Transcript PRESENTATION TITLE

Prevention of diabetic
kidney disease
SECTION E
These slides were sponsored by Janssen and developed in conjunction with the BRS CKD Strategy Group, following an advisory board
that was organised by Janssen. Bedrock Healthcare Communications provided editorial support to members of the advisory board in
developing the slides. Janssen reviewed the content for technical accuracy. The content is intended for a UK professional audience only.
JOB CODE PHGB/VOK/0914/0018d
Date of preparation: February 2015
Objectives and background for this learning resource
Introduction:
This learning resource has been developed as part of a medical education initiative supported by
Janssen. The content of this slide kit has been developed by an advisory board of renal physicians, GPs
and specialist nurses. The panel of experts includes members of the British Renal Society Chronic Kidney
Disease (CKD) Strategy Group. Bedrock Healthcare, a medical communications agency, has provided
editorial support in developing the content; Janssen has reviewed the content for technical accuracy.
Educational objectives:
•
To provide clear and applicable clinical guidance on chronic kidney disease (CKD) in people with type
2 diabetes to primary care healthcare professionals
•
To advise primary healthcare professionals on what people with diabetes need to know about their
own condition with relation to CKD
Usability objectives:
•
To provide essential, relevant and up to date information in concise presentations
•
To enable primary healthcare professionals to locate, select and use the content of the learning
resource, as appropriate to their needs
•
To enable secondary care experts in CKD to refer their primary care colleagues to the resource
1
Contents overview
This learning resource comprises the following 10 sections (A-E):
Section A
Introduction and overview of chronic kidney disease (CKD) in people
with diabetes
Section B
Long-term impact of diabetes and the importance of optimal
management of the condition
Section C
Pathophysiology of diabetic nephropathy & risk factors for the
development of CKD
Section D
Appropriate monitoring for complications of diabetes in primary care –
CKD as one of these complications
Section E
Prevention of diabetic kidney disease
2
Contents overview (cont.)
This learning resource comprises the following 10 sections (F-J):
Section F
Optimal management of diabetic kidney disease:
hypertension and glycaemia
Section G
How to involve people with diabetes and CKD in their own care – what
information must they have to manage their own condition effectively?
Section H
What does the future hold for a person with well-managed diabetes
and CKD?
Section I
What do the guidelines say and what do they mean in terms of the
day-to-day management of CKD in people with diabetes?
Section J
Sources of further information and reading list
3
Section E – 3 key learning objectives
• Early optimal blood glucose control and blood pressure control may
substantially reduce the risk of developing CKD (and other microvascular
complications)
• The benefits of early optimal blood glucose control continue in the long term
• Patient engagement in lifestyle changes may reduce the risk of diabetic kidney
disease
4
Hyperglycaemia causes macrovascular complications
• Macrovascular complications are:
– Cerebrovascular disease1
– Coronary artery disease1
Brain
Cerebrovascular disease1,2
• Stroke1,2
• Dementia (strokerelated)1
– Peripheral vascular disease1
• Proposed pathological mechanisms
include:
– Atherosclerosis causing a response that
results in the formation of a lipid-rich
atherosclerotic lesion with a fibrous cap;
rupture of this lesion leads to acute
vascular infarction1
– Increased platelet adhesion and
hypercoagulability in type 2 diabetes
increasing the risk of vascular occlusion
and cardiovascular events1
Heart
Cardiovascular disease2
• Angina2
• Myocardial infarction2
• Congestive heart failure2
Extremities
Peripheral vascular disease2
• Ulceration2
• Gangrene2
• Amputation2
Reference:
1. Fowler MJ. Clinical Diabetes 2008;26(2):77-82
2. International Diabetes Federation. What is diabetes. Available at: https://www.idf.org/node/23538. Accessed: 22/01/2014.
5
Hyperglycaemia causes microvascular complications
• Microvascular complications are:
– Diabetic retinopathy1
– Diabetic kidney disease1
– Diabetic neuropathy1
• Proposed pathological mechanisms
leading to development of these
conditions as a result of
hyperglycaemia include:
–
–
–
–
–
The formation of glycoproteins1
Increased protein kinase C activity2
Polyol accumulation1,2
Oxidative stress1,2
Involvement of growth factors, including
VEGF, growth hormone, and transforming
growth factor β1,2
– Increased osmotic stress caused by
sorbitol accumulation1
Eye
• Retinopathy3
• Cataracts3
• Glaucoma3
Kidney
• Albuminuria1
• Kidney disease3
Nerves
Neuropathy3
• Peripheral3
• Autonomic1
References:
1. Fowler MJ. Clinical Diabetes 2008;26(2):77-82. 2. Dronavalli S, Duka I and Bakris GL. Nat Clin Pract Endocrinol Metab. 2008;4(8):444-52. 3. International Diabetes
Federation. What is diabetes. Available at: https://www.idf.org/node/23538. Accessed: 22/01/2014.
6
The benefits of glycaemic control in diabetic
kidney disease
• Individual HbA1c targets are typically in the range of 48-59 mmol/mol (6.5-7.5%)1
• The benefits of good glycaemic control are summarised in the table below:
Benefits of good glycaemic control
Renal function effects:
Reduces the rate of renal function decline, particularly if combined with blood pressure
control2
Can normalise glomerular filtration rate3
Lower risk of albuminuria development4
Reduces risk for development of renal failure5
Effects on complications of
diabetic kidney disease:
Reduces incidence of autonomic neuropathy6
Impact on outcomes:
Delays the need for dialysis7
Increased survival rate in patients undergoing hemodialysis8
Improves the chances of a successful kidney transplant9
Financial outcomes:
Reduces costs - The cost of implementing UK guidelines for a practice of 10,000 patients
would be recouped by delaying dialysis for one year in one person 10
References:
1.NHS Diabetes. HbA1c Standardisation For Clinical Health Care Professionals leaflet. Available at: https://www.diabetes.org.uk/upload/Professionals/Key%20leaflets/
53130HbA1cHCPleaflet.pdf. Accessed 09 January. 2.American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004:27;S79-83. 2015. 3.Wiseman MJ et al. Effect of Blood Glucose Control on Increased
Glomerular Filtration Rate and Kidney Size in Insulin-Dependent Diabetes. N Engl J Med 1985;312:617–21. 4.Fioretto P et al. Renal Protection in Diabetes: Role of Glycemic Control. J Am Soc Nephrol 2006 17:S86 –S89.
5.UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS
33).Lancet 1998;352:837-53. 6.Ziegler D et al. The natural history of somatosensory and autonomic nerve dysfunction in relation to glycaemic control during the first 5 years after diagnosis of Type 1 (insulin-dependent) diabetes
mellitus. Diabetologica 1991;34:822-829. 7. Ruggenenti P et al. Progression, remission, regression of chronic renal diseases. Lancet 2001;357: 1601–08. 8.Morioka T et al. Glycemic Control Is a Predictor of Survival for Diabetic
Patients on Hemodialysis. Diabetes care 2001;24:909-913. 9.Wiesbauer F et al. Glucose control is associated with patient survival in diabetic patients after renal transplantation. Transplantation. 2010;89:612-9. 10.Klebe et al.
The cost of implementing UK guidelines for the management of chronic kidney disease. Nephrol Dial Transplant 2007;22:2504-2512.
.
7
Blood glucose management can reduce the risk
of death in patients with type 2 diabetes
This graph shows a 21% decrease in death related to diabetes per 1% reduction
in HbA1c1
Death related to diabetes
4
Hazard ratio
p<0.0001
1
0.5
5
6
7
8
9
10
Updated mean haemoglobin A1C concentration (%)
Adapted from Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ 2000;321:405–12.
Reference:
1. Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ 2000;321:405–12.
8
Intensified multifactorial intervention has sustained
beneficial effects1
• After a mean of 13.3
there was an absolute risk
reduction for death from any
cause of 20% among patients
who received intensive therapy
compared with those who received
conventional therapy1
years†
No. of cardiovascular events
• In patients with type 2 diabetes and
albuminuria, intensified multifactorial
intervention* had sustained beneficial
effects on vascular complications
and on rates of death1
Number of cardiovascular disease
events among patients on intensive vs.
conventional therapy1
Intensive therapy
Conventional therapy
40
35
30
25
20
15
10
5
0
Death from Stroke
cardiovascular
causes
Myocardial
infarction
CABG
PCI
Revascul- Amputation
arisation
Adapted from Gæde P, Lund-Anderson H, Parving H-H, et al. N Engl J Med 2008;358:580-91..
* tight glucose regulation and the use of renin–angiotensin system blockers, aspirin, and lipid-lowering agents
† 7.8 years of multifactorial intervention and an additional 5.5 years of follow-up
CABG=coronary artery bypass graft, PCI=Percutaneous Coronary Intervention
Reference:
1. Gæde P, Lund-Anderson H, Parving H-H, et al. N Engl J Med 2008;358:580-91.
9
Blood glucose management can reduce the risk of
microvascular complications
This graph shows a 37% decrease in microvascular end points (predominantly
retinal photo-coagulation) per 1% reduction in HbA1c1
Microvascular end points
10
Hazard ratio
p<0.0001
1
0.5
5
6
7
8
9
10
Updated mean haemoglobin A1C concentration (%)
Adapted from Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ 2000;321:405–12.
*Microvascular complications were retinopathy requiring photocoagulation, vitreous haemorrhage, and or fatal or non-fatal renal failure
Reference:
1. Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ 2000;321:405–12.
10
Blood glucose control is a predictor of kidney health
• The incidence of kidney disease for patients on insulin therapy was significantly
lower than that for patients not on insulin1
• HbA1c was not significantly associated with progression of renal failure, possibly
because all patients in the study had renal insufficiency/failure at baseline1
1.0
Cumulative ratio
0.8
Patients without
insulin therapy
n=44
Cumulative incidence ratio
for kidney failure* determined
by Kaplan-Meier curves
Patients on
insulin therapy
n=41
0.6
0.4
p=0.0022
0.2
Patients without insulin therapy
baseline HbA1c (%) 8.2±2.0
0.0
Patients on insulin therapy
baseline HbA1c (%) 7.3±1.7
0
10
20
30
40
50
60
Follow-up period (months)
*Kidney failure defined as a doubling of serum creatinine in type 2 diabetic patients with chronic renal insufficiency/failure
Adapted from Ueda H, Ishimura E, Shoji T, Emoto M, et al. UKPDS36. Diabetes Care 2003;26:1530-1534.
Reference:
1. Ueda H, Ishimura E, Shoji T, Emoto M, et al. UKPDS36. Diabetes Care 2003;26:1530-1534
11
There may be potential hazards of tight glycaemic
control in some patient groups
The ACCORD study identified a previously unrecognised harm of intensive
glucose lowering in high-risk patients with type 2 diabetes and high glycated
haemoglobin levels1
Study findings:
• 257 patients in the intensive-therapy group died, compared with 203 patients in
the standard therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; p=0.04)1
• After reviewing mortality trends for several months the intensive regimen was
discontinued for safety reasons1
• Hypoglycemia requiring assistance and weight gain of more than 10 kg were
more frequent in the intensive-therapy group (p<0.001)1
– This harm may be due either to the approach used for rapidly lowering glycated
haemoglobin levels or to the levels that were achieved1
Reference:
1. The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:2545-59.
12
Blood pressure management can reduce the risk of
death
Death related to diabetes was decreased by 17% per 10mm Hg reduction in
systolic blood pressure1
Death related to diabetes
p<0.0001
Hazard ratio
4
1
0.5
110
120
130
140
150
160
170
Updated mean systolic blood pressure (mm Hg)
Adapted from Adler AI, Stratton IM, Neil HAW, et al. UKPDS36. BMJ 2000;321:412–9.
Reference:
1. Adler AI, Stratton IM, Neil HAW, et al. UKPDS36. BMJ 2000;321:412–9.
13
Blood pressure management reduces the risk of
microvascular complications* and MI
The risk of microvascular complications and myocardial infarction (MI) are strongly
associated with increasing blood pressure1
Adjusted incidence per 1,000
person years (%)
50
Myocardial infarction
Microvascular end points (predominantly retinal photocoagulation).
40
30
20
10
0
110
120
130
140
150
160
170
Updated mean systolic blood pressure (mm Hg)
Adapted from Adler AI, Stratton IM, Neil HAW, et al. UKPDS36. BMJ 2000;321:412–9.
*Microvascular complications were retinopathy requiring photocoagulation, vitreous haemorrhage, and or fatal or non-fatal renal failure
Reference:
1. Adler AI, Stratton IM, Neil HAW, et al. UKPDS36. BMJ 2000;321:412–9.
14
Tight blood pressure management needs to be
continued in order to maintain benefits
• In the UKPDS study, tight blood pressure control in patients with hypertension
and type 2 diabetes achieved a clinically important reduction in:1
– the risk of deaths related to diabetes1
– complications related to diabetes1
– progression of diabetic retinopathy1
– deterioration in visual acuity1
• However, it appears that blood pressure control must be continued if the
benefits are to be maintained2
Reference:
1. UKPDS Group UKPDS 38. BMJ 1998;317(7160);703-13. 2. Holman RR, et al. N Engl J Med. 2008;359:1563-76.
15
Lifestyle modifications to prevent
development/progression of diabetic kidney disease
The following lifestyle modifications should be discussed with your patient to
optimise their health and reduce the chances of disease development and
progression:
– Smoking cessation1
– Weight reduction1
– Alcohol intake1
– Increase physical activity1
– Reduce sodium intake (no more than 2.3 grams per day,
equivalent to 1 tsp)1
– Reduce fat intake1
Reference:
1. National Health Institute. National Kidney Disease Education Program: Diet and Lifestyle Changes. Available at:
http://nkdep.nih.gov/living/diet-lifestyle-changes.shtml. Accessed 09 January 2015.
16
Section E – summary
• CKD development and progression can be prevented through blood glucose
control and blood pressure control
• The benefits of early optimal glycaemic control continue in the long term
– Reducing renal function decline
– Reducing complications
– Delaying dialysis
– Reducing financial costs
• Lifestyle modification reduces risk factors for the development and progression
of diabetic kidney disease
17