Transcript Understanding & Interpreting eGFR – are we doing the right

“ Understanding Chronic Kidney
Disease in General Practice”
Dr Emma Dunn
Consultant Nephrologist
Leeds Teaching Hospitals NHS Trust
• Background to CKD initiative – NSF and NICE
• eGFR
• Management of CKD in primary care
• Who to refer
• Renal anaemia/ bone disease
CKD initiative
Renal registry data 2007
Renal registry data 2008
‘Crash Landers’
The National Service Framework
for renal services
‘ to raise profile of renal disease as a chronic disease’
‘ to raise quality of care provided for people with kidney disease’
‘to increase their choice’
‘to minimise the impact of their disease on their lives’
Set 5 standards for care and identified 30 markers of good practice
to be delivered by 2014:
‘ to help NHS and its partners to manage demand’
‘to increase fairness of access and improve choice and quality in
dialysis and kidney transplant services’
Set 4 quality requirements and identified 23 markers of good
practice that aimed to support NHS organisations in:
‘ prevention of chronic kidney disease in people at risk’
‘slowing down progression of the disease’
‘minimising consequences of acute renal failure’
‘extending palliative care to patients on dialysis, or with ESRD who are
near the end of their lives’
National Service Framework for Renal
Services (part 2) – February 2005
1. People at risk of developing or having undiagnosed CKD, especially people
with diabetes or hypertension, must be identified, assessed and their
condition managed to preserve their kidney function.
2. People with a diagnosis of CKD must receive timely, appropriate and
effective investigation, treatment and follow up to reduce the risk of
progression and complications
Patients to be screened for CKD
• Diabetes
• Hypertension
• Cardiovascular disease (IHD, CHF, PVD, cerebrovascular
disease)
• Structural renal tract disease, renal calculi or prostatic
hypertrophy
• Multisystem diseases with potential renal involvement (e.g. SLE)
• Family Hx of stage 5 CKD or hereditary kidney disease
• Opportunistic detection of haematuria or proteinuria
Renal NSF part 2 - CKD
To achieve quality requirements 1 and 2:
1. Prevention and early detection of CKD
2. Minimising consequences and progression of CKD
All laboratories must measure kidney function using a formulabased estimation of glomerular filtration rate (eGFR).
CKD should be described using classification developed for the
Kidney Disease Outcomes Quality Initiative (K/DOQI) which
divides CKD into five stages depending on eGFR.
Classification of Renal Impairment
(K/DOQI)
•
•
•
•
•
Stage
Stage
Stage
Stage
Stage
1 - Kidney damage with eGFR ≥90
2 - Kidney damage with eGFR 60-89
3 - Kidney damage with eGFR 30-59
4 - Kidney damage with eGFR 15-29
5 - Kidney failure eGFR<15 or on dialysis
Classification of Renal Impairment
(NICE)
•
•
•
•
•
•
Stage
Stage
Stage
Stage
Stage
Stage
1 - Kidney damage with GFR≥90
2 - Kidney damage with GFR 60-89
3a - Kidney damage with GFR 45-59
3b - Kidney damage with GFR 30-44
4 - Kidney damage with GFR 15-29
5 - Kidney failure, eGFR <15 or on dialysis
• ‘p’ for proteinuria (ACR ≥30mg/mmol or PCR ≥50mg/mmol)
Why do we need a CKD
initiative?
Because………
1. CKD is bad for you
Outcomes of CKD
• Loss of Kidney Function (kidney failure)
• Complications associated with CKD
- hypertension
- anaemia
- bone disease
- malnutrition
- neuropathy
- decreased quality of life
• Increased Morbidity and Mortality - Cardiovascular disease
ESRD
Survival of patients on dialysis in the UK 10 years after
commencing renal replacement
(Renal Registry Report 2008)
Impact of ESRD on patient’s life
expectancy
Levey et al AJKD 1998;32:853
Renal Registry Report 2008
Renal Registry Report 2008
Relative risk of death in all prevalent RRT compared with UK general
population in 2007
Renal Registry Report 2008
Cardiovascular disease and CKD
• Life expectancy of patients with ESRD is poor
49 yr old male
Life expectancy (years)
General population
Prostate cancer
Colon cancer
ESRD
29.8
12.8
8.6
7.1
• Majority of premature death due to CVD (CVA, IHD,
Heart Failure)
Causes of death in UK dialysis patients
Renal Registry 2008
CKD patients (pre-ESRD)
CKD and cardiovascular risk
Age-standardised rate of cardiovascular events
(per 100 person-y)
36.60
40
35
30
21.80
25
20
15
11.29
10
5
2.11
3.65
0
≥60(1&2) 45–59 (3A) 30–44 (3B)
15–29 (4)
<15 (5)
Estimated GFR (ml/min/1.73 m2)
No. of events
73,108
NEJM 2004; 351: 1296
34,690
18,580
8809
3824
CKD and cardiovascular risk
Age-standardised rate of death
from any cause (per 100 person-y)
16
14.14
14
11.36
12
10
8
6
4.79
4
2
0.76
1.08
0
≥60(1&2) 45–59(3A)
30–44 (3B)
15–29 (4)
<15 (5)
Estimated GFR (ml/min/1.73 m2)
No. of events
25,803
NEJM 2004; 351: 1296
11,569
7802
4408
1842
Outcomes of patients with chronic kidney
disease
Arch Intern Med 2004;164:659-663
}1.1%
}1.3%
Kaiser Permanente health plan, Oregon USA
~28000 patients identified as having CKD
(recorded eGFR <90ml/min on 2 separate occasions at least 90 days apart)
5 year follow-up (1996-2001) -
from time of initial eGFR
estimation until required RRT, died, or disenrolled from health plan
}19.9%
Outcomes of patients with chronic kidney
disease
Arch Intern Med 2004;164:659-663
New Opportunities for Early Intervention by Computerised Assessment
(NEORICA)
Kidney International 2007;72:92-99
Because………
1. CKD is bad for you
2. CKD is common
UK Prevalence of CKD
NEOERICA project – primary care Manchester, Kent and Surrey
N=162,113
Age standardised prevalence of stage 3-5 CKD 8.5%
KI 2007,72:92-99
CKD: A Typical GP Practice of 10000
eGFR
15
Typical 10,000 GP Scenario
6 Stage 5
60
Stage 4
30
380
60
90
Stage
3a&3b
Stage 2
460
Stage 1
Because………
1. CKD is bad for you
2. CKD is common
3. Often asymptomatic in early stages,
but evidence shows that early
intervention reduces risk of
progression of early CKD to ESRF and
reduces CV risk
Diagnosing kidney disease
Screening for renal disease
Easy Assessment
• Serum Creatinine
Easy Assessment
• Serum Creatinine
but has LIMITATIONS
Creatinine and renal function
1000
115
80
0
50
% of renal function
100
Effect of Muscle Mass on Serum Creatinine
Normal
Muscle
Mass
Normal
Muscle
Mass
Increased
Muscle
Mass
Reduced
Muscle
Mass
Creatinine
Input
Plasma
Pool
Content
Output
Kidney
Normal
Kidneys
Diseased
Kidneys
Normal
Kidneys
Diseased
Kidneys
Creatinine 120 Weight 45kg
Creatinine 120 Weight 105kg
Age 75 yrs GFR 30mls/min
Age 35 yrs GFR 113mls/min
Complex assessment
• Isotopic measurement of GFR
• Gold standard, but unsuitable for screening
• Important if split function required
•
Graph = Isotopic Glomerular Filtration Rate
eGFR
eGFR
Cockcroft-Gault Equation
Crcl (ml/min) = (140-age [years] x weight [kg])x1.23(x0.85 if female)
Serum Creatinine (micromol/l)
Abbreviated (four variable) MDRD Equation
GFR (ml/min/1.73m2) = 186 x (SCr)-1.154 x (age)-0.203 x (0.742 if female)
x (1.210 if African American)
Modification of Diet in Renal Disease
(MDRD) equation
• Derived from 1628 patients with clinically diagnosed CKD ( stage
3-4 CKD)
• eGFR ~ age, creatinine, gender,race
• Results standardised to BSA of average adult (1.73m2)
• Consistently performs well against gold standard
• Superior to Cockcroft-Gault or 24 hour urine collections
• Good internal consistency
– Useful to track changes over time
Limitations of eGFR
• Accuracy - it is estimated
90% of eGFRs are within 30% of true value
– So 15 could be anywhere between 12-20
– So 60 could be anywhere between 42-78
• More accurate for estimating low GFR
– US, Australia & Scotland only report >60
– UK report up to 89
Limitations of eGFR
Largely related to problems with creatinine
• Product of muscle metabolism – can not be used to assess renal
function in:
•
•
•
•
•
Malnourished / anorectics
Body builders
Children
Pregnant women
Amputees
• Tubular secretion and gi excretion increase at low GFR
- so underestimates severe renal failure
• Trimethoprim and cimetidine block tubular secretion
Limitations of eGFR – variation in serum
creatinine
– Laboratory assay
– Biological variation
(intra-individual variation in serum
creatinine concentration can be up to 5%)
– Fluid status
– Diurnal variation (serum creatinine level peaks at 19:00 hrs)
– Delays in centrifugation of blood (>10 hours associated
with increase in serum creatinine)
– Cooked Meat
Limitations of eGFR – variation in serum
creatinine
• Ingestion of cooked meat meal increases serum
creatinine level
• Absorption of serum creatinine from gut
(converted from muscle creatine by cooking process)
• Can cause significant increase in serum creatinine
(36-65% increase 2- 4 hours postprandially)
• Advise patients not to eat any cooked meat in the 12
hours before having blood test for eGFR
Influence of age on renal
function
What is physiological?
What is ‘disease’?
Influence of age on renal function
• West Lincolnshire PCT
• Adult population 185 434
• 40 GP practices – 109 GPs
• All routine serum creatinine samples
measured on population over 18month period
(2005-6)
Age
(years)
Number tested
(% population)
CKD3
CKD4
<20
688
(4.6%)
0
0.1
0
20-29
1989
(7.1%)
0.2
0.5
2.9
30-39
3159
(10.5%)
0.9
1.4
6.8
40-49
5466
(17.3%)
2.9
2.4
9.2
50-59
8461
(28.9%)
9.3
4.2
11.6
60-69
10905
(45.5%)
21.9
10.6
20.8
70-79
10064
(59.1%)
33.8
30.6
27.1
>80
6387
(60.8%)
31.1
40.0
21.7
(% population) (%population)
CKD5
(%population)
NDT 2008 23:556-561
Management of CKD in
primary care
Aims of Management of CKD patients
•
Slow progression
– hypertension
– proteinuria
•
Manage cardiovascular risk
– hypertension
– proteinuria
– statins/aspirin
•
Manage renal-specific complications/risks
– anaemia
– bone disease
– Diet
•
Prepare for renal replacement therapy / conservative management
Importance of slowing progression
Proteinuria
PROTEINURIA
MAP 107mmHg
MAP 92mmHg
Klahr et al. MDRD study NEJM 1994
Fig 1 Time to clinical outcomes by proteinuria and kidney dysfunction
Tonelli, M. et al. BMJ 2006;332:1426
Copyright ©2006 BMJ Publishing Group Ltd.
Fig 2 Adjusted risk of all cause mortality according to proteinuria and kidney dysfunction
Tonelli, M. et al. BMJ 2006;332:1426
Copyright ©2006 BMJ Publishing Group Ltd.
Screening for Proteinuria
Proteinuria
Urine dipstick - limitations
– rely on estimation of protein concentration
(dependent on urine flow rate)
- influenced by factors other than degree of proteinuria
e.g. false +ve: dehydration, exercise, infection,
alkaline urine
false –ve: excessive hydration
- predominantly sensitive to albumin not to total protein
Proteinuria
Current NICE guidelines
Use ACR in preference to PCR or urine dipstick to detect and quantify
proteinuria in patients with CKD
If ACR <70mg/mmol or PCR<100mg/mmol confirm with emu sample
Indications for renal referral
ACR≥30mg/mmol or PCR≥50mg/mmol in assoc with haematuria
ACR ≥70mg/mmol or PCR≥100mg/mmol in absence of haematuria
N.B. Protein Creatinine Ratio (PCR) is different to Protein Creatinine
Index (PCI)
PCI = PCR x 10
Hypertension
• Well established that treatment of hypertension
reduces CVD risk and slows progression of renal disease
• Now looking for “extra value”
– blockade of renin / angiotensin / aldosterone
Guidelines for BP in Renal Disease
• Renal Association
– 125/75 for CKD patients with proteinuria
– 130/80 for non-proteinuric CKD patients
– ACEi/ARB as first line
• NICE guidelines
- Aim to keep SBP <140 (target range 120-139)
DBP <90
- Diabetic patients with CKD or proteinuria aim to keep
SBP <130 (120-129) and DBP <80
- Offer ACEi and ARB if proteinuria (microalbuminuria in
diabetes)
Antihypertensive agents
•
Anti-proteinuric effect of ACEi and ARBs are equivalent
•
Combination of ACEi/ARB is more anti-proteinuric than ACEi or ARB
alone
•
Non-dihydropyridine calcium channel blockers – diltiazem and verapamil
have significant anti-proteinuric effects
•
Dihydropyridine calcium channel blockers – amlodipine, nifedipine have
no significant effect on proteinuria
•
Sympathetic blockers e.g. methyldopa have little effect on protein
excretion
•
Beta blockers, diuretics and alpha blockers usually have a lesser antiproteinuric effect
Aims of Management of CKD 3-5
patients
• Slow progression
– hypertension
– proteinuria
• Manage cardiovascular risk
– hypertension
– proteinuria
– Statins/aspirin
Effect of statins compared with placebo on cardiovascular
events in pre-dialysis patients
• Meta-analysis included 26 trials of patients with CKD (n=~ 19000)
• Significant reduction in total and LDL cholesterol and proteinuria
• 20% reduction in risk of all cause mortality, cardiovascular mortality
and non-fatal cv events
• No increase in adverse events
Monitoring
• Check eGFR
•
•
•
•
- annually in all at risk groups
- during intercurrent illness
Stage 1 & 2 – 12 monthly
Stage 3a & 3b – 6 monthly
Stage 4 – 3 monthly
Stage 5 – 6 weekly
Management of CKD in primary care
•
Address CV risk factors
•
Avoid or minimise nephrotoxic drugs
•
BP control
-
Aim to keep SBP <140 (target range 120-139), DBP <90
-
Diabetic patients with CKD or proteinuria aim to keep SBP <130 (120-129) and DBP <80
-
Offer ACEi and ARB if proteinuria (microalbuminuria in diabetes)
•
Regular monitoring –
•
Immunization – influenza, pneumococcal
•
Refer to renal team if progressive decline in renal function etc.
stage
1&2 – annual
3 - 6 monthly
4 – 3 monthly
5 – 6 monthly
Summary
• Identification of patients with CKD is important
• Greatest risk for CKD patients is CVD
• Hypertension management is important, and part of a
general CV disease management protocol
• Proteinuria is important prognostic indicator for renal and
cardiovascular risk
• Angiotensin blockade (ACEi/ARB) is superior to other
antihypertensives
• Targets are <140/90 or <130/80 in proteinuric/diabetic
(high risk) patients
Who to refer?
If eGFR <60ml/min
•
Review previous creatinine/eGFR to assess rate of deterioration
•
Repeat bloods within 1-2 weeks to exclude rapid progression if new finding
•
Review medication, particularly recent additions
•
Assess patient – urinary symptoms, palpable bladder, BP, hypovolaemia, heart
failure, systemic symptoms
•
Dipstick urine for blood and protein, send for ACR/PCR
•
Bloods – FBC, calcium, cholesterol, HbA1c
•
Renal USS
•
Review need to refer for further assessment
Proteinuria
CKD - Who to refer?
•
Malignant hypertension
•
Hyperkalaemia (K+ >7mmol/l)
•
Nephrotic syndrome
•
Suspected underlying systemic illness
•
Uncontrolled BP despite multiple (4) agents
•
Isolated proteinuria (PCR >100mg/mmol, ACR >70mg/mmol)
•
Haematoproteinuria (PCR>50mg/mmol, ACR >30mg/mmol)
•
Declining eGFR >5-10ml/min/year
•
Renal anaemia
•
Stage 4 & 5 CKD (if appropriate)
•
Suspected renal artery stenosis
•
Diabetic patients with atypical features
Indicators of non-diabetic renal disease
•
Absence of retinopathy (especially in type 1DM)
•
Sudden rapid onset of significant proteinuria (urine ACR>70mg/mmol)
- duration of DM <5 years
- abnormal evolution without transition through usual stages
•
Macroscopic haematuria
•
Rapid decline in renal function or renal dysfunction without significant
proteinuria
•
>25% decline in eGFR post ACEi/ARB (RAS)
•
Atypical biochemical/serological abnormalities
Guidelines
• Multiple sources – difficult to weigh thoroughness
against usefulness - among the best are from renal
association (www.renal.org) and follow the links
• www.ckdonline.org
• www.nice.org.uk/guidance
Renal Anaemia
• Very unusual to develop unless stage 4-5
Renal Anaemia
• Very unusual to develop unless stage 4-5
• Exclude other possible causes
• Optimise iron levels (ferritin 150-500,
% hypochromic red blood cells <6%)
• Consider erythropoietin if remains anaemic
despite being iron replete
RENAL BONE DISEASE
• Management aims to prevent development of:
– metabolic bone disease
– established hyperparathyroidism and parathyroid hyperplasia
• Prevalence of vitamin D deficiency increases with age
– 24% women aged >75 years are deficient
• NICE guidelines – routine measurement of calcium,
phosphate and PTH not required in patients with
stage 1-3b CKD, but to be measured in stage 4/5.
RENAL BONE DISEASE
• If concerns about vitamin D deficiency (diet/sunlight
exposure/race/age) – check calcium and vitamin D
levels and replace with cholecalciferol or
ergocalciferol if vitamin D deficient.
• In stage 4/5 if PTH ≥3x upper limit of normal –
indicator of secondary hyperparathyroidism, but
intervention depends on calcium and phosphate level
(i.e. is individual to specific patient)
[email protected]