1. 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 healthcare professional audience only. JOB CODE PHGB/VOK/0914/0018g Date of preparation: February 2015 SECTION H What does the future hold for a person with well-managed diabetes and CKD?

2. 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

3. Contents overview This learning resource comprises the following 10 sections (A-E): 2 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 EPrevention of diabetic kidney disease

4. Contents overview (cont.) This learning resource comprises the following 10 sections (F-J): 3 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 JSources of further information and reading list

5. Section H – 3 key learning objectives Type 2 diabetes is a progressive chronic disease requiring long-term monitoring and interventions Optimal treatment can improve outcomes, reducing the risks of –Microvascular complications –Cardiovascular complications –Premature death Intensive management of diabetes can reduce the risk of all diabetes-related complications and have a positive impact on the financial burden of diabetes and CKD 4

6. Insulin resistance & arterial hypertension Early glomerular damage Increasing albuminuria Structural changes (throughout progression) Chronic kidney failure Untreated diabetic kidney disease can lead to kidney failure Without specific interventions, 20-40% of people with type 2 diabetes and albuminuria progress to overt kidney disease 1 5 Adapted from: NKF K/DOQI Guidelines. Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290. Adapted from: American Diabetes Association. Diabetes Care 2004;27(suppl 1):s79-s83. References: 1. American Diabetes Association. Diabetes Care 2004;27(suppl 1):s79-s83. 2. NKF K/DOQI Guidelines. Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290. Relationship of stage of kidney disease and level of albuminuria to prognosis in CKD 2 Vertical axis (Risk) shows hypothetical risks for adverse outcomes of CKD, such as progression to kidney failure or onset of cardiovascular disease

7. Type 2 diabetes increases the risk of microvascular and cardiovascular complications Microvascular complications include: Kidney damage 1 Eye damage 1 Nerve damage 1 Cardiovascular complications include: Coronary artery disease (leading to heart attacks, angina) 1 Peripheral artery disease (leg claudication, gangrene) 1 Carotid artery disease (strokes, dementia) 1 6 Type 2 diabetes Functional changes* Structural changes † Rising blood pressure Albuminuria Rising creatinine levels End stage kidney disease Cardiovascular death * Renal haemodynamics altered, glomerular hyperfiltration † Glomerular basement membrane thickening, mesangial expansion, microvascular changes References: 1. NICE clinical guideline 87. The management of type 2 diabetes. Issued: May 2009 last modified: July 2014.

8. Intensive blood glucose control decreases the risk of developing microvascular complications † 7 *Intensive control with sulphonylureas or insulin, versus **conventional treatment of diet only † Microvascular complications were retinopathy requiring photocoagulation, vitreous haemorrhage, and or fatal or non-fatal renal failure Reference: 1. UKPDS Group. UKPDS33. Lancet 1998;352:837-53

9. Intensified multifactorial intervention reduces the risk of cardiovascular and microvascular events 1 A target-driven, long-term, intensified intervention* aimed at multiple risk factors in patients with type 2 diabetes and albuminuria reduced the risk of cardiovascular and microvascular events by about 50% 1 Patients receiving intensive therapy had a significantly lower risk of: –cardiovascular disease (hazard ratio, 0.47; 95% CI, 0.24 to 0.73) 1 –nephropathy (hazard ratio, 0.39; 95% CI, 0.17 to 0.87) 1 –retinopathy (hazard ratio, 0.42; 95% CI, 0.21 to 0.86) 1 –autonomic neuropathy (hazard ratio, 0.37; 95% CI, 0.18 to 0.79) 1 * intensified intervention comprised stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. Conventional treatment comprised treatment for multiple risk factors from the patient’s GP, according to the 1988 recommendations of the Danish Medical Association 1 Kaplan–Meier estimates of the composite end point 1 Composite endpoint = death from cardiovascular causes, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation or surgery for peripheral atherosclerotic artery disease 8 Reference: 1. Gæde P et al. N Engl J Med 2003;348:383-93. 0 40 50 60 30 20 10 Intensive therapy Conventional therapy Primary composite endpoint (%) 01224364860728496 Months of follow-up p=0.007 Adapted from Gæde P et al. N Engl J Med 2003;348:383-93

10. Intensified intervention has sustained beneficial multifactorial effects 1 In patients with type 2 diabetes and albuminuria, intensified multifactorial intervention* had sustained beneficial effects on vascular complications and on rates of death 1 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 therapy 1 * 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 therapy 1 9 Reference: 1. Gæde P et al. N Engl J Med 2008;358:580-91. 0 20 25 30 35 40 15 10 5 Death from cardiovascular causes Stroke Myocardial infarction CABGPCI Revascul- arisation Amputation Intensive therapyConventional therapy No. of cardiovascular events Adapted from Gæde P et al. N Engl J Med 2008;358:580-91

11. What does the future hold for a person with well managed type 2 diabetes? Intensive blood glucose and blood pressure control decreases the risk of various complications, including microvascular and cardiovascular complications, as well as diabetes related death 1 10 References: 1. UKPDS Group UKPDS 33. The Lancet 1998;352;837-853. 2. UKPDS Group UKPDS 38. BMJ 1998;317(7160);703 Intensive glucose control (HbA1c 7.0%) vs. conventional blood glucose control (HbA1c 7.9%) reduces the risk of: Microvascular endpoints* 25% 1 Any diabetes-related endpoints 12% 1 Diabetes related death 10% 1 A tight BP control policy 144 / 82 vs. 154 / 87 mmHg reduces risk of: Stroke 44% 2 Microvascular endpoints 37% 2 Deaths related to diabetes 32% 2 Any diabetes-related endpoints 24% 2 Glycaemic control Blood pressure control *Microvascular endpoints include retinopathy, nephropathy and neuropathy. Surrogate measures of microvascular disease include urinary albumin excretion and retinal photography.

12. Treating diabetes and CKD is a significant financial burden to the NHS The most comprehensive analysis to date (data from 2010-11) showed that the direct costs to the NHS of treating type 2 diabetes was £8.8 billion 1 Diabetes (type 1 and 2) accounts for about 10 per cent of the NHS budget and 80 per cent of these costs are due to the complications of diabetes 1 Projected costs for treating type 2 diabetes by 2035-2036 are thought to be in the region of £15.1 billion 2 11 References: 1. Cost of Diabetes Report, 2014. Available at http://www.diabetes.org.uk/Documents/Diabetes%20UK%20Cost%20of%20Diabetes%20Report.pdf Website last accessed on 9.1.15. 2. N. Hex et al. Diabetic Medicine 29;855-862; 2012http://www.diabetes.org.uk/Documents/Diabetes%20UK%20Cost%20of%20Diabetes%20Report.pdf Myocardial infarction, ischaemic heart disease, heart failure and Other CVD Excess inpatient days Kidney failure, other renal (kidney-related) costs Neuropathy Stroke Foot ulcers and amputations Other: Dyslipidemia. erectile dysfunction, ketoacidosis, depression, gestational diabetes, diabetic medicine outpatients, hypoglycaemia, hyperglycaemia and retinopathy £millions 0 1000 3500 2000 3000 500 1500 2500 The cost of complications of diabetes 1 Total: £7.7bn Analysis on the complications of diabetes (type 1 and 2) revealed that kidney related conditions were among the top 3 highest costs 1

13. Treating diabetes and CKD is a significant financial burden to the NHS (cont.) The cost of treating CKD to the NHS in 2009–10 was estimated at £1.44 billion 1 –This represents ~1.3% of all NHS spending in that year 1 –Most of this budget was spent on renal replacement therapy (RRT) and CKD related cardiovascular complications [RRT accounted for more than half of the total spend] 1 –The overall spend on CKD is equivalent to ∼ £795 for every person recorded with a diagnosis of CKD in the QOF 1 Optimal management of diabetes reduces the risk of all diabetes-related complications and has a positive impact on the financial burden of diabetes and CKD –The cost of implementing the Renal Association Chronic Kidney Disease in Adults UK guidelines for a practice of 10,000 patients would be recouped by delaying dialysis for one year in one person 2 12 References: 1. Kerr M et al. Nephrol Dial Transplant. Oct 2012; 27(Suppl 3): iii73–iii80. 2. Klebe B et al. Nephrol Dial Transplant 2007;22: 2504–2512.

14. There are opportunities for improvement in the care of people with diabetes 1 The following data show the percentages of patients with type 2 diabetes recorded against criteria in the 2012-13 National Diabetes Audit NICE-recommended care processes –Completion of eight care processes (all care processes except eye screening) = 61.9% 1* –Completion was less likely to be achieved by those aged under 40 vs. older people 1 NICE-recommended treatment targets –Glucose control (HbA1c <58mmol/mol) = 64.8% 1 –Blood pressure (<140/80) = 68.7% 1 –Serum cholesterol <4mmol/L = 40.5% 1 NICE-recommended structured education* –Offered structured education = 16.7% of newly diagnosed; 6% of all people with type 2 diabetes 1 –Attended structured education = 3.6% of newly diagnosed; 1.6% of all people with type 2 diabetes 1 * Eye screening is not included because it is organised by NHS Diabetes Eye Screening. 13 NICE-recommended care processes (annual checks) 1 1.HbA1c 2.Blood pressure 3.Cholesterol 4.Serum creatinine 5.Urine albumin 6.Foot surveillance 7.BMI 8.Smoking 9.Eye screening *NICE guidance recommends that people with diabetes be offered patient education programmes, officially known as 'structured education‘ 1 Reference: 1. Health and Social Care Information Centre, National Diabetes Audit 2012-2013 Report 1: Care Processes and Treatment Targets. Available at: http://www.hqip.org.uk/assets/NCAPOP-Library/NCAPOP-2014-15/NDA-Care-Processes-report-1-Final.pdf Website last accessed on 09.01.15

15. What does the future hold for a person with well managed type 2 diabetes? There is evidence that self-management can improve outcomes for people with diabetes, including: –Quality of life outcomes 1 –HbA1c 2 –Psychosocial outcomes 2 One available initiative is the DESMOND project, a group of self management education modules, toolkits and care pathways for people with, or at risk of, type 2 diabetes 3 –Research has shown that DESMOND can provide added benefit to medical optimisation including: 4 Improvements in weight loss, self reported smoking status, physical activity levels and a decrease in depression scores 4 Recommended viewing: This short video shows how consultations in one practice have changed to encourage patients with diabetes to self manage, with consultations revolving around an agenda devised by the patient themselves and supported by healthcare professionals 5 http://personcentredcare.health.org.uk/resources/co-creating-health-programme-experience-of-practice-nurse * http://personcentredcare.health.org.uk/resources/co-creating-health-programme-experience-of-practice-nurse Recommended reading: Information on person-centred care resources can be accessed via the following website http://personcentredcare.health.org.uk/person-centred-care-intro * http://personcentredcare.health.org.uk/person-centred-care-intro References: 1. Cochran J & Conn VS. Diabetes Educ 2008;34(5):815-823. 2. Fitzpatrick SL et al. Diabetes Research and Clinical Practice. 2013;100(2):145-161. 3. NHS. The DESMOND project 2015. Available at http://www.desmond-project.org.uk. Website last accessed 15. 01.15.http://www.desmond-project.org.uk 4. Davies MJ et al. BMJ. 2008;336(7642):491-5. 5. The Health Foundation. Person-centred care resources 2014. Available at: http://personcentredcare.health.org.uk/person-centred-care-intro. Website last accessed 15.01.15.http://personcentredcare.health.org.uk/person-centred-care-intro 14 *Please note, these websites & resources are independent of this educational programme and have not been reviewed for compliance with the ABPI code of practice.

16. Section H – summary Type 2 diabetes increases the risk of microvascular and cardiovascular complications Untreated diabetic kidney disease can lead to kidney failure Intensive blood glucose and blood pressure control decreases the risk of microvascular complications such as diabetic kidney disease Optimal management of diabetes reduces the risk of all diabetes-related complications and have a positive impact on the financial burden of diabetes and CKD Patient self-management can improve outcomes for people with diabetes 15