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. 0 20 40 60 80 100 120 140 20-3435-4445-5455-6465-7475-8485+ Age bands eGFR (ml/min/1.73 m2) Mean Cov Declining eGFR

5. 0 20 40 60 80 100 120 140 20-3435-4445-5455-6465-7475-8485+ Age bands eGFR (ml/min/1.73 m2) Mean Cov Mean-1sd Declining eGFR ■

6. 0 20 40 60 80 100 120 140 20-3435-4445-5455-6465-7475-8485+ Age bands eGFR (ml/min/1.73 m2) Mean Cov Mean-1sd Mean-2sd Declining eGFR ■ ▲ ▲

7. 0 20 40 60 80 100 120 140 20-3435-4445-5455-6465-7475-8485+ Age bands eGFR (ml/min/1.73 m2) Mean Cov Mean-1sd Mean-2sd Declining eGFR ■ ▲ ▲ – – – – – – – – – – –

8. Chronic Kidney Disease KDOQI guidelines CKD Stage I CrCl > 90 with kidney disease Stage II CrCl 60-90 Stage IIICrCl 30-60 Stage IVCrCl 15-30 Stage VCrCl <15

9. 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

10. Beware of plasma/serum creatinine interpretation Creatinine 90 - 110  mol/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 >90 will need 250ugs daily.

14. Dose interval Vancomycin Loading dose 1000mgs first dose Maintenance1000mgs 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 / NSAID’s 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. Afferent Efferent Angiotensin II (vasoconstrictor) Prostacycline (vasodilator) Glomerular filtration pressure

19. Renal Toxicity ACEI / NSAID’s 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 <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.

23. What happened next?

24. 18/12/2009 14:231476 27.9 178 18/12/2009 00:301485.9 35.4 200 17/12/2009 16:121486.9 38.5 199 17/12/2009 00:101426.1 51.9 264 16/12/2009 16:151426.9 53.4 238 16/12/2009 10:221426.9 59.7 305 16/12/2009 05:241437.9 61.4 300 23/11/2009 17:461424.5 15.3 156 23/11/2009 15:261434.6 15.2 161 16/09/2009 13:441404.1 14.3 138 12/08/2009 14:191404 13.6 147 06/07/2009 16:381433.9 12.5 162 ARB added Admitted – ill!

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 Spironolactone ACEI’s NSAID’s Hyperkalaemia R I P

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?