Gout and chronic kidney disease

Hyperuricaemia, the biochemical driver of gout, develops through two main pathways: overproduction and underexcretion of urate.

Overproduction is driven by:

• High-purine foods: red meat, shellfish, organ meats.
• Alcohol (especially beer) and fructose-sweetened drinks (eg, soft drinks).
• High cell turnover states: psoriasis, myeloproliferative disorders.

Underexcretion is the dominant mechanism in CKD:

• Reduced renal urate clearance as eGFR falls.
• Diuretics (thiazides and loop diuretics) further reduce urate excretion.
• Insulin resistance impairs renal urate handling.
• Genetic factors.

Despite the association of hyperuricaemia with increased cardiovascular and chronic kidney disease risk, treatment of asymptomatic hyperuricaemia has not been shown to have any significant clinical benefit¹.

 Epidemiology and health equity

Gout is extremely prevalent among Pacific and Māori peoples in Aotearoa New Zealand. Among Pacific peoples, gout prevalence reaches 13–15%, compared with 8.5% in Māori and approximately 4–5% in non-Māori, non-Pacific New Zealanders². It is the most common health condition in Pacific men, but is not recognised as such.

Māori and Pacific peoples also develop gout almost a decade earlier than other New Zealanders, often in their 30s and 40s³.

This disparity is primarily genetic, not dietary. Variants in urate transporter genes (including SLC2A9 and ABCG2) reduce the kidney's ability to excrete urate and are far more prevalent in Māori and Pacific peoples⁴.

Diet plays only a minor contributing role. Gout is not a disease of personal moral failure or poor lifestyle choices. Stigmatisation of gout is a known barrier to care and must be actively addressed³.

NSAIDs are generally avoided in CKD due to the risk of acute kidney injury and worsening renal function⁵. In a patient with an eGFR of 35 mL/min/1.73m² (CKD stage 3b), NSAIDs are contraindicated. Māori and Pacific peoples are at significantly higher risk of NSAID-related hospitalisation for AKI, GI bleeding, and heart failure compared to non-Māori, non-Pacific patients⁶.

First-line option: Corticosteroids

In moderate–severe CKD, oral corticosteroids are often the safest first-line option for acute gout⁵.

• Prednisone 30–40 mg orally daily, reducing dose over 10–14 days.
• Consider dispensing in a blister pack -reduces confusion and improves adherence, particularly when patients are managing multiple medications.
• Monitor blood glucose closely, given his T2D, as corticosteroids can cause significant hyperglycaemia.
• Intra-articular corticosteroid injection is an alternative if the MTP joint is accessible and septic arthritis has been excluded.

Alternative: Colchicine (with dose reduction)

Colchicine can be used but requires dose reduction in CKD^5,7 (eGFR 10–50 mL/min/1.73m²):

• Reduced regimen: 500 micrograms (half the standard initial dose of 1 mg) immediately; do not exceed 1.5 mg over three days.
• Do not repeat the acute course within three days.
• Watch for interactions with statins and macrolide antibiotics (increased risk of neuromyopathy).
• Avoid in frail patients or those weighing <50 kg.

Despite the availability of effective, low-cost therapy (allopurinol), Māori and Pacific peoples continue to receive suboptimal long-term treatment for gout, with significant treatment disparities driven by barriers to healthcare access, health literacy demands, stigmatisation, and systemic bias within our health system^3,5. PHARMAC data confirm that Pacific peoples have disproportionately high dispensing rates for NSAIDs and lower rates of urate-lowering therapy access compared with non-Māori, non-Pacific New Zealanders^2,8.

The CPGMS is a PHARMAC-funded service that allows pharmacists to initiate and titrate allopurinol, provide education, and monitor serum urate levels, reducing the burden on general practice and improving access for patients.

A useful motivator for patients reluctant to commit to lifelong medication is to explain that achieving the correct ULT dose means they will no longer need to avoid seafood as effective urate control, not dietary restriction alone, is what prevents attacks.

First-line: Allopurinol

A common and important misconception is that CKD contraindicates allopurinol use or dose titration - this myth must be corrected^5,7.

Allopurinol is, in fact, first-line ULT even in CKD. The key adjustment is not to avoid titration, but to start at a lower dose and titrate gradually to achieve the target serum urate level.

Starting and titrating allopurinol^5,7:

• Start at 50–100 mg daily (lower starting dose due to CKD).
• Titrate by 50–100 mg every 2–5 weeks, monitoring serum urate and renal function.
• Standard 300 mg dosing is insufficient to achieve serum urate targets in 30–50% of patients -higher doses are often required.
• Evidence supports up to 600–800 mg/day achieving target serum urate in 75–80% of patients.
• Monitor: serum urate every 2–5 weeks during titration; once stable, every 6–12 months.
• reat-to-target goals: serum urate <0.30 mmol/L in severe tophaceous gout; <0.36 mmol/L otherwise.

Flare prophylaxis during ULT initiation

Starting ULT can trigger a gout flare during the first 3–6 months as urate crystals mobilise. Prescribe prophylaxis^5,7:

• Low-dose colchicine 500 micrograms once or twice daily (dose-adjusted for CKD), or
• Low-dose prednisone 5 mg daily if colchicine not tolerated.

If Allopurinol not tolerated: Febuxostat

• Useful alternative if allopurinol is not tolerated or causes hypersensitivity.
• Does not require renal dose adjustment in mild–moderate CKD (primarily hepatic metabolism)⁵.
• Important caveat: cardiovascular risk signals exist (CARES trial) -use with caution in patients with known cardiovascular disease⁷.

Antihypertensive choice

Losartan is the ARB (angiotensin receptor blocker) of choice in this context⁹. It has:

• Established renoprotective benefit in diabetic nephropathy/CKD with proteinuria
• A mild uricosuric effect -it lowers serum urate by promoting renal urate excretion via inhibition of URAT1, a property unique among ARBs (candesartan does not share this effect)^5,9.
• Cardiovascular protection

Start losartan 50 mg daily; titrate to 100 mg as tolerated, monitoring potassium and eGFR.

Avoid thiazide diuretics -these raise serum urate by reducing renal excretion⁵.

Diabetes management -SGLT2 inhibitor

SGLT2 inhibitor (e.g. empagliflozin) would provide¹⁰:

• Renoprotection and reduction in CKD progression
• Cardiovascular risk reduction
• Modest urate-lowering via uricosuric mechanism
• HbA1c reduction (attenuated at eGFR <60 but still clinically meaningful)
• Blood pressure lowering (~3–6 mmHg systolic).

Lipid management

A 5-year cardiovascular risk of >15% warrants statin therapy. Atorvastatin has a mild uricosuric effect as an added benefit⁵.

Given his risk, you need to consider a dose of atorvastatin to reduce his LDL to < 1.4 mmol/l. Each mmol of LDL reduction is associated with a 20-25% relative risk reduction¹¹. This may require the maximum dose and additional ezetimibe to reach the target.

Lifestyle modification is an important part of gout management, but it should be discussed in a culturally appropriate and non-judgmental way.

Gout is not simply a disease of overindulgence - it has strong genetic drivers, particularly in Pacific peoples. Framing it purely as a "lifestyle disease" can increase stigma and reduce engagement with care³.

Lifestyle advice should be practical and achievable:

• Hydration: encourage adequate fluid intake (within any CKD-related fluid restrictions).
• Diet: reduce high-purine foods (e.g. organ meats, shellfish) and fructose-sweetened drinks; moderate alcohol intake, particularly beer. Traditional foods (e.g. fish, taro) can usually be continued and do not need to be eliminated.
• Weight: modest weight loss can reduce serum urate and improve metabolic risk; consider Green Prescription or health coaching support.
• Exercise: encourage regular moderate physical activity.

Engaging family/whānau and community support can improve understanding and adherence, particularly in Pacific communities.

Practical supports such as simplified regimens or blister packaging may also help reduce confusion and improve long-term adherence.

Pacific peoples with gout are five to nine times more likely to be hospitalised for gout than non-Māori, non-Pacific patients, yet receive lower rates of urate-lowering therapy. Prescribers should actively counter this disparity by:

• Initiating ULT at first presentation (not waiting for recurrent severe flares).
• Titrating allopurinol assertively to target -not stopping at a "standard" 300 mg dose.
• Providing co-designed, culturally appropriate patient resources (e.g. Arthritis NZ, Healthify).

This MedCase was written by Dr Anthony Dewan MBChB, FRNZCGP, with expert review by Rob Walker, Consultant Nephrologist.