Systemic Urate Deposition: An Unrecognized Complication of Gout?

Abstract

Gout, an inflammatory arthritis, affects over nine million people in the US with increasing prevalence. Some medical societies do not recommend treating gout unless it is recurrent. While soft tissue urate deposits (tophi), resultant bone erosions, and joint inflammation are frequently recognized in gout, urate crystal deposits in other sites have been thought to be rare. Recent diagnostic testing, such as dual energy computed tomography (DECT), has led to the recognition that urate deposits are not uncommon in other tissues including the vasculature. To understand the potential risks for untreated gout, we reviewed the literature on extra-articular urate deposition documented by autopsy, histopathology, surgery, and radiology, including the heart, blood vessels, kidney, spine, eye, skin, and gastrointestinal system. These studies extend the significance of gout beyond the rheumatologist and emphasize the need for physicians to follow the American College of Rheumatology guidelines to treat subjects with gout to a goal of achieving serum urate <6 mg/dl. Given the growing body of literature on extraarticular urate deposition, further studies and clinical trials are needed to determine the clinical consequences of systemic urate deposition, including if reducing cardiac and vascular urate deposits may provide a survival benefit for this at-risk population.

Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities

“…As mentioned above, data on the natural history of gout (Fig. 1 ) are scarce but the application of modern imaging techniques, such as dual-energy CT, has led to the recognition of a pre-symptomatic phase of gout in some individuals in whom MSU crystal deposition occurs in joints, soft tissues and vascular sites before the first gout flare (asymptomatic MSU crystal deposition) 35 , 36 . Whether this pre-symptomatic phase is more common in people with CKD in whom the inflammatory response to crystals might be suppressed remains unknown, as does the timing of progression from asymptomatic to symptomatic gout in people with CKD.…”

Uric Acid and Hypertension: Prognostic Role and Guide for Treatment

“…In fact, both these vasoconstrictor molecules can be over-expressed in the presence of high UA concentrations, inducing the development of hypertension [65,79]. UA can also mediate the development of hypertension through a crystal-dependent pathway [80,81]. In fact, monosodium urate deposits have been found in the kidney medulla, cardiac valves, arteries, and within the atherosclerotic plaque [80,81].…”

“…UA can also mediate the development of hypertension through a crystal-dependent pathway [80,81]. In fact, monosodium urate deposits have been found in the kidney medulla, cardiac valves, arteries, and within the atherosclerotic plaque [80,81]. These deposits could lead to kidney injury and arterial stiffness, increasing the risk for hypertension [80,81].…”

Mini Review: Reappraisal of Uric Acid in Chronic Kidney Disease

“…Subjects with CKD and gout have more tophi than gouty subjects with normal kidney function (6-fold greater in stage 3 CKD) [38], suggesting they carry higher risk for extra-articular crystal deposits. Recently, it has been recognized that urate crystals can deposit in many locations, including the kidney, blood vessels, and spine [39]. One study reported that urate crystals are present in the aorta or coronary vessels in 80% of subjects with gout [40], where it can localize to plaques [41].…”