HPE Grunenthal handbook - Page 22

Effective treatment of hyperuricaemia and gout may afford considerable protection to patients and reduce their risk of chronic kidney disease order to protect kidney function and reduce the risk of CKD progression has been tested in several small clinical trials. 15–20 Although relatively small with short follow-up times, these studies provide early positive signals that lowering of serum uric acid is associated with clinical benefit. Goicoechea and colleagues evaluated the impact of low dose allopurinol (100mg daily) in 113 patients with hyperuricaemia and moderate CKD. 15 Patients assigned to the placebo arm experienced a fall in estimated glomerular filtration rate (eGFR) of –3.3ml/min/1.73m 2 whereas, those in the allopurinol group experienced a slight increase of 1.3ml/min/1.73m². The net benefit of 3.3ml/ min/1.73m² over the 24 months of follow-up was attributed to allopurinol treatment. Similarly, Sircar and colleagues tested the efficacy of febuxostat in 93 patients with GFR between 15 and 60ml/ min/1.73m². 16 After six months, patients assigned to placebo had a significant reduction in eGFR levels compared with the febuxostat-treated group (from 32.6 ml/min to 28.2ml/min), 2 and the net difference in eGFR between the groups was 6.5ml/min in favour of febuxostat. These intervention trials, albeit small, demonstrate that a ULT strategy is effective in protecting and stabilising kidney function within a 12–14 month time frame. Recent meta-analyses have confirmed the net benefit of a ULT strategy in reducing major renal events and slowing the decline in eGFR. 32 A meta-analysis of ten clinical trials with 706 patients revealed that ULT reduced the risk of major kidney events by 55% (relative risk 0.45, 95% CI (0.31–0.64). Moreover in the same analysis, restricted to eight clinical trials and 669 patients, ULT use reduced the rate of CKD progression by 4.10ml/ min/1.73m² (95% CI –1.86–6.35) per year. Given the observed renoprotective impact of ULT on measured kidney function over time, it is likely that therapeutic intervention with ULT to control gout and reduce gout flares will exert an equally impressive, if not larger, benefit. While these clinical studies lend credence to the belief that ULT should be prescribed for all patients at risk of CKD progression, they were small and were not powered to evaluate major renal outcomes of dialysis and death. However, the data from observational studies are encouraging and suggest that the benefit observed in these smaller studies may also translate into larger populations. Conclusions A compelling body of evidence has accumulated that links gout and its precursor hyperuricaemia to the development and progression of CKD. The strength and magnitude of these associations has been demonstrated in healthy populations and those with pre-existing chronic medical conditions. Recent randomised clinical trials suggest that lowering serum uric acid protects kidney function and reduces the risk of disease progression. This is an exciting development and offers new hope to patients with hyperuricaemia and gout who are at increased risk of kidney failure. Treatment with ULT therapy might confer additional kidney protection, beyond that of existing risk factors, although adequately powered randomised clinical trials are needed to confirm these early observations. While we await these studies, greater efforts should be expended to improve the quality of care of patients with gout, especially in achieving current target thresholds for uric acid to improve outcomes. 33 22 | 2018 | hospitalpharmacyeurope.com References 1 Kuo CF et al. Global epidemiology of gout: prevalence, incidence and risk factors [review]. 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