Journal of Clinical & Experimental Nephrology

New Insights into the Interaction between Increased Iron-Deposition in the Kidney and Vitamin D/Klotho Axis in Diabetic Nephropathy

Diabetic Nephropathy (DN), a chronic complication of diabetes, is characterized by glomerular hyper-trophy, albuminuria, decreased glomerular filtration rate, and renal fibrosis resulting in end stage renal disease. Diabetic Nephropathy is one of the major micro-vascular complications of long term diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial. For many years it was consensus among scientists that hyper filtration and activation of the renin angiotensin aldosterone system is enough to develop kidney injury (diabetic nephropathy). The goal of this review is to describe new pathways involved in the pathogenesis of diabetic nephropathy. Recent studies showed that new pathways are involved. One of these pathways is the increased production of free radicals via oxidative stress due to increased iron deposition in the lysosomes of the proximal convolute tubules. The increased oxidative stress in the lysosomes of the proximal convolute tubules can down regulate Klotho Protein expression and the synthesis of active vitamin D. The decrease in Klotho, active vitamin D and his receptor can aggravate the progression of diabetic nephropathy. AGEs-induced increased oxidative stress, also activated PKC-induced increased production of cytokines, chemokine’s and different inflammatory and apoptotic signals.

Another pathway involved in the pathogenesis of diabetic nephropathy is the altered autophagy process via hyperglycaemia induced activation of the mTORC1 in this review we will concentrate on new data published recently on these pathways involved in the pathogenesis of diabetic nephropathy and new treatments proposed.

Author(s):

Nakhoul Nakhoul, Dahan Inbal, Evgeny Farber, Nakhoul Farid

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