Diabetic Nephropathy:You can't cure it so you have to endure itKing, et al. Qual Health Res. 2002;12:329-46
Persistent albuminuria (>300 mg/d or >200 ug/min) that is confirmed on at least 2 occasion 3-6 months apart.Progeressive decline in the glomerular filtration rate (GFR)Elevated arterial blood pressure
Mesangial expansionThickening of Glomerular Base MembraneGlomerular Sclerosis
Grading
Gambar Glomerulus
PathophysiologyGlomerular Hiperfiltrasion and HiperperfusionAGEs (advance glycosilation end-products)Accumulate of Polyols increase Sorbitol cause by aldose reductaseActivation Protein Kinase C
HiperglicemiaOncotic pressure HiperfiltrationDiluted State, Sodium LossAfferen VasodilatationReninGlomerular HipertensionGlomerular Hiperfiltration dan hiperperfusionSRAA
Pathology of DM nephropathyNormal GlomerulusEarly Diabetic GlomerulusCapillary lumenMesangial cellThickened BMExpanded mesangiumMesangiumPodocyte damage & lossBasement membrane Afferent and efferent hyaline arteriolosclerosis Interstitial fibrosis and tubular atrophy
Renal preglomerular vasodilationSystemic hypertensionGlomerular hypertensionGlomerular sclerosisHyperglycemiaGenetic factorsD metabolism of glom. cellsSimpleminded model of pathogenesis of DM nephropathy
TGF-bAIIstretchglucosePotential mechanisms for increased matrix production in hyperglycemiaMesangial cell
Renal preglomerular vasodilationGlomerular hypertensionTreatment of DM nephropathy: Glucose controlfrom T. Hostetter
Renal preglomerular vasodilationGlomerular hypertensionTreatment of DM nephropathy: Hypertension controlfrom T. Hostetter
DMACEI or ARB
Renal preglomerular vasodilationGlomerular hypertensionTreatment of DM nephropathy: Effect of dietary protein restrictionfrom T. Hostetter
Effect of dietary protein restriction on progression of DM nephropathyGFR(ml/min)
Treatment of DM nephropathy: Effect of statins from T. HostetterRenal preglomerular vasodilationSystemic hypertensionGlomerular hypertensionGlomerular sclerosisHyperglycemiaROSGenetic factorsD metabolism of glom. cells
Renal preglomerular vasodilationSystemic hypertensionGlomerular hypertensionGlomerular sclerosisHyperglycemiaROSGenetic factorsD metabolism of glom. cellsfrom T. HostetterTreatment of DM nephropathy: All together!
The Renin-Angiotensin-SystemAngiotensinogen
RAS in cardiovascular pathologyAdapted from: Chung O. & Unger T., Am J Hypertens 1999;12:150S156SRisk factors: diabetes, obesity, smoking, ageVasoconstrictionVascular hypertrophyEndothelial dysfunctionAtherosclerosisHypertensionPro-thrombotic stateVascular diseaseApoptosisLVHFibrosisArrhythmiaHeart failureMIStrokeCognitive dysfunctionRenal failureDeathDecreased GFRProteinuria/albuminuriaGlomerulosclerosis
ANG II: Progression of Chronic Renal DiseaseRenal diseaseANG IIAngiotensinogenNF- kBTNF-aFibroblastsProfibroticCytokinesMatrixProliferationDifferentationFibrosisTubule CellsChemoattractantsAdhesion proteinsInflammationDirect CytotoxicityVasoconstrictionInflammationGrowth EffectANG II
ANG IIANG IIKlahr et al., 2000Oxidative Stress
Angiotensin-ReceptorsVasoconstrictionNa+-RetentionAldosterone-ReleaseProliferationFibrosisInflammationAnti-ProliferationAnti-FibrosisAnti-InflammationVasodilation (Neuro-)regeneration
mentsFragACEBradykininReninACEAT1ANG IIANG IIAT2ANG IIANG IAngiotensinogenAT1 Receptor BlockersRenin inhibitorsAldosterone antagonistsAldosterone+Drugs inhibiting the renin-angiotensin-aldosterone system
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