Section 1: Epidemiology and CKD

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Section 1 Epidemiology and CKD
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The Problem

• Chronic Kidney Disease is an epidemic worldwide
• Growth 6-8 per annum of dialysis patients
• Accumulating data re possibility of delaying the
  progression of kidney disease, using multiple
  drug and behaviour intervention therapies.
• Under-recognition at earlier stages of kidney
  dysfunction persists
• Late referral
• Lost opportunities for improved patient outcomes
•  

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RRT Modalities
36,542
DOD/0503-04
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Prevalence of ESRF
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Cadaveric Kidney Donors Transplants and End of
Year Kidney Waiting List, UK, 1994-2003
DOD/0503-04
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Patients Accepted in the UK for Renal Replacement
Therapy
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Incident Rates by Primary Diagnosis (per million
population, unadjusted)


USRDS, 2000
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Obesity Trends UK
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Life expectancy UK
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Section 2 Measurement of Kidney Function
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What Tests Are Available?
Accurate

• Direct GFR measurement
• Inulin clearance
• Radionuclides
• Iohexol clearance
• 3 hr CrCl with Cimetidine
• Prediction equations
• Cystatin C
• 24 hr urine CrCl
• Serum creatinine

Inaccurate
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Gold Standards

• Inulin clearance
• Tedious, time consuming unavailable
• Radionuclides
• 125Iodine-iothalamate, technetium DTPA,
  51Chromium-EDTA clearance
• Time consuming and expensive
• Research, accurate drug dosing

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Serum Creatinine Problems

• Non-renal influences
• Gender, ethnicity, age and muscle mass
• Nutrition/diet
• Drugs (e.g. cimetidine)
• Clinical utility
• Poor sensitivity for CKD
• Not useful in ARF
• Muscle wasting disorders and amputees
• Analytical problems
• Non-specificity (protein, ketones, ascorbic acid)
• No international standardization
• Spectral interferences (icterus/lipaemia/haemolysi
  s)

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Serum CreatinineHides Early Renal Damage
600
400
Serum creatinine (µmol/L)
200
Proportion misdiagnosis
0
GFR (mL/min/1.73m2)
Reproduction from the late David Newman
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Glomerular Filtration Rate

• Sum of all nephron filtration rates
• Best index of overall function
• Reduction implies a problem
• Translatable concept
• Equates to percentage Kidney function

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GFR Prediction Equations

• Cockcroft-Gault formula
• Ccr (ml/min) 1.23 x (140-age) x weight/Pcr
• (x 0.85 if female)
• MDRD Study equation
• GFR (ml/min/1.73 m2) 186 x
  (Pcr)/88.4-1.154 x (age)-0.203 x (0.742 if
  female) x (1.210 if African American)

Cockcroft Gault. Nephron 1976 16 31-41 Levey
AS, et al. Ann Intern Med 1999130 461-70
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MDRD equation vs serum creatinine
220 200 180 160 140 120 100 80
220 200 180 160 140 120 100 80
Females
Males
sCr (µmol/L)
79.4
98.4
sCr (µmol/L)
27.7
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30 40 50 60
30 40 50 60
eGFR (ml/min/1.73m2)
eGFR (ml/min/1.73m2)
Middleton et al 2004
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Scatter Increases as GFR Approaches
Physiological Levels
Froissart et al JASN 200516763-773
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MDRD Formula validation
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Section 3CKD classification and prevalence
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Estimates of Prevalence of CKD in the US NHANES
III
Adapted from Am J Kidney Dis 2002 39 (2, Suppl.
1) S17-S31
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Stages of CKD by GFR
It is helpful to think of GFR (mL/min/1.72m2)
as an approximation of Kidney function
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Prevalence CKD
Stevens et al, EDTA-ERA Lisbon 2004
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CKD A Typical GP Practice of 10000
5
6
15
4
60
Stage of Kidney Disease
30
(GFR)
380
3
60
2
460
90
1
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Section 4 CKD, CVD and mortality
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Cardiovascular diseases in CKD patients
Damage to the heart (Uraemic cardiomyopathy)
Damage to the arteries (Uraemic arteriopathy)
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Cardiovascular Mortality
Annual mortality ()
100
Dialysis
10
General population
1
0.1
Male
Female
0.01
Black
White
2534
4554
6574
?85
3544
5564
7584
Age (years)
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Synergistic effect of CKD,CHF andAnemia as risk
factors for Death
2 yr mortality (n 200,000 5 Medicare sample)

Collins, Adv studies in Med 2003
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Cardiovascular Mortality Rates are Higher among
Dialysis Patients
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CKD predicts CV events HOPE study
n908
Events per 1000 person years
n8307
Creatinine Creatinine 124 µmol/l
HOPEHeart Outcomes and Prevention Evaluation
study
Mann et al. Ann Intern Med 2001134629636
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Cause of death in dialysis patients
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CKD OutcomesMortality and Dialysis
27,998 CKD patients followed for 5 years
Keith DS, AIM 2004164659-663
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Prevalence of Co-morbidity and Level of GFR
GFR GFR ?60 ml/min

DM
CHF
Stroke/TIA
PVD
Any CVD
IHD
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Section 5 Managing progression of CKD
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The downward spiral
Glomerulosclerosis
RENAL FUNCTION
Reduction in number of functioning glomeruli
Intraglomerular hypertension
Increased blood flow to remaining nephrons
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Hypertension and Progression
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Systolic Blood Pressure and Progression of CKD
AIPRD Study Group
5569 records with non-diabetic kidney disease
Meta-analysis of 11 RCTs of ACEIs
RR
Systolic BP (mmHg)
Jafar et al, Ann Intern Med 2003139244-252
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Blood Pressure and Progression of CKD AIPRD
Study
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Number of Medications to reach target blood
pressure
Bakris et al AJKD 2001
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Renal disease dilated afferent arteriole allows
transmission of high systemic pressure leading to
glomeular capillary hypertension
MAP
Anti-hypertensives reduce MAP
GCP
ACEI/ARBs dilate the efferent arteriole the
downstream pressure valve thus controlling
glomerular capillary hypertension
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AIPRI Reduction of Risk with ACE-I
Proteinuria
Creatinine Clearance
Maschio G, et al. N Engl J Med.
1996334(15)939-945.
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Urine Protein Excretion and CKD Progression
AIPRD study group
RR
4685 records with non-diabetic kidney disease
Meta-analysis of 11 RCTs of ACEIs
Urine protein excretion (g/day)
Jafar et al 2003
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Proteinuria and ESRF
Proteinuria Screened ESRF
10,000 38
86,253 185
4007 55
1072 76
357 55
Iseki et al KI 2003
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Urine Protein Excretion and Progression of CKD
AIPRD Study Group
4685 records with non-diabetic kidney disease
Meta-analysis of 11 RCTs of ACEIs
RR
Urine protein excretion (g/day)
Jafar et al, Ann Intern Med 2003139244-252
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Proteinuria and Progression of CKDREIN Study
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Optimal ManagementSaves Patients from Dialysis

• Renoprotective strategies that decrease the rate
  of GFR decline also delay ESRD

Comparison is with expected rate of GFR decline
(7.56 mL/min/1.73m2)
Adapted from Trivedi et al. Am J Kidney Dis 2002
17371-375
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Section 6 Configuration of healthcare to manage
CKD
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The Renal NSF Part 1

• Standard 1 Patient centred service
• Standard 2 Preparation and choice
• Standard 3 Elective Dialysis access surgery
• Standard 4 Dialysis
• Standard 5 Transplantation

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The Renal NSF Part 2

• Quality requirement 1 Prevention and early
  detection of chronic kidney disease (CKD)
• Quality requirement 2 Minimising the progression
  and consequences of CKD
• Quality requirement 3 Acute renal failure
• Quality requirement 4End of life care

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Early Identification
Treat Complications
Delay Progression
Modify Co-morbidity
Prepare for RRT
Education Modality Choice Access Placement Timely
initiation Transplant Work-up
BP Control BM Control Ace Inhibitors Diet Relief
Obstruction Angioplasty
Anaemia Bone disease Acidosis Malnutrition
Statins Anti-Platelet Life Style
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Management of CKD
Think/Report eGFR
Early Detection of CKD
Early Detection of CKD
CKD chronic kidney disease RRT renal
replacement therapy
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NEOERICA percentage recording of creatinine and
prevalence of Stage 35 CKD by age
Patients ()
80
70
60
50
40
30
20
10
0
1524
2534
3544
4554
5564
6574
7584
85
Age groups
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Source of Late Referrals Lamiere - NDT 1999
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SILO MANAGEMENT
NEPHROLOGISTS
DIABETOLOGISTS
GEN. PRACTICE
CARDIOLOGISTS
GEN. MEDICINE
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SILO MANAGEMENT
INTEGRATED MANAGEMENT
CHRONIC DISEASE MANAGEMENT
DIABETOLOGISTS
GEN. PRACTICE
CARDIOLOGISTS
GEN. MEDICINE
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CKD An Overall Health Approach
Complications
GFR
Kidneyfailure
Damage
Increasedrisk
Normal
DEATH
CKD risk factorreduction, screening for CKD
Diagnosisand treatment, treatcomorbid
conditions,slow progression
Estimate progression,treatcomplications,
prepare for replacement
Replacementby dialysisand transplant
Screeningfor CKDrisk factors
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Cardiac Kidney Diabetes
Anti coagulationAnti arrhythmicsMedical
treatment of CHF
CKD Stage 1, 2,3 EducationBlood
pressureSmoking cessationLipid
controlMedicines ManagementDiet
adviceExercisePsychosocial support
CKD Stage 4 AnaemiaAcidosisBone
diseasePreparation/choice
Glycaemic control
DM
CHD
Complicationseyesfeetkidney
CKD Stage 5 RRTPDHPTp
RadiologySurgical interventions
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Renal disease A new algorithm
CHD
Management of vasculopathy
Renal Disease
Diabetes
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CKD IN PRIMARY CARE AS IT IS NOW
Patient
GP Investigation Abnormal kidney function stage
3-5 CKD
Primary
Referral for advice
Other specialty (especially diabetes)
Chronic disease management
Secondary
Renal replacement therapy
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AS IT WILL BE
Patient
GP Investigation Abnormal kidney function stage
3-5 CKD
Chronic disease management
Primary
(guidelines)
guidelines
Stage 4 CKD preparation for RRT
Referral for renal advice
Secondary
Other specialty (especially diabetes)
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Structured delivery of care
Intensive Management
ARF Stage 5
Increasing Level Of Care Needed
Hospital Based Care
Stage 4 Unstable 3 Immunosuppressed
Community based care
Stage 4 (stable) Hypertension
Stable Stage 3
Stage 1 or 2 At Risk Populations
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The new QOF indicators
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Section 7 Gallery

• To illustrate talks on CKD

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11th May 2006
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Front page PULSE April 21st 2006
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Serum Creatinine 150umol/L
51 mL/min
32 mL/min
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Serum creatinine 200umols/l.
GFR 5mls/min
GFR 55mls/min
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Atherosclerotic renovascular disease (ARVD)
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Known CKD Unrecognised CKD 10 of population
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CKD Its out there somewhere
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Section 8 Management in primary care

• Particular emphasis on nurse practitioners role

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Introduction of eGFR

• Will facilitate early recognition of CKD
• Will result in increased awareness of advanced
  CKD previously not recognised as such

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Effects of age on eGFR

• The normal eGFR is age-related
• In normal healthy individuals, the eGFR will
  fall by one percent for every year after 40 years
  of age
• An 80 year old man will have an expected eGFR of
  50-60 ml/min
• Not all patients with reduced eGFR need active
  management

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Which individuals with abnormal eGFR should we
to worry about?

• Those with very poor function for age
• Those with deteriorating function
• Those who may have reversible/treatable cause
  (unexplained proteinuria/haematuria)
• Those with functional consequences of CKD
  (anaemia, renal bone disease, persistent
  hyperkalaemia)

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What is deteriorating function?

• Average fall in eGFR of 4 ml/min/year
• OR
• Rise in creatinine of
• 10 per year in Stage 3
• 15 per year in Stage 4

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Therapeutic intervention in CKD

• Advice to reduce cardiovascular risk (weight,
  smoking, diet, lipids etc)
• Tight BP control (more stringent target if PCR
  100)
• ACE-inhibitors (check eGFR and K 7-10 days later)

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Monitoring of CKD

• Each assessment should include
• Review of symptoms and fluid status
• Blood pressure
• Medication review (metformin, NSAIDs)
• Urinalysis (PCR if protein )
• Blood test for renal and bone status
• FBC in advanced CKD

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Frequency of monitoring
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What data is required for effective referral?

• Current creatinine and eGFR
• Previous creatinines (tracing back to last
  normal)
• Blood pressures (recent and historical)
• Urine dip result (PCR if proteinuria)
• FBC, Ca, Pi
• Renal US (required only if stage 4/resistant
  HT/lower tract symptoms)

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Decisions in renal replacement

• Pre-dialysis care
• Active treatment- Peritoneal dialysis (PD)-
  Haemodialysis (HD)- Transplantation
• Conservative (non-dialytic) care. Symptom
  management.