Thanks for your astute comments. For sure we need more research and clinical trials. However, the best data that hyperuricemia may have a direct effect on vascular tone comes from the study by Dan Feig (Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008 Aug 27;300(8):924-32. doi: 10.1001/jama.300.8.924. PMID: 18728266; PMCID: PMC2684336) that showed allopurinol corrects BP and lowers systemic vascular resistance and plasma renin activity in adolescents with new onset hypertension. So there is human evidence that hyperuricemia may activate the renin angiotensin system in addition to animal studies. A second mechanism that's really emerging as important is the formation of crystals in acidic urine that can lead to tubular inflammation and kidney disease. This suggests hyperuricemia may be more likely to cause CKD when urine is acidic or urinary uric acid levels are high. Hyperuricemic subjects are known to have high urinary uric acid excretion following purine and sugar rich meals. While the fractional excretion is low, overall urinary uric acid excretion tends to be high.