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Autophagy in diabetic nephropathy: a review

  • Nephrology - Review
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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.

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Abbreviations

DM:

Diabetes Mellitus

DKD:

Diabetic Kidney Disease

VDR:

Vitamin D Receptor

SGLT2I:

Sodium-Glucose-Transport 2 Inhibitor

GFR:

Glomerular Filtration rate

ESRD:

End Stage Renal Disease

PCT:

Proximal Convolute Tubule

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Acknowledgments

This work was supported by Karim Family in memory of their son Hasan karim Magd Alkoroum, ISRAEL. MIGAL The Internal ministry for the development of Galilee-North Israel

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Authors and Affiliations

  1. Department of Dermatology, University Hospital, Erlangen, Germany

    Elias A. T. Koch

  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

    Rola Nakhoul, Farid Nakhoul & Nakhoul Nakhoul

  3. Ophtalmology Division, Baruch Padeh Poriya, Lower Galilee, Israel

    Nakhoul Nakhoul

  4. Azrieli Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel

    Farid Nakhoul

  5. Bar-Ilan University, Ramat-Gan, Israel

    Farid Nakhoul

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  1. Elias A. T. Koch
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All of the authors contributed to the formation of overall concept. Nn, Nf and KE wrote the manuscript and NR, EF, Ht edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Farid Nakhoul.

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Koch, E.A.T., Nakhoul, R., Nakhoul, F. et al. Autophagy in diabetic nephropathy: a review. Int Urol Nephrol 52, 1705–1712 (2020). https://doi.org/10.1007/s11255-020-02545-4

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