Diyabetik Nefropati
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Transcript of Diyabetik Nefropati
Diyabetik Nefropati
Prof. Dr. Meltem Pekpak
Internal Medicine/Nephrology
9th-10th Semester
If obesity and immobili-zation increases....
EpidemiologyEpidemiology
• 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 KonanHastaların Etiyolojisi (Turkish Society of Nephrology)
n=5656
Diabetes Epidemic
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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
Histology
Diabetic renal injurymetabolic and hemodynamic interactions
MetabolikMetabolic Glukose
polyol AGE
İntrasellular signal molekulesPKC, NF- , MAPK
StructurelEkstrasellular matrix
accumulation
Hemodynamicflow/pressure
ET AII
Growth factors-Cytokines
(TGFbeta, VEGF, IL)
Functional Albuminuria
Cooper ME, Diabetologia 2001,44:1957-1972
KısaltmalarAbbrev.:
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
Glomerülbasınç
Afferent arterial dilatation
Efferent arterial vasokonstriction
KB
Diabetic nephropathy stages
Type 1-Mogenson
Funktional changes*Funktional changes*
Type 2 Diabetic Nephropathy Type 2 Diabetic Nephropathy
ProteinuriaProteinuria
End stage renal failureEnd stage renal failure
Clinical type 2 diabetesClinical type 2 diabetes
Structural changes†Structural changes†
Increasing BPIncreasing BP
Increasing serum kreatininIncreasing serum kreatinin
Kardiovascular deathKardiovascular death
MicroalbuminuriaMicroalbuminuria
Diyabet başlangıcıDiyabet başlangıcı 22 55 1010 2020 3030YılYıl
*glomerular hypertension† Glomeruler basementl membrane thickeningı , mesangial expansion , microvascular changes +/-.
*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: 2003 European Society of Hypertension – European Society of Cardiology Guidelines: J Hypertens 21J Hypertens 21: : 10111011--10531053, , 20032003
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
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MICRO-HOPE TrialMICRO-HOPE Trial((MMiicroalbuminuria croalbuminuria CCardiovascular and ardiovascular and RRenal enal OOutcomes in utcomes in HHope ope SStudytudy))
Lancet 355:253-259, 2000
Stroke MICardiovaskular
Mortality
P < 0.01P = 0.0001
P = 0.01
-33-37
-22
Nefropathy
-24
P = 0.027
Ris
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Diabetes mellitus (n=3577) ramipril treatmentDiabetes mellitus (n=3577) ramipril treatment
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Overt NEFROPATHY ManifestationOvert NEFROPATHY Manifestation
%%
PlaseboPlasebo IrbesartanIrbesartan(150 mg)(150 mg)
IrbesartanIrbesartan(300 mg)(300 mg)
Risk reduction: %39Risk reduction: %39P=0.08P=0.08
Risk reduction: %70Risk reduction: %70P<0.001P<0.001
14.9
9.7
5.2
Parving et al.: N Engl J MedParving et al.: N Engl J Med 345345::870-878870-878, 200, 20011
IRMA 2IRMA 2(The (The IrIrbesartan in Patients with Type 2 Diabetes and besartan in Patients with Type 2 Diabetes and MMicroicroaalbuminuria Study)lbuminuria Study)
590 hypertensive, diabetic,microalb,crea<1.5-1.1,plasebo,150mg-300mg İrbes., 2y)
RENAAL TrialRENAAL TrialSerum Ceatinine doubling
End stage renal failure End stage renal failure,death
All
% 16 %25
%20
P=0.02 P=0.002
P=0.002 P=0.01
%28
(1513 diabetics, Urinary Alb. Excretion>500mg/gün, 42 months)(1513 diabetics, Urinary Alb. Excretion>500mg/gün, 42 months)
IDNTIDNT((IIrbesartan rbesartan DDiabetic iabetic NNephropathy ephropathy TTrial)rial)
İrbesartan vs. Plaseboİrbesartan vs. PlaseboRisk azalması: %33 (P=0.003)Risk azalması: %33 (P=0.003)
İrbesartan vs. Amlodipinİrbesartan vs. AmlodipinRisk azalması: %37 (P<0.001)Risk azalması: %37 (P<0.001)
İrbesartan vs. Plaseboİrbesartan vs. PlaseboRisk azalması: %20 (P=0.02)Risk azalması: %20 (P=0.02)
İrbesartan vs. Amlodipinİrbesartan vs. AmlodipinRisk azalması: %23 (P=0.006)Risk azalması: %23 (P=0.006)
Kreat.x2
(Macroalbuminuria== End stage renal failure(Macroalbuminuria== End stage renal failure
n=1715İrbesartan 75-300mgAmlodipine 2.5-10 mgPlasebo
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
Prognosis can 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 clearence is 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 ? • Oftalmologic control• 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!!