Uric Acid and Chronic Kidney Disease: Still More to Do

Abstract

Gout and hyperuricemia are present in 25% and 60% of patients with chronic kidney disease (CKD), respectively. Despite the common association, the role of uric acid in the progression of kidney disease and in metabolic complications remains contested. Some authorities argue that the treatment of asymptomatic hyperuricemia in CKD is not indicated, and some have even suggested hyperuricemia may be beneficial. Here, we review the various arguments both for and against treatment. The weight of the evidence suggests asymptomatic hyperuricemia is likely injurious, but it may primarily relate to subgroups, those who have systemic crystal deposits, those with frequent urinary crystalluria or kidney stones, and those with high intracellular uric acid levels. We recommend carefully designed clinical trials to test if lowering uric acid in hyperuricemic subjects with cardiometabolic complications is protective.

Keywords: chronic kidney disease; gout; hyperuricemia; metabolic syndrome; systemic inflammation.

Figure 1

Relationship of Serum Uric acid with CKD. (a) A study in which more than 48,000 Japanese that were 20 years or older who were followed for 7 years. After controlling for baseline serum creatinine and other variables, the presence or absence of baseline hyperuricemia (defined as >7 mg/dl in men and >6 mg/dl in women) markedly increased the risk for developing end stage kidney disease requiring dialysis. (b) A figure based on the study of 5707 participants aged 20 years and older from the National Health and Nutrition Examination Survey 2007–2008. There is an exponential relationship of serum uric acid levels with CKD. (a) Adapted from Iseki et al. and (b) Adapted from Zhu et al. CKD, chronic kidney disease; HyperUric, hyperuricemia.

Figure 2

Uric acid may be more Important in the Initiation of Metabolic Diseases Rather than the Maintenance. AMPK, adenosine monophosphatase-activated protein kinas; ATP, adenosine trisphosphate; CKD, chronic kidney disease; NO, nitric oxide; RAS, renin angiotensin system.

Figure 3

Examples of potential clinical trials to investigate the role of uric acid in cardio-renal diseases. BP, blood pressure; CRP, C-reactive protein; CV, cardiovascular; DECT, dual energy computed tomography; XO, xanthine oxidase.