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Prevention of diabetic kidney disease. Section E. Objectives and background for this learning resource. Introduction:
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Prevention of diabetic kidney disease Section E
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
Contents overview This learning resource comprises the following 10 sections (A-E):
Contents overview (cont.) This learning resource comprises the following 10 sections (F-J):
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
Hyperglycaemia causes macrovascular complications • Brain • Cerebrovascular disease1,2 • Stroke1,2 • Dementia (stroke-related)1 • Macrovascular complications are: • Cerebrovascular disease1 • Coronary artery disease1 • 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.
Hyperglycaemia causes microvascular complications • Eye • Retinopathy3 • Cataracts3 • Glaucoma3 • 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 • 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 diabetickidney 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: 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 SocNephrol 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. .
Blood glucose management can reduce the riskof death in patients with type 2 diabetes 0.5 4 1 This graph shows a 21% decrease in death related to diabetes per 1% reduction in HbA1c1 Death related to diabetes p<0.0001 Hazard ratio 5 6 7 8 9 10 Updated mean haemoglobin A1C concentration (%) Adapted from Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ2000;321:405–12. Reference: 1.Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ 2000;321:405–12.
Intensified multifactorial intervention has sustained beneficial effects1 • In patients with type 2 diabetes and albuminuria, intensified multifactorial intervention* had sustained beneficial effects on vascular complications and on rates of death1 • After a mean of 13.3 years†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 * 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 Number of cardiovascular disease events among patients on intensive vs. conventional therapy1 Intensive therapy Conventional therapy 40 35 30 25 No. of cardiovascular events 20 15 10 Death from cardiovascular causes Stroke Myocardial infarction CABG PCI Revascul-arisation Amputation 5 0 Adapted from Gæde P, Lund-Anderson H, Parving H-H, et al. N Engl J Med 2008;358:580-91.. Reference: 1.Gæde P, Lund-Anderson H, Parving H-H, et al. N Engl J Med 2008;358:580-91.
Blood glucose management can reduce the risk of microvascular complications 0.5 10 1 This graph shows a 37% decrease in microvascular end points (predominantly retinal photo-coagulation) per 1% reduction in HbA1c1 Microvascular end points p<0.0001 Hazard ratio 0.5 5 6 7 8 9 10 Updated mean haemoglobin A1C concentration (%) Adapted from Stratton IM, Adler AI, Neil HAW, et al. UKPDS35. BMJ2000;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.
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 Patients without insulin therapy n=44 Patients on insulin therapy n=41 Cumulative incidence ratiofor kidney failure* determined by Kaplan-Meier curves Cumulative ratio p=0.0022 Patients without insulin therapy baseline HbA1c (%) 8.2±2.0 1.0 0.6 0.8 0.2 0.0 0.4 Patients on insulin therapy baseline HbA1c (%) 7.3±1.7 30 20 50 60 40 10 0 Follow-up period (months) *Kidney failure defined as a doubling of serum creatinine in type 2 diabetic patients with chronic renal insufficiency/failure Reference: 1.Ueda H, Ishimura E, Shoji T, Emoto M, et al. UKPDS36. Diabetes Care 2003;26:1530-1534 Adapted from Ueda H, Ishimura E, Shoji T, Emoto M, et al. UKPDS36. Diabetes Care 2003;26:1530-1534.
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.
Blood pressure management can reduce the risk of death 0.5 4 1 Death related to diabetes was decreased by 17% per 10mm Hg reduction in systolic blood pressure1 p<0.0001 Death related to diabetes Hazard ratio 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.
Blood pressure management reduces the risk of microvascular complications* and MI 30 50 10 20 40 0 The risk of microvascular complications and myocardial infarction (MI) are strongly associated with increasing blood pressure1 Myocardial infarction Microvascular end points (predominantly retinal photocoagulation). Adjusted incidence per 1,000person years (%) 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.
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.
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.
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