Uric Acid: The Lower the Better?

BACKGROUND: Uric acid (UA) is still considered a risk factor, or even a causative agent, for chronic kidney disease (CKD); however, a few, important, clinical questions remain unanswered; in particular: when and whether urate-lowering therapy should be commenced in subjects with asymptomatic hyperuricemia and/or monosodium urate crystals deposition? What is the most appropriate UA target to be achieved and how long does it need to be maintained? How does treatment need be adjusted in patients with chronic kidney disease?

SUMMARY: The observational and intervention studies available do not fully answer such questions, and a treatment to target trial is required. We provide here some preliminary opinion on how such a trial might be designed. A final unresolved issue relates to the possible (if any) dangers of overtreatment of hyperuricemia, leading to "hypouricemia," which may occur more frequently with newer, more potent, drugs. A U- or J-shaped association has been found between UA levels and mortality in epidemiologic studies; patients with congenital hypouricemia are more prone to exercise-induced renal failure; a theoretical concern, linked to more complete Xanthine Oxidase inhibition, may involve xanthine nephropathy, although up to now, it has been observed almost exclusively in patients with tumor lysis syndrome. Key Messages: Although there is no definite answer to the title question at the moment, available information tends to indicate a treatment target with serum UA levels between 5.0 and 6.0 mg/dL as reasonable.