Chronic Kidney Chronic Kidney DiseaseDisease

Jennifer PeeblesJennifer Peebles

1616thth Feb 2010 Feb 2010

Chronic Kidney Disease Chronic Kidney Disease Long term condition caused by damage to the Long term condition caused by damage to the

kidneys.kidneys. Describes abnormal kidney function or structure.Describes abnormal kidney function or structure. Usually asymptomatic and so often unrecognised.Usually asymptomatic and so often unrecognised. Often occurs in the context of other chronic Often occurs in the context of other chronic

diseases such as cardiovascular disease and diseases such as cardiovascular disease and diabetes.diabetes.

Average prevalence of 6-11% in Europe and USA, Average prevalence of 6-11% in Europe and USA, rises with age. rises with age. Large UK primary care study (NEOERICA project) Large UK primary care study (NEOERICA project)

suggested prevalance of CKD stages 3-5 of 8.5% (5.8% suggested prevalance of CKD stages 3-5 of 8.5% (5.8% men and 10.6% women).men and 10.6% women).

Prevalence likely to increase with aging population Prevalence likely to increase with aging population and increase in conditions such as diabetes.and increase in conditions such as diabetes.

Why is it important?Why is it important? Major UK health burden due to its prevalenceMajor UK health burden due to its prevalence Can progress to End stage renal disease Can progress to End stage renal disease

Where no longer any sufficient function and so Where no longer any sufficient function and so dialysis/transplant necessary to maintain life.dialysis/transplant necessary to maintain life.

Renal replacement therapy accounts for over 2% of Renal replacement therapy accounts for over 2% of total NHS budget.total NHS budget.

When advanced – there is higher risk of When advanced – there is higher risk of mortality, particularly from cardiovascular mortality, particularly from cardiovascular diseasedisease 2003 UK retrospective study on incidence and 2003 UK retrospective study on incidence and

outcomes of new CKD cases showed only 4% developed outcomes of new CKD cases showed only 4% developed ESRD by 5.5 yr follow up, but 69% had died (about 50% ESRD by 5.5 yr follow up, but 69% had died (about 50% from cardiovascular cause)from cardiovascular cause)

Why is it important?Why is it important? Because it is asymptomatic, it is often diagnosed Because it is asymptomatic, it is often diagnosed

latelate currently 30% of people with advanced kidney disease currently 30% of people with advanced kidney disease

are referred late causing increased morbidity and are referred late causing increased morbidity and mortalitymortality

However, tests for detection are simple and However, tests for detection are simple and easily available.easily available.

Treatment can slow the progression of CKD, and Treatment can slow the progression of CKD, and reduce cardiovascular mortality.reduce cardiovascular mortality.

(QOF – total of 38 points for CKD indicators)(QOF – total of 38 points for CKD indicators)

Detecting kidney damageDetecting kidney damage Direct evidence:Direct evidence:

Imaging can show structural abnormalities - (Polycystic Imaging can show structural abnormalities - (Polycystic kidneys, pyelonephritis, reflux nephropathy, kidneys, pyelonephritis, reflux nephropathy, renovascular disease)renovascular disease)

UltrasoundUltrasound MRIMRI Isotope scanningIsotope scanning

Renal Biopsy Histopathology – to show underlying Renal Biopsy Histopathology – to show underlying glomerular disease (IgA nephropathy, focal glomerular disease (IgA nephropathy, focal glomerulosclerosis)glomerulosclerosis)

Indirect evidence:Indirect evidence: Urinalysis – showing leakage of blood cells or protein Urinalysis – showing leakage of blood cells or protein

into the urine.into the urine.

Detecting kidney damageDetecting kidney damage Proteinuria Proteinuria

Albumin is the principal component in proteinuria in Albumin is the principal component in proteinuria in glomerular diseaseglomerular disease

Albumin Creatinine Ratio has greater sensitivity than Protein Albumin Creatinine Ratio has greater sensitivity than Protein Creatinine Ratio for detection of low levels of proteinuria.Creatinine Ratio for detection of low levels of proteinuria.

PCR is cheaper to analyse.PCR is cheaper to analyse. NICE suggest ACR be used in preference to PCR for initial NICE suggest ACR be used in preference to PCR for initial

detection/identification in CKD, while PCR can be used later detection/identification in CKD, while PCR can be used later for quantification and monitoring except in diabetics.for quantification and monitoring except in diabetics.

SIGN suggest measurement method depends on context.SIGN suggest measurement method depends on context. Urine dipstick – widely available and low cost but not reliable for Urine dipstick – widely available and low cost but not reliable for

detection.detection. ACR – for detecting/monitoring diabetic nephropathy.ACR – for detecting/monitoring diabetic nephropathy. PCR – can be used in non-diabetics in populations with high PCR – can be used in non-diabetics in populations with high

prevalence proteinuria to exclude CKD, prevalence proteinuria to exclude CKD, - and in non-diabetics with CKD to predict risk of - and in non-diabetics with CKD to predict risk of progression.progression.

Indicates higher cardiovascular risk and risk of progression in Indicates higher cardiovascular risk and risk of progression in CVDCVD

No evidence that asymptomatic UTI causes proteinuria.No evidence that asymptomatic UTI causes proteinuria.

Detecting kidney damage - Detecting kidney damage - proteinuriaproteinuria Range for ACR/PCRRange for ACR/PCR

DefinitionDefinitionUrinary Urinary albumin albumin

excertion excertion (mg/24hrs)(mg/24hrs)

ACRACR

(mg/mmol)(mg/mmol)

PCR PCR

(mg/(mg/mmol)mmol)

24-hr urinary 24-hr urinary protein protein

excretion excretion (g/24hrs)(g/24hrs)

Normal albumin Normal albumin excertionexcertion 1010

MicroalbuminuriaMicroalbuminuria

(diabetics)(diabetics)30-30030-300

≥ ≥ 2.5 2.5 (men)(men)

≥ ≥ 3.5 3.5 (women)(women)

ProteinuriaProteinuria >300>300 ≥ ≥ 3030 ≥ ≥ 5050 0.50.5

Higher levels of Higher levels of proteinuriaproteinuria ≥ ≥ 7070 ≥ ≥ 100100 11

Detecting kidney damageDetecting kidney damage HaematuriaHaematuria

Frank – exclude infection/malignancyFrank – exclude infection/malignancy Microscopic – single reading a common (2%) Microscopic – single reading a common (2%)

finding so rpt.finding so rpt. Risk of CKD low with isolated microscopic Risk of CKD low with isolated microscopic

haematuia, however renal or urinary pathology often haematuia, however renal or urinary pathology often present.present.

Exclude infectionExclude infection >50yrs urgent referral to urology>50yrs urgent referral to urology <50yrs renal evaluation (especially if <50yrs renal evaluation (especially if

proteinuria/reduced eGFR)proteinuria/reduced eGFR)

Measuring renal functionMeasuring renal function GFR is the best measure of overall renal functionGFR is the best measure of overall renal function

Defined as the volume of plasma filtered by the glomeruli per Defined as the volume of plasma filtered by the glomeruli per unit time.unit time.

Accurate measurement difficult, and methods such as gold Accurate measurement difficult, and methods such as gold standard inulin clearance too difficult and unsuitable for standard inulin clearance too difficult and unsuitable for primary care. primary care.

Urea and Creatinine concentrationsUrea and Creatinine concentrations Convenient but insensitive Convenient but insensitive

GFR has to fall by half before significant increase in creatinine GFR has to fall by half before significant increase in creatinine becomes apparentbecomes apparent

Creatinine affected by various factors including age, sex, Creatinine affected by various factors including age, sex, ethnicity, body habitus (muscle mass), and also diet.ethnicity, body habitus (muscle mass), and also diet.

Consumption of cooked meat in particular has a rapid but Consumption of cooked meat in particular has a rapid but transient effecttransient effect

Also significant increase in creatinine if clotted sample not Also significant increase in creatinine if clotted sample not separated for amalysis within 16hrs. separated for amalysis within 16hrs.

Prediction equations for estimating GFRPrediction equations for estimating GFR

Prediction equationsPrediction equations

Equations improve correlation between Equations improve correlation between creatinine and GFR by taking into account creatinine and GFR by taking into account other variables.other variables.

Cockcroft and Gault: Cockcroft and Gault: age, sex, weight and creatinineage, sex, weight and creatinine

MDRD (Modification of Diet in Renal MDRD (Modification of Diet in Renal disease):disease): age, sex, ethnicity and creatinineage, sex, ethnicity and creatinine

Prediction equationsPrediction equations Limitations:Limitations:

Not completely accurate.Not completely accurate. Not valid in children, pregnant women or ARF.Not valid in children, pregnant women or ARF. Perform better at lower eGFRPerform better at lower eGFR At >60ml/min/1.73mAt >60ml/min/1.73m22, tends to underestimate , tends to underestimate

GFR so higher risk of false positive.GFR so higher risk of false positive. MDRD - validated only in Caucasian and African- MDRD - validated only in Caucasian and African-

American populations.American populations. MDRD – tendency to overestimate renal function MDRD – tendency to overestimate renal function

in malnourished or amputees.in malnourished or amputees.

Measuring renal functionMeasuring renal function Studies have shown that prediction equations are Studies have shown that prediction equations are

better than creatinine for urinary creatinine better than creatinine for urinary creatinine clearance.clearance.

Studies comparing MDRD and Cockcroft-Gault Studies comparing MDRD and Cockcroft-Gault equations suggest they are either comparable or that equations suggest they are either comparable or that MDRD is superior.MDRD is superior.

NICE have concluded that the MDRD equation NICE have concluded that the MDRD equation performs best.performs best.

MDRD is used by most labs in their automatic MDRD is used by most labs in their automatic reporting.reporting. Report only eGFR <60ml/min/1.73mReport only eGFR <60ml/min/1.73m22.. Patients should be advised to avoid eating meat for at least Patients should be advised to avoid eating meat for at least

12 hrs before eGFR is tested.12 hrs before eGFR is tested. Most calculate results assuming Caucasian race, so Most calculate results assuming Caucasian race, so

correction needed for African-Caribbeans.correction needed for African-Caribbeans.

Classification of CKDClassification of CKD Current system based of eGFR.Current system based of eGFR. US National Kidney Foundation Kidney Disease US National Kidney Foundation Kidney Disease

Outcomes Quality Initiative – stratified CKD into 5 stages.Outcomes Quality Initiative – stratified CKD into 5 stages. Cut off between stages arbitrary but do have clinical Cut off between stages arbitrary but do have clinical

correlatescorrelates

Classification of CKDClassification of CKD For CKD - evidence of persisting damage at 90days.For CKD - evidence of persisting damage at 90days. Stages 1 & 2 only diagnosed with Stages 1 & 2 only diagnosed with

proteinuria/albuminuria, haematuria or renal structural proteinuria/albuminuria, haematuria or renal structural abnormalities.abnormalities.

UK Consensus Conference - divided stage 3 into two UK Consensus Conference - divided stage 3 into two parts.parts. Studies had shown stage 3 encompassed a large number of Studies had shown stage 3 encompassed a large number of

asymptomatic patients. In those with eGFR <45, complications of asymptomatic patients. In those with eGFR <45, complications of CKD were far more common so this was set as lower threshold.CKD were far more common so this was set as lower threshold.

Stage 3A - eGFR 45-59ml/min/1.73mStage 3A - eGFR 45-59ml/min/1.73m22.. Stage 3B - eGFR 30-44ml/min/1.73mStage 3B - eGFR 30-44ml/min/1.73m22..

With proteinuria, the suffix p should be used e.g Stage With proteinuria, the suffix p should be used e.g Stage 3Ap.3Ap.

Patients on dialysis should be have suffix D i.e Stage 5D.Patients on dialysis should be have suffix D i.e Stage 5D. Suffix T indicates functioning transplant (can be any Suffix T indicates functioning transplant (can be any

stage).stage).

Decline in eGFR with age. Decline in eGFR with age. Classification takes no account of patient age.Classification takes no account of patient age. Unclear whether decline is ‘normal ageing’ Unclear whether decline is ‘normal ageing’

phenomenon, a true increase in prevelance in phenomenon, a true increase in prevelance in CKD with age or both.CKD with age or both.

NICE advise for those >70yrs, with eGFR >45 NICE advise for those >70yrs, with eGFR >45 if stable and no other evidence of kidney if stable and no other evidence of kidney damage is unlikely to be associated with damage is unlikely to be associated with complications of CKD.complications of CKD.

SIGN advise that age associated decline in SIGN advise that age associated decline in eGFR should be afforded the same significance eGFR should be afforded the same significance as decline in other situations.as decline in other situations.

Identification of patients with CKDIdentification of patients with CKD Routine surveillance of high risk patients:Routine surveillance of high risk patients:

Diabetes MellitusDiabetes Mellitus HypertensionHypertension Cardiovascular diseaseCardiovascular disease Structural Renal tract disease, calculi & outflow obstuction Structural Renal tract disease, calculi & outflow obstuction

incl prostaticincl prostatic Multisystem disease with potential renal involvement e.g. Multisystem disease with potential renal involvement e.g.

SLESLE Family history of CKD stage 5 or hereditary kidney diseaseFamily history of CKD stage 5 or hereditary kidney disease

Increased awareness of other risk factorsIncreased awareness of other risk factors SmokersSmokers Low socioeconomic status.Low socioeconomic status. Obese patientsObese patients Chronic NSAID use?Chronic NSAID use?

Incidental findingIncidental finding Urine Dipstick, renal function or structural abnormality on Urine Dipstick, renal function or structural abnormality on

imaging. imaging.

New eGFR < 60 – what now?New eGFR < 60 – what now?

Repeat the testRepeat the test If unwell/oliguric – repeat urgently ?AKIIf unwell/oliguric – repeat urgently ?AKI Otherwise within 2 weeks to exclude rapid Otherwise within 2 weeks to exclude rapid

deteriorationdeterioration NICE suggest at least 3 measurements over no less NICE suggest at least 3 measurements over no less

than 90 days for diagnosis.than 90 days for diagnosis. Clinical assessment of the patient.Clinical assessment of the patient.

HistoryHistory ExaminationExamination Repeat bloodsRepeat bloods Urine examinationUrine examination ? Imaging? Imaging

Clinical assessment – History takingClinical assessment – History taking Present HistoryPresent History

Urinary symptoms? (e.g. outflow obstrution/haematuria)Urinary symptoms? (e.g. outflow obstrution/haematuria) Symptoms of systemic disease?Symptoms of systemic disease? Symptoms of CKD? (tiredness, reduced appetite, itch, Symptoms of CKD? (tiredness, reduced appetite, itch,

oedema, muscle cramps)oedema, muscle cramps) PMHxPMHx

e.g. ?DM, ?CVD, HTN, ?renal stones, BPHe.g. ?DM, ?CVD, HTN, ?renal stones, BPH FMHxFMHx

PKD, ESRDPKD, ESRD MedicationMedication

Any nephrotoxic? E.g Lithium, NSAIDs, diuretics/ACEiAny nephrotoxic? E.g Lithium, NSAIDs, diuretics/ACEi Any meds needing dose adjustment?Any meds needing dose adjustment?NB - recommendations in most publications including BNF NB - recommendations in most publications including BNF

are based on creatinine clearance estimation by Cockcroft-are based on creatinine clearance estimation by Cockcroft-Gault. No evidence that this can be used interchangeably Gault. No evidence that this can be used interchangeably with MDRD. with MDRD.

Clinical assessment – Clinical assessment – Examination/InvestigationExamination/Investigation BPBP PulsePulse Signs of hypovolaemia/heart failure/sepsisSigns of hypovolaemia/heart failure/sepsis Palpable bladder/Polycystic kidneysPalpable bladder/Polycystic kidneys Prostate examination in menProstate examination in men

Urine examinationUrine examination Urinalysis – proteinuria/haematuriaUrinalysis – proteinuria/haematuria ACR/PCR on early morning sampleACR/PCR on early morning sample

Non-diabetics ACR >30mg/mmol or PCR >50Non-diabetics ACR >30mg/mmol or PCR >50 Diabetics – microalbuminauria = ACR≥2.5mg/mmol for Diabetics – microalbuminauria = ACR≥2.5mg/mmol for

males (2.5-30)males (2.5-30) = ACR≥3.5mg/mmol for = ACR≥3.5mg/mmol for females (3.5-30)females (3.5-30)

Clinical assessment – ? ImagingClinical assessment – ? Imaging

Ultrasound is 1Ultrasound is 1stst line test for imaging in CKD line test for imaging in CKD SIGN SIGN - “if relevant symptoms”- “if relevant symptoms” NICE NICE - obstuctive symptoms - obstuctive symptoms

- FMHx PKD- FMHx PKD

- progressive CKD (eGFR decline >5 in - progressive CKD (eGFR decline >5 in 1yr, >10 in 5yr),1yr, >10 in 5yr),

- macroscopic / persistant microscopic - macroscopic / persistant microscopic haematuriahaematuria

- stage 4 or 5 CKD- stage 4 or 5 CKD

- being considered for renal biopsy- being considered for renal biopsy

Management of CKD - AimsManagement of CKD - Aims

to minimise progression of CKDto minimise progression of CKD to minimise development of CVDto minimise development of CVD to identify those who with progressive decline in to identify those who with progressive decline in

renal function will develop ESRD in their renal function will develop ESRD in their lifetime.lifetime.

Identify those needing referral to nephrology:Identify those needing referral to nephrology: Significant proteinuria (ACR>70mg/mmol, Significant proteinuria (ACR>70mg/mmol,

PCR>100mg/mmol)PCR>100mg/mmol) Microscopic Haematuria <50yrs (>50yrs to urology)Microscopic Haematuria <50yrs (>50yrs to urology) Advanced CKD – stage 4 or 5Advanced CKD – stage 4 or 5 Functional consequences – e.g anaemia, bone disease, Functional consequences – e.g anaemia, bone disease,

refractory HTNrefractory HTN Immediate referral for ARF, malignant HTN, K Immediate referral for ARF, malignant HTN, K

>7mmol/L, nephritic syndrome.>7mmol/L, nephritic syndrome.

Lifestyle advice in CKDLifestyle advice in CKD

Smoking cessationSmoking cessation ExerciseExercise Weight reduction if high BMI/ abdominal Weight reduction if high BMI/ abdominal

circumferencecircumference Alcohol consumptionAlcohol consumption Low salt diet – but beware salt substitutes with Low salt diet – but beware salt substitutes with

high potassium levels.high potassium levels. Low protein diet only in advanced CKD (stage 4-Low protein diet only in advanced CKD (stage 4-

5) and after dietician assessment.5) and after dietician assessment.

Blood pressure and proteinuria Blood pressure and proteinuria reductionreduction BP should be measured at least once a year.BP should be measured at least once a year. BP should be controlled to slow CKD progression BP should be controlled to slow CKD progression

and reduce proteinuria.and reduce proteinuria. Usual HTN targets of <140/90 mm/Hg for most patients Usual HTN targets of <140/90 mm/Hg for most patients

Target maximum of 130mm/Hg systolic (& Target maximum of 130mm/Hg systolic (& 80mm/Hg diastolic) for patients with ACR 80mm/Hg diastolic) for patients with ACR >70/PCR>100mg/mmol, or for diabetics with >70/PCR>100mg/mmol, or for diabetics with microalbuminuria.microalbuminuria.

Any reduction in proteinuria in CKD reduces the Any reduction in proteinuria in CKD reduces the relative risk of disease progressionrelative risk of disease progression there should be no lower target as the greater the there should be no lower target as the greater the

reduction from baseline, the greater the effect on slowing reduction from baseline, the greater the effect on slowing reduction in GFR.reduction in GFR.

Blood pressure and proteinuria Blood pressure and proteinuria reductionreduction ACEi and ARBs offer both cardio- and ACEi and ARBs offer both cardio- and

renoprotective effectsrenoprotective effects Dilatation of the efferent renal arteriole reducing Dilatation of the efferent renal arteriole reducing

intraglomerular pressure and reducing proteinuria intraglomerular pressure and reducing proteinuria independent of systemic blood pressure effects.independent of systemic blood pressure effects.

ACEi can prevent the development of diabetic ACEi can prevent the development of diabetic nephropathy.nephropathy.

Both reduce albuminuria and progression from Both reduce albuminuria and progression from microalbuminuria to macroalbuminuria in diabetics.microalbuminuria to macroalbuminuria in diabetics.

Both reduce proteinuria in non-diabetics.Both reduce proteinuria in non-diabetics. Diabetics with microalbuminuria should be treated Diabetics with microalbuminuria should be treated

with an ACEi or ARB irrespective of BP.with an ACEi or ARB irrespective of BP. In non-diabetics with CKD and protienuria, ACEi or In non-diabetics with CKD and protienuria, ACEi or

ARB are the agents of choice to reduce proteinuria ARB are the agents of choice to reduce proteinuria & progression of CKD.& progression of CKD.

Blood pressure and proteinuria Blood pressure and proteinuria reductionreduction Some evidence that the beneficial effect of ACEi and Some evidence that the beneficial effect of ACEi and

ARBs may also apply to people with CKD without ARBs may also apply to people with CKD without diabetes or proteinuria, but NICE conclude not strong diabetes or proteinuria, but NICE conclude not strong enough to recommend these over other enough to recommend these over other antihypertensives.antihypertensives.

Commencing ACEi/ARBs:Commencing ACEi/ARBs: Before starting check creatinine, eGFR and K.Before starting check creatinine, eGFR and K. Check again 1-2 weeks after starting and after each dose Check again 1-2 weeks after starting and after each dose

change.change. A fall in eGFR of ≤25% is acceptable/good – suggests they are A fall in eGFR of ≤25% is acceptable/good – suggests they are

working.working. A fall in eGFR of >25% from pre-treatment level may indicate A fall in eGFR of >25% from pre-treatment level may indicate

renal artery stenosis, also stop if K>6mmol/l.renal artery stenosis, also stop if K>6mmol/l. Some evidence that non-dihydropyridine calcium Some evidence that non-dihydropyridine calcium

channel blockers may also reduce proteinuriachannel blockers may also reduce proteinuria Should be considered for those intolerant of ACEi/ARBsShould be considered for those intolerant of ACEi/ARBs

Cardiovascular prophylaxisCardiovascular prophylaxis

Risk assessment as for patients without CKD.Risk assessment as for patients without CKD. Statin for 10yr CVD risk >20%.Statin for 10yr CVD risk >20%. Antiplatelet therapy Antiplatelet therapy

NICE: no mention for primary preventionNICE: no mention for primary prevention SIGN: should be considered for stage 1-3 for 10yr CVD SIGN: should be considered for stage 1-3 for 10yr CVD

risk>20%risk>20%

Other considerationsOther considerations

Complications to be aware of:Complications to be aware of: Anaemia – monitor Hb in Stages 3(B) – Stage 5, Anaemia – monitor Hb in Stages 3(B) – Stage 5,

consideration for EPO.consideration for EPO. Renal bone disease - stage 4-5, tends to be evaluated in Renal bone disease - stage 4-5, tends to be evaluated in

2dry care.2dry care.

Patient educationPatient education Particularly ‘predialysis psychoeducation’ for those with Particularly ‘predialysis psychoeducation’ for those with

progressive CKD who may eventually need RRT.progressive CKD who may eventually need RRT.

QOFQOF

IndicatorIndicator PoinPointsts

CKD1CKD1 Practice can produce a register of patients >18yrs with Practice can produce a register of patients >18yrs with CKD stage 3-5CKD stage 3-5 66

CKD2CKD2 % of patients on register with record of BP in last % of patients on register with record of BP in last 15months15months 66

CKD3CKD3 % of patients on register with BP in last 15months of % of patients on register with BP in last 15months of 140/85 or less140/85 or less 1111

CKD5CKD5% of patients on register with HTN and proteinuria on % of patients on register with HTN and proteinuria on ACEi or ARBACEi or ARB

(unless contraindicated or adverse reaction)(unless contraindicated or adverse reaction)99

CKD6CKD6 % of patients on register with record of urinary ACR/PCR % of patients on register with record of urinary ACR/PCR in last 15monthsin last 15months 66

SummarySummary

CKD is Common, under recognised and under CKD is Common, under recognised and under diagnoseddiagnosed

Early identification and treatment can slow Early identification and treatment can slow progression of CKD and also reduce associated progression of CKD and also reduce associated increased risk of CVD.increased risk of CVD.

Questions?Questions?