Pr FaiçalJARRAYA, MD - Promotion de l’épidémiologie...

Pr Faiçal JARRAYA, MDNéphrologue

ESH Clinical Hypertension SpecialistService de Néphrologie, CHU Hédi Chaker, Sfax, Tunisie

Unité de Recherche 12ES14 Pathologie rénale, Faculté de médecine, Sfax

Nouakchott, le 15 Novembre 2015

Global maps for level 3 risk factors in 2013 of attributable DALYs for females (B)

DALYs=disability-adjusted life-years / années de vie ajustées sur l'incapacité

Global, regional and national comparative risk assessment of 79 behavioural, environmental

and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a

systematic analysis for the Global Burden of Disease Study 2013.

GBD 2013 Risk Factors Collaborations

Lancet. Published Online September 11, 2015

Global maps for level 3 risk factors in 2013 of attributable DALYs for males (A)

DALYs=disability-adjusted life-years / années de vie ajustées sur l'incapacité

Global, regional and national comparative risk assessment of 79 behavioural, environmental

and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a

systematic analysis for the Global Burden of Disease Study 2013.

GBD 2013 Risk Factors Collaborations

Lancet. Published Online September 11, 2015

TRANSITION EPIDEMIOLOGIQUE

« l'âge de la pestilence et de la

famine »(1er stade)

« recul des pandémies » (2ème stade).

« l'âge des maladies de dégénérescence et des maladies de société »

(3ème stade)

•Omran A. The Epidemiologic Transition: A theory of epidemiology of population change. Millibank Q. 1971;49:509–38.

PRINCIPAUX GROUPES DE MALADIES OU CAUSES EXTERIEURES

2009

N %MALADIES DU SYSTEME CIRCULATOIRE 6461 28.9TUMEURS MALIGNES 3599 16.1

MALADIES ENDOCRINIENNES, NUTRITIONNELLES ET METABOLIQUES 2289 10.2

MALADIES DE L’APPAREIL RESPIRATOIRE 2502 11.2

AFFECTIONS DONT L’ORIGINE SE SITUE DANS LA PERIODE PERINATALE 1480 6.6

CAUSES EXTERIEURES DE MORTALITE (ACCIDENTS, CHUTES,…) 648 2.9

MALADIES DE L’APPAREIL GENITO-URINAIRE 674 3.0MALADIES DE L’APPAREIL DIGESTIF 683 3.1

LESIONS TRAUMATIQUES ET EMPOISONNEMENTS 795 3.6

MALADIES DU SYSTEME NERVEUX ET DES ORGANES DES SENS 623 2.8

MALADIES INFECTIEUSES ET PARASITAIRES 674 3.0

MALFORMATIONS CONGENITALES ET ANOMALIES CHROMOSOMIQUES 424 1.9

MALADIES DU SANG ET DES ORGANES HEMATOPOIETIQUES 151 0.7

AUTRES CAUSES 1355 6.0TOTAL 22358 100.0

Janvier 2013

9- Hyper tension among Tunisian adults : Results of the TAHINA project. Hypertens Res 2012;35:341-7.

http://www.era-edta-reg.org

INCIDENCE: 2008 = 135 pmpDiabetes 29pmp

PREVALENCE: 2008 = 750pmpDiabetes: 154pmp

Tunisie 2010

NEPHROPATHIES CODES EFFECTIF %Glomérulosclérose Diabétique / Néphropathies Diabétiques

80 1 786 21. 0 %

Néphropathie Vasculaire due à une HTA / HTA Maligne

72 - 71 1 157 13. 6 %

Glomérulonéphrite sans Preuve Histologique 10 715 8. 4 %

Pyélonéphrite de Cause Non Précisée 20 459 5. 4%

Polykystoses de l’Adulte /Polyk. Non Précisées 40 - 41 289 3. 4 %

Pyélonéphrite due à une Lithiase Rénale / Urinaire ou uropathie

25 - 23 230 2. 7 %

Néphropathie Vasculaire Cause Non Précisée 70 170 2. 0 %

Néphropathie Interstitielle Autre ou de Cause Non Précisée

30 127 1. 5 %

Amylose Rénale 83 85 1. 0 %

Pyélonéphrite due à une Uropathie Obstructive Congénitale avec ou sans Réflux Vésico-Urétéral

22 68 0. 8 %

Incidence : 133 patients par million d’habitants.

Prévalence : 806 patients par million d’habitants.

Dr C Mahjoubi, Registre de dialyse, MSP

PROGRESSION OF DIABETIC NEPHROPATHY

Microalbuminuria

150

100

50

0

GF

R (

mL/

min

)

5000

1000

200

20

Alb

umin

uria

(m

g/24

h)

5 10 15 20 25Years

Pre- MacroproteinuriaEnd-stagerenal disease

Strippoli et al. J Nephrol 2003;16:487–499

Baseline proteinuria as a determinant for renal eventsin type 2 diabetes

De Zeeuw et al; Kidney Int 2004

Primary composite Endpoint

0

10

15

5

Ha

zard

ra

tio

<.5 2.0 2.95 4.4 ≥5.25≥≥≥≥≥≥≥

Baseline Albuminuria (g/g) Baseline Albuminuria (g/g)

0

<.5 2.0 2.95 4.4 5.25

ESRD

10

20

30

≥H

aza

rd r

atio

F. JARRAYA 17-3-09

HYPERTENSION PREDICT ESRD

Cumulative Incidence of ESRF (without considering causal nephropathy), regarding to BP level in 332 544 mens included in MRFIT trial

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Years since Screening

Klag MJ et al. NEJM 1996;334:13-8.

Stage 4 hypertensionStage 3 hypertensionStage 2 hypertensionStage 1 hypertensionHigh normalNormal but not optimal

ES

RD

Due

to A

ny C

aus

e (

%)

1/creatinin x 103

T1 DM + NPDIRCT après 7 ans (5 - 15 ans) RH Jones et al. Lancet 1979

Evolution Spontanée

de la Fonction

Rénale chez les Patients Atteint de

Néphropathie Diabétique

Si on ne fait rien…..!!!

PREVENIR, RALENTIR LA PROGRESSION…

1. HTA2. Prot-urie3. Lipides4. Néphro

toxicité5. Tabac,

protides

Temps (an)2 4 6 8 10 12 14

-4ml/min/anralentissement-12ml/min/an

Ccr (ml/min)

100

50

Dialyse10

60

Intervention

rémission

Facteurs

de progression :


Microalbuminuria

150

100

50

0

GF

R (

mL/

min

)

5000

1000

200

20

Alb

umin

uria

(m

g/24

h)

5 10 15 20 25Years



M Mauer et al. JCI 1984;74:1143-55

0

10

20

0 6 12 18 24 30 36 42 48

5

Cum

ulat

ive

inci

denc

e

of m

icro

albu

min

uria

(%

)

Time (months)

ACE inhibitor35 events

No ACE inhibitor66 events15

Estimated acceleration factor 0.44; P <0.001

Ruggenenti P, et al. N Engl J Med2004; 351: 1941-51.

Hasslacher, Nephrol Dial Transpl (1989) 4: 859

Diabète Type 2

� 50% vont présenter une microalbuminurie au moment du diagnostic (probablement secondaire (?) à l’HTA)

� 20% avec µ-albuminurie vont progresser à une NPD protéinurique

� Près de 100% avec une ‘‘macro' protéinurie vont progresser à une IRCT

Diabète Type 1

� 25 - 45% développeront une NPD

� 80-90% avec µ-albuminurie vont progresser à une NPD protéinurique dans 5 - 10 ans

� Près de 100% avec une ‘‘macro' protéinurie vont progresser à une IRCT dans 7 - 10 ans

Epidemiologie de la néphropathie diabétique

Gene and protein markers of diabetic nephropathy. C Granier, K Makni, L Molina, B Jardin-Watelet, H Ayadi and F Jarraya. Nephrol Dial Transplant (2008) 23: 792–799

N Engl J Med 1998;339:69-75.

T1DM+

NPD(PBR1)

Greffe Pancreas

5 ansStable(PBR2)

10 ansRegression

(PBR3)

P=0.04


Microalbuminuria

150

100

50

0

GF

R (

mL/

min

)

5000

1000

200

20

Alb

umin

uria

(m

g/24

h)

5 10 15 20 25Years



Conditions: Repetition de la mesureAbsence d’infection uro-génitaleAbsence de fiévre et d’état inflammatoireNon précédée d’un effort

Kidney International Suppl. (2013) 3, 19–62

Le continuum réno-cardio-vasculaire

Dyslipidémie

Diabètes

Hypertension

S Métabolique

Facteurs de risques

Atheroscleroses

& HVG

microalbuminurie

Syndrome

Coronarien

Aigu--------

AIT-AVC

IC Congestive

IC terminale

Décès

modified from Ungur et al

Am J Cardiol 2002;89

Normo Albu µ Albu ↓ Cl. Créatinine IRCT DécèsAlbu - SN

CONTROVERSE

!!!!

Nephroprotection

FDR

renaux

Diabète

HTA

Micro

albuminurie

Proteinure

↑Crea>nine

↓eGFR

↓eGFR

IRC

x2 Creatinine

IRCT

Décès

Critères

intermédiaires

Critères

Hard End Point

F. JARRAYA 2015

*p <0.01 vs placebo.Parving H-H et al. N Engl J Med. 2001; 345: 870–8

0

5

10

15

20

0 6 12 18 22 24

Follow-up (months)

Incidence of diabeticnephropathy (%)

Placebo

Irbesartan(150 mg/d)

Irbesartan (300 mg/d) *

RR = 70%

THE EFFECT OF IRBESARTAN ON MICRO-ALBUMINURIA IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES « IRMA2 »

31

MARVAL: …For Same Level of BP Reduction!

BP reduction in hypertensive patients at 24 weeks

Adapted from Viberti et al. Circulation 2002;106:672–8

Valsartan 80/160 mg(n=169)

Amlodipine 5/10 mg(n=163)

Tolerance:

7.4% des patients with amlodipine develop legs oedema vs 1.2% of patients with valsartan(difference 6.2%, p=0.006

DBP SBP

BP

red

uctio

n (m

mH

g)

p=NS

p=NS

–8

–6

–4

–2

0

–10

–12

–14

–16

–18

32 Viberti et al. Circulation 2002;106:672–8

MARVAL: Valsartan is Significantly More Effective Than Amlod ipine in Reducing UAER in Type 2 Diabetes Patients With Micr oalbuminuria …

**p<0.001 vs amlodipine Time (week)

Cha

nge

in u

rinar

y al

bum

inex

cret

ion

rate

(%)

20

10

0

–10

–20

–30

–40

–500 4 8 12 18 24

Valsartan-based Tx (n=146)

Amlodipine-based Tx (n=145)

–8%

–44%**

Results from a 24-week study in 291 patients† with type 2 diabetes and microalbuminuria‡ (MARVAL study )

33

MARVAL: Valsartan Provides Regression to Normo-albuminuria

in T2DM Patients vs. Amlodipine

0

5

10

15

20

25

30

35

14.5

29.9*

Valsartan 80/160 mg Amlodipine 5/10 mg

Viberti et al. Circulation 2002;106:672–8

Results from a 24-week study in 291 patients† with type 2 diabetes and microalbuminuria‡

†Patients completing the study; ‡Median UAER 20-200 µg/min; *p<0.001 vs. amlodipine; # DIOVAN 80 mg and amlodipine 5 mg doses doubled at 4 weeks if BP uncontrolled (BP >135/85 mmHg); bendrofluazide 12.5 mg and doxazosin added as needed at 8 and 12 weeks, respectively, if BP still uncontrolled; UAER=Urinary albumin excretion rate

Pat

ient

s re

gres

sing

to

norm

oalb

umin

uria

(%)

34

Hypertensive patients Normotensivepatients

AmlodipineAmlodipineAmlodipineAmlodipine

ValsartanValsartanValsartanValsartan

AmlodipineAmlodipineAmlodipineAmlodipine

ValsartanValsartanValsartanValsartan

MARVAL: Valsartan more effective in reducing UAER not only in hypertensive but also in normotensive patients

Viberti et al. Circulation 2002;106:672–8

35

P=0.02


Microalbuminuria

150

100

50

0

GF

R (

mL/

min

)

5000

1000

200

20

Alb

umin

uria

(m

g/24

h)

5 10 15 20 25Years



Col IV

Fibronecti

ne

Laminine

RANDOMIZED EVALUATION OF NONINSULIN DEPENDENT DIABETES MELLITUS WITH THE ANGIOTENSIN-II ANTAGONIST LOSARTAN

« RENAAL »

CJP composite de 16%. p: 0.02taux de la protéinurie de 35% p: <0,001

incidence de dédoublement de créatinine de 25% p: 0.006

incidence d’IRCT de 28%. p: 0.002

BM Brenner et al. NEJM 2001

Créat x 2Proteinurie IRCT

IDNT : Time to x2creatinine, ESRF or deathpa

tient

s (

%)

0 6 12 18 24 30 36 42 48 54

Follow up (months)60

0

10

20

30

40

50

60

70Irbésartan

Amlodipine

Contrôle

RRR 20 %p = 0.02

p = NS

RRR 23 %p = 0.006

EJ Lewis et al. N Engl J Med 2001

B1 B2 3 6 12 18 24 30 36 42 48

Study Visit (mos.)

1.0

1.5

2.0

2.5

3.0

3.5U

rine

prot

ein,

g/2

4h

Geometric Mean 24 hour Urine Protein by Follow-up V isitCorrected for Missing Data

IrbesartanAmlodipinePlacebo

Proteinuria was reduced 33% in the irbesartan group compared to

10% with placebo

Albumin Glycation in diabetes render UAE more toxic for nephron

ML. Gross et al, Kidney Int, Vol. 62 (2002), pp. 51–59 and unpublished data

More renal scarring by glycated albumin

ScoresProtein Peritubular

droplets fibrosis

NaCl 1.23±0.5 0.40±0.05

Albumin 2.74±0.4 2.87±0.7

Glycated albumin 3.70±0.4 3.3±0.6

†UAER 20-700 µg/min; *p<0.001 vs.160 mg (30 weeks vs. 4 weeks); **p<0.05 vs. 160 mg; T2D=Type 2 diabetes mellitus; UAER=Urinary albumin excretion rate

Valsartan160 mg(n=130)



Cha

nge

in U

AE

R fr

om

base

line

(%)

-25%

-51%*-49%*

-55

-45

-35

-25

-15

-5

12%

19%

24%**

0

5

10

15

20

25




Pat

ient

s re

gres

sing

tono

rmoa

lbum

inur

ia(%

)

DROP Study: Valsartan Reduces UAER in Patients withT2D, HTN and Albuminuria

Hollenberg et al J Hypertens 2007,25:1921-1926

Results from a 30-week study in 391 patients with T2D, HTN and albuminuria† (DROP study)

-60

-50

-40

-30

-20

-10

0

10

Change inproteinuriaat 6 months(%)

Ramipril 5 mg Ramipril 5 mg +irbesartan 150 mg

Ramipril 5 mg +aldactone 25 mg

Ramipril 5 mg +irbesartan 150 mg+ aldactone 25 mg

Optamizing blockade of RAAS for optimal antiproteinuric effect

N=10 patients per group,Double-blind, placebo-controlled

Chrysostomou et al, Clin JASN, 2006; 1:256-262

43

Bakris GL et al. Am J Kidney Dis 2000; 36(3): 646-661

95 98 101 104 107 110 113 116 119

r = 0.69;P < 0.05

MBP1 (mmHg)

130/85

1Mean Blood Pressure

140/90

Untreated HT

0

-2

-4

-6

-8

-10

-12

-14

Meta-analysis: relation between BP reduction and GFR in Type 2 diabetic patients with proteinuric DPN

Normal GFR 120ml/mn/1.73m²

Objectifs tensionnels changent selon les recommandations…

(American Diabetes Association.Clinical Practice Recommendations 2013.Diabetes Care 2013;36(Suppl.1):S109-S110.)

Chez le diabétique: PA<140/80mmHg

Chez l’hypertendus: PA<140/80mmHg

Chez le ccoronarien: PA<140/90mmHg

Chez le patient atteint de MRC ND:

Non Diabétique +Albu <30mg/24h: PA<140/90mmHgNon Diabétique +Albu 30-300mg/24h: PA<130/80mmHgNon Diabétique +Albu >300mg/24h: PA<130/80mmHg

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease. J Am Coll Cardiol.2012Dec 18;60(24):e44-e164

2012 KDIGO Clinical Practice Guideline for management of Blood Pressure in CKD . Kidney Int 2012

Diabétique +Albu <30mg/24h: PA<140/90mmHgDiabétique +Albu 30-300mg/24h: PA<130/80mmHgDiabétique+ Albu >300mg/24h: PA<130/80mmHg

HTA>130/80

HTA>130/80

2013 ESH/ESC Guidelines for themanagement of arterial hypertension. Journal of Hypertension 2013, 31:1281–1357 2014 JNC 8

F Jarraya 2013

IDNTIrbesartan Diabetic Nephropathy

Trial

Independent and Additive Impact of BP Control and ARB on Renal Outcomes in the Irbesartan Diabetic Nephropathy Trial:Clinical Implications and Limitations

M A Pohl et al. J Am Soc Nephrol 2005.

SPRINT

INCREASE IN NOCTURNAL BLOOD PRESSURE AND PROGRESSION TO MICRO-

ALBUMINURIA IN TYPE 1 DIABETES E. Lurbe et al. N Engl J Med 2002;347:797-805.)

Quelle stratégie devant uneHTA – Proteinurie ?Associer un diurétique vs Amlodipine :

diurétique > Amlodipine sur l’excretion urinaire d’album ine

� MRC non diabétique, protéinurie >1g/j, lisinopril 40 mg/j

� Restriction sodée + BSRA >> BSRA + BSRA

Slagman M. BMJ 2011

IEC

PuPAS

IEC

+

A

R

A

2IEC

IEC

+

ARA

2

IEC IEC

+

A

R

A

2

IEC IEC

+

ARA2

Hypertension Treatment: Compelling indications

2013 ESH Guidelines2013

Valsartan in Combination with ACEIis more effective in Reducing Proteinuria

†SBP/DBP >140/90 mmHg, proteinuria >1.5 g/day while on therapy with an ACEi alone or in combination with other antihypertensive drugs for at least 3 months, creatinine clearance values >30 mL/min; *p<0.05 vs. benazepril group; Therapy doses are per daily doses; UPER=Urinary protein excretion rateSegura et al. J Renin Angiotensin Aldosterone Syst 2003;4:43-47.

Results from a 6-month study in 36 patients with primary renal disease,†

assessing the change in proteinuria

Mea

n re

duct

ion

in U

PE

R(g

/day

)

-1.0

-2.0

Combination(n=12)

0

Benazepril 10-20 mg(n=12)

Valsartan 80-160 mg(n=12)

-0.5

-1.2

-2.5*-2.5

-0.5

-1.5

1- Controler l’HyperTension Artérielle (IEC, ARA2)<130/80mmHgSauf si pathologie coronarienne 130<PAS<140mmHg

2- Réduire la Proteinurie (IEC,ARA2)Microalbuminurie <30mg/gcreatinine (<30mg/24h) chez le T1DMRegression ou non-progression de la Microalbuminurie chez le T2DM et/ou HTAProtéinurie <0,5g/24h

3- Adapter le régimeProtéines: environs 0,8g/kg/jSel 3à 5 g/j

4- Traiter le diabète (Adapter les antidiabétiques selon le DFG)HbA1C<7%

5- corriger la dyslipidémie (Statine)LDL Ct < 1g/l (2,5mmo/l)

6- Corriger l’anémie (EPO)Hb: 11-13g/dl

7- Prescrire un antiagrégant plaquettaire8- Arrêter le tabac9- Favoriser l’exercice physique10- Eviter les médicaments/produits néphrotoxiques

NEPHROPATHIE DIABETIQUENouveautés en 2015?

NPD

Perspectives!!!!

Diabetic kidney disease causes significant morbidity and mortality among people with type 1

diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately

curb this problem and therefore a major need for novel treatment approaches exists. Multiple

observations link serum uric acid levels to kidney disease development and progression in

diabetes and strongly argue that uric acid lowering should be tested as one such novel

intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the

Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D

individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective

agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is

inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the

completion of appropriate trials at earlier stages

he study is done to find out whether the combined use of the nutritional supplements N-acetylcysteine and Siliphos

(milk thistle extract) corrects the shedding of urine protein and oxidative damage (damage to cells and organs often

compared to fast aging) in patients with Type 2 Diabetes Mellitus (T2DM) and diabetic kidney disease.

failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year

J Am Soc Nephrol 23: 131–136, 2012.

J Am Soc Nephrol22: 1144–1151, 2011In conclusion: these results suggest that pirfenidone is a promising agent for

individuals with overt diabetic nephropathy

mean eGFR increased in the pirfenidone 1200-mg/d group (3.3 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (2.24.8 ml/min per 1.73m2; P=0.026 versus pirfenidone at 1200 mg/d).The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group,

J Am Soc Nephrol 22: 1144–1151, 2011.


Facteurs de transcription

Facteurs de transcription

BEACON Trial

N Engl J Med 2013;369:2492-503.


Voies de signalisation

Pentoxifylline for renoprotection in Diabetic

Nephropathy: the PREDIAN study. Rationale and

basal results

Juan F. Navarro-González, et al. Journal of Diabetes

and its Complications, 2011;25:314-319

Conclusions :The PREDIAN study will provide evidence on the renoprotective benefit of PTF in addition to interventions of proven efficacy (RAS blockade) in DN.

Activation des voies signalisation

ASCEND Study. Avosentan for overt diabetic nephropathy. Mann, J. F. et al. J. Am. Soc. Nephrol. 21, 527–535 (2010).

X2creat, IRCT, décèsN= 1392

the median

reduction

(%) in ACR

Av.44.3%,

Av. 49.3,

Pc. 9.7%

Survie

Diabetes perte de la charge negative de la matice extracellulaire

MBG

Normale

Perte des GAG de MBG ALBUMINURIE��

Phase initiale

de La ND

Phase avancée

de la ND

Deckert et al Diabetologia 1989

Hypothéses de la DeckertJ Am Soc Nephrol 23: 123– 130, 2012

Faut pas réver!!!

Nat. Rev. Nephrol. 10, 325–346 (2014)

1- Controler l’HyperTension Artérielle (IEC, ARA2)<130/80mmHgSauf si pathologie coronarienne 130<PAS<140mmHg

2- Réduire la Proteinurie (IEC,ARA2)Microalbuminurie <30mg/gcreatinine (<30mg/24h) chez le T1DMRegression ou non-progression de la Microalbuminurie chez le T2DM et/ou HTAProtéinurie <0,5g/24h

3- Adapter le régimeProtéines: environs 0,8g/kg/jSel 3à 5 g/j

4- Traiter le diabète (Adapter les antidiabétiques selon le DFG)HbA1C<7%

5- corriger la dyslipidémie (Statine)LDL Ct < 1g/l (2,5mmo/l)

6- Corriger l’anémie (EPO)Hb: 11-13g/dl

7- Prescrire un antiagrégant plaquettaire8- Arrêter le tabac9- Favoriser l’exercice physique10- Eviter les médicaments/produits néphrotoxiques

Take Home Messages:Les 10 Commandements du traitement néphroprotecteur

heinn!!!!

Ruggenenti, P. et al. Clin J Am Soc Nephrol 2007;2:146-150

Annual ESRD incidence in the United States from 1980 to 2004 according to the Annual ESRD incidence in the United States from 1980 to 2004 according to the Annual ESRD incidence in the United States from 1980 to 2004 according to the Annual ESRD incidence in the United States from 1980 to 2004 according to the publication of randomized clinical trials providing the evidence of a protective publication of randomized clinical trials providing the evidence of a protective publication of randomized clinical trials providing the evidence of a protective publication of randomized clinical trials providing the evidence of a protective

effect of RAS inhibitor therapy against the development of ESRDeffect of RAS inhibitor therapy against the development of ESRDeffect of RAS inhibitor therapy against the development of ESRDeffect of RAS inhibitor therapy against the development of ESRD

Lewis REIN RENAAL-IRMA2- IDNT-

Merci pour votre attention

Agissons ensemble pour préserver les

néphrons de diabétiques

Pr FaiçalJARRAYA, MD - Promotion de l’épidémiologie...

Documents

Transcript of Pr FaiçalJARRAYA, MD - Promotion de l’épidémiologie...