chronic kidney disease and aki an update...the burden of ckd to the nhs •chronic kidney disease is...
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Chronic Kidney Disease and AKI – an update
Dr Simon Roe
Consultant Nephrologist
April 2015
CKD and AKI
• CKD-
– Definition
– Risk Factors
– NICE Guidance- What’s new 2014
– eGFR measurement- limitations and interpretation
– Diagnosis and who to test
– When to do renal USS
– GFR Categories
– Progression
– Management • Including General rules, Lifestyle and Pharmacotherapy
• AKI-
– Definition
– Risk factors
– Recognising risk
– Rules for management (incl. sick day rules)
• Why is CKD important
• 2014 NICE CKD guidelines – what’s new
• Management of CKD
• AKI – what’s the relevance for primary care
Outline
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 (without decreased GFR) for ≥3 months:
• albuminuria
• haematuria after exclusion of urological causes
• structural abnormalities
What is CKD?
The Burden of CKD to the NHS
• Chronic Kidney Disease is an epidemic worldwide – 8.5% people in UK have CKD
• 1.3% of all NHS spending is on CKD
– 50% of this goes on the 2% of the CKD population that require dialysis and transplantation
• Overall RRT incidence rate stabilised at 108 pts/million/yr
• Late presentation rates have dropped from 24% to 19% over the last 6 years (but still show variability 13-23% for EM units)
Causes of Established Renal Failure
Uncertain15%
GN14%
Pyelo7%Diabetes
25%Vascular5%
Polycystic 8%
Other18%
Hypertension8%
UK Renal Registry 2014 report
Primary diagnosis in UK patients who started dialysis in 2013
Diabetes and hypertension/ vascular diseases are
leading causes of ESRD
People at increased risk of CKD
Eight major risk factors for CKD
Diabetes
High blood pressure
Age over 60 years
Smoking
Obesity
Family history of kidney disease
Ethnic minorities
Established cardiovascular disease
95% of patients with CKD 3 are also on hypertension, diabetes or CHD registers
Variability in Care
• Evidence based guidelines exist for managing CKD in primary care but evidence of inconsistency of care
– Variation in CKD prevalence
– Variability in achievement of key treatment priorities
– BP QOF vs NICE targets
– Variation in late presentation
How much of this variability is unwarranted?
CKD Prevalence by CCG
____England
NICE guidelines 2014 – what’s new?
• Investigations for CKD – Enzymatic creatinine assay
– use CKD-EPI equation to estimate GFR
– Cystatin C to confirm stage 3A CKD
• Revised classification – GFR and ACR categories
• Definition of progression
• Relationship with AKI
Limitations of eGFR measurements
eGFR is an ESTIMATE!!
Increasing uncertainty at values >60ml/min
Based on serum creatinine Measurements subject to variation
eg. recent vigorous exercise, large meat meal, extremes of muscle mass, lab variation/delays, drugs (trimethoprim)
Not valid in AKI, children, pregnancy, dialysis
Always confirm with 2nd blood test
Changes to lab GFR estimating equation
12
Levey AS et al. Ann Int Med 2009;150:604-612
NICE 2014 recommends that labs use the CKD-EPI formula to calculate eGFR instead of the MDRD formula
Advise patients not to eat meat in the 12 hours before a blood test for eGFR
Making a Diagnosis of CKD
• New finding of eGFR <60 – Repeat within 1-2 weeks
– Exclude acute kidney injury
– Review previous U&E results
– Review drugs eg NSAIDS
– Exclude UTI, palpable bladder etc
– Urine dipstick for haematuria
• Send urine for ACR
• Only label as CKD if at least 2 abnormal readings over 3 months
Who to test for CKD?
Offer annual eGFR and ACR if: – Diabetes
– Hypertension
– Previous acute kidney injury
– Cardiovascular disease
– Structural renal disease, stones or BPH
– Family history • Stage 5 CKD or hereditary renal disease
– Haematuria or proteinuria
– Multisystem disease with potential renal involvement
– Monitor GFR in people prescribed nephrotoxic drugs eg lithium, CNI, NSAIDS
When to do a renal ultrasound
• Accelerated progression of CKD
• Visible or persistent invisible haematuria
• Symptoms of urinary tract obstruction
• Family history of polycystic kidney disease and aged over 20
• GFR <30ml/min (GFR category G4 or G5)
• Considered by a nephrologist to require a renal biopsy
GFR Categories in CKD
16
A higher profile for albuminuria
Prognostic significance of abnormal ACR
• Albuminuria was linearly related to events along its entire distribution
• An ACR >3 is not normal and is associated with a higher risk of CKD, AKI, cardiovascular mortality, all cause mortality, even if GFR normal
• These effects are independent of GFR and independent of traditional cardiac risk factors
Blue – normal/ mild ACR Green – moderate ACR Red – severe ACR
Adapted from Levey et al, 2010, Kidney International
Proteinuria and urine A/PCR
• Urine dipstick semi-quantative – Depends on concentration; sticks detect >0.3g/l protein
• Spot urine albumin or protein: creatinine ratio – Good correlation with 24hr urine protein
– ACR more sensitive than PCR at low levels
– Use ACR in diabetes and CKD
– If ACR 3-70mg/mmol confirm with early am sample
Urine Protein
Urine PCR (mg/mmol)
Urine ACR
(mg/mmol)
Category
> 3 Proteinuria
0.5g/day > 50 > 30 Severe proteinuria
> 1g > 100 > 70 Heavy proteinuria
> 3g > 300 > 220 Nephrotic
Integration of GFR and albuminuria when evaluating risk
20
No CKD (88%)
Mild risk (9.2%)
Moderate risk (2%)
High risk (<1%)
Levey, Eckardt, Gansevoort et al, KI 2011
Based on 4 meta-analyses of
45 cohorts with 1.5million
individuals, studying 5 endpoints
Rising currency of Cystatin C
• A low molecular weight cysteine protease inhibitor- produced by all nucleated cells
– Filtered at the glomerulus and not reabsorbed
– Serum concentration mainly determined by GFR
– Inflammation, thyroid disease, and steroids may affect levels
– Less dependent on race and body mass
• Potential uses:
– Confirming stage 3a CKD (eGFR 45-59 ml/min)
• NICE: Consider using Cystatin C to confirm CKD in patients with eGFR 45-59 and ACR <3mg/mmol
• Assessing for CKD in malnourished patients
• BUT not widely available in UK; cost implications
Progression of CKD
• Small fluctuations in GFR are common and not necessarily indicative of progression
• Accelerated progression is defined as:
– a drop in GFR category accompanied by a 25% or greater drop in GFR from baseline over 12 months
– a sustained decline in eGFR of more than 15ml/1.73m2/year
– this group is at increased risk of progression to established kidney failure
Increased confidence in assessing progression with more serum creatinine measurements and longer follow-up
Guide to frequency of monitoring by GFR and albuminuria category
Management of Patients with CKD
• Identify patients with CKD
• Treat reversible causes
• Reduce cardiovascular risk
• Delay progression
• Treat complications
• Dialysis preparation
Patients with CKD are more likely to die than require dialysis
Stage GFR (ml/min) RRT Death
2 60-89 1.1% 19.5%
3 30-59 1.3% 24.3%
4 15-29 19.9% 45.7%
27,998 CKD patients followed for 5 years Keith DS, AIM 2004;164:659-663
CKD is an independent and major risk factor for cardiovascular disease
Outcome for patients with CKD
Life style measures
• Smoking cessation
• Weight management – Target BMI 20 – 25 kg/m2
• Physical activity – At least 30 min 5 days per week
160/95
Adequate BP management delays the progression of CKD
Bakris et al., Am J Kid Disease, 2000
If blood pressure is consistently below target, the GFR loss per year would be reduced by 80%
Management - hypertension
• Treatment target – <140/90mmHg (SBP range 120-139)
• If CKD and diabetes or ACR >70mg/mmol – <130/80mmHg (SBP range 120-129)
• ACE inhibitors first line – Diabetes (microalbuminuria) or proteinuria
– All patients under 55 years
• Calcium channel antagonist or diuretic 2nd line – Thiazide-like if eGFR>30, loop if eGFR<30
Pharmacotherapy
ACE inhibitors/ARBs* should be offered to the following:
ACE inhibitors are first line treatment for all
Change to ARB only if ACE not tolerated
Diabetic Non-diabetic
Non-diabetic
ACR (mg/mmol) >3 >30 >70
PCR (mg/mmol) >50 >100
Need to confirm CKD No Yes Yes
Need to confirm high BP No Yes No
Prescribing ACE I and ARB safely
• Check baseline eGFR and K+ (start if K <5 only)
• Avoid NSAIDs and other K+ drugs if possible
• Avoid combination of ACE and ARB
• Repeat eGFR and K+ 1-2 weeks after initiation and after each increase in dose
• If eGFR/K+ change excessive repeat and ? refer (?RAS)
• Review other causes/drugs; ?stop ACE
• Stop if K+ >6, consider low K diet or loop diuretic
• Allow 30% creatinine / 25% in eGFR
Lipid lowering therapy
• Simvastatin 20mg + ezetimibe 10mg vs placebo
• 9,000 patients CKD and dialysis, 4.9 yrs
• 17% reduction in major atherosclerotic events
• No effect on progression of CKD
• Prevent 30-40 events per 1000 over 5 years
• Well tolerated
Lancet 377: 2181-92, 2011
SHARP Study
Offer atorvastatin 20mg to all patients with CKD (NICE Lipid Guideline 2014)
Optimal glycemic control prevents progression of CKD
32
(>300mg/g)
Study HbA1C goals New ACR
(3-30mg/mmol)
ACR progression
ADVANCE
6.5% vs 7.3%
9% less
30% less
ACCORD
6.3% vs 7.6%
21% less
32% less
VADT
6.9% vs 8.4%
32% less
37% less
Patel A et al. NEJM 2008;358:2560-72 Ismail-Beigi F et al. Lancet 2010;376:419-30 Duckworth W et al. NEJM 2009;360:129-39
Target HbA1C of ~7% (53 mmol/mol) recommended to prevent or delay
progression of diabetic renal disease
Medicines management
• Review medications (eg NSAIDS)
• Trimethoprim may increase creatinine
• Metformin – stop if eGFR <30-40
• Consult BNF or SPC for new medications
• Use eGFR for dose adjustment except at extremes of weight
• Vaccinate - Hep B, pneumonia, influenza
Management - Bone disease
• Use bisphosphonates if indicated in stage 1-3
• Check calcium, phosphate and PTH if eGFR <30
• If PTH high (>2x normal range) check Vitamin D and treat deficiency (25OH Vit D <50nmol/l)
– Stage 3-4 CKD use cholecalciferol
– Stage 4-5 CKD use 1-alfacalcidol
• Dietary phosphate restriction
Management – Anaemia
• More common if GFR <45 or diabetes
• Rule out other causes eg iron deficiency
• Consider Rx if Hb <105-110g/l
• Consider iron deficiency - Ferritin <100µg/l
• Trial of oral iron
• If no response refer for IV iron
• No evidence to support normalisation Hb, ESA/EPO improves QoL
Acute Kidney Injury
-Everybody’s problem
www.thinkkidneys.nhs.uk
What is AKI?
• An abrupt decline in renal function….
• Defined by:
an acute rise in serum creatinine
OR
a fall in urine output
Definition of AKI AKIN Stage Serum creatinine criteria Urine output criteria
1 An increase of more than 26µmol/l above baseline OR An increase of more than or equal to 1.5 to 2 fold from baseline
<0.5mg/kg/hr for at least 6hours
2 An increase of more than or equal to 2 to 3 fold from baseline
<0.5mg/kg/hr for at least 12hours
3 An increase of more than 3 fold from baseline OR Serum creatinine >355 µmol/l with an acute rise of at least 45 µmol/l OR Initiation of RRT
<0.3mg/kg/hr for at least 24 hours OR Anuria for >12hours
2727
782
636
total: 4145
Number of patients per annum sustaining each
stage of AKI in a 1000 bed hospital
Electronic Alerts for AKI
and why does it matter?
• AKI is common
• AKI is serious
• AKI is expensive
• 16-18% of hospital admission
• ↑ mortality/ LOS, ↑ CKD
• Probably > £500M/yr to NHS
AKI is relevant to primary care and all specialities
Porter C, Devonald M. NDT 2014;(0):1-6 • Half to 2/3rds of AKI cases are community derived
• Over 92% of AKI cases are admitted as an emergency
AKI is sub-optimally managed
• AKI avoidable in 14%
• Only 50% received “good care”
• Post admission AKI: poor
recognition and care
• 24% did not receive adequate
senior review
• 85% did not have documented
evidence of critical care outreach
involvement June 2009
AKI in Primary
Care
Prevention
Follow up after AKI
Recognition & management
Cause and risk of AKI
Risk factors
CKD + albuminuria
Diabetes
CCF
PVD
Chronic Liver disease
Previous AKI
Age >75
Triggers Sepsis or infection
Hypovolaemia
Hypotension
Post-op
Iodinated contrast
Medication ACEI/ARB/NSAIDS/diuretics Aminoglycosides
Albuminuria and CKD are both
independent risk factors for AKI
Grams et al, J Am Soc Nephrol, 21: 1757-1764, 2010
Prevention: Recognise the risk
Medicines Management • Medicines reconciliation and review • Sick day rules • IV contrast
Close monitoring • Repeat U+E’s
• During acute illness • After starting high risk medication
Hydration
‘Sick day rules’
Rule 1
Hydration
Rule 3
Avoid NSAIDS
Rule 2
Omit ARB/ACEI/diuretics
(Metformin)
Rule 4
Monitor renal function
Patients & carers
- Consider for patients at increased risk of AKI - Primary & secondary care
Case study
78yrs old female
CKD 3A (baseline 160), CCF, on ramipril, bisoprolol and furosemide
Becomes unwell with symptoms of UTI and vomiting
Scenario 1
Poor oral intake Continues to take medication Seen by out of hrs – Rx trimethroprim Seen by GP D5 – UE’s : Na 149, K6.3, Ur38, Cr 500 Admitted to hospital
Scenario 2 Contacts GP/community matron Keep hydrated ‘Pill holiday’ for 48hrs Rx- amoxycillin/antiemetic UE – Creat 180 GP review 48hrs – Creat 168, clinical improvement
Drugs and AKI
• Very common cause/ contributor to AKI
• Various mechanisms
– Pre-renal (diuretics, ACE-I and ARBs, NSAIDs)
– Direct tubular toxicity (aminoglycosides, contrast agents)
– Interstitial nephritis – “allergic” (antibiotics, NSAIDs, PPIs and many more drugs)
Trimethoprim
Trimethoprim inhibits tubular secretion of creatinine – Increase serum creatinine
Apparent ‘AKI’ – Creatinine normalises after cessation
Hyperkalaemia Less effective at lower eGFR
Management of AKI
Fluid management and resuscitation
Medication review • Stop nephrotoxic medication • Early antibiotics for sepsis
Undertake relevant investigations • Importance of urine dip
Hospital / nephrology referral when needed
CKD Prevalence by Practice
____Prevalence (England) ---- Prevalence (East Midlands SCN)
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
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AKI Causes
54
Pre-Renal/ ATN (70-80% of cases)
Post-Renal Obstruction (5-10% of cases)
Drugs / TIN
Immunological renal diseases
Myeloma
Renal
Effects of ACE, ARB & NSAIDs on renal perfusion in hypovolaemia • Hypovolaemia efferent arteriolar vasoconstriction
maintains glomerular perfusion pressure
• ACE/ARB blocks this effect of angiotensin 2 on efferent arteriole
• Glomerular pressure falls GFR falls
• Prostaglandins cause afferent arteriolar vasodilatation; blocked by NSAIDs
Referral – NICE AKI Guideline Nephrology:
Discuss AKI management with a nephrologist as soon as possible
(and within 24 hours) if one of the following is present:
Potential diagnosis requiring
specialist treatment (for
example, vasculitis or
glomerulonephritis)
AKI with no
clear cause
Inadequate treatment
response
Complications associated with
AKI
Stage 3 AKI
eGFR is less than < 30 ml/min/1.73 m2
after AKI episode
Patients with renal transplant
and AKI
CKD stage 4 or
5
Renal replacement therapy:
Refer adults, children and young people immediately for RRT if any
of the following are not responding to medical management:
Hyperkalaemia Metabolic
acidosis
Symptoms or
complications of uraemia
such as pericarditis or
encephalopathy
Fluid
overload +/-
pulmonary
oedema