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)

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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