Prescribing in renal

Question 1

What pain killers are okay?

Answer 1

Codeine phosphate is a weak opioid and could be considered in this patient. Bear in mind that codeine can cause adverse effects such as constipation and sedation, the latter of which will be more pronounced in patients with renal impairment.
Dihydrocodeine is a reasonable alternative to codeine and can be less constipating.

Diclofenac: even low doses of NSAIDs can precipitate AKI, especially if the patient is dehydrated.
Topical NSAIDs are recommended by NICE guidelines for osteoarthritis. There may be some systemic (albeit erratic) absorption of topical NSAIDs. Low level evidence suggests it may precipitate or exacerbate AKI.

Strong opioids should be avoided in CKD where possible. The adverse effects will be more pronounced in patients with renal impairment.

Fentanyl is a reasonable option for this patient if codeine is not tolerated or is ineffective. Unlike morphine, fentanyl does not have known active metabolites that are eliminated through the kidneys. Try to maintain a low dose and monitor the patient for adverse effects.

Question 2

Causes of Aki

Answer 2

Classification and Causes of AKI
Acute Kidney Injury (AKI) is not a single disease: there are three main groups of causes, and more than one cause can contribute to a patient’s renal failure.

1. Pre-renal: reversible impairment of renal function from relative hypovolaemia or hypoperfusion. Any condition reducing renal perfusion can potentially impair renal function.
2. Renal: damage within the kidney could result from more severe ischaemia, sepsis, inflammation, or toxicity (renal cells are very sensitive to inflammatory or ischaemic injury).
3. Post-renal: obstruction to urine outflow (e.g. enlarged prostate in men) causes a damaging ‘back pressure’ within the kidney.

Question 3

What is stage 1 AKI?

Answer 3

Creatinine rise of 26 micromol/litre or more within 48 hours; or
Creatinine rise of ≥ x 1.5 from baseline in 7 days ; or
Reduced urine output of < 0.5 ml/kg/hour for more than 6 hours.

Question 4

What is stage 2 Aki?

Answer 4

Creatinine rise of ≥ x 2 from baseline; or

Reduced urine output of < 0.5 ml/kg/hour for 12 hours or more.

Question 5

What is stage 3 AKI?

Answer 5

Creatinine rise of ≥ x 3 from baseline within 7 days
OR
Creatinine rise to ≥ 354 micromol/litre with either:
Acute rise in creatinine of ≥ 26 micromol/litre within 48 hours or
≥ 50% rise from baseline within 7 days
OR
Urine output of < 0.3 ml/kg/hour for 24 hours
OR
Anuria for 12 hours
OR
Any requirement for renal replacement therapy.

Question 6

Optimal prescribing in aki

Answer 6

Knowing how AKI is classified and the causes, you will understand that optimal prescribing should:

Correct hypovolaemia;

Minimise renal hypoperfusion (often caused by drug therapy);

Treat other causes, such as sepsis;

Avoid the use of (or withdraw) nephrotoxic agents; and

Consider drugs that are renally excreted and may need adjustment.

Question 7

Nephrotoxic pathological states

Answer 7

Nephrotoxic Pathological States
Pathological states that are nephrotoxic include:

Hypoperfusion: reduces oxygen and nutrient supply to the kidney.

Sepsis: endotoxins and inflammatory mediators from infection can damage the renal vascular endothelium resulting in thrombosis.

Rhabdomyolysis: myoglobin released from damaged muscles precipitates in renal tubules and also reduces blood flow in the outer medulla.

Hepatorenal syndrome: patients with end-stage liver disease often have renal vasoconstriction.

Question 8

cockrolt

Answer 8

Assessment of Kidney Function (1)
In patients with kidney disease the best indicator of function is the glomerular filtration rate (GFR). Usually, surrogate measures are used to estimate the GFR.

Most laboratories report renal function based on eGFR normalised to a body surface area of 1.73 m2. This is derived from either the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or the Modification of Diet in Renal Disease (MDRD) formula. In the UK, it is now recommended that clinical laboratories use CKD-EPI to routinely report eGFR.

The Cockcroft-Gault formula
Creatinine clearance (ClCr) is used as an estimate of GFR (eGFR).  ClCr and the eGFR are not strictly interchangeable. The Cockcroft-Gault formula can be used to calculate estimated creatinine clearance and is the preferred method in the following scenarios:

Estimating renal function or calculating drug doses in patients with renal impairment
Older adults
Patients at extremes of muscle mass
Patients on a medicine with a low therapeutic index

Alternatively the absolute GFR or specific nomograms should be used to estimate drug doses in these patient groups.
Most studies of drug pharmacokinetics in renal dysfunction have used the Cockcroft-Gault formula. Much of the published literature on dose adjustment in renal impairment is still based on creatinine clearance, calculated using the Cockcroft-Gault formula.

Question 9

CCB

Answer 9

These agents are very useful in CKD and hypertension. They can produce oedema, which is resistant to diuretics and can be confused with volume overload.

Question 10

Dieuretics

Answer 10

Their use is crucial for blood pressure control in patients with salt and volume overload, particularly in CKD stage G4/5, and/or when oedematous (see diuretics in CKD).

Question 11

beta blockers

Answer 11

Managing Hypertension (3)
Calcium-channel blockersDiureticsBeta-blockersSelective alpha1 blockers (e.g. doxazosin)
Beta-blockers have a limited role in hypertension management.  They are now mainly used in resistant hypertension (4th line), hypertension accompanied by ischaemic heart disease, or hypertension with heart failure (uncommon).  In CKD, use beta-blockers that have significant non-renal elimination, such as bisoprolol or metoprolol.  Always beware of pharmacodynamic changes and start with cautious low doses.