There are at least four randomized interventional
studies using allopurinol in renal disease. Siu et al. randomized
54 patients with CKD 3-4 to allopurinol or placebo
for 12 months. Allopurinol decreased systolic blood
pressure (from 140 to 127 mmHg; control unchanged at
135 mmHg) and slowed CKD progression (defined as >40%
rise in serum creatinine; 12 versus 42% of patients) [37].
Goicoechea et al. randomized 113 patients with eGFR 0.2 mL/min/1.73 m2; adjusted HR 0.53) and
hs-CRP (from 4.4 to 3.0 versus 3.4-3.2 mg/l) favouring allopurinol
treatment, and a beneficial effect on cardiovascular
endpoints (7/57 versus 15/56), but no effect on blood pressure
[38]. Momeni et al. randomized 40 patients with type
2 diabetes mellitus and diabetic nephropathy to allopurinol
or placebo, with a reduction in proteinuria (from 1.8 to 1.0
versus 1.7 to 1.6 g per 24 h) in the allopurinol-treated group
[39]. Shi et al. randomized 40 IgA nephropathy patients to
allopurinol or usual treatment for 6 months. There was indirect
evidence for a reduction in blood pressure on allopurinol
(the antihypertensive drug doses were reduced in
7/9 cases with hypertension on allopurinol versus 0/9 in the control group), but no difference in eGFR [40]. In a posthoc
analysis of the RENAAL trial, losartan reduced urate
levels by 0.16 mg/dL (0.01 mmol/L) from 6.7 mg/dL (0.4
mmol/L) during the first 6 months; adjustment for the
urate effect indicated that 1/5 of losartan's renoprotective
effect could be attributed to this reduction in urate [41].
However, it is difficult to draw any firm or generalizable
conclusion for CKD, although there could be an effect of
allopurinol on blood pressure and possibly an effect on
eGFR.