presentation PDF - BVN

6/10/2014
Chronic Kidney Disease General management and standard of care
Dr Nathalie Demoulin , Prof Michel Jadoul
Cliniques universitaires Saint-Luc
Université Catholique de Louvain
What should and can be done when managing a CKD patient
• Above all, clinical care !
• Pathophysiology is presented only to explain why a
practice is recommended
• The following topics will not be covered:
- diagnosis of the cause of CKD (frequently crucial)
- the methods to estimate GFR
Management of CKD according to stage (KDOQI 2002)
Stage
Description
GFR
(mL/min./1,73m²)
Action
At increased risk
>90
(with CKD risk factors)
Screening,
CKD risk reduction
1
Kidney damage
With normal or ↑ GFR
>90
Diagnosis and treatment,
Treatment of comorbid conditions,
Slowing progression,
CVD risk reduction
2
Kidney damage
With mild ↓ GFR
60-89
Estimating progression
3
Moderate ↓ GFR
30-59
Evaluating and treating
complications
4
Severe ↓ GFR
15-29
Preparation for kidney
replacement therapy
5
Kidney failure
< 15
(or dialysis)
Replacement (if uremia present)
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KDIGO CKD Guidelines 2012
Section 1: Definition and classification of CKD
Section 2: Definition, identification and prediction of CKD progression
Section 3: Management of progression and complications of CKD
Section 4: Other Complications of CKD: CVD, medication dosing,
patient safety, infections, hospitalizations, and caveats for
investigating complications of CKD
Section 5: Referral to specialists and models of care
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Definition and Classification
1.1. Definition of CKD: CKD is defined as abnormalities of
kidney structure or function for ≥3 months with
implications for health
- this definition specifically excludes simple renal cysts, …..
- If duration < 3 months -> could be CKD or AKI or both
Definition and Classification
Staging of CKD (CGA staging)
Cause
GFR Categories
(ml/min/1.73m2)
Diabetes
G1
≥90
Hypertension
G2
60-89
Glom Disease
G3a
45-59
Transplant
G3b
30-44
Unknown
G4
15-29
etc
G5
<15
Albuminuria Categories
(ACR, mg/g)
A1
<30
N to midly increased
A2
30-299
Moderately increased
A3
≥300
Severly increased
Tigette OK
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Staging of CKD – GFR and mortality
5,9
3,2
1,8
1
1,2
Go et al, NEJM 2004
Evaluation of Albuminuria
• The reference point= accurately timed 24h specimen
• Early morning urine preferred
Designation
Trace
1+
2+
3+
4+
Protein dipstick grading
Approx. amount
Concentration
Daily
5–20 mg/dL
30 mg/dL
< 0.5 g/day
100 mg/dL
0.5–1 g/day
300 mg/dL
1–2 g/day
> 2000 mg/dL
>2 g/day
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Relationship between categories of
albuminuria and proteinuria
Staging of CKD (CGA staging)
Cause
GFR Categories
(ml/min/1.73m2)
Diabetes
G1
≥90
Hypertension
G2
60-89
Glom Disease
G3a
45-59
Transplant
G3b
30-44
Unknown
G4
15-29
etc
G5
<15
Albuminuria Categories
(ACR, mg/g)
<30
A1
N to midly increased
Dipstick neg to trace
A2
30-299
Moderately increased
Dipstick trace to +
A3
≥300
Severely increased
Dipstick > +
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
Predictive ability of albuminuria at all categories of GFR:
Meta-analysis from General Population Cohorts CKD Prognosis Consortium
ACR>=300
ACR 30-299
ACR <30
Levey, KI 2011
Predictive ability of albuminuria at all categories of GFR:
General Population Cohorts
ACR>=300
ACR 30-299
ACR <30
Levey, KI 2011
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Adjusted relative risk of renal and cardiovascular outcomes
for GP cohorts with ACR
Levey et al, Kidney Int 2011
KDIGO CKD Guidelines 2012
Section 1: Definition and classification of CKD
Section 2: Definition, identification and prediction of CKD progression
Section 3: Management of progression and complications of CKD
Section 4: Other Complications of CKD: CVD, medication dosing,
patient safety, infections, hospitalizations, and caveats for
investigating complications of CKD
Section 5: Referral to specialists and models of care
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Definition of CKD progression
• Decline in GFR category (G1-G4)
accompanied by ≥ 25% drop in eGFR from baseline
• Rapid progression defined as sustained decline in
eGFR > 5ml/min/1,73m2/year
Predictors of progression of CKD
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Cause of CKD
Level of GFR
Level of albuminuria
Age
Gender
Elevated BP
Hyperglycemia
Dyslipidemia
Smoking
Obesity
History of CVD
Ongoing exposure to nephrotoxic agents
Anemia, acidosis, bone metabolism, hyperuricemia….
Minimising CKD progression (and CV risk) – BP control
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Minimising CKD progression (and CV risk) – BP control
ACR
<30mg/g
30-300 mg/g
Diabetic ≤ 140/90 mmHg ≤ 130/80 mmHg
(1B)
(2D)
Non
≤ 140/90 mmHg ≤ 130/80 mmHg
diabetic
(1B)
(2D)
> 300 mg/g
≤ 130/80 mmHg
(2D)
≤ 130/80 mmHg
(2D)
Minimising CKD progression
Captopril protects against deterioration in renal function in insulindependent diabetic nephropathy independently of BP control
Lewis et al. NEJM 1993; 329, 1456-1462
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The angiotensin-II-receptor blocker irbesartan is effective in protecting against
progression in type 2 diabetes nephropathy, independently of BP control
Irbesartan
Amlodipine
Placebo
1715 patients, Target BP ≤ 135/58 mmHg
Lewis et al. N Engl J Med 2001; 345: 851-860
Mean BP + 3,3 mmHg in placebo vs amlodipine and irbesartan (p=0,001)
Lewis et al. N Engl J Med 2001; 345: 851-860
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ACEi and ARBs are beneficial agents in CKD
• Hemodynamic/antihypertensive actions
– ↓ capillary hypertension by ↓ perfusion pressure and efferent
arteriole relaxation
• Anti-inflammatory/anti-fibrotic actions
Turner et al, Kidney Int 2012
The anti-proteinuric effect of lisinopril is dose and time related,
and strongly dependent on dietary sodium restriction
Salt intake 50 and 200 mmol/day
Heeg et al, Kidney Int 1989
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Salt restriction or diuretics :
similar potentiation of ACE-I effect
Addition of HCT ->
↓ 10% BP
↓ 40% proteinuria
low= sodium 50 mmol/d
high= sodium 200 mmol/d
Buter et al, Nephrol Dial Transplant 1998
The optimal clinical use of diuretics
• eGFR > 30 : thiazide ( Chlortalidone, « Co…. », « Plus »)
• eGFR < 30 or poor response to thiazide: loop diuretic
(furosemide / bumetanide)
– works for max 6-8h, thus if still poor response , give 2-3 times a day
(8am, 12am and 5pm)
– ! tolerance : cramps (volume –related (not K, Ca, Mg)),
pollakiuria ( prostate…)
– adapt timing of administration to daily activities
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Estimating salt intake from 24 h urine sample?
• Prerequisite 1) Volume IN = Volume OUT (steady state)
• Thus not valid if diarrhea or vomiting, ileostomia or
intense sweating or recent start or change of dosage or
variable adherence to diuretics
• Prerequisite 2) Na IN = Cl IN
• Thus not valid if Vichy water or NaHCO3 taken orally
• 100 mmol Na = roughly 6g de salt
• Prerequisite 3) 24h urine collection is complete
• Estimated from creatininuria (10-25 mg/kg (depending
on age, gender, ethnicity))
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ACE-I, ARB : should we stop them if creatinine rises?
No if creatinine < 3 mg/dl and rising by less than < 30 %
Treatment is associated +++ with preservation of GFR
(if creatinine rises +++ (double or triple): look for renal artery
stenosis or stenoses)
Bakris et al. Arch Int Med 2000; 160: 685-693
Example of a patient with diabetic nephropathy patient already
under Irbesartan: loop diuretic increased progressively
Hyperkalemia with ACE inhibitors /
angiotensin II receptor antagonist / aliskiren (I)
 Is it true hyperkalemia?
(to avoid stopping valuable drug because of a laboratory
error)
• Time between blood sampling and analysis?
• Hemolysis?
• Confirmed (precautions), severe? (> 5.8 mmol/l)
 Dietary ?
• Salt substitute
• (Dried) fruit, bananas, chocolate, instant coffee,....
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Hyperkalemia with ACE inhibitors /
angiotensin II receptor antagonist / aliskiren (I)
 Correct any acidosis (Vichy 1-2 glasses/d)
 ACE inhibitor + angiotensin II receptor or aliskiren:
stop or reduce 1 of the 2
 ACE inhibitor (angiotensin II receptor ) + spironolactone:
stop or reduce spironolactone
 ACE inhibitor or angiotensin II receptor or aliskiren monotherapy:
 dose - add Furosemide
 If persistence, add calcium kayexalate 15 g/2 days per os
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Dual RAAS blockade in CKD ?
Similar results in « Altitude » with Aliskiren + ACEI or A2RB
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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 microdose « cardio »
spironolactone
 Association ACE inhibitor + ARB : only if heavy
proteinuria (« glomerular), close, careful
nephrology follow-up in reliable patients
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Protein intake
Rationale:
If BP and proteinuria are well controlled, the slope of CKD
progression will not change much with lower protein intake
In > 65 y old patients, potential for malnutrition !
Glycemic control
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Lifestyle measures
KDIGO CKD Guidelines 2012
Section 1: Definition and classification of CKD
Section 2: Definition, identification and prediction of CKD progression
Section 3: Management of progression and complications of CKD
Section 4: Other Complications of CKD: CVD, medication dosing,
patient safety, infections, hospitalizations, and caveats for
investigating complications of CKD
Section 5: Referral to specialists and models of care
• Strong and independent associations between GFR and albuminuria
categories and risk of CVD in people with CKD
• Cardiovascular risk in CKD is multifactorial
• Cardiovascular disease is more frequent and severe, often not
recognised and undertreated in patients with CKD
• Patients with CKD should be viewed amongst the highest risk
groups for CVD
• To prevent progression of CKD is to prevent CVD
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The burden of cardiovascular disease:
Causes of death per CKD stage (Canadian data)
Gansevoort et al, Lancet 2013
Classical CV risk factors
Not modifiable
Modifiable but no
proven benefit
Modifiable with
clinical benefit
Older age
Uric acid
Smoking
Male gender
Homocysteine
Obesity
Ethnicity
Hypertension
Lp (a)
Diabetes
HDL cholesterol
LDL cholesterol
Physical activity
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Lipid control and antiplatelet therapy
• No specific lipid targets are established in CKD patients
-> treat in accordance with guidelines for other highrisk populations
• Antiplatelet therapy should be offered to high risk
patients unless bleeding risk outweighs CV benefits.
Gansevoort et al, Lancet 2013
Chronic Kidney Disease General management and standard of care
• Even if cause of CKD not treatable, much can and should
be done for any CKD patient
• Treat BP to target and aggressively substantial
albuminuria; both interventions delay CKD progression
• Underuse of salt restriction/diuretics !!
• Manage aggressively classical CV risk factors
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