CKD: Does it really matter?

Richard SmithConsultant Nephrologist

KIDNEYS

Significant biochemical changes have no ‘immediate’ clinical correlate

Therefore for CKD(3) and AKI clinical awareness is essential

Recognise the patient at risk

Recognise the risk associated with CKD(3):Confers significant cardiovascular risk and risk of AKIProgression to RRT is rare (1.3%)Progression to worse CKD (and therefore worse cardiovascular risk) is common

The talk in one slide: Risk management

RRT

60

50

40

30

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eGFR

CKD3CKD3

CKD4CKD4

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CKD: Does it really matter?

RRT

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50

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eGFR

CKD3

CKD4

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CKD3: Does it really matter?

RRT

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eGFR

CKD3

CKD4

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CKD3: Does it really matter?

RRT

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eGFR

CKD3

CKD4

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CKD3: Does it really matter?

Mrs MA 74 year old eGFR 46ml/min/1.73m2

Dipstick of urine revealed + protein

Serum electrophoresis revealed a paraprotein with urinary BJP

May be flag for significant underlying disease

Haematuria and proteinuria are flags for further investigation

Relevant at all ages

Risks associated with CKD

Cardiovascular Risk

(N=1,120,295)

1.0

1.4

2.0

2.8

3.4

Ha

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1

2

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Reduced kidney function is associated with a higher risk of CV events

≥60 45-59 30-44 15-29 <15

eGFR (mL/min/1.73m2)

Go et al. N Engl J Med 2004 351: 1296–1305 Tonelli et al. J Am Soc Nephrol 2006 17: 2034–2047Eeg-Olofsson et al. J Internal Medicine 2010 268: 471–482 Khaw Nature Reviews Endocrinology 2009 5: 130-131

8.0-8.9

9.0-9.9

CKD3

Age-related glomerulosclerosis is amplified by systemic atherosclerosis

Kasiske BL. Kidney Int 1987; 31: 1153-1159

Risk factors for cardiovascular disease

Risk factors for chronic kidney disease

Hypertension

Smoking

Obesity

Diabetes

Dyslipidaemia

Reduced GFR

Proteinuria

Hypertension

Smoking

Obesity

Diabetes

Dyslipidaemia

Atherosclerosis

Heart failure

Patients with CKD are more likely to die than require dialysis

Kaiser Permanente, Oregon: 27,998 CKD patients followed for 5y

Stage GFR RRT Death

2 60-89 1.1% 19.5%

3 30-59 1.3% 24.3%

4 15-29 19.9% 45.7%

Keith DS. Arch Intern Med 2004; 164: 659-663

SHARP: Major Atherosclerotic Events5-year benefit per 1000 patients

http://www.ctsu.ox.ac.uk/~sharp/

Risks associated with CKD

Acute Kidney Injury

Mr PS 80 year old ‘Stable’ IHD Not diabetic No ACEI

Acutely SOB with possible rigor

Few crackles L base

Clarithromycin prescribed

24 hours later confused and hypotensive

Emergency admission

Treated as CAP according to hospitalprotocol

Rx Vancomycin 1g x 2Gentamicin 160mg x 2

48 hours later AKI diagnosedBaseline eGFR 42ml/min/1.73m2

4 week hospital admission

Probably avoidable with recognition that patient likely to have CKD and risk conferred by this CKD

Admission eGFR 22ml/min/1.73m2

‘48h’ eGFR 12ml/min/1.73m2

Mrs JD 80 year old T2DM and IHD Rx ACEI eGFR 35ml/min/1.73m2

eGFR 16ml/min/1.73m2

Pharmacist recommended ibuprofen for hip pain

Should not deprive patients with CKD of potential benefits of ACEI/ARB

Combination of CKD3 and ACEI/ARB carries significant risk of AKI

Sick day rules important for patient and doctor

Equivalent to diabetes

Recognising the at risk patient: ACEI

ACEI/ARB essential part of managing IHD and preventing progression of CKD

ACEI/ARB, IHD and CKD are important risk factors for AKI

What to do: Medications

Acutely unwell patient with proven or possible CKD

ACEI/ARB StopLoop Diuretics StopMetformin StopSUs ReviewMetiglinides No changeGliptins No changeStatins No changeAspirin No changeNSAIDs Stop/AvoidTrimethoprim Avoid

Check GFR if

Diabetes

Hypertension

Cardiovascular disease

Structural renal tract disease

Renal calculi

Prostatic hypertrophy

Multisystem diseases with potential kidney involvement

Opportunistic detection of haematuria or proteinuria

Family history of stage 5 CKD or hereditary kidney disease

Risks associated with CKD

Risk of progression (including to renal replacement therapy)

CKD progression

Steps to identify progressive CKD

Obtain a minimum of three eGFR over not less than 90 days

In new cases of reduced eGFR repeat within 2 weeks

to exclude acute deterioration

CKD progression is a decline in eGFR of:

> 5 ml/min/1.73m2 within 1 year

> 10 ml/min/1.73m2 within 5 years

Hemmelgarn BR. Kidney International 2006: 29: 2155

10,184 community-dwelling subjects aged 66 or over

Decline in eGFR greatest in diabetics (2.1 and 2.7 ml/min/1.73m2/year in F and M respectively)

Decline in eGFR in non-diabetics: 0.8 and 1.4 ml/min/1.73m2/year in F and M respectively

Decline more likely if baseline eGFR <30

Risk of decline of GFR in elderly people

Patients with CKD are more likely to die than require dialysis

Kaiser Permanente, Oregon: 27,998 CKD patients followed for 5y

Stage GFR RRT Death

2 60-89 1.1% 19.5%

3 30-59 1.3% 24.3%

4 15-29 19.9% 45.7%

Keith DS. Arch Intern Med 2004; 164: 659-663

(N=1,120,295)

1.0

1.4

2.0

2.8

3.4

Ha

zard

ra

tio fo

r C

V e

ven

t

0

1

2

3

4

Reduced kidney function is associated with a higher risk of CV events

≥60 45-59 30-44 15-29 <15

eGFR (mL/min/1.73 m2)

Go et al. N Engl J Med 2004 351: 1296–1305 Tonelli et al. J Am Soc Nephrol 2006 17: 2034–2047Eeg-Olofsson et al. J Internal Medicine 2010 268: 471–482 Khaw Nature Reviews Endocrinology 2009 5: 130-131

8.0-8.9

9.0-9.9

CKD3

Ongoing management to slow progression important

RRT

60

50

40

30

20

10

eGFR

CKD3

CKD4

X

CKD3: What is all the fuss about?

Blood pressure control

In people with CKD aim for:

Systolic blood pressure below 140 mmHg(target range 120–139 mmHg)

Diastolic blood pressure below 90 mmHg

In people with CKD and diabetes or when ACR 70mg/mmol aim for:

Systolic blood pressure below 130 mmHg(target range 120–129 mmHg)

Diastolic blood pressure below 80 mmHg

ACEI/ARB in CKD

Glomerulopathy/Hyperfiltration: Good

Real world kidney disease: More complicated!

Microvascular disease v macrovascular disease

ACEI and ARB

Macrovascular disease affecting the kidneys

Angiotensin II

Glomerular permeability

Glomerular pressure

Interstitialfibrosis

ProteinuriaProgressive

Renal Failure

Heads you win…….

X

……. Tails you lose

If primary problem is macrovascular disease ACEI/ARB will precipitate progressive decline in GFR

Time

GF

RSlowly deteriorating CKD

ACEI/ARB

Acute reduction in glomerular perfusion pressure – expected and OK – up to 20%

Long-term stabilisation in GFR – most likely in proteinuric patients, because proteinuria indicates glomerular hyperperfusion/overwork

Progressive fall in GFR, caused by macrovascular renal disease or other cause of global reduction in renal perfusion

How does diabetes damage the kidneys?

Microvascular diseaseDiabetic nephropathy: Damage to

glomerulus AND haemodynamic changesManifest by albuminuria

Macrovascular diseaseDecreased perfusion pressure

Does not cause albuminuria

T1DM Micro > macroT2DM Macro > micro

RAS blockade beneficial

RAS blockade not beneficial

250

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Time (months)

Diabetic Nephropathy

Treatment

MA

BP

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115

105

95

105

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85

75

65

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R

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250Alb

um

inur

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-24 -18 -12 -6 0 6 12 18 24 30

All is not lost

CKD3 matters!

Be brave with ACEI/ARB but frequent monitoring necessary

Be aware of possibility for AKI

eGFR below 30ml/min makes secondary hyperparathyroidism and anaemia possible

eGFR below 20ml/min should prompt RRT discussions

eGFR below 15ml/min may need dialysis

Number of patients with haemoglobin <110 g/l in diabetic vs non-diabetic patients at various CKD stages

Patients with diabetic Patients with

nephropathy, n (%) non-diabetic

kidney disease, n (%)

CKD 1 1 (8) 3 (2.3) CKD 2 1 (3.5) 9 (

2.6) CKD 3 11 (10.4) 21 (3.2) CKD 4 25 (21.3) 33 (7.1) CKD 5 34 (85) 37 (20.1)

How prevalent is anaemia of CKD?

eGFR (ml/min/1.73m2

Median Hb in men (g/dl)

Median Hb in women (g/dl)

Prevalence of anaemia

60 14.9 13.5 1%

30 13.8 12.2 9%

15 12.0 10.3 33%