Uric Acid, Cardiovascular Mortality, and Long-Term Outcomes in CKD

We were interested to read the study of Madero et al1 reporting that hyperuricemia was associated with increased risk of all-cause and cardiovascular (CV) mortality, but not with kidney failure, in patients with stage 3 to 4 chronic kidney disease (CKD). Interestingly, there is a dilemma in the article. Putative mechanisms for increased all-cause and CV mortality are said to include inflammation, endothelial dysfunction, and vascular smooth muscle proliferation; all of which also are risk factors for the progression of CKD.2, 3 However, as the results of this study show, these mechanisms did not have an effect on CKD progression, but on CV mortality, which is an unexpected finding. Thus, the mechanism of increased CV mortality, but not CKD progression, is not clear.

Because the renin-angiotensin system is involved in the pathological mechanisms of target-organ damage, renin-angiotensin system blockade decreases CV mortality and CKD progression.4 However, in this study, there are no data dealing with antihypertensive medication use by the patients. Moreover, because losartan has a uricosuric effect,5 use of this drug may have some effects on results of this study. Another point is nonsteroidal anti-inflammatory drug (NSAID) use in the study population. Unfortunately, NSAIDs are widely prescribed all over the world, and their regular use in large quantities may increase the risk of CKD.6 However, data dealing with NSAID use of the patients also are missing in this study.