Retinopathy - Canadian Diabetes Association

Report
Canadian Diabetes Association
Clinical Practice Guidelines
Chronic Kidney Disease in Diabetes
Chapter 29
Phil McFarlane, Richard E. Gilbert,
Lori MacCallum, Peter Senior
Chronic Kidney Disease (CKD) Checklist
2013
 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
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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
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Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).
2013
ACR ≥2.0 mg/mmol
CKD
in Diabetes
and / or
eGFR <60 mL/min
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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)”
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Stages of Diabetic Nephropathy
Note: change in definition of microalbuminuria
ACR ≥2.0 mg/mmol
2013
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Screening and
Diagnosis of CKD in
Diabetes
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Beware of Transient Albuminuria
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2013
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2
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Beware
of Other
Causes
of CKD
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When to Consider Other Causes of CKD
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2
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Care Gap Still Exists for Screening
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Canadian Institute of Health Information – Diabetes Care Gap 2009
Prevention of Diabetic Nephropathy
•
Optimal glycemic control in type 1 and type 2
diabetes has been shown to reduce the development
and progression of nephropathy
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DCCT: Reduction in Albuminuria
Primary Prevention
Secondary Intervention
34% RRR
43% RRR
(p<0.04)
(p=0.001)
56% RRR
(p=0.01)
RRR = relative risk reduction
Solid line = risk of developing microalbuminuria
Dashed line = risk of developing macroalbuminuria CI = confidence interval
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.
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EDIC: Continued Reduction in Albuminuria
Return to normoalbuminuria
Macroalbuminuria
HR 1.92
HR 0.64
(p<0.05)
(95% CI 0.40-1.02)
HR = hazard ratio
CI = confidence interval
deBoer IH et al. Arch Intern Med 2011;171(5):412-420.
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EDIC: Early Glycemic Control Reduces
Long-term Risk of Impaired GFR
Risk reduction with intensive therapy
50%
(95% CI 18-69; p=0.006)
DCCT/EDIC Research Group. N Engl J Med 2011;365:2366-76.
UKPDS: Post-trial Monitoring “Legacy Effect”
After median 8.5 years post-trial follow-up
Aggregate Endpoint
Any diabetes related endpoint
RRR:
P:
1997
12%
0.029
2007
9%
0.040
Microvascular disease
RRR:
25%
P: 0.0099
Myocardial infarction
RRR:
P:
16%
0.052
15%
0.014
All-cause mortality
RRR:
P:
6%
0.44
13%
0.007
Holman R, et al. N Engl J Med 2008;359.
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24%
0.001
ADVANCE: Primary Microvascular
Outcomes
New/worsening nephropathy, retinopathy
25
20
HR 0.86 (0.77-0.97)
p = 0.01
15
Cumulative
incidence (%)
Standard
control
10
Intensive
control
5
0
0
6
12
18
24
30
36
42
48
54
60
66
Follow-up (months)
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
NS
Adapted from:
ADVANCE
Collaborative
Group.
N Engl J Med
ADVANCE
Collaborative
Group. N Engl
J Med 2008;358:2560-72.
2008;358:24.
Reducing Progression of Diabetic Nephropathy
•
Optimal glycemic control (as shown)
•
Optimal blood pressure control
•
ACE-inhibitor (ACEi) or Angiotensin Receptor
Blocker (ARB)
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Proportion with Event
ACE-inhibitor in T1DM with MAU Reduces
Progression to Clinical Proteinuria
Months of Therapy
Laffel LM et al. Am J Med 1995;99(5):497-504.
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ACE-inhibitor in T1DM with
Macroalbuminuria Reduces Renal Outcomes
Lewis EJ et al. N Engl J Med 1993;329:1456-62.
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ARB in T2DM with MAU reduces
progression
Incidence of diabetic nephropathy (%)
Primary endpoint: Time to onset of diabetic nephropathy* (n=590)
20
Placebo
15
Irbesartan
150mg
10
Irbesartan
300mg
5
0
0
3
6
9
12
15
18
Follow-up (months)
*defined by persistent albuminuria in overnight specimens,
with urinary albumin excretion rate <200 μg/min and ≥30% higher than baseline level
Parving et al. N Engl J Med 2001;345:870-8
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21
24
ARB in T2DM with Macroalbuminuria
Reduces Renal Outcomes
Cumulative % of
patients with event
Primary endpoint: Time to doubling of serum creatinine,
ESRD, or death (n=1513)
50
Placebo
Risk reduction = 16%
40
p=0.02
30
20
Losartan
10
0
0
12
Brenner et al. N Engl J Med 2001;345:861-9
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24
Months
36
48
ARB in T2DM with Macroalbuminuria
Reduces Renal Outcomes
Primary endpoint: Time to doubling of serum creatinine,
ESRD, or death (n=1,715)
70
Irbesartan
60
Amlodipine
RRR 20%
p=0.02
p=NS
50
Patients (%)
RRR 23%
p=0.006
Placebo
40
30
20
10
0
0
6
12
Lewis et al. N Engl J Med 2001;345:851-60
18
24
30
36
Follow-up (mo)
42
48
54
60
Safe use of treatments in kidney
disease…..
Practical Tips: Potassium (K+) and
Creatinine (Cr)
•
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
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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
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Counsel all
Patients
About
Sick Day
Medication
List
2013
See
CPG Appendix 6
for therapeutic
considerations
for renal
impairment
2013
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When to Refer…..
•
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)
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Recommendation 1: Screening
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.
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2013
Recommendation 1: Screening (continued)
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].
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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].
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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].
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Recommendation 4 and 5
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
2013
medications should be held during times of acute
illness (see CPG Appendix) [Grade D, Consensus].
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Recommendation 6
2013
6. Combination of agents that block the reninangiotensin-aldosterone system (ACE-inhibitor,
ARB, DRI) should not be routinely used in the
management of diabetes and CKD [Grade A, Level 1].
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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]
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CDA Clinical Practice Guidelines
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www.diabetes.ca – for patients

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