Comprehensive Monitoring for Diabetes Complications in Primary Care

1. Appropriate monitoring for complications of diabetes in primary care – with a focus on CKD as one of these complications Section D

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 tothe resource

3. Contents overview This learning resource comprises the following 10 sections (A-E):

4. Contents overview (cont.) This learning resource comprises the following 10 sections (F-J):

5. Section D – 3 key learning objectives • People with diabetes should be offered testing for CKD • Use eGFR to detect and monitor impaired renal excretory function • Use albumin:creatinine ratio (ACR) to detect and monitor albuminuria • Monitoring should become more frequent as diabetic kidney disease progresses • Test results should be interpreted according to guidelines; however, consideration of individual patient factors (e.g. age, weight) that may affect test results need to be taken into account

6. NICE guidance – who to test • Offer testing for CKD using eGFR (estimated using serum creatinine) and ACR to people with any of the following risk factors:1 • Diabetes • Hypertension • Recent history of acute kidney injury • Cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease or cerebral vascular disease) • Structural renal tract disease, recurrent renal calculi or prostatic hypertrophy • Multi-system diseases with potential kidney involvement – for example, systemiclupus erythematosus • Family history of end-stage kidney disease (eGFR category 5) or hereditarykidney disease • Opportunistic detection of haematuria Reference: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14

7. Diagnosing CKD • At least one of these factors is necessary for a diagnosis of CKD: • Impaired renal excretory function (measured by eGFR)1 • Albuminuria (measured by ACR)1 • Structural changes to the kidneys1 • When screening people at possible risk of CKD it is only necessary to test for the first two of the above1 • Ultrasounds are not indicated as a screening test for CKD except in highly specific circumstances e.g. diagnosis of autosomal dominant polycystic kidney disease1 • A mistaken diagnosis of CKD (or incorrect coding as CKD) is not benign: • There may be a psychological impact of being labelled with a chronic disease1 • It can affect insurance premiums and future life choices, etc1 • Therefore, it is important to diagnose CKD correctly, to prevent unnecessary or inappropriate intervention1 Reference: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

8. Factors affecting creatinine-based eGFR results Persistently erroneous results • In people with extremes of muscle mass (e.g. a bodybuilder) eGFR needs to be interpreted with caution, as increased muscle mass can lead to underestimation of eGFR1,2 • In people with reduced muscle mass (e.g. in elderly patients or those with a muscle wasting disorder) eGFR needs to be interpreted with caution, as reduced muscle mass can lead to overestimation of eGFR1,2 Variably erroneous results • People should be advised not to eat any meat in the 12 hours before a blood test for eGFR as exogenous creatinine from the diet enters the blood, affecting the assay1,2 • Dehydration can lower eGFR2 • Blood samples should be received and processed by the laboratory within 12 hours of venepuncture1,2 • Trimethoprim (antibiotic) interferes with creatinine secretion by the kidneys and can lower eGFR2 References: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14 2. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal 2014.

9. Considerations when using creatinine based eGFR • An eGFR less than 60 mL/min/1.73m2 is abnormal, but a single result is not sufficient to make a diagnosis of CKD1 • eGFR results have an intra-individual variation of +/-5% in CKD, therefore a difference of +/-5% between blood tests is not significant1 • Other factors may also affect the interpretation of the result, such as diet and hydration state1 • A diagnosis of CKD should only be made if eGFR <60 mL/min/1.73m2 on at least 2 separate occasions over a duration of 90 days1 • The accuracy of eGFR testing improves as renal function declines. It is less accurate with a normal eGFR1 • Thus, it is important to take repeated readings and to consider the effect of confounding factors (such as diet or hydration state) • 60 mL/min/1.73m2 is the level below which CKD can be diagnosed on the basis of eGFR alone. However, it is important to realise that it is possible for CKD to exist in patients with results higher than this, if another marker of kidney damage is present1 References: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

10. Cystatin C eGFR vs. creatinine based eGFR • Cystatin C is not a new test, but it has only recently found its place in clinical medicine and is not yet widely available from laboratories1 • NHS England is developing a plan to expand the availability of Cystatin C testing1 • Cystatin C can be used to estimate GFR and is less susceptible to the errors which effect a creatinine-based estimation e.g. muscle mass and medication1 • Even though the cystatin C assay is ten times more expensive than the standard creatinine assay, this cost is justified if it reduces inappropriate diagnosis of CKD1 • Cystatin C estimation should be used as a “one off” to confirm a diagnosis of CKD, and is not intended as a substitute for creatinine measurements1 Reference: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

11. Cystatin C may be a useful alternative to creatinine for estimation of GFR when early CKD is suspected Reference: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

12. NICE 2014 diagnosis of CKD When to use cystatin C based eGFR: • Consider using eGFR (estimated using cystatin C) at initial diagnosis to confirm or rule out CKD in people with: • An eGFR (estimated using serum creatinine) of 45–59 mL/min/1.73m2,sustained for at least 90 days and:1 • No albuminuria (ACR less than 3 mg/mmol) or other marker of kidney disease1 How to interpret the result: • Do not diagnose CKD in people with: • An eGFR (estimated using serum creatinine) of 45–59 mL/min/1.73m2 and1 • An eGFR (estimated using cystatin C) of more than 60 mL/min/1.73m2 and1 • No other marker of kidney disease e.g. albuminuria or structural changes to kidneys1 Reference: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14 .

13. Detecting albuminuria: ACR When: • Recommended for initial detection of albuminuria and subsequent monitoring How: • Preferably early morning spot urine (not dipstick or 24 hour urine collection) • ACR>3mg/mmol = abnormal1 • An early morning sample may not be practical. If so, send available spot urine. Once spot urine result has been returned then:2 • If ACR<3mg/mmol there is no need to obtain early morning sample – the resultis normal 2 • For ACR between 3 mg/mmol and 70 mg/mmol, proteinuria should be confirmed using a subsequent early morning sample1,2 • If the ACR is >70 mg/mmol, a repeat morning sample need not be tested because this level of albuminuria is unequivocally abnormal and significant2 References: 1. Adapted from: NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14 2. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

14. ACR categories ACR is categorised according to the following levels of severity: normal to mild, moderate, or severe1 Adapted from: NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Reference: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14

15. Factors that may cause a misleading ACR result • It is often stated that the ACR should be measured in a fresh early-morning sample; this is because a misleading increase in ACR may result from exercise or even from being up-and-about during the day1 • Strenuous exercise can cause an increase in proteinuria, so it is important that this be avoided in the 72 hours prior to giving the urine sample2 • Other factors that may affect ACR result include: • Urinary tract infection3 • High dietary protein intake3 • Congestive cardiac failure3 • Acute febrile illness3 • Menstruation or vaginal discharge3 • Drugs (NSAIDs, ACE inhibitors, ARBs)3 • Urine creatinine levels are also lower in people with lower muscle mass e.g. women compared to men and certain racial/ethnic groups4 References: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal 2014. 2. Lewis R,. Prim Care Cardiovasc J 2014;7:92-97. 3. Johnson DW, Jones GRD, Mathew TH, et al. Med J Aust2012; 197 (4): 224-225. 4. Mattix H, Hsu C, Shaykevich S et al. J Am SocNephrol2002;13:1034-1039.

16. Monitoring CKD: what to do next NICE recommends that people with CKD in the following groups should normally be referred for specialist assessment1,2 • eGFR less than 30 mL/min/1.73m2 (GFR category G4 or G5), with or without diabetes • ACR 70 mg/mmol or more, unless known to be caused by diabetes (e.g. presence of retinopathy or absence of haematuria) and alreadyappropriately treated • ACR 30 mg/mmol (ACR category A3) or more, together with haematuria • Accelerated progression (defined as a sustained decrease in GFR of 25% or more, and a change in GFR category or sustained decrease in GFR of 15 ml/min/1.73m2 or more within 12 months) • Hypertension that remains poorly controlled despite the use of at least four antihypertensive drugs at therapeutic doses • Known or suspected rare or genetic causes of CKD • Suspected renal artery stenosis Reference: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14 2. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal2014.

17. Monitoring people with CKD • Once diagnosed, people with CKD should be monitored regularly to: • Ensure that all remedial factors are being optimally addressed e.g. blood pressure control, glycaemic control, avoiding nephrotoxins • Identify those people who are progressing and may need additional input • People diagnosed with CKD should be entered onto the CKD register • Frequency of monitoring should be influenced by various clinical circumstances, including: • The underlying cause of CKD • Past patterns of eGFR and ACR (but be aware that CKD progression is oftennon-linear) • Comorbidities, especially heart failure • Changes to their treatment (such as ACE-inhibitors, NSAIDs and diuretics) • Intercurrent illness • If a patient has chosen conservative management of CKD Reference: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal 2014.

18. Frequency of monitoring • NICE recommends that frequency of monitoring increases from ≤once a year to ≥four times a year depending on kidney disease severity, as shown in the table opposite1 • The frequency of monitoring should be agreed with the patient, bearing in mind that CKD is not progressive in many people1 • ACR is an important indicator of cardiovascular risk and progression1 • Increasing risk • Increasing risk Adapted from: NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. GFR = glomerular filtration rate, ACR = albumin creatinine ratio. Reference: 1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014. Available at http://www.nice.org.uk/guidance/cg182/resources/guidance-chronic-kidney-disease-pdf. Website last accessed on 12.11.14

19. What to monitor in people with CKD • Conduct at least one review of blood pressure and eGFR per year in allCKD patients1 • All patients being screened for CKD should have urine ACR measured to establish the baseline level1 • At least annual measurements of ACR in all people with diabetes1 • Monitoring of ACR will be necessary, with the frequency depending upon a number of factors, including the underlying cause and initial results1 • It should be borne in mind that: • Albuminuria is a marker of worse cardiovascular outcomes and there is a relationship between the amount of albuminuria and risk1 • ACR monitoring of patients with diabetes and CKD is a performance indicator in the diabetes QOF (in England)1 • Frequency of monitoring should be acceptable to the primary care team andthe patient1 Reference: 1. Lewis R. Updated NICE guidelines for the diagnosis and management of chronic kidney disease: what they mean for your practice. Article submitted to Primary Care Cardiovascular Journal 2014.

20. Section D – summary • Offer testing for CKD to people with diabetes • After diagnosis of kidney disease, frequency of monitoring should increase as diabetic kidney disease progresses • Use albumin:creatinine ratio (ACR) to detect and quantify albuminuria • Use eGFR to diagnose and monitor progression of diabetic kidney disease • Interpret test results according to guidelines, taking into consideration individual patient factors that may affect test results