Uric acid and chronic kidney disease: A time to act?

Table 5 Studies of uric-acid-lowering therapy in patients with chronic kidney disease

Ref.	Study population	Intervention	Study findings	Limitations
Neal et al[61], 2001	18 liver transplant recipients with gout (n = 8) and hyperuricemia (n = 10)	Allopurinol (dose not stated)	Mean serum creatinine decreased from 2.0 to 1.8 mg/dL over a median period of 3 mo	Retrospective study; indication bias; small sample size
Fairbanks et al[62], 2002	27 patients with FJHN	Allopurinol (dose not stated)	Early treatment associated with slower decline of renal function	Case series, single center, partially inadequate controls
Siu et al[63], 2006	54 CKD patients with proteinuria > 0.5 g per day, serum creatinine > 1.4 mg/dL and serum uric acid > 7.6 mg/dL	Allopurinol 100-200 mg daily or their usual therapy for 12 mo	Lower serum creatinine in the allopurinol arm than the control arm (2.0 ± 0.9 vs 2.9 ± 0.9 mg/dL; P = 0.08) and no differences in effect on proteinuria (2.53 ± 4.85 g per day vs 2.16 ± 1.93 g per day; P = NS)	Small sample size, open-label design, short duration of follow-up
Shelmadine et al[64], 2009	12 prevalent adult hemodialysis patients	Allopurinol 300 mg twice daily for 3 mo	Reduction in LDL cholesterol by 0.36 μmol/L (14 mg/dL) (P = 0.04)	No control arm; small sample size; no safety data; no data on hemodynamic parameters; dose of allopurinol higher than recommended
Goicoechea et al[65], 2010	113 CKD patients with eGFR < 60 mL/min per 1.73 m2	Allopurinol 100 mg daily or no study medication for 24 mo	Allopurinol slowed the decline in eGFR (1.3 ± 1.3 mL/min per 1.73 m2vs–3.3 ± 1.2 mL/min per 1.73 m2); no effect on BP	Small sample size; open label and single-center study; allocation concealment unclear; assessor blinding unclear
Kao et al[66], 2011	53 stage 3 CKD patients with LVH	Allopurinol 300 mg daily or placebo for 9 mo	Allopurinol reduced LVMI (–1.42 ± 4.67 g/m2vs 1.28 ± 4.45 g/m2) and improved brachial artery FMD (1.26% ± 3.06% vs -1.05% ± 2.84%); improved augmentation index (P = 0.015)	Surrogate end-points only
Momeni et al[67], 2010	40 patients with type 2 diabetes and overt nephropathy (proteinuria > 500 mg/24 h, and serum creatinine < 3.0 mg/dL)	Allopurinol 100 mg or placebo	Treated patients had lower serum UA and 24 h proteinuria after 4 mo of follow-up	Small sample size, single-center, short follow-up, blinding unclear
Kanbay et al[68], 2011	30 hyperuricemic subjects vs 37 hyperuricemic and 30 normouricemic controls	4 mo treatment with allopurinol, 300 mg vs no study medication	Allopurinol treated patients had increased e-GFR with respect to baseline	Small sample size, short duration, blinding unclear

FJHN: Familial juvenile hyperuricemic nephropathy; CKD: Chronic kidney disease; e-GFR: Estimated glomerular filtration rate; LDL: Low-density lipoprotein; LVH: Left ventricular hypertrophy; FMD: Flow-mediated dilation; LVMI: Left ventricular mass index; UA: Uric acid.