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Guidelines for Medicines
Optimisation in Patients with
Acute Kidney Injury in
Secondary Care

Caroline Ashley
Marlies Ostermann
Renal Pharmacist, Royal Free London NHS
Consultant in Nephrology and Critical Care,
Foundation Trust
Guys and St Thomas' NHS Foundation Trust

Sue Shaw
Renal Pharmacist, Derby Teaching Hospitals
NHS Foundation Trust
Publication date 01.06.2015

Guidelines for Medicines Optimisation in
Patients with Acute Kidney injury in
Secondary Care
Review date 01.12.2015
Table of Contents
2. Acute kidney injury – Medication Optimisation Pro forma 3. High risk medications and actions Thanks to the UK Renal Pharmacy Group, who developed the original AKI pharmacists' toolkit and allowed us to tailor this specifically for the Think Kidneys programme. This document is being issued as a draft after some small scale piloting. We would welcome comments which would help improve future versions. Please e-mail any comments to Julie Slevin at Guidelines for medicines optimisation in patients with acute kidney injury in secondary care

1. Introduction
Acute kidney injury (AKI) is the sudden loss of kidney function over a period of hours or days. Since the kidneys are one of the major excretory pathways for the removal of drugs from the body, this sudden loss of kidney function can have major implications for a patient's prescribed medication regime. The term ‘nephrotoxic' should be used with caution. Few medications truly have direct toxic effects on the kidneys, but several have the potential to impair renal function if used under certain circumstances, such as where the patient has a degree of chronic kidney disease in conjunction with hypovolaemia and acute illness. Under these circumstances, continued use of these medications may further exacerbate an episode of AKI. The Think Kidneys Programme has taken the decision to avoid the use of the term nephrotoxic. Many medications are cleared via the kidneys, so have the potential to accumulate during an episode of AKI. The result of this may be a further deterioration in kidney function, or there may be other adverse effects such as bone marrow or CNS toxicity. Hence it is necessary to review the use of these medications and amend the doses appropriate to the level of the patient's renal function. When a patient is either admitted with AKI, or develops AKI during an admission episode, a thorough review of medication is required in order to:  Eliminate the potential cause/risk/contributory factor for AKI  Avoid inappropriate combinations of medications in the context of AKI  Reduce adverse events  Ensure that doses of prescribed medication are appropriate for the patient's level of  Ensure that all medicines prescribed are clinically appropriate Points to note and questions to ask in the medicines management of these patients include:  Which medications should be suspended?  Which medications should not be suspended?  Which medications may be used with caution?  Are there any alternative therapeutic options? If a medication must be used, in order to minimise harm:  Amend doses appropriate to the patient's level of renal function  Monitor blood levels of drugs wherever possible  Keep course of treatment as short as possible  Discuss treatment with pharmacist/microbiologist Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Ensure appropriate information and advice is given on discharge:  From the ICU to the ward  From the ward to the GP (and care home if required)  From the ward to the patient and their family/carers 2. Acute kidney injury – Medication Optimisation Pro forma
In order to optimise the prescribing of medications to a patient with AKI, the following points should be considered: 1. Is the patient receiving medication which may impair renal function? • Contrast media • ACE Inhibitor • Angiotensin receptor blocker Consider withholding these agents during an episode of AKI.  Is the patient taking any other medications which could exacerbate AKI? Consider withholding them.  Is the patient prescribed any medications where the dose needs to be amended in renal impairment?  Amend medication doses appropriate to the patient's degree of renal  In house guidelines for drug use in AKI are recommended for example for. antibiotics, analgesia, contrast media, chemotherapy. 3. Educate the patient before discharge about which medications to restart and when, which medicines to avoid etc. 4. Ensure comprehensive information on which medications to restart and when is communicated to the GP or next care setting. Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Other useful reference sources to facilitate dose adjustment in AKI include: Suggested guidelines
medicines
Anti-retrovirals 3. High risk medicines and actions

The following list of medications is not exhaustive. Remember to consider ALL medications
including any ‘usual' long term medications. Remember to check medication history
thoroughly and ask about ‘over the counter' preparations, herbal remedies/teas and
alternative therapies. Check recreational use of drugs (cocaine, ketamine etc) as these have
been implicated in rhabdomyolysis.
Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Analgesics
Acute interstitial nephritis. Altered haemodynamics within Avoid taking whilst at risk the kidney leading to underperfusion and reduced glomerular May accumulate in acute Accumulation of active kidney injury. Seek advice metabolites (especially if at risk of dehydration morphine, pethidine Opioid analgesics and codeine) – If needed, use opiates Reduce dose and use short increased incidence of with minimal renal acting preparations CNS side effects & excretion e.g. fentanyl, wherever possible respiratory depression Accumulation leading May accumulate in acute to increased sedation, mental confusion and Avoid XL preparations respiratory depression Accumulation of drug & active metabolites leading to increased sedation & mental Antibiotics / Antifungals / Antivirals
Crystal nephropathy Accumulates in reduced Encourage patient to renal function leading to mental confusion, Beware if patient is at risk Avoid rapid infusions. Infuse IV over one hour Avoid if possible. If use is unavoidable, reduce dose &/or increase dosing Tubular cell toxicity, Monitor drug levels and renal function 2 – 3 times Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Tubular cell toxicity, Amphotericin IV – Consider Ambisome® Avoid rapid infusion Encourage patient to Crystal nephropathy Seek medical advice if patient is fluid restricted Beware if patient is at risk and requiring IV infusion Accumulation leading Interactions, e.g. withholding statins as risk confusion, coma, interactions that may be of rhabdomyolysis contributing to AKI Crystal nephropathy Accumulates in reduced renal function leading Monitor renal function and full blood count thrombocytopenia Avoid rapid infusions Acute interstitial Glomerulonephritis Accumulation leading CNS side effects including seizures Accumulation leading to CNS excitation, seizures, & blood Acute interstitial Accumulation leading to renal dysfunction, hypertension, jaundice, Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Increased risk of Acute interstitial nephritis (rare) Interferes with tubular secretion of creatinine leading to a rise in serum creatinine Avoid or reduce dose (without affecting actual GFR), which can make the diagnosis of AKI more difficult Accumulation leading to hyperkalaemia (particularly with high doses), nausea and Accumulates in reduced renal function leading Monitor renal function and full blood count thrombocytopenia Acute interstitial Reduce dose / increase Accumulation leading to renal toxicity, Antiepileptics (including drugs used for neuropathic pain)
Accumulation in kidney Monitor for excessive impairment – increase sleepiness or confusion in CNS side effects Acute interstitial Risk of phenytoin Correct phenytoin levels toxicity if patient has for uraemia and low low serum albumen Accumulation leading Monitor for excessive to increase in CNS side sleepiness or confusion Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Accumulation leading to increase in CNS side Antihypertensives Some patients who May exacerbate renal Consider withholding / -blockers during an reduce dose depending on episode of AKI have Longer acting, renally developed complete cleared drugs may heart block and required accumulate in renal temporary pacing These drugs can impair the kidneys' ability to maintain GFR when perfusion is Avoid taking whilst at risk In some situations, e.g. heart failure with a decent blood pressure; continuing them might actually be If patient is hypertensive, consider alternative antihypertensive agents, Seek nephrologist advice if eg, calcium channel undergoing contrast blockers, alfa-blockers, procedure or at risk of AKI. beta-blockers if ACEI/ARBs be withheld pre-contrast exposure Ensure patient is well hydrated pre-exposure to contrast, PROVIDED the Direct tubular toxic patient is able to tolerate Incidence of CIN higher Seek nephrologist advice if with high- & iso- undergoing contrast osmolar contrast procedure or at risk of AKI patients with congestive media, and lower with heart failure pre-coronary low-osmolar, non-ionic IV sodium chloride or sodium bicarbonate are Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Hypoperfusion of the bumetanide) preferred as thiazides less effective if GFR very low However thiazides can Dose reduction may be potentiate the effects Monitor and adjust dose of loop diuretics Seek medical advice if at Use of loop diuretics risk of hypovolaemia depends on volume Higher doses may be needed to achieve a diuresis in patients with fluid overload. Over- diuresis causing fluid depletion can cause or Dose reduction may be potassium sparing Beware if patient at risk Avoid MR / longer acting Accumulation leading to hypoglycaemia Monitor blood glucose Avoid if GFR < 30 ml/min Avoid taking whilst at risk Seek nephrologist advice if Accumulation leading of hypovolaemia or sepsis undergoing contrast to hypoglycaemia procedure or at risk of AKI Immunosuppressants (DMARDs, chemotherapy)
Increased risk of Seek advice of transplant Seek medical advice / centre regarding advice from transplant neurotoxicity and monitoring levels and dose team if at risk of Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Crystal nephropathy Accumulation increases May accumulate in side effects e.g. reduced renal function Monitor levels and excessive bone marrow consider folinic acid rescue suppression, mucositis, Avoid if patient is at risk acute hepatic toxicity, Correct fluid balance acute interstitial Acute interstitial Allopurinol and its metabolites accumulate in renal impairment agranulocytosis, aplastic anaemia, thrombocytopenia Tubular and glomerular aminosalicylates Urinary retention Monitor patient for Consider as possible difficulty in passing urine cause of drug induced Avoid XL preparations impairment have been Seek medical advice if Check drug history considering alternative medicines for effects on disease, side effects and Patients may not consider medicines also contain possible interactions herbal preparations/teas Can cause impaired Advantages of correction renal function – of severe hypercalcaemia Reduce dose and infuse at especially when given in may outweigh risks high doses and short duration infusions Seek specialist advice Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Short course of 2 -3 days treatment should be Diarrhoea / vomiting Seek medical advice if causing hypovolaemia diarrhoea and vomiting Low doses e.g. 500mcg bd or tds are effective hypoperfusion if also Do not use NSAIDs for gout; if Colchicine causes unacceptable adverse effects, consider a short course of corticosteroids Accumulation leading to bradycardia, visual disturbances, mental May accumulate in acute Monitor drug level aristocholic acid implicated in interstitial Some herbal medicines also interact with prescribed medicines e.g. Cat's Claw has anti- potentiates the effects of Seek medical advice if properties and has ciclosporin & tacrolimus. considering alternative been implicated in medicines for effects on disease, side effects and hypotension with possible interactions antihypertensives Check drug history The toxic effects of herbal remedies to the Patients may not consider herbal preparations/teas exacerbated when used with concomitant medicines which can affect kidney function Stop if patient develops unexplained/persistent fibrates, statins Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Action in presence of AKI
Education Points
Accumulation leading to nausea, diarrhoea, blurred vision, light Encourage patient to headedness, fine muscular weakness and Seek medical advice if at drowsiness, increasing risk of dehydration confusion, blackouts, fasciculation and Be aware that patients on increased deep tendon long-term lithium nearly reflexes, myoclonic always have a degree of twitches and jerks, Avoid where possible diabetes insipidus and are therefore at serious risk movements, urinary or faecal incontinence, hypernatraemia due to increasing restlessness Seek advice for alternative true dehydration when followed by stupor unwell without ready access to adequate water Chronic interstitial Be prepared to use high Kidney impairment volumes of iv 5% dextrose and monitor serum hypovolaemia and in sodium concentration combination with ACE inhibitors / ARB / Avoid taking whilst at risk Consider withholding / reduce dose depending on Seek medical advice if at Monitor anti-Xa levels and Risk of accumulation in consider reducing dose or AKI leading to increased switching to an alternative risk of bleeding agent as per local INR may be raised due Monitor INR and consider Beware if unexplained to acute rise in urea and reducing dose or bruising or bleeding warfarin displacement withholding depending on from binding sites indication for use Guidelines for medicines optimisation in patients with acute kidney injury in secondary care 4. Conclusion
These guidelines are not exhaustive and are only intended to act as an aide memoire to the medicines optimisation of patients with AKI. For further advice, please contact a renal pharmacist or nephrologist. Guidelines for medicines optimisation in patients with acute kidney injury in secondary care Checklist for medicines optimisation in patients with acute kidney injury (AKI)
in secondary care
1. Is the patient on any of the following medications?

Consider withholding them – discuss with the medical team

2. Is the patient taking any other medications which could exacerbate AKI?
Consider withholding them
3. Is the patient prescribed any medications where the dose needs to be amended in renal
impairment?

Amend doses appropriate to level of renal function

4. Monitor U&Es & re-assess renal function daily

5. Monitor blood levels of relevant drugs e.g. Aminoglycosides
6. Ensure the patient is counselled before discharge in regards to which medications to restart and
when, and which medications to avoid
7. Ensure comprehensive information on which medications to restart and when is communicated
via the discharge summary to the GP and/or next care setting
Acute Kidney Injury Warning Algorithm Best Practice Guidance

Source: http://www.afpp.org.uk/filegrab/medicines-optimisation-toolkit-for-aki.pdf?ref=1976