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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).
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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).
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
CKD in Diabetes
ACR ≥2.0 mg/mmol
and / or
eGFR <60 mL/min
2013
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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)”
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Stages of Diabetic Nephropathy
Note: change in definition of microalbuminuria ACR ≥2.0 mg/mmol2013
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Screening and
Diagnosis of CKD in
Diabetes
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Beware of Transient Albuminuria
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
2013
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
2
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Beware
of Other
Causes
of CKD
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
When to Consider Other Causes of CKD
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
2
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Care Gap Still Exists for Screening
Canadian Institute of Health Information – Diabetes Care Gap 2009
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
• 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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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”
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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)
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Lewis EJ et al. N Engl J Med 1993;329:1456-62.
ACE-inhibitor in T1DM with Macroalbuminuria Reduces Renal Outcomes
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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)
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
• 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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
Practical Tips: Potassium (K+) and Creatinine (Cr)
Counsel all Patients About
Sick Day Medication
List
2013
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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…..
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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)
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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].
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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].
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association
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