kidney disease is associated with many structural and functional alterations. Autophagy is a cellular mechanism that transports intracytoplasmic components to lysosomes to preserve cellular function and homeostasis. Autophagy integrity is essential for cell homeostasis, its alteration can drive to cell damage or death. Diabetic kidney disease is associated with profound autophagy dysregulation. Autophagy rate and flux alterations were described in several models of diabetic kidney disease. Some of them are closely linked with disease progression and severity. Some antidiabetic agents have shown significant effects on autophagy. A few of them have also demonstrated to modify disease progression and improved outcomes in affected patients. Other drugs also target autophagy and are being explored for clinical use in patients with diabetic kidney disease. The modulation of autophagy could be relevant for the pharmacological treatment and prevention of this disease in the future. Therefore, this is an evolving area that requires further experimental and clinical research. Here we discuss the relationship between autophagy and Diabetic kidney disease and the potential value of autophagy modulation as a target for pharmacological intervention.

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“…The process begins with glomerular hyperfiltration progressing to microalbuminuria, macroalbuminuria, and subsequent decrease in the glomerular filtration rate (GFR), eventually leading to ESKD. In recent years, however, a growing number of cases of chronic kidney disease (CKD) associated with diabetes mellitus, in which GFR decreases without albuminuria, has been recognized as a new subgroup of DKD [2]. This form of progression is thought to be due to the aging of the diabetic population and the widespread use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which suppress intraglomerular pressure.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease

2021

Self Cite

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Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease, and it is crucial to understand the pathophysiology of DKD. The control of blood glucose levels by various glucose-lowering drugs, the common use of inhibitors of the renin–angiotensin system, and the aging of patients with diabetes can alter the disease course of DKD. Moreover, metabolic changes and associated atherosclerosis play a major role in the etiology of DKD. The pathophysiology of DKD is largely attributed to the disruption of various cellular stress responses due to metabolic changes, especially an increase in oxidative stress. Therefore, many antioxidants have been studied as therapeutic agents. Recently, it has been found that NRF2, a master regulator of oxidative stress, plays a major role in the pathogenesis of DKD and bardoxolone methyl, an activator of NRF2, has attracted attention as a drug that increases the estimated glomerular filtration rate in patients with DKD. This review outlines the altered stress responses of cellular organelles in DKD, their involvement in the pathogenesis of DKD, and discusses strategies for developing therapeutic agents, especially bardoxolone methyl.

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Update on diagnosis, pathophysiology, and management of diabetic kidney disease

Cited by 76 publications

References 116 publications

The role of inflammation in diabetic kidney disease

The role of inflammation in diabetic kidney disease

Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions

Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease

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