∆ιαβητική νεφροπάθεια και υπέρτασηstatic.livemedia.gr/emedip/cfiles/Matgimata_manes_09_06...V Pathology • Expansion of mesangial matrix with diffuse

∆ιαβητική νεφροπάθεια

και υπέρταση

∆ιαβητική νεφροπάθεια

και υπέρταση

Μιχάλης ∆ούμας

ΠαθολόγοςΒ’ΠΠ

Κλινική

ΑΠΘ

ΜιχάληςΜιχάλης ∆ούμας∆ούμας

ΠαθολόγοςΠαθολόγοςΒΒ’’ΠΠΠΠ

ΚλινικήΚλινική

ΑΠΘΑΠΘ

Diabetic nephropathy

• Diabetic nephropathy is irreversible in humans

• No cases of recovery or cure have been reported in the literature

• Once the clinical signs of nephropathy have become manifest, the natural course is inexorably progressive to death

• The rate of progression is accelerated in the later stages

Kussman et al. Jama 1976

33

"ΘΑΥΜΑΖΩ

ΤΙΣ ΚΑΤΑΚΤΗΣΕΙΣ

ΤΙΣ

ΕΠΙΣΤΗΜΗΣ,

ΥΠΟΚΛΙΝΟΜΑΙ, ΟΜΩΣ, ΜΕ

∆ΕΟΣ

ΜΠΡΟΣΤΑ

ΣΤΗΝ

ΑΠΕΡΑΝΤΩΣΥΝΗ

ΟΣΩΝ ΘΑ

ΜΕΙΝΟΥΝ

Α∆ΙΕΡΕΥΝΗΤΑ.

"ΘΑΥΜΑΖΩ

ΤΙΣ ΚΑΤΑΚΤΗΣΕΙΣ

ΤΙΣ

ΕΠΙΣΤΗΜΗΣ,

ΥΠΟΚΛΙΝΟΜΑΙ, ΟΜΩΣ, ΜΕ

∆ΕΟΣ

ΜΠΡΟΣΤΑ

ΣΤΗΝ

ΑΠΕΡΑΝΤΩΣΥΝΗ

ΟΣΩΝ ΘΑ

ΜΕΙΝΟΥΝ

Α∆ΙΕΡΕΥΝΗΤΑ.

GOETHEGOETHE

Diabetic nephropathy and Hypertension

Ορισμός

Μία μικροαγγειακή

επιπλοκή

του

σακχαρώδη διαβήτη

που

χαρακτηρίζεται

από

μικρολευκωματινουρία

και

προοδευτική επιδείνωση

της

νεφρικής

λειτουργίας.

EpidemiologyType 1 Diabetic

– 25 - 45% will develop diabetic nephropathy– 80 - 90% with microalbuminuria will progress to

overt diabetic nephropathy in 5 - 10 years – nearly 100% with gross proteinuria will

progress to ESRD in 7 - 10 yrs

Type 2 Diabetic– 50% will have microalbuminuria at the

time of presentation probably secondary to HTN– 10-20% with microalbuminuria will

progress to overt nephropathy

Diabetes:Diabetes: The Most Common Cause of ESRDThe Most Common Cause of ESRDPrimary Diagnosis for Patients Who Start Dialysis

Diabetes50.1%

Hypertension27%

Glomerulonephritis

13%Other

10%

United States Renal Data System. Annual data report. 2000.

No. of patientsProjection95% CI

1984 1988 1992 1996 2000 2004 20080

100

200

300

400

500

600

700

r2=99.8%243,524

281,355520,240

No.

of d

ialy

sis

patie

nts

(thou

sand

s)

ΥπέρτασηΥπέρταση σεσε

χρόνιαχρόνια νεφρικάνεφρικά

νοσήματανοσήματα

0

10

20

30

40

50

60

70

80

Hyp

erte

nsi

on P

reva

lence

(%

)

MCN CIN IgA MGN APKD DN MPGN FSGN

MCN=minimal change nephropathy CIN=chronic interstitial nephritis IgA=IgA nephropathyMGN=membranous glomerulonephritis APKD=adult-onset polycystic kidney disease DN=diabetic nephropathyMPGN=membranoproliferative glomerulonephritis FSGN=focal segmental glomerulonephritis

Smith MC and Dunn MJ, in Hypertension. Laragh JH, Brenner BM. Raven Press; 1995:2081-2101.

Sleep and his half-brother Death (Hypnos and Thanatos) by John William Waterhouse (1874)

Natural history

Diabetics with Macroalbuminuria are More Likely to Die than Develop ESRD

CV

DEATHElevated Serum Creatinine

19%

No albuminruia1.4%

2.0%

Microalbuminruia3.0%

2.8%

Macroalbuminruia4.6%

2.3%

The United Kingdom Prospective Diabetes Study (approx. 5000 Type

2 Diabetics)Newly diagnosed, predominantly white, medically treated

Adler et al. Kid Int, 2003

What are Diabetics with Nephropathy Dying From?

Stroke MyocardialInfarctionHeartFailure

SuddenDeath

Diabetes and Cardiovascular Disease

• Diabetics have similar risk of

CVD as non-diabetic with

existing CVD.

• Diabetics with renal disease

has CVD risk that is 6-7 fold

that of diabetic without renal

disease.

0

5

10

15

20

25

30

RR

CVD

1st Qtr

No DM, No CVD No DM, + CVD+ DM, no CKD +DM, + CKD

Pathophysiology

Stages of Diabetic Nephropathy

020406080

100120140160180

0 5 10 15 20 25 30

Duration of Diabetes

GFR

III III

IV

V

Pathology•

Expansion of mesangial matrix with diffuse and nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)

• Thickening of glomerular and tubular BM

• Arteriosclerosis and hyalinosis of afferent and efferent arterioles

• Tubulointerstitial fibrosis

Σπάνια γίνονται

πια

βιοψίες νεφρού

Pathogenesis•

Exposure to the diabetic milieu

• Hyperglycemia–

Induce mesangial expansion and injury

– Increased activity of growth factors

– Activation of cytokines

– Formation of ROS

– accumulation of advanced glycosylation endproducts in tissues

• Accumulation of ECM components, such as collagen

• Genetic predisposition to or protection from diabetic

nephropathy

Risk Factors

Hyperglycemia

Hypertension

Microalbuminuria

Ethnicity

Male gender

Family history

Cigarette smoking

Most Common Cause of Failing to Reduce Proteinuria with ACE Inhibitor or ARB

High SALT intake(>5 grams/day)

DeZeeuw D et.al Kidney Int., 1989, Mishra SI et.al, Curr Hypertens Rep, 2005

Detection Prevention

Improving Outcomes in Diabetic Nephropathy

Prevention of Cardiovascular Events

Prevention of End-Stage Renal Disease

Diabetic Nephropathy

Primary care physicians have the most frequent contact with diabetic

patients and therefore have the greatest potential to favorably affect

their health

How are we doing?Studies show that primary care physicians screen only 20% of

their diabetic patients for diabetic nephropathy

e-GFR

MDRDeGFR =

186 x (κρεατινίνη)-1.154

x (ηλικία)-0.203

x

(0.742 εάν♀) x (1.210 για αφροαμερικανούς)

Cockcroft-GaultGFR = (140-ηλικία) x

(Βάρος

kg) x (0.85 για

γυναίκες)

/ (72 x κρεατινίνη)

http://www.mdcalc.com

http://clinicalculator.com/english/nephrology/cockroft/cc.htm

Κρεατινίνη: 1.6 mg/dl

GFR 122

mL/min/1.73 m2

Κρεατινίνη: 1.6 mg/dl

GFR 22

mL/min/1.73 m2

Ορισμοί Μικρολευκωματινουρίας

& Λευκωματινουρίας

Παράμετρος Φ.Τ Mικρολευκωματ ινουρίαΛευκωματι-νουρία

Urine AER(g/min) < 20 20 -

200 >200

Urine AER(mg/24h) < 30 30 -

300 >300

Urine albumin/Cr#

ratio

(mg/gm)

< 30 30 - 300 >300

AER=Albumin excretion rate CR#

=creatinine

Συσχέτιση χρόνιας

νεφρικής

βλάβης

και

μικρολευκωματουρίας . I-Demand project

122 (13.2%)

99 (10.7%)

134 (14.5%)

renal dysfunction: 38.5% of pts

microalbuminuria

N=233 (25.3%)

eGFR

60 ml/min

N=221 (24.0%)

927 subjects

Parving et al, Kidney Int 2006

Treatment

Η σημασία

της

πρώιμης

αντιμετώπισης

American Society of HypertensionAmerican Society of Hypertension

Bakris, JASH 2010

Intensive Multiple Risk Factor ManagementIntensive Multiple Risk Factor Management

Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%).*Death from CV causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke,

amputation, or surgery for peripheral atherosclerotic artery disease.†Behavior modification and pharmacologic therapy.

Prim

ary

Com

posi

te E

nd P

oint

* (%

)

Months of Follow-up

60

40

20

12 24 36 48 60 72 84 96

Conventional Therapy

Intensive Therapy†

20% Absolute Risk Reduction

N=160; follow-up = 7.8 years

Patients with Type 2 Diabetes and Microalbuminuria

Aggressive treatment of†:– Microalbuminuria with

ACEIs, ARBs, or combination– Hypertension– Hyperglycemia– Dyslipidemia– Secondary prevention of CVD

Adapted from Gæde P et al. N Eng J Med. 2003;348:383-393

©2006. American College of Physicians. All Rights Reserved.

Steno 2 study: Extended Follow‐up: Effect of a multi‐factorial vascular protective strategy on total mortality

60

50

40

30

20

10Total m

ortality (%

)

3

Years of follow‐up

0 1 2 4 5 6 7 8 9 10 11 12 13

Conventional therapy

Intensive therapy

END OF TRIAL

HR = 0.54 (0.32‐0.88)p

= 0.015

HR = 0.54 (0.32‐0.88)p

= 0.015

Gaede 2008.33


Bakris, JASH 2010

Blood pressure control

Blood Pressure Control and Rate of Renal Decline in Diabetic Nephropathy

• Parving et al. (1983 Lancet)

• Ten Type 1 Diabetics followed before (mean of 29 months) and after initiation of antihypertensives (mean 39 months)

• Antihypertensive agents were metoprolol, hydralazine, furosemide or thiazide

• BP fell from 144/97 mmHg before treatment to 128/84 mmHg with treatment

• Albumin excretion rate decreased from 977 mg/min before treatment to 433 mg/min with treatment

ΕλάττωσηΕλάττωση έκπτωσηςέκπτωσης

νεφρικήςνεφρικής

λειτουργίαςλειτουργίας

--ΑΠΑΠ

9595 9898 101101 104104 107107 110110 113113 116116 119119

r = 0.69; P

< 0.05

MAP (mmHg)G

FR (m

L/m

in/y

ear)

130/85 140/90

UntreatedHTN

00

--22

--44

--66

--88

--1010

--1212

--1414

Bakris GL, et al. Am J Kidney Dis.

2000;36(3):646-661.

ACCORD ????

The Renal Injury Triad

Angiotensin II

ProteinuriaHypertension


Σακχαρώδης ∆ιαβήτης

Bakris, JASH 2010

AASK

MAP

Σακχαρώδης ∆ιαβήτης

Bakris, JASH 2010


Bakris, JASH 2010

Normoalbuminuria Normotension

Αντικρουόμενα δεδομένα

• Επιβράδυνση

της

εμφάνισης

μικρολευκωματουρίας

στη

μελέτη

του

Ravid

Ann Intern Med 1998

• Δεν

υπάρχουν

ευνοϊκά

αποτελέσματα

στη

μελέτη

DIRECT Ann Intern Med 2009, καθώς

και

στη

μελέτη

του

Mauer N Engl J Med 2009.

• Στην

πρώτη

μελέτη

τα

επίπεδα

της

πίεσης

και

του

λευκώματος

στα

ούρα

ήταν

υψηλότερα

από

τις

άλλες.

Normoalbuminuria Hypertension

47

Οι

ΑΜΕΑ

προλαβαίνουν

τη

ΜΛ

σε

ασθενείς

με Σ∆

τύπου

2

P

= ,01

Χωρίς

ΑΜΕΑ

ΑΜΕΑ(Τραντολαπρίλη)

Ασθ

ενείςμε

ΜΛ

(%)

Ν=1204 ασθενείς

με

υπέρταση, Σ∆

τύπου

2 και

φυσιολογικό

AER

0 6 12 18 24 30 36 42 480

5

10

15

20

Ruggeneti et al. N Engl J Med 2004;351:541-51For the Bergami Nephrological Complication Trial (BENEDICT) Investigators

-

Κατάλληλη

χρονική στιγμή

χορήγησης;

Αρχικά

στάδια

Σ∆;

Εμφάνιση

ΜΛ;

Παρακολούθηση

(μήνες)

ROADMAP

Haller, NEJM 2011Haller, NEJM 2011

Microalbuminuria or Low-grade proteinuria

ARBs vs placebo or Ca-antagonistsAlbuminuria

Kunz, Ann Intern Med 2008Kunz, Ann Intern Med 2008

ARBs vs ACE-inhAlbuminuria


-50

-40

-30

-20

-10

0

10

20

% c

hang

e in

uri

nary

albu

min

exc

reti

on

0 3 6 12 18 22 24Months of Follow-up

150 mg of irbesartan


Placebo

*P

0

5

10

15

20

Inci

denc

e of

Dia

beti

c N

ephr

opat

hy (

%)

0 3 6 12 18 22 24

201 201 164 154 139

195 195 167 161 148

194 194 180 172 159

129

142

150

36

45

49

Placebo (n)Irbesartan 150 mg (n)Irbesartan 300 mg

Months of Follow-up

Placebo 150 mg of irbesartan


P

Barnett AH et.al N Engl J Med 2004;351:1952-1961.

Angiotensin-Receptor Blockade versus Converting–Enzyme Inhibition in Type 2 Diabetes and Nephropathy-RESULTS

Baseline GFR 91 ml/min


ARBs and ACEi combination

57

ΑθροιστικήΑθροιστική

δράσηδράση

τωντων

ΑΜΕΑΑΜΕΑ

καικαι

ARBARB

σεσε

ασθενείςασθενείς

μεμε

∆Ν∆Ν

ΕΦ

Βαλσαρ-

τάνη

Και

τα

2 ΑΦΕΦ Μπεναζε-

πρίλη

Βαλσαρ-

τάνηΚαι

τα

2 ΑΦ

ΑΠΑΠ

(( mm

Hg

mm

Hg ))

Λευκω

ματουρία

(mg/

24ωρο

)

5050

250250

450450

650650

850850

10501050

50506600

770088009090

100100110110

120120130130

140140

150150

ΣΑΠΣΑΠ ∆ΑΠ∆ΑΠ

Μπεναζε-

πρίλη

Jacobsen et al. J Am Soc Nephrol 2003;14:992-99

ARBs -

ACEi comboAlbuminuria


ARBs or ACEi comboAlbuminuria


Co-operate trial

Nakao, Lancet 2003Nakao, Lancet 2003

Co-operate trial

Lancet 2009Lancet 2009

ONTARGET sub-analysisCKD -

Albuminuria

Tobe, Circulation 2011Tobe, Circulation 2011

GFR>60 GFR60 GFR

ARBs or ACEi comboBenefit according to albuminuria levels

REIN study, Kidney International 2003REIN study, Kidney International 2003

Direct renin inhibitors

65

Optimal treatment + aliskiren 300 mg

Mean change from baseline§

in UACR at Month 6 (%)

0

−15

−20

−10

−5

n=289n=287

−18

52

* Optimal treatment + placebo

Aliskiren provides significantly greater reductions in UACR compared with placebo

Parving H-H, et al. 2007 (AVOID)Parving H-H, et al. 2008 (AVOID)

Spironolactone

Spironolactone -Albuminuria

Mehdi, JASN 2009Mehdi, JASN 2009

Spironolactone and ARBs or ACEi comboAlbuminuria

Bomback, Am J Hypertens 2009Bomback, Am J Hypertens 2009

Advanced Diabetic Nephropathy

ACE-I is More Renoprotective than Conventional Therapy in Type 1 Diabetes (Total N = 409)

ACE-I is More Renoprotective than Conventional Therapy in Type 1 Diabetes (Total N = 409)

- 40 –

- 20 –

0 –

- 20 –

- 40 –

- 60 –

% Reductionin

Proteinuria

P 1.5 mg/dl

0

25

50

75

100

0 1 2 3 4

CaptoprilConventional therapy

- 2 –

0 –

- 2 –

- 4 –

- 6 –

- 8 –

Decrease inMean Blood

Pressure(mm Hg)

NS

CKD, albuminuria -

RENAAL

43.5%

47.1%

30

34

38

42

46

50

Losartan Placebo

(16% )

P

= .02(Adapted from Brenner B, et al. N Engl J Med.

2001)

Doubling of Serum Creatinine, ESRD, and/or DeathPa

tient

s (%

)

RENAAL – ARB Reduction of Renal Failure

Brenner BM et al, N Eng J Med 345:861, 2001

16% 25%

28% 20%

CKD, albuminuria - IDNT

32.6%

41.1%39.0%

20

25

30

35

40

45

Irbesartan Amlodipine Placebo

*

*P

= .02 vs. placebo; P

= .006 vs. amlodipine.

20%

-

irb vs. pla23%

-

irb vs. aml

(Adapted from Lewis E, et al. N Engl J Med.

2001)

Patie

nts

(%)

Doubling of Serum Creatinine, ESRD, and/or Death

IDNT – ARB Reduction of Renal Failure

Lewis EJ et al, N Eng J Med 345:851, 2001

20%

33%

23%

ALTITUDE

• Διαβητικοί

τύπου

ΙΙ

• Λευκωματουρία

• Μικρολευκωματινουρία

και

ΧΝΑ

στάδιο

ΙΙΙ

• Καρδιαγγειακή

και

νεφρική

νόσο

• Αλισκιρένη

vs placebo

• Νεφρικά

και

καρδιαγγειακά

τελικά

σημεία

∆ιαβητική νεφροπάθεια: Take Home Message

• Lower blood pressure < 130 / 80 mmHg

• Reducing Proteinuria

• Inhibition of Renin-Angiotensin System

• Multiple risk factor intervention–

Glycemia

– Dyslipidemia

– Physical activity

– Aspirin

– Smoking cessation

ΑρχίζειΑρχίζει απόαπό

τοντον

άρρωστοάρρωστο

ΣυνεχίζεταιΣυνεχίζεται μεμε

τοντον

άρρωστάρρωστoo

καικαιΤελειώνειΤελειώνει

στονστον

άρρωστοάρρωστο

Saydah S et.al JAMA 2004;291:335

Percentage of Adults with Diabetes Who Achieved Recommended Goals of Cardiovascular Risk Factors in NHANES

0

10

20

30

40

50

HbA1c

Future ???

Μελλοντικές θεραπείες

διαβητικής

νεφροπάθειας

• Αναστολείς

ουροτενσίνης

–

Αποτυχία

Hypertension 2011

• Γλυκοζαμινογλυκάνες

– Suledoxide

(Αποτυχία

στη

μελέτη

SUN-micro-trial)


πρωτεϊνικής

κινάσης

C

– Ruboxistaurin (Αντικρουόμενα

αποτελέσματα

–

stop)


AGEs (advance glycation end-products)

– Pimagedine

(Αποτελεσματικά

αλλά

μη-ασφαλής)

– Pyridoxamine (Επιτυχία

σε

φάση

ΙΙ)

ImplantablePulse GeneratorImplantablePulse Generator

BaroreflexActivation LeadsBaroreflexActivation Leads

ProgrammingSystem

ProgrammingSystem

∆ιέγερση καρωτιδικών

τασεο-υποδοχέων

Doumas, Doumas, Int J HypertensInt J Hypertens 20201111

Doumas, Am J Cardiol 2010

Sympathetic Innervations and Hypertension

Peet, Am J Surg 1948

BP control was maintained long-term

Grimson, Ann Surg 1941

Doumas, Current Opinion Nephrology Hypertension 2011Doumas, Current Opinion Nephrology Hypertension 2011

Renal sympathetic denervation

Circulation, 2011Circulation, 2011

Renal sympathetic denervation

J Hypertension, 2011J Hypertension, 2011

• New Catheter Design

• Completed two animal studies

• Large in house data base

• Studies in diabetic nephropathy

• Feasibility Human study Coming Soon“ARSENAL”

study

Ablation-induced Renal Sympathetic dENervation triAL

• RSD in CKD –

VA protocol

Νεφρική συμπαθητική

απονεύρωση

Μελλοντικά πρωτόκολλα

91

ΕυχαριστώΕυχαριστώ πολύπολύ γιαγια τηντην προσοχήπροσοχή σαςσας

Ορισμοί Μικρολευκωματινουρίας

& Λευκωματινουρίας

Παράμετρος Φ.Τ Mικρολευκωματ ινουρίαΛευκωματι-νουρία

Urine AER(g/min) < 20 20 -

200 >200

Urine AER(mg/24h) < 30 30 -

300 >300

Urine albumin/Cr#

ratio

(mg/gm)

< 30 30 - 300 >300

AER=Albumin excretion rate CR#

=creatinine

ΧΡΟΝΙΑΧΡΟΝΙΑ ΝΕΦΡΙΚΗΝΕΦΡΙΚΗ

ΝΟΣΟΣΝΟΣΟΣ

((ΧΝΝΧΝΝ) ) ΣΤΑ∆ΙΑΣΤΑ∆ΙΑ

Στάδιο Περιγραφή GFR ml/min/1,73m2

1 Νεφρική βλάβη

με

κφ

ή

GFR

90

2 Νεφρική βλάβη

με

ήπια

GFR 60-89

3 Μέτρια

GFR 30-59

4 Σοβαρή

GFR 15-29

5 Νεφρική ανεπάρκεια < 15

NFK. K/DOQI, AJKD 2002; 39 (Suppl 1)

Definitions

Epidemiology

Prevalence of CKD by Stage of Disease

Stage Definition # in millions % of population

1 Albuminuria, GFR >

90 ml/min

~ 6.0 3.3

2 GFR 60 -

89 5.3 3.0

3 GFR 30 -

59 7.6 4.3

4 GFR 15 -

39 .4 0.2

5 GFR < 15 .3 0.1NHANES III (1988 –

1994, USRDS 1998

∆ιαβητική νεφροπάθεια: Take Home Message 1

• Η

κυριότερη

αιτία

ΧΝΑ

• Χαρακτηρίζεται

από

αυξημένη

αποβολή

λευκώματος

στα

ούρα, επιδείνωση

της

νεφρικής

λειτουργίας

και

υπέρταση

• Μεγάλη

αύξηση

των

ΚΑ

επεισοδίων

• Οι

ασθενείς

είναι

πιθανότερο

να

πεθάνουν

παρά

να

φθάσουν

σε

ΧΝΑ

Take Home Message

Diabetic nephropathy is progressive kidney disease

Most common cause of ESRD in the US

More likely to die than progress to ESRD

Multi-risk factor intervention is critical

Lowering blood pressure with RAAS blockade is critical

Combinations of ACEi

or ARB with MRA or DRIs

sensible

–

No long term efficacy or safety data

Prevent cardiovascular morbidity and mortality

Slide Number 1Diabetic nephropathySlide Number 3Slide Number 4ΟρισμόςEpidemiologyDiabetes:�The Most Common Cause of ESRDΥπέρταση σε �χρόνια νεφρικά νοσήματαSlide Number 9Natural history�Diabetics with Macroalbuminuria are More Likely to Die than Develop ESRDWhat are Diabetics with Nephropathy Dying From?Diabetes and Cardiovascular DiseasePathophysiologyStages of �Diabetic NephropathyPathologyPathogenesisSlide Number 18Most Common Cause of Failing to Reduce Proteinuria with ACE Inhibitor or ARBDetection�Prevention �Diabetic NephropathySlide Number 22How are we doing?e-GFRSlide Number 25Slide Number 26Ορισμοί Μικρολευκωματινουρίας �& ΛευκωματινουρίαςΣυσχέτιση χρόνιας νεφρικής βλάβης και μικρολευκωματουρίας . I-Demand project�TreatmentSlide Number 30American Society of HypertensionIntensive Multiple Risk Factor ManagementSteno 2 study: Extended Follow-up: �Effect of a multi-factorial vascular protective strategy on total mortalityAmerican Society of HypertensionBlood pressure controlBlood Pressure Control and Rate of Renal Decline in Diabetic NephropathyΕλάττωση έκπτωσης νεφρικής λειτουργίας -ΑΠSlide Number 38The Renal Injury TriadΣακχαρώδης ΔιαβήτηςSlide Number 41Σακχαρώδης ΔιαβήτηςAmerican Society of HypertensionNormoalbuminuria�NormotensionSlide Number 45Normoalbuminuria�HypertensionSlide Number 47ROADMAPROADMAPMicroalbuminuria�or�Low-grade proteinuriaSlide Number 51Slide Number 52Slide Number 53Slide Number 54Angiotensin-Receptor Blockade versus Converting–Enzyme Inhibition in Type 2 Diabetes and Nephropathy-RESULTSARBs and ACEi�combinationSlide Number 57Slide Number 58Slide Number 59Slide Number 60Slide Number 61Slide Number 62Slide Number 63Direct renin inhibitorsAliskiren provides significantly greater reductions�in UACR compared with placeboSpironolactoneSlide Number 67Slide Number 68Advanced�Diabetic NephropathyACE-I is More Renoprotective than Conventional Therapy in Type 1 Diabetes (Total N = 409) CKD, albuminuria - RENAALRENAAL – ARB Reduction of Renal Failure CKD, albuminuria - IDNTIDNT – ARB Reduction of Renal Failure Slide Number 75Διαβητική νεφροπάθεια: Take Home Message Slide Number 77Percentage of Adults with Diabetes Who Achieved Recommended Goals of Cardiovascular Risk Factors in NHANESFuture ???Slide Number 80Slide Number 81Slide Number 82Slide Number 83Slide Number 84Slide Number 85Slide Number 86Slide Number 87Slide Number 88Slide Number 89Slide Number 90Slide Number 91Ορισμοί Μικρολευκωματινουρίας �& ΛευκωματινουρίαςΧΡΟΝΙΑ ΝΕΦΡΙΚΗ ΝΟΣΟΣ (ΧΝΝ) ΣΤΑΔΙΑ�DefinitionsEpidemiologyPrevalence of CKD by Stage of DiseaseΔιαβητική νεφροπάθεια: Take Home Message 1Take Home Message

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∆ιαβητική νεφροπάθεια και υπέρτασηstatic.livemedia.gr/emedip/cfiles/Matgimata_manes_09_06...V Pathology • Expansion of mesangial matrix with diffuse