Prescribing in Chronic

Renal Disease

Who has chronic renal disease (CKD)?

CKD stages 1-V

How common is it?

Creatinine v GFR

Basic Principles

Scenarios

Effect of ageing on renal function

Creatinine Clearance with age

0

20

40

60

80

100

120

0 2 4 6 8 10 12 14

Decade of life

CrC

l

CrCl

0

20

40

60

80

100

120

140

20-34 35-44 45-54 55-64 65-74 75-84 85+

Age bands

eGF

R (

ml/

min

/1.7

3 m

2)

Mean Cov

Declining eGFR

0

20

40

60

80

100

120

140

20-34 35-44 45-54 55-64 65-74 75-84 85+

Age bands

eGF

R (

ml/

min

/1.7

3 m

2)

Mean Cov

Mean-1sd

Declining eGFR

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0

20

40

60

80

100

120

140

20-34 35-44 45-54 55-64 65-74 75-84 85+

Age bands

eGF

R (

ml/

min

/1.7

3 m

2)

Mean Cov

Mean-1sd

Mean-2sd

Declining eGFR

■

▲

▲

0

20

40

60

80

100

120

140

20-34 35-44 45-54 55-64 65-74 75-84 85+

Age bands

eGF

R (

ml/

min

/1.7

3 m

2)

Mean Cov

Mean-1sd

Mean-2sd

Declining eGFR

■

▲

▲

•

•

– – – – – – – – – –

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Chronic Kidney DiseaseKDOQI guidelines

CKD Stage I CrCl > 90

with kidney disease

Stage II CrCl 60-90

Stage III CrCl 30-60

Stage IV CrCl 15-30

Stage V CrCl <15

Chronic Kidney Disease

CKD Stage

No of patients in Coventry

(I+II)

(III)(IV)(V)

93,826

10,196 1666 678

Total

Total III to V

106,366

12,540

Raymond et al. 2004

Beware of plasma/serum creatinine interpretation

Creatinine

90 - 110 mol/l

GFR40-50 ml/min

CKD III

Principles

Loading dose

Maintenance dose

Dose interval

Excretion / Secretion

Therapeutic range

Renal toxicity

PrinciplesLoading doseMaintenance dose

If start with a maintenance dose then will take some time to reach therapeutic concentration eg Amiodarone / Digoxin. If look up maintenance dose in BNF in renal failure and prescribe small dose then will take ages to reach target. How quick is a response required?

Give normal loading dose and then a renal adjusted maintenance dose to ensure effective therapy.

Digoxin

Loading 1000ugs over 24 hours

Maintenance

If anuric (on dialysis) need 62.5 ugs daily

For every 30mls of GFR add another 62.5 ugs.

If GFR >90 will need 250ugs daily.

Dose intervalVancomycin

Loading dose 1000mgs first dose

Maintenance 1000mgs every 5-7 days for dialysis patient

Monitor with levels

Excretion / secretionTrimethoprim / NitrofurantoinThese drugs work well because they are secreted into the renal tubules and achieves good therapeutic levels. Favoured options for UTI.

Less useful for systemic infections.

If GFR reduced excretion and tubular secretion is reduced and the drug is less effective.

Less reliable as antibiotic for UTI in renal patients. Still used by many doctors as popular choice for UTI.

Therapeutic rangeMay be narrow or wide - toxicity

Aminoglycosides

Antibiotics

Cardiac Drugs – Digoxin, Amiodarone

Analgesics – especially post op. Delayed action can lead to overdose.

“No-one should be in pain”

Renal ToxicityACEI / NSAID’sAction on the kidney can be directly deleterious

Effects on glomerular filtration pressure

Can predispose a kidney to hypoperfusion. More likely to cause a problem in context of chronic renal disease (reduced renal reserve).

Common cause of admission to hospital

Common cause of renal referral

Common cause of death

Afferent

Efferent

Angiotensin II

(vasoconstrictor)Prostacycline

(vasodilator)

Glomerular filtration pressure

Renal ToxicityACEI / NSAID’sThese are good drugs

Widely prescribed

Modern drugs are very powerful

Many hospital admissions are down to drug adverse effects

Role of trials

Evidence based medicine - protocols

Common sense

Doctors v Robots

Scenario75 yr old lady being treated for hypertension and mild heart failure.

1) Prescribed diuretics as first line. Diuretic used to reduce salt load. Potassium sparing.

2) Subsequently prescribed Spironolactone (25mgs) to improve outcome from heart failure.

3) ARB added to improve BP and reduce diuretic load

Age 75

Clinic BP: 185/90

Drug therapy:

Hydrochlorothiazide /Amiloride 50/5 mg, Spironolactone 25 mg o.d.,

Torasemide 2.5 mg o.d, Aspirin 75 mg o.d., Simvastatin 40 mg o.d.,

Conditions: High BP, type 2 diabetes, chronic renal failure

This lady came to see me again today. Her creatinine has settled down at 147 with an eGFR of 30 and potassium is 4 mmol/L, despite the heavy use of loop diuretics and thiazide.

I think it is time to break the vicious circle of the excessive use of diuretics in this lady and I have taken the liberty of advising to start Losartan at a dose of 50 mg or even 25 mg for a few weeks in order to reduce BP until she sees me again.

CommentsBHS says ACEI is first line for hypertension especially in the <55 year age group.

Diuretics are cheap and effective in mild hypertension and are often first line in the elderly

Spironolactone has been shown to improve survival in heart failure.

Lots of trial evidence for these individual drugs.

What happened next?

18/12/2009 14:23 147 6 27.9 178

18/12/2009 00:30 148 5.9 35.4 200

17/12/2009 16:12 148 6.9 38.5 199

17/12/2009 00:10 142 6.1 51.9 264

16/12/2009 16:15 142 6.9 53.4 238

16/12/2009 10:22 142 6.9 59.7 305

16/12/2009 05:24 143 7.9 61.4 300

23/11/2009 17:46 142 4.5 15.3 156

23/11/2009 15:26 143 4.6 15.2 161

16/09/2009 13:44 140 4.1 14.3 138

12/08/2009 14:19 140 4 13.6 147

06/07/2009 16:38 143 3.9 12.5 162

ARB added

Admitted – ill!

Trials and their application

What type of patient was recruited.

Do we stick to the indications highlighted by the trial.

How many 80 and 90 year olds in trials??

Common sense

Trials and protocols guide practise in the individual patient.

Cardiology and hyperkalaemia

IHD

SpironolactoneACEI’s

NSAID’s

Hyperkalaemia

R I P

Scenario

“Please see and advise on Mr X who has CKD and in whom we are having difficulty in controlling his potassium which is 6.5”.

Mr X is a diabetic and is unwell with nausea. He has been on an insulin sliding scale according to Trust protocol for several days.

How would you prescribe the sliding scale?

ScenarioPatient with CKD IV admitted with fracture of neck of femur. On ACEI for hypertension.

Surgery successful. Patient in pain and started on MST 10mgs bd and regular oramorph. Also given Ibuprofen for additional pain control. This is in keeping with analgesic protocol on the ward.

Day 1 Pt awake and sat up. Catheter in situ.

Day 2 Patient drowsy so physio postponed.

Day 3 ????

Day 3 More drowsy and probable infection, ? Chest or urine. Cultures taken. Given Augmentin and Gentamicin (protocol?)

How would you write up the gentamicin?

Day 4 Unconscious. Urea 45, K 7.6

Call for help!!

Day 6 RIP

Any comments?