albuminuria in diabetic patients

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MICHEL JADOUL Disclosure of Interest Scientific advice to companies: Amgen, ZS-Pharma, Fresenius, Sanofi, Shire, Amgen, Menarini Travel refunds, congress registration fees: Amgen Research grant: Amgen, Baxter, Fresenius, Janssen-Cilag, Roche The details of each Disclosure of Interest are available at the Invited Speakers’ desk (located in the Registration Area).

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Page 1: Albuminuria in Diabetic Patients

MICHEL JADOUL

Disclosure of Interest

Scientific advice to companies:

Amgen, ZS-Pharma, Fresenius, Sanofi, Shire, Amgen,

Menarini

Travel refunds, congress registration fees:

Amgen

Research grant:

Amgen, Baxter, Fresenius, Janssen-Cilag, Roche

The details of each Disclosure of Interest are available at the Invited Speakers’ desk (located

in the Registration Area).

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Professor Michel JadoulCliniques Universitaires St. LucUniversité Catholique de LouvainBrussels, Belgium

Albuminuria in diabetic patients : prognosis and management

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Albuminuria in diabetics

• Prognostic impact of albuminuria in generaland in diabetics

• Is albuminuria measured in T2D?

• How should albuminuria best be managed?

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Prognostic value of GFR and albuminuria:

Cohorts and Subjects of CKD Consortium

• Community based populations– With ACR data, 14 studies, n=105,872

– With dipstick data, 10 studies, n=1,239,447

• Populations at increased CVD risk (HTN, diab, CV)– 10 studies, n=266,975

• CKD cohorts– 14 studies, n= 21,688

45 cohorts in total, >1.5 million subjects

Collaborative meta-analysis

Major publications: Lancet, KI, JAMA

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Prognostic value of GFR and albuminuria:

Cohorts and Subjects of CKD Consortium

• Community based populations– With ACR data, 14 studies, n=105,872

– With dipstick data, 10 studies, n=1,239,447

• Populations at increased CVD risk (HTN, diab, CV)– 10 studies, n=266,975

• CKD cohorts– 14 studies, n= 21,688

45 cohorts in total, >1.5 million subjects

Collaborative meta-analysis

Major publications: Lancet, KI, JAMA

Matsushita et al, Lancet 2010

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Adjusted relative risk of renal and cardiovascular outcomes

for GP cohorts with ACR

Levey et al, Kidney Int 2011

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Cause GFR Categories

(ml/min/1.73m2)

Albuminuria Categories

(ACR, mg/g)

Diabetes G1 ≥90

A1 <30

Hypertension G2 60-89

Glom Disease G3a 45-59

A2 30-299

Transplant G3b 30-44

Unknown G4 15-29

A3 ≥300

etc G5 <15

N to mildly increased

Dipstick neg to trace

Moderately increased

Dipstick trace to +

Severely increased

Dipstick > +

Staging of CKD (CGA staging)

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Dialysis or serum creat X2

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Albuminuria in diabetics

• Prognostic impact of albuminuria in generaland in diabetics

• Is albuminuria measured in T2D?

• How should albuminuria best be managed?

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75.6 % of pts with T2D have a urine test for albuminuria within the 1st year after startingantidiabetic medication

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Albuminuria in diabetics

• Prognostic impact of albuminuria in generaland in diabetics

• Is albuminuria measured in T2D?

• How should albuminuria best be managedwith currently available (registered) drugs?

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ACR <30mg/g 30-300 mg/g > 300 mg/g

Diabetic ≤ 140/90 mmHg

(1B)

≤ 130/80 mmHg

(2D)

≤ 130/80 mmHg

(2D)

Non

diabetic

≤ 140/90 mmHg

(1B)

≤ 130/80 mmHg

(2D)

≤ 130/80 mmHg

(2D)

Minimising CKD progression (and CV risk) – BP control

ACE-I or ARB 1st choice

A1 A2 A3

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Heeg et al, KI 1989

The anti-proteinuric effect of lisinopril is dose and time related,

and strongly dependent on dietary sodium restriction

Low Salt intake= 50 High salt = 200 mmol/day

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Salt restriction or diuretics :

similar potentiation of ACE-I effect

Buter et al, Nephrol Dial Transplant 1998

Low sodium= 50 mmol/dHigh sodium = 200 mmol/d

Addition of HCT -> ↓ 10% BP↓ 40% proteinuria

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Dual RAAS blockade in CKD ?

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Dual RAAS blockade ?

Nephro-protection : reducing proteinuria with

medium to long-term renoprotective effect (dialysis

later ... or never)

Nephro-risk: acute worsening of renal failure and

hyperK if intercurrent disease (gastroenteritis ++,..)

So block RAAS : YES but usually single agent (ACEi

or ARB) + possibly micro « cardio » dose of

spironolactone

Association ACE I + ARB : only if heavy proteinuria

(“ glomerular”), with close, careful nephrology

follow-up in reliable patients32

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No BP differences between groups

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Conclusions

• Albuminuria = a strong , independentprognostic marker of high risk of poor outcomes• Urinalysis still underused in the follow-up of diabetic patients• Albuminuria /proteinuria can /should betreated

- optimal BP control- RAS blockade (usually single agent)- low salt intake and /or diuretics- other drugs ? (pentoxyfilline?)