Diyabetik Nefropati
Prof. Dr. Meltem Pekpak
Internal Medicine/Nephrology
9th-10th Semester
If obesity
and
immobilization
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
World Increase rate: % 209
Turkey Increase rate %214
7
6
400
5
milyon kişi
350
milyon kişi
300
250
200
4
3
150
2
100
1
50
0
0
2000
2030
http://www.who.int/ncd/dia/databases4.htm
2000
2030
Basics
• 1936 Kimmelstiel ve Wilson
• Only %30-40 of all diabetics type 2
Histology
Diabetic renal injury
metabolic and hemodynamic interactions
Metabolic
Metabolik
Glukose
polyol
AGE
İntrasellular
signal molekules
PKC, NF- , MAPK
Structurel
Ekstrasellular matrix
accumulation
Hemodynamic
flow/pressure
AII
ET
Growth factors
-Cytokines
(TGFbeta, VEGF, IL)
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
Glomerül
basınç 
Afferent arterial dilatation
Efferent arterial vasokonstriction
KB
Diabetic nephropathy stages
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
*glomerular hypertension.
†
5
10
Yıl
20
Glomeruler basementl membrane thickeningı , mesangial expansion ,
microvascular changes +/-.
30
Clinic
• Early signs of nephropathy
–Microalbuminuria
–Hypertension
–Kolesterol ve Triglyseride 
Clinic
•
•
•
•
•
•
Other microangiopathic changes:
Proliferative fundus ophtalmicus
Corpus vitreum bleeding
Blindness
Polineuropathy
Coronary microangiyopathySmall vessel disease of the heart
Clinical classification and
approach for treatment
• ‘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
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
Clinical classification and
approach for treatment
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 and
approach 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
MICRO-HOPE Trial
(Microalbuminuria Cardiovascular and Renal Outcomes in Hope Study)
Diabetes mellitus (n=3577) ramipril treatment
Stroke
MI
Cardiovaskular Nefropathy
Mortality
0
-5
-10
-15
-20
-22
-25
P = 0.01
-30
-33
-35
P < 0.01
-40
Lancet 355:253-259, 2000
-24
P = 0.027
-37
P = 0.0001
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
%
20
18
16
14
12
10
8
6
4
2
0
Risk reduction: %70
P<0.001
Risk reduction: %39
P=0.08
14.9
9.7
5.2
Plasebo
Irbesartan
(150 mg)
Parving et al.: N Engl J Med 345:870-878, 2001
Irbesartan
(300 mg)
RENAAL Trial
(1513 diabetics, Urinary Alb. Excretion>500mg/gün, 42 months)
All
% 16
%25
P=0.002
P=0.02
End stage renal failure
%28
P=0.002
Serum Ceatinine doubling
End stage renal failure,death
%20
P=0.01
IDNT
(Irbesartan Diabetic Nephropathy Trial)
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
n=1715
İrbesartan 75-300mg
Amlodipine 2.5-10 mg
Plasebo
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 LDLfractions) 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., BetaBlockerler, Alpha-Blockers,
Vasodilataters
(ACE, ARB)+ Diuretics
(Hydrochlorothiazide comb., later LoopDiuretics)
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!!