Note on Uric Acid as "Marker" for the Metabolic Syndrome

Before I forget to mention this, there are many articles in which the argument or implication is made that uric acid, as a marker, or "disease marker," plays some sort of undefined, causal role in diabetes, heart disease, etc. Uric acid tends to be elevated in these syndromes, but the idea that uric acid is causal in heart disease or the metabolic syndrome has been refuted on multiple levels. There can be some effects on the kidneys, worsening of proteinuria in people with kidney disease, and many years of hyperuricemia can produce gout. But the basic idea is that all those diseases are accompanied by one degree or another of ischemia and metabolic derangements, and ischemia, along with other disease processes, more or less always elevated xanthine oxidase activity and increases purine export from endothelial cells, etc. Sometimes the statement is made that free radical production by xanthine oxidase is harmful, but, even if this were the case (it actually is a minor contributor to oxidative stress), this wouldn't implicate an elevation of uric acid per se as a causal factor in atherogenesis or any process associated with elevated xanthine oxidase activity (because uric acid is produced by xanthine oxidase or xanthine dehydrogenase). I'll try to post some of the articles on this "issue," but it's sort of a non-issue. I know of some studies showing uric acid crystals in the kidney, or maybe uric acid per se, can upregulate renin release by the kidneys (and thereby potentially raise blood pressure by the renin-angiotensin system), but I'm not sure about the validity of that. I saw one study showing that urate can inhibit Na+/K+-ATPase, but the concentration used was probably supraphysiological. I can't remember the concentration, but I remember that the authors were suggesting urate could produce neurotoxicity. That's not plausible, regardless of the concentration, though, the idea that urate either inhibits Na+/K+-ATPase significantly, at physiologically-relevant concentrations, or would cause neurotoxicity by that mechanism. In Lesch-Nyhan syndrome, urate is elevated dramatically and is well-known not to produce neurotoxicity. I mean, I've read many articles on Lesch-Nyhan syndrome, and the neurotoxicity associated with that disorder would be easy to manage if urate were the cause of it. The authors of the articles tend to complain that it's not the cause, etc. The article talking about the interaction of urate with the sodium-potassium pump is interesting, though. The article implies that urate may interact with purine transporters, given that it's a purine and can apparently be transported in and out of endothelial cells, among other cell types. It's not just confined to the extracellular fluid and blood. There's reason to think that elevations in uric acid could raise blood pressure slightly, given that elevations in uric acid tend to promote sodium retention by the kidneys. In any case, the idea in neurological disorders is not to elevate uric acid to supraphysiological levels but to remedy the pathologically low levels that tend to accompany diseases like Alzheimer's, multiple sclerosis, and Parkinson's disease.