Prescribing in patients with kidney disease

With up to 25% of hospital inpatients developing an acute kidney injury (Challiner et al, 2014) and approximately three million people with chronic kidney disease (CKD), there are an increasing number of kidney patients in daily practice (Public Health England, 2014). The kidney has important physiological roles, and when kidney function is impaired, numerous medications may be required to manage kidney-related problems. Medication review is required to ensure drug-related issues are not contributing to decline in kidney function, and with the major role the kidney plays in drug excretion, careful consideration needs to be given to choice and dosing of drug therapies. Recently, the Medicines And Healthcare Regulatory Agency (gov.uk, 2019) issued guidance on renal dosing of drugs, because of confusion over which method should be used to calculate renal function.

This paper encompasses areas of kidney disease where prescribing decisions are encountered on a regular basis in both primary and secondary care, with discussion of common medications and practical advice to support the management of these complex patients.

Prescribing in chronic kidney disease

Diabetes accounts for nearly half of CKD diagnoses in the UK and over 10 000 people have end-stage kidney disease as a result of their diabetes (UK Renal Registry, 2018). An ageing population, coupled with the increasing incidence of diabetes and hypertension, will increase future CKD incidence. There are large cost implications of CKD; NHS England estimate CKD spending is £1.45 billion (NHS Kidney Care, 2012). This is amplified by the increased cardiovascular risk in this population, with an estimated 7000 strokes and 12 000 heart attacks caused by CKD annually (NHS Kidney Care, 2012).

CKD is defined by the National Institute for Health and Care Excellence (NICE, 2015a) as ‘a reduction in kidney function or structural damage (or both) present for more than 3 months, with associated health implications'. It is classified into the stages shown in Table 1 (NICE, 2015a).

CKD is a progressive disease that can be slowed with good management of underlying conditions, such as blood pressure and blood sugar, but may eventually result in the requirement of renal replacement therapies, such as dialysis or renal transplantation. Patients with stage 4 and 5 kidney disease are under the care of specialist renal teams and this is the stage when specialist medications are likely to be commenced.

Antihypertensives

Hypertension can either be a primary cause for kidney damage or may be secondary to the underlying condition. Kidney impairment can lead to fluid retention because of an impaired ability to remove fluid and over-activation of the reninangiotensin aldosterone system (RAAS) because of poor renal perfusion. Target blood pressure (BP) in CKD patients is <140/90 mmHg, or <130/80 mmHg if the patient has albuminuria or diabetes (NICE, 2015a). It is not uncommon for CKD patients to be on multiple antihypertensive medicines from different classes to try and attain these targets. To reduce unnecessary polypharmacy, each drug should be titrated to the maximum dose and adherence checked before initiation of a further agent (Parker and Wong, 2019).

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to delay progression of renal disease and would be first choice to consider in those with:

• Diabetes and an albumin to creatinine ratio (ACR) of 3 mg/mmol or more
• Hypertension and an ACR of 30 mg/mmol or more
• An ACR of 70 mg/mmol or more.

As a result of their potential for potentiating renal decline and hyperkalaemia, both should usually be started at a low dose and titrated gradually. A rise in creatinine of up to 30% is acceptable when initiating an ACE inhibitor or ARB, but more than this, in the absence of any other causes, should necessitate the drug being held or reduced. However, because of their benefits in CKD patients with diabetes and cardiac failure, NICE has recently recommended sodium zirconium (Lokelma) and patiromer (Veltassa) to support potassium control in patients with CKD stage 3b–5 who require RAAS inhibition (NICE, 2019a; 2020).

Diuretics

Fluid retention can become a problem in patients with advanced CKD, leading to life-threatening pulmonary odema. Anuric patients who pass no urine are fluid restricted to 500 ml intake per day. To manage fluid overload, diuretics may be used in those with a urine output, alongside salt and fluid restriction. Higher doses of diuretics may be required to overcome diuretic resistance, which arises because of low albumin and competition of diuretic transport to its site of action with other ions, such as uric acid and poor renal blood flow (Parker et al, 2015). Large doses of furosemide, up to a maximum of 500 mg twice daily, can be used. Another way to overcome diuretic resistance is add in another class of diuretic, such as a thiazide (Parker et al, 2015).

Phosphate binders, vitamin D analogs and calcimimetics

Chronic kidney disease-mineral bone disorder (CKDMBD) encompasses the disruption in phosphate, calcium and parathyroid hormone (PTH) balance that occurs in kidney disease and leads to increased bone turnover and the occurrence of vascular calcification. By stage 3 CKD, approximately 50% of patients will have started to develop CKD-MBD, probably with few symptoms (Elder, 2002). The complex pathophysiology is beyond the scope of this article.

Elevated serum phosphate levels can lead to raised parathyroid hormone levels, causing bone destruction (Martin and Gonzalez, 2007). It can also precipitate with calcium, leading to vascular calcification and renal stones. To maintain phosphate levels, dietary advice is provided by specialist dietitians. However, as many protein-rich foods contain phosphate, avoidance of these foods is not possible. This is where phosphate binders play a role. Phosphate binders bind to phosphate in the gut to prevent absorption, so it is key that patients are counselled to take their binders with food. Patients may split their daily dose to reflect the amount of phosphate in each meal. Table 2 outlines common phosphate binders; choice should be discussed with the patient, as tablet burden and palatability are common reasons for non-adherence.

As well as binding to phosphate, they can also prevent absorption of certain drugs, most commonly quinolone antibiotics and levothyroxine, so concomitant administration should be separated by 2 hours.

Vitamin D and its analogs

With the kidney responsible for 1-alpha hydroxylation of vitamin D to its active form 1, 25-dihydroxycholecacliferol issues relating to low levels and poor absorption of calcium from the gut can present as hypocalcaemia. This drives high parathyroid hormone levels and bone destruction.

Early treatment is required with activated vitamin D in the form of calcitriol or alfacalcidol to raise blood calcium levels and stabilise PTH secretion. Adjusted calcium levels and PTH should be monitored at one month, then three monthly, to prevent hypercalcaemia and over-suppression of PTH. This may be more frequent in those on haemodialysis. Calcitriol and alfacalcidol can also be used as ‘pulse therapy’, where they are prescribed 2–3 times weekly, to target the parathyroid gland and reduce PTH levels when calcium levels are normal or slightly elevated (Parker and Alderdice, 2016). Prescribing errors relating to the frequency of dosing are common and can be problematic with calcium levels.

The use of cholecalciferol is somewhat debatable in CKD stages 4 and 5 (Agarwal and Georgianos, 2016; Goldsmith, 2016). With uncertainty of its benefits if it cannot be activated, but some believing it has a role in improving cardiovascular events and immune function, its use can vary depending on the patient's renal consultant and specialist advice should be sought if considering commencing cholecalciferol in this population.

Cinacalcet

The calcimimetic cinacalcet is used when PTH remains >85 pmol/L despite other therapies. Currently, NICE only advocates its use for patients on dialysis who are unsuitable for a parathyroidectomy (NICE, 2007). Cinacalcet binds to calcium receptors on the parathyroid gland and reduces PTH secretion by increasing the glands sensitivity to calcium, thereby lowering blood calcium and phosphate. To avoid the severe nausea and vomiting experienced by 10% of patients, it should be taken with food, ideally with the evening meal (Electronic Medicines Compendium, 2019c). The dose can also be split into two daily doses if the patient is still struggling to tolerate it.

Epoeitins

In CKD, reduced EPO secretion, hyperparathyroidism, poor iron absorption, inflammation and blood loss on dialysis contribute to renal anaemia (NICE, 2015b). Iron deficiency can be corrected with oral iron supplementation up to CKD stage 4, where absorption of iron is limited because of uraemia and other circulating inflammatory proteins (NICE, 2015b).

The hormone erythropoietin (EPO) is excreted by the kidneys to stimulate red blood cell production. Erythropoetin-stimulating agents (ESAs), such as darbepoetin alfa, and epoetin alfa and beta, can be initiated to maintain haemoglobin levels above those at which patients become symptomatic. NICE (2015b) recommends haemoglobin levels are kept between 10–12 g/dL(lower than that of the non-CKD population) as higher Hb levels have been associated with an increased risk of stroke and thromboembolism. Epoetins are contraindicated in uncontrolled hypertension (SBP>180 mmHg) because of a potential effect on RAAS, which may lead to an increase in BP (NICE, 2015b).

Diabetes in chronic kisney disease

Managing diabetes in this population can be challenging and requires individual considerations and specialist input from nephrology and diabetes teams.

The role the kidneys play in glucose homeostasis and insulin metabolism is underappreciated. They are responsible for 25% of the glucose released into plasma from gluconeogenesis (Gerich, 2010) and they filter around 180 g of glucose per day, most of which is reabsorbed via sodium-glucose linked transporter (SGLT2) (Wright, 2001). The kidney is estimated to be responsible for metabolism of around 30% of systemic insulin, which could be up to 80% for exogenous insulin therapy (Ferrannini, 1983).

In early stages of renal impairment, resistance to the effects of insulin predominate and may lead to a greater requirement for insulin (Eidemak et al, 1995). In more advanced renal impairment, the reduced insulin clearance leads to reduced requirements and a higher risk of hypoglycaemia if insulin is not reduced.

In some type 2 diabetics, a ‘burnt-out diabetes' phenomenon can be seen, where patients with severe CKD may need reduced doses of anti-diabetic medications, with cessation of treatments in a number of cases (Park et al, 2012).

Insulin therapy

A basal-bolus regime may be most flexible and best suited to the glycaemic variability seen in patients with severe CKD and those on haemodialysis. In patients who are less likely to be able to comply with the requirements of a basal-bolus regime, consideration should be given to once-daily regimes with longer-acting insulins (Joint British Diabetes Society for Inpatient care (JBDS-IP), 2016).

Table 3 details the non-insulin anti-diabetic medications and their use in CKD.

Diabetes in dialysis patients

Haemodialysis can remove insulin, glucose and glucose-regulating hormones (JBDS-IP, 2016). Furthermore, blood glucose tends to fall during a haemodialysis session, with the nadir during the third hour, including in non-diabetic patients, although hypoglycaemic episodes are not common in this population (Gai et al, 2014). Therefore, glucose control on dialysis days may be different to that on non-dialysis days with varying doses. Patients with diabetes on maintenance haemodialysis should be adequately counselled on the increased risk of hypoglycaemia and that hypoglycaemia can occur with diminished classical symptoms. For example, a haemodialysis patient on insulin may administer 12 units glargine at night on non-dialysis days but have a lower requirement of 8 units at night on dialysis days.

General advice for drug dosing in chronic kidney disease

If a patient is prescribed some of the above specific renal medications, it is likely they have severe CKD (stages 4 and 5) and should highlight to the prescriber that it is necessary to check the patient's renal function before initiating new therapies, especially those that are excreted by the kidney.

The issues of medication use in someone with renal impairment include:

• The reduced renal excretion of a drug or its metabolites may lead toxicity, for example, morphine and 6-glucoronide
• Patients have an increased sensitivity to centrally acting drugs, even if elimination is not impaired, because of the effects of uraemia and other toxins on the blood-brain barrier
• Some drugs are not effective when renal function is reduced, for example, nitrofurantoin, thiazide diuretics (when used alone).

The BNF usually expresses drug dosing in terms of estimated glomerular filtration rate from the lab-calculated modification of diet in renal disease and CKD-EPI equations, and this is appropriate for dosing most drugs (British National Formulary (BNF) Online, 2020a). However, drugs that are extensively renally excreted with a narrow therapeutic window, as well as drugs in elderly patients and patients at extremes of body weight would require calculation of Cockcroft-Gault creatinine clearance (C-G CrCl). This was also highlighted by a recent MHRA alert (gov. uk, 2019). Online calculators are available to support the calculation of C-G CrCl. Bodyweight can be a contentious issue when calculating C-G CrCl, for obese patients and a UKMI (2018) review summarises these issues. In the authors' practice, they would mainly use an adjusted body weight for obese patients. Examples of drugs where C-G CrCl calculation would be required for dosing adjustments include:

• Anticoagulants (eg low molecular weight heparins or direct oral anticoagulants)
• Antivirals (eg aciclovir and ganciclovir)
• IV antimicrobials (vancomycin, gentamicin, fluconazole).

The Renal Drug Handbook/Renal Drug Database (2020) is a practical resource for supporting drug dosing, along with trust guidelines or local formulary advice for antimicrobials. Drug doses in the renal drug handbook may be higher than those seen in the BNF or manufacturers SPC, for example, oral and IV co-amoxiclav. The renal drug database combines evidence from renal units practice and published studies. In the case of antimicrobials, this would prevent underdosing, which could lead to treatment failure and antimicrobial resistance.

For patients who undergo intermittent haemodialysis, it is important to consider the timing of drug administration around the dialysis sessions. Frequently, this involves antibiotics, as the majority are removed, so dosing should be at the end of dialysis. Newer antiepileptic drugs, such as levetiracetam, can also be dialysed and some patients are given supplemental doses on dialysis days. Advice may be found in the renal drug database or the Electronic Medicines Compendium, but prescribers can always seek advice from your local specialist renal pharmacist in complex cases.

Acute kidney injury

Background

Acute kidney injury (AKI) is defined as a sudden deterioration in kidney function over hours to days, resulting in the inability of the kidneys to excrete wastes or maintain fluid and electrolyte homeostasis (Kidney Disease: Improving Global Outcomes (KDIGO), 2012). In AKI, it is important to review medications to reduce the risk of drug accumulation and adverse effects, as well as identifying any potential causative agents (NICE, 2019a).

There are three types of AKI that include pre-, intra- and post-renal causes:

• Pre-renal AKI is caused by reduced perfusion of the kidney, which can lead to ischaemic damage if not appropriately treated. Common causes of pre-renal AKI include volume depletion (haemorrhage, vomiting, diarrhoea and burns), hypotension (sepsis and anaphylaxis), renal artery stenosis, liver failure, heart failure and drugs
• Intrinsic AKI is a result of direct damage affecting one or more the kidneys structures. Causes include autoimmune kidney disease (such as vasculitis and glomerulonephritis), drug-induced (such as acute interstitial nephritis induced by proton pump inhibitors), myeloma and rhabdomyolysis
• Post-renal AKI is caused by obstruction to outflow from the kidneys. This can be caused by enlarged prostate, kidney stones, bladder cancer and prostate cancer. These are usually urological problems so patients are most likely seen by urology teams not renal.

Medicines review in acute kidney injury

A report from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD, 2009) investigated the care of patients who died in hospital with a primary diagnosis of AKI. Only 50% of the study population were considered to have received a good standard of care. The expert group identified medications as one of the top three risk factors for the development of AKI. Medicines were one of the most common risk factors not assessed, with only 56% of patients having nephrotoxic drugs stopped and only 15% of patients having doses of renally excreted medicines dose adjusted.

All patients presenting with AKI should have a full medication review. Things to consider include (Think Kidneys, 2016):

• Identifying any potential causative agents
• Stopping nephrotoxic drugs to prevent further deterioration in kidney function
• Reviewing the doses of regular medication to prevent accumulation and adverse effects
• Consider therapeutic drug monitoring where available, especially for nephrotoxic drugs or those with a narrow therapeutic index (such as vancomycin and digoxin).

Drug causes of acute kidney injury

Certain drugs may cause further deterioration of renal function during an episode of AKI. The following list of drugs, which is not exhaustive, should be stopped or reviewed (Think Kidneys, 2016) :

• Angiotensin converting ezyme inhibitors (ACEi)
• ARBs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Diuretics
• Trimethoprim
• Aminoglycosides
• Contrast media
• Antihypertensives.

Drugs such as ACEi, ARBs and NSAIDs alter renal haemodynamics, causing hypoperfusion of the kidney and reduction in glomerular filtration, and so these drugs should be held. Hyperkalaemia can occur during AKI, so drugs contributing to this, such as potassium-sparing diuretics, should be held. Diuretics should be reviewed, especially in pre-renal AKI, as they can cause hypovolaemia and exacerbate hypoperfusion of the kidney. However, diuretics can be used if fluid overload accompanies AKI, such as in an episode of decompensated heart failure. Aminoglycosides and iodinated contrast agents can cause direct tubular damage and should be avoided wherever possible. In a sepsis-driven AKI, full doses of non-nephrotoxic antibiotics, such as penicillins, may be used for the first 48 hours before dose review. This aims to adequately treat the infection and reduce morbidity and mortality from sepsis (Garnacho-Montero et al, 2008). Review is essential, as continuation of supratherapeutic doses may lead to adverse effects, such as seizures with flucloxacillin or agranulocytosis with meropenem (Electronic Medicines Compendium, 2018)

Drug dosing and acute kidney injury

The use of the renal function estimating equations (CKD-EPI, MDRD, C-G) as a measure of renal function is not accurate in an AKI situation. A lag in the rise of creatinine in AKI means that kidney function is over-estimated initially, but in a resolving AKI there is a lag in creatinine reduction, resulting in underestimation of kidney function.

If a patient has AKI requiring hospital admission, then renal function should be monitored and reassessed daily, including urine output, creatinine, urea and electrolytes. For dosing drugs with high renal excretion and narrow therapeutic window, use C-G CrCL and re-calculate every 24–48 hours with creatinine changes. Examples of drugs where regular monitoring and dosing adjustments would be required are:

• Anticoagulants (such as low molecular weight heparins, warfarin, direct oral anticoagulants)
• Anticonvulsants (such as phenytoin, gabapentin, pregabalin and levetiracetam)
• Antivirals (such as aciclovir and oseltamivir)
• Hypoglycaemic agents (such as gliclazide, gliptins)
• IV antibiotics
• Digoxin and allopurinol.

Lithium and methotrexate are mainly excreted by the kidneys and must be stopped in AKI,because of the risk of accumulation and toxicity.

Think Kidneys (2020) has advice for management of AKI in primary care, with recommendations of review ranging from 72 hours up to requiring hospital admission. ‘Think medications' is one of the four key themes it suggests as part of the review.

Restarting medication once the acute kidney injury has resolved

Once AKI has resolved, it is important to review drugs that have been held or dose reduced. For medicines that were held, consider the indication for the drug and whether it is still clinically indicated (Think Kidneys, 2016). If the patient was on an ACEi or ARB for heart failure, it is important that these are restarted and titrated back to maximum tolerated doses, in order to control symptoms. If the patient does not recover their renal function, drugs that were held may have to be stopped permanently and suitable alternatives considered, if treatment is still required. If antihypertensives were held, then the patient should have follow up in primary care within six weeks for a review.

Kidney transplant

Kidney transplantation is the preferred option of renal replacement therapy for many patients. Not only does kidney transplantation improve mortality and morbidity, but also the quality of life of kidney patients (Mohammed et al, 2018).There were 4647 patients waiting for a cadaveric kidney transplant in the UK in 2019, and the median waiting time is about 675 days. Around 30% of patients needing a transplant will receive a living donor transplant where a relative or friend may donate a kidney (NHS Blood And Transplant, 2019). All patients who receive a kidney transplant are required to be on immunosuppressive therapy for the life of the transplanted kidney graft, to avoid rejection from the patients' immune system.

Immunosuppressive therapy

Immunosuppressive therapy is administered at the time of the transplant and continued for maintenance therapy. Kidney transplant recipients are initiated on a combination of different agents as maintenance therapy. The combination chosen depends on individual factors, such as side effects and patient preference. It is a very fine balance to try and achieve the therapeutic effect but minimise the risk of the undesired consequences of immunodeficiency and non-immune toxicity (Halloran, 2005). The majority of patients at the authors' large transplant centre are commenced on tacrolimus and mycophenolate dual therapy.

Calcineurin inhibitors

Ciclosporin and tacrolimus are both calcineurin inhibitors. Calcineurin is involved in the T-cell signal transduction pathway. The pathway activates the transcription of molecules, such as interleukin 2 and cytokines, which leads to the proliferation and differentiation of T cells (Halloran, 2005). T cells are responsible for transplant rejection, through recognising the transplant organ as non-self and, once activated, they then trigger a pro-inflammatory response, which can lead to graft damage and potentially graft loss (Issa et al, 2010).

The different brands of tacrolimus and ciclosporin are not interchangeable, they should be prescribed by brand and switching from different brands should only be done under specialist advice and supervision. Tacrolimus is available in once daily as well as twice daily preparations and this could potentially be a source of error.

Ciclosporin and tacrolimus require routine monitoring of trough level to prevent graft rejection and to minimise adverse effects. Chronic exposure to the CNIs can lead to nephrotoxicity, which is usually irreversible. Tacrolimus is now the preferred agent of choice but this may be switched to ciclosporin if the side effects are unacceptable (Ekberg et al, 2009). Table 4 shows the possible side effects.

Cyclosporin and tacrolimus are largely metabolised by cytochrome P450 enzymes in the liver and effluxed in the intestinal wall by P-glycoprotein. Therefore, they have a number of interactions with other medicines. Table 5 shows examples of such interaction, please note this is not an exhaustive list.

Anti-metabolites

Mycophenolate and azathioprine are both anti-metabolites. Mycophenolate and azthioprine affect pathway of nucleotide synthesis. T and B lymphocytes are dependent on this pathway to provide building blocks required for proliferation. When activated, B lymphocytes can infiltrate the transplanted kidney and activate the complement proteolytic cascade and cause antibody dependent cellular cytotoxicity. These mechanisms can lead to graft damage and potentially graft loss (Durand and Chiffoleau, 2015). Both mycophenolate and azathioprine can cause myelosuppression. Mycophenolate causes more gastrointestinal side effects compared to azathioprine. It is important to note that allopurinol inhibits one of the pathways of inactivation of azathioprine and the combination can be dangerous and is generally avoided (Electronic Medicines Compendium, 2019d; 2019e).

Steroids

Gluococorticoids inhibit a range of immune cells, and prednisolone is an immunosuppressive agent that is sometimes used in kidney transplant patients. Long-term use of steroids increases the risk of diabetes and osteoporosis, promotes weight gain and can lead to Cushing syndrome (Baker et al, 2017). Most centres now have maintenance regimens that are steroids sparing. The use of steroids is usually reserved for patients with high risk of rejection or when other immunosuppressive therapy is clinically inappropriate or intolerable. Patients on long-term steroids should not have it stopped abruptly to avoid withdrawal symptoms. Dose increases may be required in times of severe infection or sepsis.

Infection prophylaxis

Immunosuppressive therapy puts kidney transplant patients at risk of infections. Depending on individual risk factors and the donor serology at the time of transplant, patients may be on a combination of prophylactic antibiotics and/or antiviral medication. Table 6 shows of some of the agents commonly used, please note the duration of prophylaxis may vary slightly between centres.

Urinary tract infections

Urinary tract infections (UTIs) are the most common bacterial infections in kidney transplant patients, with one study suggesting that it affects around 60% of female and 47% of male patients (Karuthu and Blumberg, 2012) and this is because of the structural anatomy of the new transplant and associated reduction in a patient's immune system. Before prescribing antibiotics for kidney transplant recipients, it is important to remember that these patients are still defined as CKD patients and so certain antibiotics may not be appropriate. Nitrofurantoin is usually avoided, as it is not effective in treating upper UTIs and also has a lack of efficacy in renal impairment (BNF online, 2020b). Trimethoprim can cause a hyperkalaemic acidosis and can increase serum creatinine, so it is also not recommended (Electronic Medicines Compendium, 2019f) first line agents include cephalexin or pivmecillinam, but these will be based on local resistance patterns and treatment should always be reviewed with the patients' urine culture, sensitivities and allergies.

Conclusions

All professionals who are involved in the care of renal patients need to be mindful of medication use. Appropriate drug dosing is required to minimise adverse effects and toxicity and different renal function estimating equations may be required to ascertain the required dose. In AKI, medication needs to be reviewed to identify and stop potential causes. Optimisation of medications is key in controlling CKD decline and its associated symptoms, whilst inappropriate medication use may hasten kidney decline. Patients with renal transplants need to be careful with interacting medications as they may pose a risk to the function of the kidney. This article covers these main themes but there are still certain gaps in the evidence, including which bodyweight should be used when calculating CrCl and which renal estimating equation should be used for dosing drugs.

Key Points

• Good control of blood pressure (BP) and blood sugars in patients with CKD may slow kidney decline so it is key to optimise their treatment of these conditions and identify any issues with non-compliance
• In patients with kidney impairment, Cockcroft-Gault creatinine clearance (C-G CrCl) should be used to calculate doses for drugs with a narrow therapeutic index and high renal excretion. Examples include DOACs and antiviral medications
• In AKI none of the renal function estimating equations are accurate for drug dosing but C-G CrCl should be used to dose drugs with high renal excretion and adjusted regularly with changes in creatinine
• In AKI reviewing medications is essential to identify potential medication causes as well as adjusting doses appropriately to prevent drug adverse effects
• Renal transplant patients are likely to be taking calcineurin inhibitors (CNIs) which interact with medications affecting CYP3A4 and P-glycoprotein. Be mindful with interactions that could have drastic consequences

CPD reflective questions

• Thinking back to a patient you have seen with AKI, would you manage them differently now? Was there anything that might have prevented that episode of AKI?
• Is there anything that you could do in your practice that could support patients with CKD, with the aim of reducing renal decline?