canadian diabetes association clinical practice guidelines chronic kidney disease in diabetes...

Canadian Diabetes Association Clinical Practice Guidelines

Chronic Kidney Disease in Diabetes

Chapter 29

Phil McFarlane, Richard E. Gilbert,

Lori MacCallum, Peter Senior

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

SCREEN regularly with random urine albumin

creatinine ratio (ACR) and serum creatinine for

estimated glomerular filtration rate (eGFR) DIAGNOSE with repeat confirmed

ACR ≥2.0 mg/mmol and/or eGFR <60 mL/min

DELAY onset and/or progression with glycemic and

blood pressure control and ACE-inhibitor or Angiotensin

Receptor Blocker (ARB)

PREVENT complications with “sick day management”

counselling and referral when appropriate

2013Chronic Kidney Disease (CKD) Checklist

Patients with DM 6-12X more likely to be hospitalized for CKD or End-stage renal disease (ESRD)

Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).


Diabetes is #1 Cause of New Cases of ESRD

Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).


CKD in Diabetes

ACR ≥2.0 mg/mmol

and / or

eGFR <60 mL/min

2013


Diabetic Nephropathy

“ Progressive increase in proteinuria in people

with longstanding diabetes, followed by

declining function which can eventually lead to

End-Stage Renal Disease (ESRD)”


Stages of Diabetic Nephropathy

Note: change in definition of microalbuminuria ACR ≥2.0 mg/mmol2013


Screening and

Diagnosis of CKD in

Diabetes


Beware of Transient Albuminuria


2013


2


Beware

of Other

Causes

of CKD


When to Consider Other Causes of CKD


2


Care Gap Still Exists for Screening

Canadian Institute of Health Information – Diabetes Care Gap 2009


• Optimal glycemic control in type 1 and type 2

diabetes has been shown to reduce the development

and progression of nephropathy

Prevention of Diabetic Nephropathy

The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.

34% RRR (p<0.04)

43% RRR(p=0.001)

56% RRR(p=0.01)

Primary Prevention Secondary Intervention

Solid line = risk of developing microalbuminuriaDashed line = risk of developing macroalbuminuria

DCCT: Reduction in Albuminuria

RRR = relative risk reductionCI = confidence interval


deBoer IH et al. Arch Intern Med 2011;171(5):412-420.

HR 1.92 (p<0.05)

HR 0.64(95% CI 0.40-

1.02)

Return to normoalbuminuria

Macroalbuminuria

HR = hazard ratioCI = confidence interval


EDIC: Continued Reduction in Albuminuria

EDIC: Early Glycemic Control Reduces Long-term Risk of Impaired GFR

Risk reduction with intensive therapy50%

(95% CI 18-69; p=0.006)

DCCT/EDIC Research Group. N Engl J Med 2011;365:2366-76.

After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040

Microvascular disease RRR: 25% 24% P: 0.0099 0.001

Myocardial infarction RRR: 16% 15% P: 0.052 0.014

All-cause mortality RRR: 6% 13% P: 0.44 0.007

Holman R, et al. N Engl J Med 2008;359.

UKPDS: Post-trial Monitoring “Legacy Effect”


New/worsening nephropathy, retinopathy

66

Cumulative incidence (%)

Follow-up (months)

HR 0.86 (0.77-0.97)p = 0.01 Standard

control

Intensive control

25

20

15

10

5

00 6 12 18 24 30 36 42 48 54 60

Intensive Standard HR p

Nephropathy/retinopathy (%) 9.4 10.9 0.86 0.01

Nephropathy (%) 4.1 5.2 0.79 0.006

Retinopathy (%) 6.0 6.3 0.95 NSAdapted from:ADVANCE Collaborative Group. N Engl J Med 2008;358:2560-72.ADVANCE Collaborative Group. N Engl J Med 2008;358:24.

ADVANCE: Primary Microvascular Outcomes

Reducing Progression of Diabetic Nephropathy

• Optimal glycemic control (as shown)

• Optimal blood pressure control

• ACE-inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB)


ACE-inhibitor in T1DM with MAU Reduces Progression to Clinical Proteinuria

Laffel LM et al. Am J Med 1995;99(5):497-504.

Months of Therapy

Pro

po

rtio

n w

ith

Eve

nt


Lewis EJ et al. N Engl J Med 1993;329:1456-62.

ACE-inhibitor in T1DM with Macroalbuminuria Reduces Renal Outcomes


ARB in T2DM with MAU reduces progression

0 3 6 9 12 15 18 21 240

5

10

15

20

Follow-up (months)

Inc

ide

nc

e o

f d

iab

eti

c n

ep

hro

pa

thy

(%

)

Parving et al. N Engl J Med 2001;345:870-8

Primary endpoint: Time to onset of diabetic nephropathy* (n=590)

*defined by persistent albuminuria in overnight specimens,with urinary albumin excretion rate <200 μg/min and ≥30% higher than baseline level

Placebo

Irbesartan 150mg

Irbesartan 300mg


Brenner et al. N Engl J Med 2001;345:861-9

Cu

mu

lati

ve %

of

pat

ien

ts w

ith

eve

nt

Months240 12 36 48

Placebo

Losartan

Risk reduction = 16%

p=0.02

0

10

20

30

40

50

Primary endpoint: Time to doubling of serum creatinine, ESRD, or death (n=1513)

ARB in T2DM with Macroalbuminuria Reduces Renal Outcomes


Lewis et al. N Engl J Med 2001;345:851-60

Primary endpoint: Time to doubling of serum creatinine,ESRD, or death (n=1,715)

Pat

ien

ts (

%)

0 6 12 18 24 30 36 42 48 54

Follow-up (mo)

60

0

10

20

30

40

50

60

70

Irbesartan

Amlodipine

Placebo

RRR 20%p=0.02p=NS

RRR 23%p=0.006

ARB in T2DM with Macroalbuminuria Reduces Renal Outcomes

Safe use of treatments in kidney

disease…..

• Check serum K+ and Cr– Baseline– Within 1-2 weeks of initiation or titration– During acute illness

If K+ becomes elevated or Cr >30% increase

Review therapy

Recheck serum K+ and Cr

Practical Tips: Potassium (K+) and Creatinine (Cr)


• Mild to moderate stable hyperkalemia– Counsel on a low potassium diet

– If persistent, consider adding non-potassium sparing

diuretics and/or oral sodium bicarbonate (in those with

metabolic acidosis)

– Consider temporarily holding or discontinuing ACEi, ARB or

Direct Renin Inhibitor (DRI)

• Severe hyperkalemia– Hold or discontinue ACEi, ARB or DRI

– Emergency management strategies


Practical Tips: Potassium (K+) and Creatinine (Cr)

Counsel all Patients About

Sick Day Medication

List

2013


See CPG Appendix 6 for therapeutic considerations

for renal impairment

2013

• Chronic, progressive loss of kidney function

• ACR persistently >60 mg/mmol

• eGFR <30 mL/min

• Unable to remain on renal-protective therapies due to

adverse effects such as hyperkalemia or a >30%

increase in serum Cr within 3 months of starting ACEi

or ARB

• Unable to achieve target BP (could be referred to any

specialist in hypertension)

When to Refer…..



1. In adults, screening for CKD in diabetes should be

conducted using a random urine ACR and a

serum creatinine converted into an eGFR [Grade D,

Consensus].

Screening should commence at diagnosis of

diabetes in individuals with type 2 diabetes and 5

years after diagnosis in adults with type 1

diabetes and repeated yearly thereafter.

Recommendation 1: Screening


A diagnosis of chronic kidney disease should be made

in patients with a random urine ACR ≥2.0 mg/mmol

and/or an eGFR<60 mL/min on at least two out of

three samples over a three month period [Grade D,

Consensus].

2013

Recommendation 1: Screening (continued)


Recommendation 2: Vascular Protection

2. All patients with diabetes and chronic kidney

disease should receive a comprehensive,

multifaceted approach to reduce cardiovascular

risk (see Vascular Protection, CPG Chapter 22) [Grade A, Level 1A].


Recommendation 3: Treatment

3. Adults with diabetes and CKD with either

hypertension or albuminuria should receive an

ACE inhibitor or an ARB to delay progression of

CKD [Grade A, Level 1A for ACE-inhibitor use in type 1 and type 2

diabetes, and for ARB use in type 2 diabetes; Grade D, Consensus, for ARB

use in type 1 diabetes].


4. People with diabetes on an ACE inhibitor or an ARB

should have their serum creatinine and potassium

levels checked at baseline and within 1 to 2 weeks

of initiation or titration of therapy and during times

of acute illness [Grade D, Consensus].

5. Adults with diabetes and CKD should be given a

“sick day” medication list that outlines which

medications should be held during times of acute

illness (see CPG Appendix) [Grade D, Consensus].

2013

Recommendation 4 and 5


Recommendation 6

6. Combination of agents that block the renin-

angiotensin-aldosterone system (ACE-inhibitor,

ARB, DRI) should not be routinely used in the

management of diabetes and CKD [Grade A, Level 1].

2013


Recommendation 7: When to Refer

7. People with diabetes should be referred to a

nephrologist or internist with an expertise in chronic

kidney disease in the following situations:– Chronic, progressive loss of kidney function

– ACR persistently >60 mg/mmol

– eGFR<30 mL/min

– Unable to remain on renal-protective therapies due to

adverse effects such as hyperkalemia or a >30% increase in

serum creatinine within 3 months of starting an ACE-inhibitor

or ARB

– Unable to achieve target BP (could be referred to any

specialist in hypertension) [Grade D, Consensus]

CDA Clinical Practice Guidelines

www.guidelines.diabetes.ca – for professionals

1-800-BANTING (226-8464)

www.diabetes.ca – for patients

http://guidelines.diabetes.ca/

http://diabetes.ca/

canadian diabetes association clinical practice guidelines chronic kidney disease in diabetes...

Documents

diabetes slide

diabetes acr

diabetes chapter

longstanding diabetes

causes of ckd slide

peter senior slide

transient albuminuria

mgmmol andor egfr slide