Prescribing in Chronic

1

• Prescribing in Chronic
• Renal Disease

2

• Who has chronic renal disease (CKD)?
• CKD stages 1-V
• How common is it?
• Creatinine v GFR
• Basic Principles
• Scenarios

3
Effect of ageing on renal function
4
Declining eGFR
140
Mean Cov
120
100
80
eGFR (ml/min/1.73 m2)
60
40
20
0
20-34
35-44
45-54
55-64
65-74
75-84
85
Age bands
5
Declining eGFR
140
Mean Cov
120
Mean-1sd
100
80
eGFR (ml/min/1.73 m2)
60

40
20
0
20-34
35-44
45-54
55-64
65-74
75-84
85
Age bands
6
Declining eGFR
140
Mean Cov
120
Mean-1sd
Mean-2sd
100
80
eGFR (ml/min/1.73 m2)
60

40
?
20
?
0
20-34
35-44
45-54
55-64
65-74
75-84
85
Age bands
7
Declining eGFR
140
Mean Cov
120
Mean-1sd
Mean-2sd
100
80

eGFR (ml/min/1.73 m2)





60





40



?
20
?
0
20-34
35-44
45-54
55-64
65-74
75-84
85
Age bands
8
Chronic Kidney Disease

• KDOQI guidelines
• CKD Stage I CrCl gt 90
• with kidney disease
• Stage II CrCl 60-90
• Stage III CrCl 30-60
• Stage IV CrCl 15-30
• Stage V CrCl lt15

9
Chronic Kidney Disease
CKD Stage No of patients in Coventry
(III) (III) (IV) (V) 93,826 10,196 1666 678
Total Total III to V 106,366 12,540
Raymond et al. 2004
10
Beware of plasma/serum creatinine interpretation
Creatinine 90 - 110 mmol/l
GFR 40-50 ml/min
CKD III
11

• Principles
• Loading dose
• Maintenance dose
• Dose interval
• Excretion / Secretion
• Therapeutic range
• Renal toxicity

12

• Principles
• Loading dose
• Maintenance 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.

13

• 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 gt90 will need 250ugs daily.

14

• Dose interval
• Vancomycin
• Loading dose 1000mgs first dose
• Maintenance 1000mgs every 5-7 days for
  dialysis patient
• Monitor with levels

15

• Excretion / secretion
• Trimethoprim / Nitrofurantoin
• These 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.

16

• Therapeutic range
• May 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

17

• Renal Toxicity
• ACEI / NSAIDs
• Action 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

18
Angiotensin II (vasoconstrictor)

Prostacycline (vasodilator)
Efferent
Afferent
Glomerular filtration pressure
19

• Renal Toxicity
• ACEI / NSAIDs
• These 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

20

• Scenario
• 75 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

21

• 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.

22

• Comments
• BHS says ACEI is first line for hypertension
  especially in the lt55 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.

23

• What happened next?

24
18/12/2009 1423 147 6 27.9 178
18/12/2009 0030 148 5.9 35.4 200
17/12/2009 1612 148 6.9 38.5 199
17/12/2009 0010 142 6.1 51.9 264
16/12/2009 1615 142 6.9 53.4 238
16/12/2009 1022 142 6.9 59.7 305
16/12/2009 0524 143 7.9 61.4 300
23/11/2009 1746 142 4.5 15.3 156
23/11/2009 1526 143 4.6 15.2 161
16/09/2009 1344 140 4.1 14.3 138
12/08/2009 1419 140 4 13.6 147
06/07/2009 1638 143 3.9 12.5 162
Admitted ill!
ARB added
25

• 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.

26

• Cardiology and hyperkalaemia
• IHD

ACEIs
Spironolactone
NSAIDs
R I P
Hyperkalaemia
27

• 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?

28

• Scenario
• Patient 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 ????

29

• 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?