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 Important Updates in the Early Detection & Management of Chronic Kidney Disease
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General Practitioner Workshop This workshop was conceived and developed by the Kidney Check Australia Taskforce with particular thanks to A/Prof Robyn.
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General Practitioner WorkshopThis workshop was conceived and developed by the Kidney Check Australia Taskforce with particular thanks to A/Prof Robyn Langham & A/Prof Timothy Mathew
2013
Important Updates in the Early Detection & Management of
Chronic Kidney Disease
Learning Objectives
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.
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
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
5 MILLION AT RISK
856,000
19,000
40,000
827,000
Stage 5 CKD
Stage 4 CKD
Stage 3 CKD
Hypertension Diabetes
Stage 1 – 2 CKD
Kidney disease in Australia
Australians aged ≥ 25 years
CKD staging is according to the CKD-EPI equation
AusDiab Report, 2001; White et al 2010; Jun 10 ABS data; 2011 ANZDATA report
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
Costs of treating current and new ESKD cases to 2020
Risk of ESKD related to baseline proteinuria (dipstick) over 18 year period
Blue – normal ACRGreen – microalbuminuriaRed - macroalbuminuria
Note log scale on Y axis for Hazard Ratio
Adapted from Levey et al, 2010, Kidney International
The new Australian CKD staging schema
Albuminuria Stage
GFR Stage
GFR (mL/min/1.73m2)
Normal(urine ACR mg/mmol)
Male: < 2.5Female: < 3.5
Microalbuminuria (urine ACR mg/mmol)
Male: 2.5-25Female: 3.5-35
Macroalbuminuria(urine ACR mg/mmol)
Male: > 25Female: > 35
1 ≥90 Not CKD unless haematuria, structural or
pathological abnormalities present2 60-89
3a 45-59
3b 30-44
4 15-29
5 <15 or on dialysis
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
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
People at increased risk of CKD
Eight major risk factors for CKD Diabetes
High blood pressureAge over 60 years
Smoking Obesity
Family history of kidney diseaseAboriginal or Torres Strait Islander origin
Established cardiovascular disease
1 in 3 Australian adults is at increased risk of CKD due to the above risk factors!
How do we detect CKD?
New Recommendations for CKD detection
Test Kidney Function Blood test for eGFR (creatinine)
Test for Albuminuria Urine test for albumin / creatinine ratio (ACR)
Test for Hypertension Check patient’s blood pressure
Remember…
CKD screening should be undertaken as a part of a systematic chronic disease assessment
What is GFR?
• 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/1.73m2 indicates 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
GFR = Glomerular Filtration Rate
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%
What’s new in CKD?
What Old New Rationale
eGFR & elderly
If aged >70 years, stable eGFR between 45-59 mL/min/1.73m2 may be ok for age in some cases
Age-related decision points are not recommended
eGFR<60 mL/min/1.73m2 is associated with significantly increased risks of adverse clinical outcomes irrespective of age
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
What is eGFR?
This is consistent with USA, UK & Australian clinical guidelines
Since 2005 it has been recommended that eGFR be automatically reported with every request for serum
creatinine in adults.
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
Comparing eGFR and creatinine
CKD 1&2
CKD 5CKD 4CKD 3
GFR mL/min120 90 60 30 0
Seru
m
crea
tinin
e
Normal Serum Creatinine Level
Actual Serum Creatinine Level
Limitations of eGFR
• 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 (may overestimate
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)
Clinical situations where eGFR results may be unreliable and/or misleading:
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
Remember…
CKD screening should be undertaken as a part of a systematic chronic disease assessment
Urine Albumin/ Creatinine ratio (ACR) recommended for everyone
Clinical Tip The preferred method for assessment of albuminuria in both diabetes and non-
diabetes is urinary ACR measurement in a first void spot specimenWhere a first void specimen is not possible or practical, a random spot urine
specimen for urine ACR is acceptable
Urine Tests for proteinuria
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
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
Approximate equivalents between urine ACR & other measure of albumin & protein
CKD screening should be undertaken as a part of a systematic chronic disease assessment
What’s new in CKD?
What Old New
Blood Pressure Targets
People with >1g proteinuria/ day – BP target 125/75 mmHg
People with CKD (or other conditions) – BP target 130/80 mmHg
All other conditions – BP target 140/90 mmHg
People with CKD - should maintain a BP consistently below 140/90 mmHg
People with diabetes or microalbuminuria should maintain a BP consistently below 130/80 mmHg
Blood Pressure Targets
Case study
RitaRita is a new patient to your practice
• 63 years old• Accountant• History of mild asthma
• Overweight (BMI 29)• Mild intermittent asthma• Chronic low back pain• Mild hypertension• Smoker 25 pack year history
Past medical 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
High blood pressure SmokingAge over 60 yearsFamily history of kidney diseaseDiabetes ObesityAboriginal or Torres Strait Islander originEstablished cardiovascular disease
Rita has 4 of the 8 Risk Factors
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)
CKD risk factors: Obesity
Hallan et al, Am J Kid Dis 2006
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
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
Rela
tive
Risk
of C
KD*
(95%
CI)
Hallan et al, Am J Kid Dis 2006*CKD with eGFR <45mL/min/1.73m2
Or……damaged kidneys cause high blood pressure and high blood pressure damages kidneys
Parenchymal Renal Disease
Hypertension
CKD risk factors: High blood pressure
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.
You can now diagnose Rita as having CKD stage 3a with microalbuminuria
Case study - Rita
Orange Clinical Action PlaneGFR 30-59 mL/min/1.73m2 with microalbuminuria or eGFR 30-44 with normoalbuminuria
• Investigations to exclude treatable disease• Reduce progression of disease• Reduce cardiovascular risk• Early detection & management of complications• Avoidance of nephrotoxic medications or volume
depletion• Adjustment of medication doses to levels appropriate for
kidney function• Appropriate referral to a Nephrologist
Goals of Management
Case study - Rita
Monitoring 3-6 monthly clinical review
Clinical assessment
Blood pressureWeight
Laboratory assessment
Urine ACRBiochemical profile including urea, creatinine,
electrolyteseGFRHbA1c (for people with diabetes)Fasting lipidsFull blood countCalcium and phosphateParathyroid hormone (6-12 monthly if eGFR <45
mL/min/1.73m2)
Orange Clinical Action PlaneGFR 30-59 mL/min/1.73m2 with microalbuminuria or eGFR 30-44 with normoalbuminuria
• The tool is approved by NH&MRC • If Rita had moderate to severe CKD defined as eGFR <45
mL/min/1.73m2 or macroalbuminuria (ACR >25mg/mmol men; >35mg/mmol women) she would be at the highest CVD risk and in this case the tool should not be applied
Rita’s Cardiovascular Risk (www.cvdcheck.org.au)
Blood pressure reduction• CKD can cause and aggravate hypertension and hypertension
can contribute to the progression of CKD
• Reducing blood pressure to below target levels is one of the most important goals of CKD management
• ACE inhibitor or ARB is recommended first line therapy
• Combined therapy of ACE & ARB is not recommended
• Maximal tolerated doses of ACE inhibitor or ARB is recommended
• Hypertension may be difficult to control and multiple (3-4) medications are frequently required
Rita has stage 3a CKD with microalbuminuria so her blood pressure needs to be maintained consistently below 130/80 mmHg
Blood pressure reduction
Clinical Tips• ACE inhibitors and ARBs can cause a reversible
reduction in GFR when treatment initiated
• If the reduction is less than 25% and stabilises within two months of starting therapy, the ACE inhibitor or ARB should be continued
• If the reduction in GFR exceeds 25% below the baseline value, the ACE inhibitor or ARB should be ceased and consideration given to referral to a Nephrologist for bilateral renal artery stenosis
160/95
Adequate BP management delays the progression of CKD
Bakris et al., Am J Kid Disease, 2000
If Rita’s blood pressure was consistently below target, the GFR loss per year would be
reduced by 80%
Lifestyle modificationLifestyle approaches are essential in reducing the overall cardiovascular risk - the key elements are:
Stop smoking A low calorie diet to reduce BMI A low salt diet Weight reduction A reduction in alcohol intake Physical activity
Lifestyle modification effects on BP
* Dietary Approaches to Stop Hypertension
Modification Recommendation Approx SBP reduction
Weight reduction BMI 18-24.9 kg/m2 5-20 mmHg / 10kg lost
DASH* diet Fruit, vegies, low saturated and total fat 8-14 mmHg
Dietary salt restriction <100 mmol/day 2-8 mmHg
Physical activity Aerobic activity for 30mins most days 4-9 mmHg
Moderate alcohol consumption only 1-2 standard drinks/day 2-4 mmHg
Lipid lowering & glycaemic controlLipids•Margaret’s lipids should be assessed•Lipid-lowering treatment should be considered for CVD risk reduction
Glycaemic control•Margaret’s glycaemic control should be assessed•For people with diabetes, blood glucose control significantly reduces the risk of developing CKD, and in those with CKD reduces the rate of progression
Case study - Question
Referral to a Nephrologist is recommended if:• eGFR <30mL/min/1.73m2
• Persistent significant albuminuria (urine ACR ≥ 30mg/mmol)• Rapidly declining eGFR from a baseline of <60 mL/min/1.73m2
(a decline of >5mL/min/1.73m2 over a six-month period which is confirmed on at least three separate readings)
• CKD and hypertension that is hard to get to target despite at least three anti-hypertensive agents
• glomerular haematuria with macroalbuminuria
Clinical tipWhen referring to a Nephrologist ensure patient has had a recent urine ACR, current blood chemistry and haematology and a urinary tract ultrasound.
Anyone with an acute presentation and signs of acute nephritis (oliguria, haematuria, acute hypertension, and oedema) should be regarded as a medical emergency and referred without delay
Referral is NOT usually necessary if:• Stable eGFR ≥30 mL/min/1.73m2
Useful Tips Pay attention to CVD risk reduction Consider discussing management issues with a Nephrologist in
cases where uncertainty regarding referral exists. Don’t refer to Nephrologist if targets of therapy are achieved Spiral CT angiogram for hypertension is not recommended
without specialty advice
• Follow the ‘Orange’ clinical action plan (found in ‘CKD management in General Practice’ 2nd ed)
• Cardiovascular risk reduction• Blood Pressure should be consistently below 130/80
mmHg – use of ACE or ARB as appropriate• Lifestyle modification• Avoid nephrotoxic medications• Adjust dose of other medications to levels appropriate
for her kidney function• No need for Nephrology referral at this stage• Continue to monitor 3-6 monthly
Orange Clinical Action PlaneGFR 30-59 mL/min/1.73m2 with microalbuminuria or eGFR 30-44 with normoalbuminuria
Case study – Action plan
Treatment target for people with CKD
Parameter Target Treatment
Blood Pressure≤ 140/90 mmHg or≤ 130/80 mmHg if albuminuria is present(ACR > 2.5 mg/mmol males; >3.5 mg/mmol females)
Lifestyle modificationACE inhibitor or ARB
Albuminuria >50% reduction of baseline value ACE inhibitor or ARB
• Treatment targets and choices of therapy may differ with a CKD diagnosis
• Early detection and management of CKD complications
• Greater consideration of any prescribing - avoidance of nephrotoxic medications and ensuring dosages of other prescribed drugs are appropriate for the level of kidney function
• Timely referral of CKD patients to a Nephrologist for more severe CKD or complications
The diagnosis of CKD brings with it the need to identify risk reduction measures both for kidney and
cardiovascular diseases
Summary…• CKD is common, harmful and treatable• Early detection is beneficial• Systematically identify patients at high risk of CKD (the 8 risk factors)• Perform a Kidney Health Check (urine ACR, eGFR, blood pressure) on
at risk patients • CKD is present if 2 /3 urine ACR tests in 3 month period are positive• Repeat the eGFR if <60mL/min/1.73m2
• Maintain blood pressure consistently below the relevant threshold• Refer to the CKD staging table and clinical action plans in ‘CKD
Management in General Practice (2nd ed)’• GPs play a vital role in the management of CKD• Most CKD patients can be managed in general practice
Remember…
New Edition!
now available at www.kcat.org.au
Further resources…
CKD Management in General Practice
2012 Guidelines booklet
Kidney Health Information Service
• Free call information service for people living with / affected by kidney disease
Join the Kidney Community…
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Use of eGFR in different ethnic populations -recommendations
• The CKD-EPI formula is a useful tool to estimate GFR in all people, including various ethnic populations
• The CKD-EPI formula has been validated as a tool to estimate
GFR in some non-Caucasian populations, including South-East Asian, African, Indian and Chinese individuals living in Western countries
• The different methods to estimate GFR from serum creatinine concentration have not been validated in Indigenous Australians, although these studies are currently underway
Australasian Creatinine Consensus statement, 2012
Urine tests
• The term albuminuria includes increased urinary excretion of albumin and increased urinary excretion of other proteins
• It is very rare for a patient to have increased excretion of non-albumin proteins without concomitant increased excretion of albumin
• Excessive amounts of proteins in the urine are a key marker of kidney damage and of increased renal and cardiovascular disease risk
• These proteins are mainly albumin (albuminuria), but also consist of low molecular weight immunoglobulin, lysozyme, insulin and beta-2 microglobulin
Albuminuria or Proteinuria? That is the question!!