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).

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

Albuminuria in diabetic patients : prognosis and management

Albuminuria in diabetics

• Prognostic impact of albuminuria in generaland in diabetics

• Is albuminuria measured in T2D?

• How should albuminuria best be managed?

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

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

Adjusted relative risk of renal and cardiovascular outcomes

for GP cohorts with ACR

Levey et al, Kidney Int 2011

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)

Dialysis or serum creat X2




• How should albuminuria best be managed?

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




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

20

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

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

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

Dual RAAS blockade in CKD ?

28

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

No BP differences between groups

44

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?)

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Albuminuria in Diabetic Patients