Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets

Toth‐Manikowski, Stephanie M.; Atta, Mohamed G.

doi:10.1155/2015/697010

Cited by 158 publications

(168 citation statements)

References 178 publications

(204 reference statements)

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“…In addition to CVD, chronic hyperglycaemia leads to microvascular complications in patients with T2D, including kidney disease, retinopathy and neuropathy . The underlying mechanisms of diabetic kidney disease include changes in haemodynamic, metabolic and inflammatory pathways that result in impaired renal function (Figure ) . Chronic hyperglycaemia in patients with T2D may also contribute to the development of diabetic kidney disease by inducing thickening of the glomerular basement membrane and podocyte injury .…”

Section: Mechanisms Of CV and Renal Protection With Sglt‐2 Inhibitorsmentioning

confidence: 99%

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Chilton

2019

Diabetes Obesity Metabolism

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Sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) have been shown to mitigate the risks of cardiovascular (CV) and renal complications in patients with type 2 diabetes (T2D) and CV risk factors or CV disease (CVD). In CV outcomes trials (CVOTs) of patients with T2D and established CVD or multiple CV risk factors, empagliflozin and canagliflozin were associated with significant reductions in the risks of major adverse CV events (MACE), hospitalization for heart failure (HF) and kidney disease progression. In the DECLARE–TIMI 58 study, in which the majority of patients did not have established CVD, dapagliflozin was associated with significant reductions in the composite end point of CV death or hospitalization for HF and was noninferior to placebo with regard to MACE; although patients had relatively good renal function, dapagliflozin also showed renal benefits similar to those seen with empagliflozin and canagliflozin. This article reviews the increased risk of CVD and renal disease in patients with T2D and discusses the potential mechanisms of the cardioprotective and renoprotective effects of SGLT‐2i therapy. The observed improvements in CV and renal outcomes with SGLT‐2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add‐on therapy to metformin is initiated in patients with T2D and high CV risk. The overall cardioprotective and renoprotective effects of SGLT‐2is in patients with T2D and high CV risk are most likely attributable to multiple mechanisms, including cardiac, haemodynamic, metabolic, anti‐inflammatory and renal effects.

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Section: Mechanisms Of CV and Renal Protection With Sglt‐2 Inhibitorsmentioning

confidence: 99%

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Chilton

2019

Diabetes Obesity Metabolism

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“…This increased filtration pressure promotes glomerular injury, eventually leading to glomerular sclerosis (Figure ) . Additionally, endothelin 1 is thought to play a role in increasing efferent arteriolar vasoconstriction . Metabolism and inflammation in the context of diabetic nephropathy are intimately related.…”

Section: Sglt2 Inhibitors and Diabetic Vascular Complicationsmentioning

confidence: 99%

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

Silva-Cardoso

Sheikh

Nashawi

et al. 2019

Journal of Diabetes

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Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs that were primarily developed for the treatment of type 2 diabetes mellitus. However, these agents have shown to provide additional beneficial effects. We will discuss three main topics regarding the use of SGLT2 inhibitors: noncardiovascular effects, cardiovascular benefits, and novel clinical indications. Multiple clinical trials and preliminary studies across varying disciplines have shown that these agents exhibit cardiorenal‐protective benefits, retinoprotective benefits, and may aid in weight loss without causing marked hypoglycemia. Therefore, these agents represent an avenue in clinical practice to manage comorbid conditions in the hyperglycemic patient. Because of their multifaceted effects and robust action, SGLT2 inhibitors represent therapy options for providers that not only provide beneficial clinical results but also reduce total patient drug burden.

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“…Diabetic nephropathy (DN), also called diabetic kidney disease (DKD), is one of the long‐term complications of diabetes mellitus and globally represents the leading cause of end‐stage renal disease (ESRD), since it affects nearly 20–40% of patients undergoing dialysis (Toth‐Manikowski & Atta, ). Due to the higher prevalence of diabetes, estimated for the next years (King et al ., ; Guariguata et al ., ), this percentage is expected to further increase.…”

Section: Diabetic Nephropathymentioning

confidence: 99%

The role of mass spectrometry in studies of glycation processes and diabetes management

DaRonco

Crotti

Agostini

et al. 2018

Mass Spectrometry Reviews

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In the last decade, mass spectrometry has been widely employed in the study of diabetes. This was mainly due to the development of new, highly sensitive, and specific methods representing powerful tools to go deep into the biochemical and pathogenetic processes typical of the disease. The aim of this review is to give a panorama of the scientifically valid results obtained in this contest. The recent studies on glycation processes, in particular those devoted to the mechanism of production and to the reactivity of advanced glycation end products (AGEs, AGE peptides, glyoxal, methylglyoxal, dicarbonyl compounds) allowed to obtain a different view on short and long term complications of diabetes. These results have been employed in the research of effective markers and mass spectrometry represented a precious tool allowing the monitoring of diabetic nephropathy, cardiovascular complications, and gestational diabetes. The same approaches have been employed to monitor the non‐insulinic diabetes pharmacological treatments, as well as in the discovery and characterization of antidiabetic agents from natural products. © 2018 Wiley Periodicals, Inc. Mass Spec Rev 38:112–146, 2019.

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Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets

Cited by 158 publications

References 178 publications

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

The role of mass spectrometry in studies of glycation processes and diabetes management

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