SEARCH RESULTS FOR: Diabetic-Nephropathy

Diabetic-Nephropathy

Diabetic Nephropathy: Pathogenesis Type I or Type II Diabetes ↑ Glucose uptake & glycolysis in glomerular & tubular cells Poor glycemic control = ↑ Glucose load ↑ Proximal tubule reabsorption of Na via Na/glucose co-transporter ↓ NaCl to distal tubule Activation of tubulo- glomerular feedback at macula densa to kidney ↑ Activation of renin- angiotensin system (RAS) ↑ Intrarenal angiotensin II ↑ Advanced glycation end products (AGE) Shunting of glucose through non- glycolytic pathways (e.g. polyol) Activation of Protein Kinase C (PKC) pathway Excessive production and accumulation of glycolytic intermediates (e.g. sorbitol, hexosamine, succinate) hyperglycemia Succinate via GPR91 ↑ Free radical production (oxidative stress) Activation of cellular signalling, transcription factors and cytokines (e.g. TGF-β-Smad-MAPK, IGF-1, NF-κB) ↑NADPH oxidase activity ↑Blood volume ↑ Blood pressure ↑ Renal perfusion Relative afferent arteriole dilatation, efferent arteriole constriction Initial ↑ in glomerular filtration rate (GFR) Podocyte loss/injury Authors: Steven Chen Shannon Gui Yan Yu* Reviewers: Julia Heighton Ryan Brenneis Sophia Chou* * MD at time of publication Initial glomerular hyperfiltration at time of diagnosis ↓ Production of matrix metallo- proteinases Aberrant extracellular matrix (ECM) protein expression and accumulation Sheer stress to glomeruli à pressure-induced damage ↑ Glomerular basement membrane permeability to proteins like albumin ↓ Extracellular matrix regulation “Metabolic Pathway” Mesangial matrix expansion Kimmelstiel- Wilson lesions (pink hyaline nodules due to accumulation of damaged proteins) Tubular fibrosis Scarred glomeruli are less able to effectively filter blood ↓ in glomerular filtration rate (GFR) Albuminuria Usually occurs after ~5 years from time of diagnosis in T1DM; can occur at time of diagnosis in T2DM Abbreviations IGF: Insulin-like growth factor MAPK: Mitogen-activated protein kinases NADPH: Nicotinamide adenine dinucleotide phosphate NF-κB: Nuclear factor kappa-light-chain- enhancer of activated B cells TGF-β: Transforming growth factor-β Protein endocytosis into tubular cells causing inflammation “Hemodynamic Pathway” Diabetic Nephropathy Overt diabetic nephropathy may take upwards of 15-25 years to develop Note: The mechanisms presented here have been simplified. The cross- talk and signaling between the metabolic and hemodynamic factors do not manifest in a step-wise fashion, but rather occur in parallel. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 3, 2020 on www.thecalgaryguide.com

Diabetische Nephropathie: Pathogenese

Diabetische Nephropathie: Pathogenese