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
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