Are Polynesians with Chronic Kidney Disease (CKD) more susceptible to gout?

Polynesians with CKD Have Increased Susceptibility to Gout

Yes, Polynesians with Chronic Kidney Disease (CKD) are more susceptible to gout due to a genetic defect in renal urate handling that reduces fractional uric acid clearance. 1

Genetic Predisposition in Polynesians

• Polynesian populations (Maoris, Cook Islanders, Samoans, Tongans) demonstrate a high prevalence of asymptomatic hyperuricemia (44% in women), resulting from reduced fractional uric acid clearance (FEur) compared to other populations 1
• This genetic defect in renal urate handling is similar to that reported as the basis for hyperuricemia susceptibility in Maori men, confirming a shared genetic predisposition across indigenous Pacific races 1
• The reduced FEur in Polynesian women (6.7±1.5%) is significantly lower than in healthy UK women (12.8±2.9%), but not as severe as in those with familial juvenile hyperuricaemic nephropathy (5.1±1.5%) 1

CKD as a Risk Factor for Gout

• CKD is a major risk factor for gout, with approximately 47-54% of gout patients having comorbid CKD 2
• The prevalence of hyperuricemia in CKD patients is approximately 60%, while gout affects about 25% of CKD patients 3
• Declining kidney function reduces uric acid excretion, leading to hyperuricemia and increased risk of gout 4

Combined Effect of Polynesian Heritage and CKD

• When CKD is present in Polynesians, the already compromised urate excretion is further reduced, creating a "double hit" effect that significantly increases gout risk 1, 3
• Additional risk factors in Polynesian populations include:
  • High purine intake compared to European counterparts 1
  • Strong tendency toward obesity which increases with age 1
  • These factors, combined with reduced FEur and CKD, create a substantially elevated risk profile for gout 1

Management Considerations for Polynesians with CKD and Gout

• Treatment options for gout flares are limited in CKD patients, as NSAIDs can exacerbate kidney injury and colchicine requires dosage reduction based on kidney function 2
• Urate-lowering therapy (ULT) should be initiated after the first gout attack in patients with CKD, particularly when serum urate is >9 mg/dL 4
• Allopurinol is the preferred first-line agent for all patients, including those with moderate-to-severe CKD (stage ≥3) 4
• Starting at low doses (50-100 mg daily) with gradual titration is strongly recommended for patients with CKD 4
• Losartan may be preferred over other angiotensin receptor blockers in hyperuricemic patients with CKD as it increases urinary urate excretion 4

Special Considerations

• Diuretics should be used with caution in patients with gout and CKD as they may aggravate hyperuricemia 4
• A low-salt diet frequently prescribed in CKD is not recommended for patients with certain genetic forms of kidney disease (ADTKD-UMOD and ADTKD-REN) as it may aggravate hyperuricemia 4
• Patients with onset of hyperuricemia and gout in childhood or adolescence should receive genetic testing for autosomal dominant tubulointerstitial kidney disease 4

Monitoring and Follow-up

• Regular monitoring of serum urate levels is essential to guide ULT dose escalation to reach target levels of <6 mg/dL (or <5 mg/dL for patients with tophi) 5
• Estimated glomerular filtration rate (eGFR) should be calculated at the time of diagnosis and monitored regularly in parallel with serum urate measurement 4
• Screening for other comorbidities is important as hyperuricemia and gout are independent risk factors for cardiovascular diseases 4

The combination of genetic predisposition to reduced urate excretion in Polynesians and the further reduction in excretion caused by CKD creates a significantly higher risk profile for gout in this population, requiring careful monitoring and management.