Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

Abstract

The relationship between hyperuricemia, gout, and renal disease has been investigated for several years. From the beginning, kidney disease has been considered a complication of gout; however, the viewpoints changed, claiming that hypertension and elevated uric acid (UA) levels are caused by decreased urate excretion in patients with renal impairment. To date, several examples of evidence support the role of hyperuricemia in cardiovascular or renal diseases. Several mechanisms have been identified that explain the relationship between hyperuricemia and chronic kidney disease, including the crystal effect, renin–angiotensin–aldosterone system activation, nitric oxide synthesis inhibition, and intracellular oxidative stress stimulation, and urate-lowering therapy (ULT) has been proven to reduce renal disease progression in the past few years. In this comprehensive review, the source and physiology of UA are introduced, and the mechanisms that explain the reciprocal relationship between hyperuricemia and kidney disease are reviewed. Lastly, current evidence supporting the use of ULT to postpone renal disease progression in patients with hyperuricemia and gout are summarized.

Natural Flavonoid Pectolinarigenin Alleviated Hyperuricemic Nephropathy via Suppressing TGFβ/SMAD3 and JAK2/STAT3 Signaling Pathways

“…Disturbance of the balance between UA production and excretion would lead to HUA that is considered as an independent risk factor for CKD progression (Johnson et al, 2013). Persistently high-serum UA levels was reported to trigger kidney inflammation and fibrosis that might contribute to HN (Lee et al, 2021). Current standard treatment for HUA is UAlowering drugs represented by XO inhibitors and uricosuric agents, the nephroprotective effect of which remains controversy in CKD patients (Liu et al, 2021).…”

“…Kidney fibrosis, the ultimate pathological outcome of HN, is characterized by the expression of mesenchymal cell products such as α-SMA, FN, and Col I (Lee et al, 2021). The TGF-β/ Smad3 signaling pathway plays a critical role in mediating profibrotic response of renal epithelial cells and activating renal fibroblasts (Liu et al, 2015).…”

Early Diagnosis of Kidney Damage Associated with Tobacco Use: Preventive Application

“…Finally, in relation to the cessation of tobacco consumption, there is evidence indicating that it is one of the most effective measures to prevent the progression of renal failure [ 8 , 9 , 41 ]. In a study on patients with diabetic nephropathy, disease progression was observed in 53% of smokers, but only in 33% of former smokers and 11% of non-smokers [ 42 ].…”

Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study

“…With the increase in XOi use among gouty CKD patients, potential side effects of these medications have become important. This rise in prescription is at least partially contributed to hyperuricemia's suggested role in the progression to end-stage renal disease with studies demonstrating renoprotective potential of XOis (25)(26)(27)(28). Furthermore, hyperuricemia is widely accepted as a risk factor for cardiovascular diseases, perhaps partially due to promotion of chronic formation of neutrophil extracellular traps, thereby contributing to vascular damage (29).…”