Practical tips from the newly updated Handbook

Along with information on new pharmacological therapies, the Chronic Kidney Disease (CKD) Management in Primary Care (5th edition) Handbook contains several other key updates around managing CKD in general practice.

CKD and cardiovascular disease

CKD has a major impact on cardiovascular health. For people with CKD, the risk of dying from a cardiovascular event is up to 20 times greater than the risk of requiring dialysis or transplantation, for example.

The Handbook notes that:

• All people with CKD are at increased risk of experiencing a cardiovascular event and this risk is high for people with moderate to severe CKD
• A reduced eGFR and albuminuria are independent risk factors for cardiovascular disease (CVD)
• CKD is a more potent risk factor for CVD than diabetes
• Even early-stage CKD is a significant risk factor for cardiovascular events and death, particularly when albuminuria is present

How to assess CVD risk in patients with CKD

If you’re using the Australian CVD risk calculator to estimate a person’s cardiovascular risk, the Handbook recommends some adjustments in people with CKD.

1. “People with moderate to severe CKD (eGFR 30 mg/mmol) are considered to have pre-determined high risk of experiencing a cardiovascular event in the next 5 years (≥10% probability).”

2. “For people with eGFR 45-59 mL/ min/1.73m2 and/or uACR 3-30 mg/mmol, we recommend that their CVD risk is reclassified to a higher risk category to reflect albuminuria as a significant driver of CVD.”

The CVD risk guidelines include steps on how manage each risk category, while pages 26-28 of the updated CKD Handbook include colour coded management plans.

Managing CKD and heart failure

CKD and heart failure are common comorbidities, and heart failure is a leading cause of hospitalisation, morbidity and mortality in people with CKD.

Medication management of CKD in people with heart failure can be challenging due to the need to balance the differing effects of medications on the kidney and heart, says Breonny Robson General Manager of Clinical and Research at Kidney Heath Australia, who has been involved in developing the last four editions of the Handbook.

“We would recommend a ‘person-first’ approach where the overall wellbeing of the patient is considered. In some cases, a higher serum creatinine as a result of fluid management in heart failure may be acceptable if it means the patient can breathe normally,” Ms Robson says.

The Handbook includes a new section on managing CKD and heart failure, with detailed advice on how to safely prescribe medications.

RAS inhibitors, ARNIs, MRAs

Follow the usual advised precautions i.e. if eGFR declines by more than 25%, adjust the dose or stop the medication(s) temporarily, then restart at low doses and up-titrate slowly.

Angiotensin receptor neprilysin inhibitors (ARNIs) should not be prescribed with an ACE inhibitor, nor should steroidal mineralocorticoid receptor antagonists (MRAs) be used together with non-steroidal MRAs.

Carefully monitor potassium.

SGLT2 inhibitors

SGLT2 inhibitor use is recommended to manage heart failure in patients with CKD of any stage provided indications for use are met. (The prescribing criteria differ depending on if the primary indication is for heart failure or CKD, so check pbs.gov.au for details).

IV iron

IV iron therapy is recommended for managing heart failure in patients with CKD of any stage, provided indications for its use are met.

Additionally, the Handbook recommends:

• A sick day plan that uses the SADMANS mnemonic (sulfonylureas, ACE inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatory drugs and SGLT2 inhibitors) to remember which medications patients should pause when acutely unwell and unable to maintain their fluid intake
• Seeking input from kidney and heart failure specialists if necessary
• Considering the patient’s overall wellbeing, noting that a higher serum creatinine resulting from fluid management may be acceptable if it helps the patient breathe normally

Managing hyperuricaemia

The Handbook also has a new section to guide GPs in managing hyperuricaemia, which commonly occurs with the metabolic syndrome often seen in people with CKD.

It advises that dietary approaches used to lower insulin resistance also reduce serum urate.

For managing gout in people with CKD, the Handbook notes therapy to lower uric acid may be indicated. It recommends:

• Avoiding allopurinol except in cases of acute gout, in which case a starting dose of 50-100 mg/day is recommended depending on the stage of CKD
• Colchicine may be used to manage an acute gout flare, noting that a reduced individual dose size, longer interval between doses or a reduction in total daily dosage may be necessary in patients with CKD. Specifically, the Handbook advises reducing the dose by half if eGFR <50 mL/min/1.73m2 and avoiding colchicine altogether if eGFR <10 mL/min/1.73m2. A short course of prednisolone may be helpful in this case.

Managing pain

Pain is common in patients with advanced CKD and kidney failure and can have a significant adverse effect on function and quality of life.

The Handbook recommends conducting a detailed history and examination to determine the type of pain syndrome and the following management strategies.

Localised pain

This can be treated with topical therapies such as herbal liniments or creams containing capsaicin or salicylates, or a gel based NSAID.

Severe pain

This necessitates systemic treatment, and the Handbook recommends following the WHO analgesic ladder.

Step 1: Non-opioid analgesia

• Regular paracetamol is safe and the first line of treatment. Use 1g qid if needed.
• Avoid systemic NSAIDs.

Step 2: Weak opioids

Codeine and tramadol can be used with caution.

• Use normal doses in people with eGFR between 20-50 mL/min/1.73m2 but monitor kidney function closely.
• These drugs are not used routinely in people with advanced CKD. They must be avoided when eGFR is <20 mL/min/1.73m2, in which case the drugs often accumulate and lead to serious side effects.

Step 3: Strong opioids

With appropriate dose adjustment, many short- and long-acting strong opioids can be used in people with CKD.

Treatment should be tailored in accordance with the person’s medical history and commenced in consultation with a specialist.

Morphine should be avoided in kidney failure but can be used at 75% of normal dose in people with an eGFR of 20-50 mL/min/ min/1.73m2.

Neuropathic pain

You can use the following medications as first-line treatments, or in conjunction with nociceptive pain management, as per the WHO analgesic ladder.

1. Gabapentinoids

• Use in restless legs syndrome and uraemic pruritus.
• Dose adjustment is advised in patients with reduced kidney function and/ or those undergoing haemodialysis. Refer to product information for specifics.

2. Tricyclic antidepressants

• Start amitriptyline at 10 mg nocte, titrate up to 25 mg nocte after 3-7 days, then to 50 mg nocte after 1-2 weeks.
• Consider alternatives if no efficacy at 50 mg nocte.

3. Duloxetine (SNRI)

• There is evidence for duloxetine’s efficacy in painful diabetic peripheral neuropathy.
• Use 30 mg daily.

4. Other medications

Other medications that may be useful include lignocaine, mexiletine, and methadone, with guidance from a pain or palliative care team.

Managing contraception and pregnancy

Pregnancy can be likened to a “CKD stress test”, the Handbook notes, and may unmask undiagnosed CKD or worsen known CKD. Pregnancies in people with CKD are high risk, with risk increasing along with worsening CKD stage.

While fertility declines as CKD stage worsens, ovulation can still occur even in advanced kidney failure and patients on dialysis, and an unplanned pregnancy can lead to some challenging decisions.

To support the best possible outcomes, the Handbook recommends:

• considering contraception for all women with CKD of childbearing age who are sexually active, especially in those taking teratogenic medication or who have uncontrolled hypertension or uncontrolled underlying kidney disease
• choosing a highly effective form of contraception (not barrier contraception alone) in higher risk people
• Caution with oestrogen-based contraception in people with hypertension, past thrombosis, proteinuria and some conditions (such as lupus), noting IUDs are generally safe
• Considering permanent strategies (vasectomy or tubal ligation) in patients who have completed their family or are not planning a future pregnancy
• Referring patients who are pregnant or planning a pregnancy to a high-risk pregnancy clinician (e.g., maternal medicine, obstetric physician, obstetric nephrologist), ideally before conception occurs.

When to refer

In Australia, 17% of people are ‘late referrals’ to a kidney service and start dialysis within 90 days of first visiting a nephrologist, Ms Robson says.

“This allows little time for treatment choices for kidney failure to be explored and weighed up in the context of what is best for the individual.”

At the same time, kidney services around the country have limited capacity to see patients with very early-stage disease, she says, noting primary care providers play a key role in managing these patients.

The Handbook has an algorithm to guide decisions about when to refer to a nephrologist.

Figure 3: Algorithm for appropriate referral of people with CKD to a Nephrologist

For more information:
Chronic Kidney Disease (CKD) Management in Primary Care | Kidney Health Australia
CKD medical management – key updates | Healthed