Older people, First Nations Australians, and those with a history of hypertension, cardiovascular disease (CVD) or diabetes are at increased risk of developing CKD¹. These populations are commonly prescribed medicines that can result in problems when used in the context of reduced kidney function⁴, increasing risk of serious adverse drug reactions² which are associated with poor outcomes^{3, 4} including reduced quality of life, hospital admissions and death^{2, 4}.

By stopping and thinking ‘kidney function’ each time you prescribe medicine for someone you suspect of having reduced kidney function, you can identify patients with CKD and ensure their medicines are safe and effective for them⁵.

Does the patient have reduced kidney function?

Reduced kidney function can be acute (lasting less than 3 months) or chronic (lasting more than 3 months)¹². Both conditions are interconnected, sharing risk factors, outcomes and prognostic factors⁶. CKD increases a person’s risk of experiencing AKI, while AKI increases risk of developing incident CKD further progression of existing CKD².

Patients with a risk factor for CKD (Table 1) should be offered a Kidney Health Check every one to two years^{1, 13}. This includes:

• eGFR
• Urine albumin/creatinine ratio (uACR)
• Blood pressure monitoring

What actions to take, and when?

Check the patient’s kidney function before prescribing medicines if you suspect reduced kidney function

Prescribing a medicine for the management of hypertension, CVD, or diabetes can serve as a useful trigger to consider the patient’s kidney function and ensure their medicines are safe and effective⁸. Stopping to think about kidney function when prescribing medicines for people who are older age, or First Nations Australians can also help to ensure CKD is not overlooked, reducing medicine-related risk.

If the patient’s health has been stable, a recent estimate of kidney function (within the past three months) can be used to guide medication dosing. If there has been a change in context (see Table 1) a current estimate of kidney function is recommended. In situations where kidney function is not stable, consult a nephrologist for advice.

Both methods provide estimates of kidney function that can be used to guide dosing of medicines in most cases⁹.

Situations where estimates can be less accurate include:

• underweight (BMI < 18.5kg/m2)¹⁰
• obesity (BMI > 30kg/m2)¹⁰
• low or high muscle mass^{1, 10, 11}
• very low or high intake of dietary protein^{1, 10}
• rapidly changing or unstable kidney function^{1, 10, 11}
• taking a medicine that elevates serum creatinine (e.g. trimethoprim)^{1, 11}

Code the CKD diagnosis in the practice software

If your patient has a diagnosis of CKD, make sure this is coded in the practice software¹. Doing so will provide you with electronic decision support to ensure safe prescribing and can assist with audit activities.

Use medicines information and decision support to inform prescribing

If reduced kidney function is detected, it may be necessary to reduce the dose, extend the dosing interval, or avoid a particular medicine⁹. The action required will depend on the patient’s level of kidney function, the properties of the medicine, and the clinical context⁹.

Most practice software has inbuilt decision support to guide safe prescribing when CKD is coded as a diagnosis. In other cases, consult a medicines information resource such as:

• The Australian Medicines Handbook (AMH)
• Therapeutic Guidelines (see antimicrobial dosage modification in renal impairment) If in doubt, or if your practice does not have access to these resources, contact your local pharmacist or Medicines Information Service for advice.

Undertake ongoing monitoring and review of prescribed medicines

After starting a medicine, monitor your patient for clinical and adverse effects, measure drug concentrations when relevant (e.g. lithium, digoxin), and adjust the dose if necessary.¹²

A reversible drop in eGFR is expected after the introduction of ACE inhibitors, ARBs and SGLT2 inhibitors:

• ACE inhibitors and ARBs: check eGFR within 2 weeks of initiation. If reduction of eGFR is more than 25% from baseline value, cease the medication and consider referral to nephrologist.^{1, 12}
• SGLT2 inhibitors: a drop in eGFR (by 3-5mL/minute/1.73m²)¹² is expected to peak at 4 weeks following initiation, after which eGFR rebounds.¹ Specific testing of eGFR for this purpose is not necessary.¹

The optimal frequency of kidney function testing for the ongoing monitoring of medicines more generally is unclear. Consider testing kidney function routinely every three to six months and more frequently if there are clinical concerns.

Refer for a Medicines Review

Refer patients with reduced kidney function for a Home Medicines Review (HMR) or a Residential Medication Management Review (RMMR) to reduce adverse medicine-related effects.¹³ An HMR or an RMMR is an effective way to:

• review all medicines used by the patient, including those purchased over the counter
• identify medicines that can accumulate and cause adverse effects as a result of slower elimination in reduced kidney function
• identify medicines that can worsen kidney function or cause acute kidney injury
• identify medicines that are less effective in reduced kidney function
• highlight for review, or calculate appropriate dosing of medicines based on the patient’s kidney function
• identify medicines that may need to be stopped.

Advise the pharmacist why the review is being requested and include kidney function test results and medical history in the referral. The MBS item numbers for an HMR and an RMMR are 900 and 903, respectively.¹⁴

Educate and empower your patients

If your patient is diagnosed with CKD, take the time to explain this to them.

• Provide patients with their eGFR results and current medication lists to communicate to other care providers (e.g., My Health Record, print outs)

• Guide your patients toward credible sources of consumer information:
  • The MAIA patient information brochure ‘Medicines review in chronic kidney disease’.
  • Kidney Health Australia has an array of consumer resources.

• Talk to your patients with CKD about the risk of AKI and ask them to seek advice from a health practitioner immediately if they experience acute illness or dehydration or consider a Sick Day Action Plan.

What medicines should be front of mind?

Medicines that cause adverse effects

Medicines excreted by the kidneys can accumulate in people with reduced kidney function. Examples include metformin, pregabalin, venlafaxine and apixaban. These medicines may require a dose reduction or extended dosage interval to reduce the risk of adverse effects.¹⁵ In patients with severe loss of kidney function, some medicines such as dabigatran and eplerenone should be avoided or a safer alternative chosen.¹²

Medicines that contribute to kidney injury

Nephrotoxic medicines (e.g., aminoglycosides, lithium) require precaution when used in people with reduced kidney function and may need to be avoided when loss of function is severe. NSAIDs including COX-2 inhibitors have direct action on the kidney and increase risk of AKI⁷ so should be avoided in people with reduced kidney function.¹²

Risk of AKI increases when NSAIDs are used in combination with medicines that affect fluid and electrolyte balance such as diuretics, ACE inhibitors, and ARBs.¹

Medicines that become less effective

Some medicines become less effective in people with reduced kidney function. Loop diuretics (e.g. furosemide) typically require a dose increase to maintain effectiveness.¹² Thiazide diuretics (e.g. hydrochlorothiazide) become less effective as diuretics but may retain their anti-hypertensive effects in reduced kidney function.¹² SGLT2 inhibitors (dapagliflozin, empagliflozin) are used to slow the progression of CKD, but their glucose-lowering effect is decreased in people with reduced kidney function.¹² They should not be started in people with severe reduction of kidney function but may be continued with ongoing monitoring depending on the individual patient’s needs.¹²

Abbreviations

ACE - Angiotensin converting enzyme

AKI - Acute kidney injury

ARB - Angiotensin receptor blocker

BMI - Body mass index

BSA - Body surface area

CKD - Chronic kidney disease

CKD-EPI - Chronic kidney disease epidemiology collaboration equation

COX-2 - Cyclo-oxygenase 2

CrCl - Creatinine clearance

eGFR - Estimated glomerular filtration rate

GFR - Glomerular filtration rate

GP - General Practitioner

HMR - Home medicines review

MAIA - Medicines Advice Initiative Australia

NSAIDs - Non-steroidal anti-inflammatory drugs

RMMR - Residential medication management review

SGLT2 - Sodium-glucose co-transportase 2