Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound

Abstract

Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four ‘indirect’ drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels.

Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial

“…This result raises the possibility that febuxostat was effective for attenuating earlier progression of carotid atherosclerosis, suggesting a limited role of febuxostat on the development of atherosclerosis. Further research is therefore warranted to determine the optimal patients with asymptomatic hyperuricemia who could potentially obtain cardiovascular and renal benefits from treatment with febuxostat [30].…”

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

“…Another option for treating hyperuricemia is the use of medications with secondary SUA lowering capabilities such as losartan, atorvastatin, calcium channel blockers, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, fenofibrate, sevelamer, metformin, and angiotensin-II/ neprilysin inhibitors (ARNI). Some medications that should be considered for discontinuation because of their known effect to raise SUA are acetylsalicylic acid, cyclosporine, theophylline, mycophenolate, beta-and alpha-1-adrenergic antagonists, and angiotensin-converting enzyme (ACE) inhibitors [5,15,[41][42][43][44].…”

Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study

“…The tubular atrophy/interstitial fibrosis caused by SUA might be explained by the following mechanisms. Urate crystals deposit in the renal tubules can directly damage or block the renal tubules, and also form uric acid renal stones to damage the kidney, which results in renal tubular atrophy and interstitial fibrosis, even renal failure (Viggiano et al, 2018). HUA could also promote the production of inflammatory factors such as MCP-1 and TNF-β1, which stimulates the inflammatory response and induce renal tubular injury and renal interstitial fibrosis (Romi et al, 2017).…”

“…Numerous studies have shown that the level of uric acid can predict the incidence of atherosclerosis (Feig, 2014;Gustafsson & Unwin, 2013;Li et al, 2014), hypertension (Wang et al, 2014), and coronary heart disease (Kim et al, 2010;Braga et al, 2016). Moreover, some studies have emphasized that high levels of serum uric acid (SUA) would form urates crystals that deposit in renal tubules and interstitial, leading to kidney fibrosis and failure (Su et al, 2020;Viggiano et al, 2018). Recently, some studies have found that there is a correlation between the SUA level and the progression of IgAN.…”