Abstract
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.
Highlights
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food (100–200 mg/day), and endogenously (500–600 mg/day) from damaged, dying, and dead cells, whereby nucleic acids, adenine and guanine, are degraded into UA [1]
Hyperuricemia is significantly associated with the development and severity of metabolic syndrome
The meta-analyses which studied whether UA-Lowering Treatment (ULT) reduces the progression of chronic kidney disease (CKD) showed insufficient data on incidence of end-stage renal disease (ESRD) for analysis and the heterogeneity across included studies, suggesting that adequately powered randomized controlled trials (RCTs) are needed to establish whether ULT has beneficial renal effects [87,88]
Summary
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food (100–200 mg/day), and endogenously (500–600 mg/day) from damaged, dying, and dead cells, whereby nucleic acids, adenine and guanine, are degraded into UA [1]. Hyperuricemia is induced by UA over-production due to acquired factors such as high purine diet, fructose ingestion, alcohol intake, myeloproliferative disorders, and rare genetic causes such as hypoxanthine-guanine phosphor-ribosyl-transferase (HPRT) deficiency and phosphor-ribosyl-pyrophosphate (PPRP) synthetase (PRS) hyperactivity [6]. The hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure since the kidney excretes approximately 70% of daily produced UA [2]. Meta-analysis showed that higher serum UA levels led to an increased risk of metabolic syndrome regardless of the study characteristics, and were consistent with a linear dose-response relationship [19]. Insulin resistance due to visceral fat accumulation may increase serum UA by decreasing renal UA clearance in patients with the metabolic syndrome. For a 1 mg/dL increase in UA level, the pooled RR for incident hypertension after adjusting for potential confounding was 1.13 (95%CI, 1.06 to 1.20)
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