Management of Stage3 Chronic KidneyDisease in GeneralPracticePrimary Care Education WorkshopThis module was conceived and developed by PEAK*Presented By: Dr Sharad Ratanjee1V1117

Collaborators*This Education was conceived anddeveloped by the ‘Primary Care EducationAdvisory Committee for KHA’ (PEAK)With special thanks to Dr Paul SnellingKHA’s Primary Care Education program is proudlysupported by unrestricted educational grants from:2

Speaker Disclosure Statement Kidney Health Australia Primary CareWorkshops are presented by volunteerspeakers (Nephrologists, Renal Nurses& other Health Professionals). Speaker disclosure:3

Learning outcomesAt the end of this presentation participants will be able to:Demonstrate the ability to stage chronickidney disease (CKD) through accurateinterpretation of kidney functionDefine the goals for best practicemanagement of CKD, particularly Stage 3Determine when to refer patients with CKD toa Nephrologist according to the recommendedclinical indicatorsImplement a practice-based system, forpatient safety, to identify patients at higherrisk of CKD for a kidney health check4

What is CKD?Chronic kidney disease is defined as:Glomerular Filtration Rate (GFR) 60mL/min/1.73m2 for 3 months with or withoutevidence of kidney damage.OREvidence of kidney damage (with or withoutdecreased GFR) for 3 months: 5albuminuriahaematuria after exclusion of urologicalcausespathological abnormalitiesanatomical abnormalitiesChronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia:Melbourne, 2015

Kidney disease in AustraliaAustraliansaged 18yearsLess than10% ofthesepeople areaware theyhave CKD23,000Dialysis ortransplant54,000Stage 4-5CKD591,0001,146,0005 MILLION AT RISK6Stage 3CKDStage 1-2CKDHypertension/ DiabetesAustralian Health Survey 2013; ABS population estimates June 2013; ANZDATA 2016 ReportCKD staging is according to the CKD-EPI equation

Australians living with signsof CKD 12% ofpopulation withsigns of CKD8-11% ofpopulation withsigns of CKD 7% ofpopulation withsigns of CKDNo data available7State of the Nation Report 2016, Kidney Health Australia

State of the Nation8State of the Nation Report 2016, Kidney Health Australia

Staging CKDCombine eGFR stage, albuminuria stage and underlying diagnosis to specifyCKD stage e.g. stage 3b CKD with microalbuminuria secondary to diabetic kidney diseaseAlbuminuria StageGFRStageGFRmL/min/1.73m21 90260-893a45-593b30-44415-295 15 or ine ACR mg/mmol urine ACR mg/mmol urine ACR mg/mmolMale: 2.5Male: 2.5-25Male: 25Female: 3.5Female: 3.5-35Female: 35Not CKD unlesshaematuria, structuralor pathologicalabnormalities presentXColour-coded Clinical Action Plans in handbookand on CKD-Go! App9Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia: Melbourne, 2015

Staging CKD‘CKD management in GeneralPractice’ handbook uses colourcoded action plans indicatingthe overall risk of– Progression of CKD– Cardiovascular eventsNormalLowModerateHigh10Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia:

Why worry about CKD & ESKD?Prevalence of registered and projected treated-ESKD, for allpatients and by incident age, 2003-202011AIHW analysis of ANZDATA Registry data

CKD survival5 year survival of patients aged 60 years withcommon cancers compared with CKD100959085% of 5 Year ge 5 CKDon dialysisDiagnosis12Nat. Rev Nephrol 2011; 7:578-589Ovarian

ESKD & cardiovascular mortalityDialysis patientsGeneralpopulation13Foley et al; AJKD 1998

CVD riskeGFR 60mL/min defines a coronary heartdisease risk greater than diabetesCKD defined as eGFR 15-59.5ml/min/1.73m2CKD14DiabetesTonelli, Lancet 2012

CVD risk in CKDKidney & cardiovascular outcomes in patients with CKDKaiser Permanente Longitudinal Study50Event (%)Death40Dialysis/Tx30n 27988, FU 66 mo2010089-6089-60(prot)30-6929-15GFR (ml/min)Patients with CKD are 20 times more likely to die fromcardiovascular events than survive to reach dialysis15Keith et al Arch Int Med 164 (6) 659, 2004

Stages of nephropathy indiabetesAnnualtransitionrate inT2DMAnnual riskof all-causedeath oalbuminuria4.6%S-creat 175 µmol/L orESKD19.2%2.0%2.8%2.3%16Adapted from: UKPDS 64. Kidney Int 2003: 63: 225-32

Intervention & managementGFR (ml/min/1.73m2 )6050EffectiveInterventionsResidual RenalFunction40302010Late Referral0Timely Start?17

Age and kidneysRelationship between age & nship of eGFR to age00000002.50%Median97.50%20-24 25-2930-34 35-39 40-44 45-49 50-5455-59 60-64 65-69 70-74 75-79 80-84 85-90Age (years)18Australasian Creatinine Consensus group. MJA 2007; 187(8): 459-46390

Case study Bruce BBackground 74 years oldRetired small business ownerBruce sees you about abdominalpain19

Case study - BruceMedical history20Smoker20 cigarettes/day(35 pack-year history)Alcohol30g/day (3 standard drinks)Hypertension20 yearsType 2 Diabetes5 years - takes oral hypoglycaemicsInfra-renal AAA4cmIncidental finding on CT forabdominal painStress echoNo inducible eAspirin (low dose)

Case study – visit 1Blood pressure190/84 mmHgPeripheral pulses presentCreatinine160 µmol/LOn Review TodayeGFR2136 mL/min/1.73m2 (has beenconsistently below 40 mL/min/1.73m2 for 6months)Total cholesterol6.7 mmol/LTriglycerides4.1 mmol/LFull blood countNormalUrine ACR2.4 mg/mmolFundiNormal

Case study - BruceAlbuminuria 1.73m2urine ACR mg/mmolMale: 2.5Female: 3.5urine ACR mg/mmolMale: 2.5-25Female: 3.5-35urine ACR mg/mmolMale: 25Female: 351 90260-89Not CKD unlesshaematuria, structural orpathological abnormalitiespresent3a45-593b30-44415-295 15 or ondialysisGFRStage22GFRBruce’s resultsstage him hereChronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney HealthAustralia: Melbourne, 2015

ResourcesMy Kidneys, My Health Handbook & AppFree resource for patients newly diagnosed withearly stage CKDApp available oniTunes andGoogle Play appstores23Hardcopy books availableto order

Case studyAnswer True or False to each of thestatements belowa) The absence of albuminuria excludes diabetic kidney diseaseb) Quantitation of albuminuria will give important prognosticinformationc) He should not be started on an Angiotensin convertingenzyme (ACE) inhibitors and angiotensin II receptor blockers(ARB)to slow progression of kidney disease as he has CKDStage 3bd) His smoking will worsen his kidney functione) Lipid lowering therapy has been proven to slow progressionof kidney diseasef) Cardiovascular disease risk - Bruce's CVD risk should bedetermined using the absolute risk tool24

Case study - answera) The absence of albuminuria excludesdiabetic kidney diseaseFALSE– 20-30% of diabetic patients may havechronic kidney disease withoutevidence of albuminuria Mechanism not well understood- Likely to progress with time25MacIsaac & Jerums; Minerva Endocrinol 2005

Case study - answerb) Quantitation of albuminuria will giveimportant prognostic informationTRUE– Increasing degrees of albuminuria lead toincreasing risk of ESKD Albuminuriais a stronger marker of risk ofprogression to ESKD than baseline eGFR But eGFR strong predictor of morbidity andmortality– Reduction of albuminuria predicts reducedmortality and reduced progression to ESKD26

CKD riskUrine ACR 1.1 mg/mmol is an independent predictor forall cause and CVD mortality in the general populationAll-cause mortalityMeta analysis105 872participants730 577 personyears14 studiesCardiovascular mortality27CKD prognosis consortium; Lancet 2010

Kidney function markerMacroalbuminuria is a better marker than GFR inpredicting loss of kidney functionN 8952 – F/U 4yrsChange in eGFR(ml/min/1.73m2)Impaired Renal Function (n 40)Total Population (n 4772)Erythrocyturia (n 69)Macroalbuminuria (n 59)28Follow-up (yr)PREVEND Study; J Am Soc Nephrol 2006

Albuminuria & GFR predictmortality & morbidity uria GFRCV12.63.4non CV11.53.0CV11.42.3PREVEND Study; J Am Soc Nephrol 2006

Case study - answerc) He should not be started on an ACEinhibitor or ARB to slow progression ofkidney disease as he has CKD Stage 3bFALSE– ACEi’s and ARB’s have been shownto reduce the risk of CV events anddeath in people with CKD30

Treatment of BP in CKD ACE inhibitor (ACEi) or Angiotensin Receptor Blocker(ARB) Independent beneficial effect on CKD irrespective of effect onBP CKD patients often need multiple medications toachieve BP control Achieving BP goals improves outcomesNumber of BP Meds4321090-993180-8960-6950-5940-49GFR (ml/min)Bakris et al, AJKD 2000;36:646-661

BP lowering in CKDBlood pressure lowering in CKD: PROGRESS trialACE /- diuretic in people with previous cerebrovascular disease,similar subgroup analyses published from several other trialsCCr 60 ml/minCCr 60 ml/min0.3PlaceboActiveCumulative incidence ofMajor vascular eventsCumulative incidence ofMajor vascular events0.3RR 0.74 (95%CI 0.63-0.86)p 0.00010. at risk32RR 0.70 (95%CI 0.58-0.86)p 0.0030.212304Follow-up (years)Number at risk1234Follow-up (years)Placebo2,1772,0551,9441,8311,085Placebo al1,7571,6191,4831,365825Perkovic et al, JASN 2007

Intervention and outcomesACE inhibitors in Type 2 Diabetes with hypertensionThe BENEDICT TrialAdjusted Health Risks (HR) for major cardiovascular eventsaccording to baseline albuminurian 1208No ACEiACEi33Risk of CVDissignificantlyreducedRuggenenti et al; JASN 2012

Target blood pressure inadultsBlood pressure goalsPeople with.34Maintain BPconsistently BELOW(mmHg)Albuminuria 130/80Diabetes 130/80Chronic KidneyDisease 140/90KHA-Cari guidelines-Primary prevention of chronic kidney disease: Blood pressure target

Risk stratification – bloodpressure 10 mmHg SystolicBlood Pressure resultsin 10.9% increase inRelative Risk of ESKD(RENAAL Study*) 35Greatest reduction inmortality in those withPulse Pressure 90mmHg in RENAAL*RENAAL Study, Keane et al 2003; 63: 1499-1507

Case study – true or false?d) His smoking will worsen hiskidney function40TRUE Smoking is associated with kidney damage inthe population AusDiab Study Smoking increases proteinuria and acceleratesloss of GFR*3020Adjusted for age, education, physical activity,diabetes, CVD, BP medication, systolic BP, lipids,WC, eGFR & ACR)**100Never smokers361-9 pack years10-19 pack years* p 0.05 compared with ‘never smokers’20-39 pack years 40 pack yearsHallan & Orth; Kidney Int 2011

Case study - Answere) Lipid lowering therapy has been provento slow progression of kidney functionFALSE Post hoc analysis of CKD trials show noconsistent pattern of responses Major trial recently showed CV eventreduction in CKD (non-dialysis) but noimpact on slowing progression of CKD*37*Baigent et al, Lancet 2011

Lipid lowering in CKDStudy of Heart And Renal Protection(SHARP)There is strong evidence that lipid lowering in people withCKD will decrease the risk of atherosclerotic events Recruited 9438 patients with CKD, including 1/3 ondialysis No previous cardiovascular events Randomised to 20 mg simvastatin 10 mg ezetimibe vsplacebo Mean baseline LDL-C level of 2.8mmol/L Outcome was first major atherosclerotic event (non-fatalmyocardial infarction or coronary death, nonhaemorrhagic stroke, or any arterial revascularisationprocedure) Followed for an average of 5 years38Baigent et al, Lancet 2011

CV eventsSHARP results: 17% reduction in major atheroscleroticevents*Proportion suffering event* (%)2520in riskPlacebo15Eze/simv10*Major atherosclerotic events(coronary death, MI, nonhaemorrhagic stroke, or anyrevascularization)*Average 0.85mmol/L decrease inLDL-C vs. placebo5039Risk ratio 0.83 (0.74 – 0.94)Log rank p 0.002217% reduction0123Years of follow-up45Baigent et al, Lancet 2011

Statin statementIn adults with newly identified CKD, evaluation with afasting lipid profile is recommended. Follow-upmeasurement of lipid levels may not be needed If aged 50 years with any stage of CKD (irrespective oflipid levels):– Statin if eGFR is 60 mL/min/1.73m2– Statin or statin/ezetimibe combination if eGFR is 60Ml/min/1.73m2 If aged 50 years with any stage of CKD (irrespective oflipid levels):– Statin if presence of one or more of: coronary disease, previousischaemic stroke, diabetes or estimated 10-year incidence of fatalor non-fatal myocardial infarction above 10% Lifestyle advice if hypertriglyceridaemia is present40Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia: Melbourne, 2015

Case study - Answerf) Assessment for cardiovascular diseaserisk- Bruce's CVD risk should bedetermined using the absolute risk tool.FALSE People with moderate or severe CKD* areconsidered to be at the highest risk of acardiovascular event and do not need to beassessed by the cardiovascular risk tool*defined as persistently having a urineACR 25mg/mmol (males) or 35mg/mmol (females)or eGFR 45ml/min/1.73m241Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney HealthAustralia: Melbourne, 2015

CKD riskAustralian Absolute Cardiovascular Disease Risk has an eGFR of 36 mL/min/1.73m2His high BP automatically means he is at high risk( 15% chance) of a CVD event in next 5 years.He should not have the Absolute CVD risk toolapplied.42

CVD riskanyone with eGFR 45 mL/min/1.73m2 or persistent proteinuriaDiabetes and microalbuminuriaDiabetes and age 60 yearsEstablished cardiovascular diseaseFamilial hypercholesterolemia or total cholesterol above 7.5Severe hypertension– Systolic 180 mmHg or greater– Diastolic 110 mmHg or greateris already at the highest risk of a cardiovascularevent,therefore the calculator should not be used43Guidelines for the management of Absolute cardiovascular disease risk: National Vascular Prevention Alliance.

CVD risk reduction in CKD CKD is a potent risk factor essential to determine CKD beforeusing the tool with CKD, individuals cardiac deathrisk is 2-3 greater than without CKD with CKD, individuals are 20 timesmore likely to die from CVD thansurvive to need dialysis or transplant44Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia:Melbourne, 2015

Case study - Bruce Commenced on perindopril/ indapamide* Seen 4 weeks later and reassessed4 Weeks agoTodayBP190/84 mmHg150/76 mmHgCreatinine160 µmol/L189 µmol/LeGFR36 mL/min/1.73m229 mL/min/1.73m2Potassium-5.8 mmol/LUrine ACR2.4 mg/mmol2.6 mg/mmol*Usual practice is to increase by one antihypertensiveagent at a time45

Case study - questionQ2: Do You a) Cease the ACEi and commence anotherdrugb) Cease the ACEi and check for a renalartery stenosisc) Continue the ACEi and check for a renalartery stenosisd) Add another drug for better BP control46

Case study - answerd) Add another drug for better bloodpressure controlRationale: Decrease in eGFR of 25%, not unexpected afterBP lowering; a result of decreased perfusion Target BP in CKD is 140/90 mmHg ACEi may have benefit for kidney disease K needs watching but not a concern at this level-prescribe low K diet47

Case study - BruceSeen 1 month later1st visit4 weeks laterToday (8 weeks later)BP190/84 mmHg150/76 mmHg134/68 mmHgCreatinine160 µmol/L189 µmol/L180 µmol/LeGFR3629mL/min/1.73m2 mL/min/1.73m2Potassium-5.8 mmol/L5.4 mmol/LCa2.05 mmol/LPO41.54 mmol/L98g/L Normocytic /HbUrine ACR4831 mL/min/1.73m2normochromic2.4 mg/mmol2.6 mg/mmol2.6 mg/mmol

Case study - questionQ3: What would you do?a) Implement anb) Check iron studiesc) Check Vitamin B12 and folate levelsd) Check Vitamin D and PTHe) All of the above49

Case study - answere. All of the aboveResults50Iron studiesNormal rangeB12 and folateNormalTSHNormalPTH18 pmol/L (N 8 pmol/L)Vitamin D25 nmol/L - moderate deficiency

Anaemia Anaemia of CKD is related to both:- reduced erythropoietin production by the kidney- resistance to the action of erythropoietin Anaemia due to CKD begins at GFR 60mL/min- Prevalence of anaemia increases markedly withdecreasing GFR- Common when GFR 30 mL/min (30-40%) CKD anaemia is a diagnosis of exclusion- Need to ensure not Fe deficient or B12/ folatedeficient, or hypothyroid51Gouva et al; Kidney Int 2004

Anaemia is associated withmortality in dialysis patientsAdjusted Relative Risk of death due to any cardiac cause, accordingto Haematocritn 50,57952Li & Collins; Kidney International 2004

Target Hb for anaemia in CKDOptimal Hb level not knownRCT – no benefit above 120 g/LIndividualise treatmentRefer to PBS criteria53

ResourcesCKD patient fact sheetsAvailable along with more kidney health factsheets at

CKD & anaemia summary Common and important to correct PBS criteria - can’t start EPO till Hb 100g/L Need to have Nephrologist endorsement tostart Ensure not iron deficient All respond – need to dose titrate Most self administer SC every 1-4 weeks All will need extra iron (oral or i.v.)All iron deficiency needs investigation55

Case study - BruceCalcium and phosphate at today’s visit561st visit4 weeks laterToday (8 weekslater)BP190/84 mmHg150/76 mmHg134/68 mmHgCreatinine160 µmol/L189 µmol/L180 µmol/LeGFR36mL/min/1.73m229mL/min/1.73m231 mL/min/1.73m2Urine ACR2.4 mg/mmol2.6 mg/mmol2.6 mg/mmolCa2.05 mmol/LPO41.54 mmol/LHb98g/LNormocytic /normochromic

Complications – mineral andbone disorder Changes in metabolism of calcium,phosphate, parathyroid hormone andVitamin D common when eGFR 60mL/min/1.73m257 Leads to: Bone disease Soft tissue calcification (coronaries &valves) Pruritus Proximal myopathy Premature death

Mortality and PhosphateIncreased PO4 associated with increasedmortality even in normal kidney functionHazardratio58S. PO4 mg/dLTonelli et al, Circulation 2006

Mechanisms of Ca/PO4 disturbance Phosphate retention with reduced GFR results in increasedserum PO4 and suppresses Vitamin D3 production Reduced Vitamin D3 leads to reduced Ca absorption and thisplus high serum PO4 leads to low serum Calcium Ca x PO4 increases favouring tissue deposition PTH stimulated by low Ca, high PO4 & low Vit D3Clinical effects: Low serum Calcium High serum Phosphate High serum PTH Low Vitamin D3 [1,25 (OH)2D3 calcitriol]59

Changes with reducing GFRGFR60(mL/min/1.73m2)CKDStage60-90Changes in serum levels1,25DPhosphateCalciumPTH2 30-593 2-fold15-304 4-fold 155 8-foldAndress et al., Semin Dial 2005

Assessment of Ca/PO4disturbance(CKD mineral and bone disorder)What to measure & how oftenProgressive CKDstage 3CKD stage 46-12 months3-6 monthsPTH & minDBaselineBaselineCalcium &phosphate61KDIGO Guidelines; Kidney International 2009

Goals of therapy for mineral andbone disorderKeep PO4 in normal range (0.8-1.5 mmol/L)Keep Ca in normal range (2.2-2.6 mmol/L)Keep PTH 2-9 x upper limit of normal andavoid trends towards the extremes of thisrange25-hydroxyvitamin D optimal levels may be 75 nmol/L62

Therapy for Ca/PO4disturbance Control sPO4Dietary restrictionPhosphate binders (preventuptake) Control sCaAdequate calcium uptakeCalcitrol (increases uptake)Calcitrol Control sPTH (Cinacalcet)Parathyroidectomy63

Referral is recommended if: eGFR 30mL/min/1.73m2 (stage 4 or 5 of any cause) Persistent significant albuminuria (urine ACR 30mg/mmol) A sustained decrease in eGFR of 25% or more OR asustained decrease in eGFR of 15mL/min/1.73m2,peryear Uncontrolled hypertension with at least three antihypertensive agentsClinical tipAnyone with rapidly declining eGFR and/or signs of acute nephritis(oliguria, haematuria, acute hypertension and oedema) should beregarded as a medical emergency and referred with out delayRecommended tests prior to referral64Current blood chemistry and haematologyUrine ACR and urine microscopy for red cell morphology and castsCurrent and historical blood pressureUrinary tract ultrasoundChronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia:Melbourne, 2015

Unnecessary referral if: eGFR 30 mL/min/1.73m2 is stable Urine ACR 30mg/mmol (with no haematuria) Controlled blood pressureThe decision to refer or not must always beindividualised, and particularly in youngerindividuals the indications for referral may beless stringent.Useful tips Pay attention to CVD risk reduction Consider discussing management issues with a nephrologist incases where uncertainty regarding referral exists. Don’t refer to a nephrologist if targets of therapy are achieved Spiral CT angiogram for hypertension is not recommendedwithout specialty advice65Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia:Melbourne, 2015

Managing CKDProgressive CKD is often associatedwith: Depression Macular degeneration Impaired cognitive function66

ResourcesKidney Health Information ServiceFree call information servicefor people living with kidneydisease and their families67

Conclusion Early CKD is common and can be primarily bemanaged in general practice Therapy overlaps significantly with bestpractice in CV risk reduction and diabetes careKey CKD management tasks Lifestyle – Healthy diet & exercise, no smoking,weight control Reduce CV risk BP at target with ACEi or ARB and other agents asrequired Reduce albuminuria with ACEi or ARB68 Optimise haemoglobin, Ca/P and glycaemia

ResourcesCKD management in General Practice2015 guidelines handbookAvailable

ResourcesCKD-GO! Phone AppRated a‘must have’Appby MedicalObserverAvailable oniTunes and GooglePlay app storesAll the best bits of the‘CKD Management inGeneral Practice’ handbooknow in a handy app!70

FactsheetResourcesHealthshare fact sheetsChronic Kidney Disease fact sheets forpatients. Available for Medical Directorand Best Practice softwareUrinary tract infectionsHow to look after your kidneysKidney Health Check upGP only – Chronic KidneyDiseaseAll about Chronic KidneyDiseaseLooking after yourself with CKDKidney stonesKidney transplantPeritoneal dialysisConsent and kidney testsKidney health testsKidney cystsAccess for dialysisKidney cancerTreating kidney diseaseHomes haemodialysisHaemodialysisLife with a single kidney71All about GFR

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Case study - Bruce Chronic Kidney Disease (CKD) Management in General Practice, 3rd edition. Kidney Health Australia: Melbourne, 2015. 23 Resources My Kidneys, My Health Handbook & App Free resource for patients newly diagnosed with early stage