REN and chronic kidney disease: Gout has been identified as an independent risk factor for chronic kidney disease, nephrolithiasis and acute kidney injury, wherein uric acid excretion by the kidneys participate in facilitating crystal-induced direct tubular toxicity.310 This finding underscores the close interconnection between uric acid and nitric oxide regulation in this particular clinical context.329 Kidney damage mediated by UA involves the stimulation of the renin-angiotensin-aldosterone system.