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Diyabetik Nefropati. Prof. Dr. Meltem Pekpak Internal Medicine/Nephrology 9th-10th Semester. If obesity and immobili-zation increases. Epidemiology. In the year 2000 151.000.000 2010 221.000.000 2025 300.000.000 Amos,A et al:Diab Med 1997;14(suppl 5):S1-S85
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Diyabetik Nefropati Prof. Dr. Meltem Pekpak Internal Medicine/Nephrology 9th-10th Semester
If obesity and immobili-zation increases....
Epidemiology • In the year • 2000 151.000.000 • 2010 221.000.000 • 2025 300.000.000 • Amos,A et al:Diab Med 1997;14(suppl 5):S1-S85 • King,H et al: Diabetes Care 1998; 21:1414-1431
Yeni Son Dönem Böbrek Yetersizliği Tanısı Konan Hastaların Etiyolojisi (Turkish Society of Nephrology) n=5656
Diabetes Epidemic Turkey Increase rate %214 World Increase rate: % 209 http://www.who.int/ncd/dia/databases4.htm
Basics • 1936 Kimmelstiel ve Wilson • Only %30-40 of all diabetics type 2
Diabetic renal injury metabolic and hemodynamic interactions Metabolic Glukose polyolAGE Metabolik Hemodynamic flow/pressure ET AII İntrasellular signal molekules PKC, NF- , MAPK Growth factors -Cytokines (TGFbeta, VEGF, IL) Structurel Ekstrasellular matrix accumulation Functional Albuminuria Kısaltmalar Abbrev.: Cooper ME, Diabetologia 2001,44:1957-1972
A II-Diabetic nephropathy pathogenesis Systemic hypertension Glomeruler hypertension Increased glomeruler permability Increased oxidatifve stress/inflammation Increased growth factors Increased TGF-, fibroblasts and fibrozis Monocyte migration and activation
Glomeruler hypertension Increase in Albuminuria Afferent arterial dilatation Glomerül basınç KB Efferent arterial vasokonstriction
Diabetic nephropathy stages Type 1-Mogenson
Type 2 Diabetic Nephropathy Clinical type 2 diabetes Funktional changes* Structural changes† Increasing BP Microalbuminuria Proteinuria Increasing serum kreatinin End stage renal failure Kardiovascular death Diyabet başlangıcı 2 5 10 20 30 Yıl *glomerular hypertension. †Glomeruler basementl membrane thickeningı, mesangial expansion, microvascular changes +/-.
Clinic • Early signs of nephropathy • Microalbuminuria • Hypertension • Kolesterol ve Triglyseride
Clinic • Other microangiopathic changes: • Proliferative fundus ophtalmicus • Corpus vitreum bleeding • Blindness • Polineuropathy • Coronary microangiyopathy- Small vessel disease of the heart
‘Incipient’ nefphropathy REVERSIBLE Microalbuminuria= Albumin-excretion 30-300 mg/ 24 saat= 20-200 microgram/dak. Blood pressure (N) GFR (N) Good control of BP Exercise Good control of blood sugar Smoking restriction SLOWS PROGRESSİON Clinical classification andapproach for treatment
Diabetes Control and Complications Trial Research Group (DCCT) • Type 1 diabetes • 1. group : Intensive insulin (at least 3 injektion/day) • 2. group : Conventionel 2 inj./day • HbA1c: mean 1. group :%7 -- 2. group:% 9 • 9 years follow-up • Microalbuminuria 1. group <<<< (%35-40) • UKPDS Type 2 diabetes: > 10 years follow-up • Mikroalb.uria, proteinuria in intensive insulin treatment <<< % 25-30, • creatinine doubling % 50↓↓
Mikroalbuminuria(not only stage 3 in DM) • Vascular endothelial damage • is related with target organ injury • Is a sign of injury in the kidney, vessel wall and the heart • It is not a potential risk factor like ‘Hyperkolesterolemia’, ‘hypertension’ • It should be diagnosed when still reversibel (in diabetics, hypertensives) 2003 European Society of Hypertension – European Society of Cardiology Guidelines: J Hypertens 21: 1011-1053, 2003
Microalbüminuria • Shows that there is already a vascular injury ! • Lipids ? • Blood pressure control ? • Micro-ve macrovaskular complications ? • Goal = Normoalbuminuria
Overt proteinuria: Albuminuria: >300 mg/ 24 h GFR: normal or Blood pressure: Good control of BP Good control of blood sugar Little protein restriction Clinical classification andapproach for treatment
Dialysis (or other Renal Replacement Therapy) Albuminuria: >1000 mg/ 24 saat GFR: <15- 10 ml/min Blood pressure : Intervention: Hemodialysis Contineous Ambulatory Peritoneal Dialysis Kidney Tx Pankreas and kidney Tx Clinical classification andapproach for treatment
MICRO-HOPE Trial(Microalbuminuria Cardiovascular and Renal Outcomes in Hope Study) Diabetes mellitus (n=3577) ramipril treatment Cardiovaskular Mortality Nefropathy MI Stroke Risk Reduction (%) -22 -24 P = 0.01 P = 0.027 -33 -37 P < 0.01 P = 0.0001 Lancet 355:253-259, 2000
IRMA 2(The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study) 590 hypertensive, diabetic,microalb,crea<1.5-1.1,plasebo,150mg-300mg İrbes., 2y) Overt NEFROPATHY Manifestation Risk reduction: %70 % P<0.001 Risk reduction: %39 P=0.08 14.9 9.7 5.2 Plasebo Irbesartan (150 mg) Irbesartan (300 mg) Parving et al.: N Engl J Med345:870-878, 2001
RENAAL Trial (1513 diabetics, Urinary Alb. Excretion>500mg/gün, 42 months) All Serum Ceatinine doubling % 16 %25 P=0.002 P=0.02 End stage renal failure End stage renal failure,death %28 %20 P=0.002 P=0.01
IDNT(Irbesartan Diabetic Nephropathy Trial) n=1715 İrbesartan 75-300mg Amlodipine 2.5-10 mg Plasebo İrbesartan vs. Plasebo Risk azalması: %20 (P=0.02) İrbesartan vs. Amlodipin Risk azalması: %23 (P=0.006) İrbesartan vs. Plasebo Risk azalması: %33 (P=0.003) Kreat. x2 İrbesartan vs. Amlodipin Risk azalması: %37 (P<0.001) (Macroalbuminuria== End stage renal failure
Follow- up • Fundus ophtalmicus diagnostic • Kidney biopsy:especially if proteinuria is too high and you can not diagnose any eye background signs • Urine for microalbuminuria twice a year • Blood tests for Cholesterol (HDL and LDL-fractions) triglyceride • Every visit:ECG, blood pressure control, education for self assessment of BP, 24 hours blood pressure records if necessary
Treatment and Progression • Increase of cardiovascular mortality to % 40 Prognosiscan be changed by: • Early and good blood pressure control • Goal : BP <120/80 mm Hg • Good glycemic control (HbA1c = < %7) • Exercise • Moderate protein restriction (0.8 g/kg) • STOP smoking
Blood pressure control • Teach self assessment • Microalbuminuria- Antihypertensives • Angiotensin Converting Enzyme Inh., Angiotension-Reseptor Antag., Beta-Blockerler, Alpha-Blockers, Vasodilataters (ACE, ARB)+ Diuretics (Hydrochlorothiazide comb., later Loop-Diuretics)
Blood sugar control • Renal insulin clearenceis reduced: RISK: HYPOGLYSEMIA ! • Reduce insulin latest in overt proteinurics • Regular HbA1c control • Self assessment ! Records
Renal Replacement Therapy Preperation • Creatinine >2 mg/dl every month control • Creatinine, urea, Na, K, phos., calcium and hemoglobin control • Feet ulcerations ? • Oftalmologiccontrol • Education for RRT alternatives !
Renal Replacement Therapy • Hemodialysis (arterio-venous fistula = creatinine-clearance <20 ml/min), • CAPD ( transperitoneal katheter implantation and education, • Transplantation (cadaveric or from living donor)
Be careful !! • Contrast dye may precipitate acute renal failure (good hydration !) • Renal replacement therapy should be started earlier (Serum-creatinine 4-6 mg/dl, Creatinine-clearance < 20 ml/min • The patient should not be severe hypertensive or hypo- and hypervolemic before starting RRT!!