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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
■
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
■
▲
▲
•
•
– – – – – – – – – –
–
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?