Insights into renal damage in hyperuricemia: Focus on renal protection (Review)

Abstract

The incidence of hyperuricemia has increased recently, posing a serious threat to public health. Hyperuricemia is associated with an increased risk of gout, chronic kidney disease (CKD), obesity, metabolic syndrome, type 2 diabetes mellitus, hypertension, hypertriglyceridaemia, metabolic dysfunction‑associated steatotic liver disease, acute kidney injury, coronary heart disease and cardiovascular disease (CVD). These diseases are commonly accompanied by varying degrees of kidney damage. A number of randomized controlled clinical trials have investigated the effectiveness of UA‑lowering therapies in preventing kidney disease progression. The present review provided fundamental insights into the pathogenesis, principles and therapeutic approaches for managing hyperuricemia in patients with aforementioned diseases and assesses the effect of uric acid‑lowering therapy on diabetic nephropathy, systemic lupus erythematosus, CKD, CVD and obesity progression.

Keywords: Hyperuricaemia; Uric acid; Renal damage; Urate-lowering therapy.

Figure 1.

UA is the final product of purine, with ~80 and 20% derived from the endogenous purine metabolism and exogenous purine sources (such as high purine diet, alcohol intake and fructose intake), respectively. The conversion, decomposition and metabolism of amino acids, nucleic acids and phosphate ribose groups in the body generates endogenous UA. XOR enzyme catalyzes the terminal two reactions of purine catabolism in humans. In particular, XOR catalyzes the oxidation from hypoxanthine to xanthine and from xanthine to UA, with the simultaneous reduction of NAD+ or O₂. Notably, 70 and 30% UA is excreted through the kidneys and intestine, respectively. UA, uric acid; XOR, xanthine oxidoreductase.

Figure 2.

Uric acid is considered a mediator in the pathological process, including inflammation, cell apoptosis, oxidative stress, vascular smooth muscle cell proliferation and endothelial dysfunction, involving the development of various diseases, including gout, hypertension, cardiovascular disease, atherosclerosis and chronic kidney disease. ROS, reactive oxygen species; eNOS, endothelial nitric oxide synthase; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; CVD, cardiovascular disease; CKD, chronic kidney disease.