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Chronic Kidney Disease -

General management and standard of care

Dr Nathalie Demoulin , Prof Michel Jadoul

Cliniques universitaires Saint-Luc

Université Catholique de Louvain

• 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

What should and can be done when managing a CKD patient

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)

Management of CKD according to stage (KDOQI 2002)

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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

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

Tigette OK

N to midly increased

Moderately increased

Severly increased

Staging of CKD (CGA staging)

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Go et al, NEJM 2004

Staging of CKD – GFR and mortality

5,9

3,2

1,8

1,2 1

• The reference point= accurately timed 24h specimen

• Early morning urine preferred

Evaluation of Albuminuria

Protein dipstick grading

Designation Approx. amount

Concentration Daily

Trace 5–20 mg/dL

1+ 30 mg/dL < 0.5 g/day

2+ 100 mg/dL 0.5–1 g/day

3+ 300 mg/dL 1–2 g/day

4+ > 2000 mg/dL >2 g/day

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Relationship between categories of

albuminuria and proteinuria

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 midly increased

Dipstick neg to trace

Moderately increased

Dipstick trace to +

Severely increased

Dipstick > +

Staging of CKD (CGA staging)

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

Levey, KI 2011

ACR>=300

ACR 30-299

ACR <30

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

• 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

Predictors of progression of CKD

Anemia, acidosis, bone metabolism, hyperuricemia….

Minimising CKD progression (and CV risk) – BP control

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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

Minimising CKD progression

Lewis et al. NEJM 1993; 329, 1456-1462

Captopril protects against deterioration in renal function in insulin-

dependent diabetic nephropathy independently of BP control

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Lewis et al. N Engl J Med 2001; 345: 851-860

Irbesartan

Amlodipine

Placebo

The angiotensin-II-receptor blocker irbesartan is effective in protecting against

progression in type 2 diabetes nephropathy, independently of BP control

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)

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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

Heeg et al, Kidney Int 1989

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

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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/d high= sodium 200 mmol/d

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

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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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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Hyperkalemia with ACE inhibitors /

angiotensin II receptor antagonist / aliskiren (I)

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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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 !

Protein intake

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 high-

risk populations

• Antiplatelet therapy should be offered to high risk

patients unless bleeding risk outweighs CV benefits.

Gansevoort et al, Lancet 2013

• 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

Chronic Kidney Disease -

General management and standard of care