Autophagy in diabetic nephropathy: a review
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NEPHROLOGY - REVIEW
Autophagy in diabetic nephropathy: a review Elias A. T. Koch1 · Rola Nakhoul2 · Farid Nakhoul2,4,5 · Nakhoul Nakhoul2,3 Received: 26 March 2020 / Accepted: 15 June 2020 © Springer Nature B.V. 2020
Abstract Diabetes mellitus (DM) is the leading cause of end stage renal disease. 40% of the patients worldwide will require replacement therapy after 20 years of DM worldwide. Early-stage diabetic nephropathy is characterized by hyperfiltration related to hypeglycemia-induced afferent artery vasodilatation with micro-and macroalbuminuria. Later on, proteinuria with arterial hypertension may appear, culminating in glomerular filtration rate (GFR) decline and end stage renal disease. Forty percent of diabetic patients develop microvascular and macrovascular complications, with increased risk among patients with genetic predisposition, such as Haptoglobin 2–2 phenotype. The most frequent complications in the daily clinical practice are diabetic kidney disease, diabetic retinopathy and vascular disease, such as coronary artery disease and stroke. Various pathways are involved in the pathogenesis of diabetic kidney disease. Chronic systemic inflammation and the inflammatory response, such as increased circulating cytokines (Interleukins), have been recognized as main players in the development and progression of diabetic kidney disease. DM is also associated with increased oxidative stress, and alterations in carbohydrate, lipid and protein metabolism. Overexpression of the renin-angiotensin-aldosterone system (RAAS) in the kidney, the vitamin D-Vitamin D receptor-klotho axis, and autophagy. Differences in the ATG5 protein levels or ATG5 gene expression involved in the autophagy process have been associated with diabetic complications such as diabetic kidney disease. Under normal blood glucose level, autophagy is an important protective mechanism in renal epithelial cells, including podocytes, proximal tubular, mesangial and endothelial cells. Down regulation of the autophagic mechanism, as in hyperglycemic condition, can contribute to the development and progression of diabetic kidney disease. Keyword Diabetic nephropathy · Retinopathy · Autophagy · Atg5 · Vitamin D · Sodium-glucose cotransporter inhibitors · Rapamune Abbreviations DM Diabetes Mellitus DKD Diabetic Kidney Disease VDR Vitamin D Receptor SGLT2I Sodium-Glucose-Transport 2 Inhibitor * Farid Nakhoul [email protected]; [email protected] 1
Department of Dermatology, University Hospital, Erlangen, Germany
2
Division of Nephrology and Hypertension, Diabetes and Metabolism Lab, Azrieli Faculty of Medicine in Galilee, Baruch Padeh Poriya Medical Center, Lower galilee 15208, Ramat‑Gan, Israel
3
Ophtalmology Division, Baruch Padeh Poriya, Lower Galilee, Israel
4
Azrieli Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel
5
Bar-Ilan University, Ramat‑Gan, Israel
GFR Glomerular Filtration rate ESRD End Stage Renal Disease PCT Proximal Convolute Tubule
Introduction Diabetic kidney disease (DKD
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