General Practitioner Workshop

1. Important Updates in the Early Detection & Management of Chronic Kidney Disease General Practitioner Workshop This workshop was conceived and developed by the Kidney Check Australia Taskforce with particular thanks to A/Prof Robyn Langham& A/Prof Timothy Mathew 2013

2. Learning Objectives

3. What is CKD? • Chronic kidney disease is defined as: Glomerular Filtration Rate (GFR) < 60 mL/min/1.73m2 for ≥3 months with or without evidence of kidney damage. OR Evidence of kidney damage (with or without decreased GFR) for ≥3 months: • albuminuria • haematuria after exclusion of urological causes • pathological abnormalities • anatomical abnormalities.

4. CKD is a major public health problem • 1 in 9 Australian adults has CKD • You can lose up to 90% of your kidney function before experiencing any symptoms • Major risk factor for cardiovascular disease • Usual setting for initial assessment and diagnosis is in general practice • Common, harmful & treatable

5. What is the role of the GP? • early detection and management of CKD • management of early CKD without referral to specialist • assessing and modifying cardiovascular risk factors • treatment to slow or prevent progression of kidney failure • avoiding nephrotoxic drugs

6. Kidney disease in Australia Australians aged ≥ 25 years 19,000 Stage 3 CKD Stage 4 CKD Stage 5 CKD Hypertension Diabetes CKD staging is according to the CKD-EPI equation 40,000 827,000 Stage 1 – 2 CKD 856,000 5 MILLION AT RISK AusDiab Report, 2001; White et al 2010; Jun 10 ABS data; 2011 ANZDATA report

7. Growth in incidence rate of new treated ESKD and projections to 2020 AIHW, 2011. Projections of the incidence of treated End-Stage Kidney Disease in Australia, 2010-2020

8. Costs of treating current and new ESKD cases to 2020 In 2009 dollars the cumulative cost of RRT between $11.3 billion and $12.3 billion by the end of 2020 $13,000 $12,000 $11,000 $10,000 $9,000 $8,000 Cumulative Cost ($millions) $7,000 $6,000 $5,000 Annual cost of RRT service provision between $1.58 billion and $1.86 in 2020 dollars $4,000 $3,000 $2,000 $1,000 $0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Cumulative present value costs, Model 1 Cumulative present value costs, Model 2 Cass et al, 2010, economic impact ESKD in Australia, KHA

9. Number of treated or non-treated cases by age group at ESKD onset 2003-2007 No dialysis / transplant dialysis / transplant Source: Linked ANZDATA Registry, AIHW National Mortality Database and National Death Index

10. What’s new in CKD? • New CKD staging • New recommendations for testing for urine protein • New recommendations for eGFR and elderly people with CKD • New blood pressure targets

11. 2012 sees the introduction of a new CKD staging system because it: Had a better correlation with progression Factored in albuminuria Resulted in quantification of risk for CKD progression CV events The new CKD staging system for Australia

12. What’s new in CKD? Staging of Chronic Kidney Disease

13. Risk of ESKD related to baseline proteinuria (dipstick) over 18 year period N= 106,000 Iseki et al, Kidney Int 2003;63:1468-1476

14. Blue – normal ACR Green – microalbuminuria Red - macroalbuminuria Note log scale on Y axis for Hazard Ratio Adapted from Levey et al, 2010, Kidney International

15. The new Australian CKD staging schema

16. Using the new CKD staging schema ‘CKD Management in General Practice’ booklet has colour-coded action plans for overall risk of Progression of CKD Cardiovascular events Normal Low Moderate High

17. The new CKD staging system for Australia CKD Stages are described by both eGFR & Albuminuria status Underlying cause of CKD e.g Mrs S is a 55 year old lady with CKD 3b with microalbuminuria secondary to type 2 Diabetes

18. People at increased risk of CKD 1 in 3 Australian adults is at increased risk of CKD due to the above risk factors!

19. How do we detect CKD?

20. Remember… CKD screening should be undertaken as a part of a systematic chronic disease assessment

21. What is GFR? GFR = Glomerular Filtration Rate • GFR is accepted as the best measure of kidney function • May fall substantially before serum creatinine is outside thenormal range • Normal GFR in healthy adults is >90mL/min/1.73m2 anddeclines with age • A GFR consistently <60mL/min/1.73m2indicates CKD • A GFR of 60-90mL/min/1.73m2 should not be considered abnormal unless there is evidence of kidney damage. • A fall in GFR always precedes kidney failure • There is no direct way of measuring GFR • GFR can be estimated from serum creatinine using prediction equations • The eGFR is reported by all Australian pathology labs

22. How will eGFR help me and my patients? Early detection & management of CKD: • slows progression • prevents complications • reduces cardiovascular risk • reduces morbidity & mortality Early detection and treatment may reduce the rate of progression of kidney failure and cardiovascular risk by 20 – 50%

23. What’s new in CKD? eGFR – estimated Glomerular Filtration Rate It is now recommended that the CKD-EPI formula is used to calculate eGFR instead of the previously used MDRD formula This will lead to improved risk stratification and will make little or no difference to your practice

24. What is eGFR? Since 2005 it has been recommended that eGFR be automatically reported with every request for serumcreatinine in adults. This is consistent with USA, UK & Australian clinical guidelines

25. Advantages of eGFR • eGFR is a more sensitive marker for mild/moderate CKD than creatinine alone • Serum creatinine concentration is an insensitive marker fordetecting mild to moderate kidney failure • Patients may lose 50% or more of their kidney function beforethe serum creatinine rises above the upper limit of normal • Normal serum creatinine measurements do not excludeserious loss of kidney function

26. CKD 1&2 Comparing eGFR and creatinine CKD 4 CKD 5 CKD 3 Serum creatinine 120 90 60 30 0 GFR mL/min Actual Serum Creatinine Level Normal Serum Creatinine Level

27. Limitations of eGFR Clinical situations where eGFR results may be unreliable and/or misleading: • acute changes in kidney function • people on dialysis • exceptional dietary intake (e.g. vegetarian diet, high protein diet, recent consumption of cooked meat, creatine supplements) • extremes of body size • diseases of skeletal muscle, paraplegia or amputees (mayoverestimate eGFR) or high muscle mass (may underestimate eGFR) • children under the age of 18 years • severe liver disease present • eGFR values above 90 mL/min/1.73m2 • drugs interacting with creatinine excretion (eg fenofibrate, trimethoprim)

28. eGFR and drug dosing • Where an eGFR (using CKD-EPI or MDRD) is on hand it is clinically appropriate to use this to assist drug dosing decision making Recommendation: • Dose reduction of some drugs is recommended for patients with reduced kidney function • Both eGFR (mL/min/1.73m2) and estimated CrCl (mL/min) provide an estimate of relative renal drug clearance • If using eGFR for drug dosing body size should be considered, in addition to referring to the approved Product Information • For drugs with a narrow therapeutic index, therapeutic drug monitoring or a valid marker of drug effect should be used to individualise dosing

29. Remember… CKD screening should be undertaken as a part of a systematic chronic disease assessment

30. What’s new in CKD? Urine Tests for proteinuria Clinical Tip The preferred method for assessment of albuminuria in both diabetes and non-diabetes is urinary ACR measurement in a first void spot specimen Where a first void specimen is not possible or practical, a random spot urine specimen for urine ACR is acceptable

31. Urine Albumin / Creatinine Ratio (ACR) • Exhibits greater sensitivity than protein:creatinine ratio (PCR) • An initial ACR test should be repeated on a first void sample • Albuminuria is present if at least two out of three ACR tests are positive (including the initial test). CKD is present if the albuminuria is persistent for at least three months • Dipsticks for protein in the urine are now no longer recommended for this purpose as their sensitivity and specificity is not optimal

32. Albuminuria • There is an association between albuminuria and progressive kidney disease in population studies • The severity of albuminuria is predictive of outcome • Therapeutic intervention can delay progression of disease and is most effective where there is significant albuminuria • Microalbuminuria is predictive of progressive renal disease in people with diabetes and Indigenous people. • Urine ACR accurately predicts renal and cardiovascular risks in population studies and reduction in urine ACR predicts renoprotective benefit in intervention trials

33. Approximate equivalents between urine ACR & other measure of albumin & protein

34. CKD screening should be undertaken as a part of a systematic chronic disease assessment

35. What’s new in CKD? Blood Pressure Targets

36. Case study Rita Rita is a new patient to your practice • 63 years old • Accountant • History of mild asthma

37. Case study - Rita Past medical history • Overweight (BMI 29) • Mild intermittent asthma • Chronic low back pain • Mild hypertension • Smoker 25 pack year history Family history • Maternal grandmother died of a heart attack in her 60’s but also had a history of ‘kidney problems’ • Mother has type 2 diabetes • Father has angina and hypertension

38. Case study - Rita

39. Case study - Question Q1. Does Rita have an increased risk of CKD?

40. Groups at increased risk of CKD Rita has 4 of the 8 Risk Factors

41. CKD risk factors: Diabetes • Patients who have diabetes develop CKD in up to 25% of cases. • 1% of adult Australians develop diabetes each year (Barr et al. 2006, Int. Diab Institute)

42. CKD risk factors: Obesity Being overweight (BMI 25-29 kg/m2 did not increase CKD risk, but all classes of obesity (BMI ≥ 30kg/m2) increased risk *CKD with eGFR <45mL/min/1.73m2 Hallan et al, Am J Kid Dis 2006

43. CKD risk factor: Smoking Smokers with a 25-49 pack-year history had an increased risk of 42% compared with non-smokers and those with >50 pack years had 105% increased risk Relative Risk of CKD* (95% CI) *CKD with eGFR <45mL/min/1.73m2 Hallan et al, Am J Kid Dis 2006

44. CKD risk factors: High blood pressure Parenchymal Renal Disease High Blood pressure can damage the small blood vessels in the kidneys. The damaged vessels cannot filter waste products from the blood the way they should. Hypertension Or……damaged kidneys cause high blood pressure and high blood pressure damages kidneys

45. 160 140 120 100 80 60 40 20 CKD risk factors: Age > 60 Years Relationship of eGFR to age 2.50% Median 97.50% eGFR (mL/min/1.73m2) 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-90 90+ Age (years) Australasian Creatinine Consensus group. MJA 2007; 187(8): 459-463

46. CKD risk factors: Family history 23.9 22.9 20 14.6 14.4 Family history (%) of ESKD in incident dialysis patients 10 African-American women African-American men Caucasian women Caucasian men Freedman et al., JASN 1997

47. Indigenous Australians starting treatment for ESKD • CKD risk factors: Aboriginal or Torres Strait Islander Origin Age group (years) Australian Institute of Health and Welfare, 2011

48. Case study - Answer Rita has 4 risk factors for CKD • Smoking • Age over 60 • Family history • High blood pressure

49. Case study - Question Q2. What would you do next?

50. Who should be tested for kidney disease? *yearly for people with diabetes or hypertension If an individual has multiple risk factors, follow the more frequent regime