Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications

Abstract

Asymptomatic hyperuricemia (HU) is considered a pathogenic factor in multiple disease contexts but a causative role is only proven for the crystalline form of uric acid in gouty arthritis and urate nephropathy. Epidemiological studies document a robust association of HU with hypertension, cardiovascular disease, and CKD progression, but CKD-related impaired uric acid clearance and the use of diuretics which further impair uric acid clearance likely accounts for these associations. Interpreting the available trial evidence is further complicated by referring to xanthine oxidase inhibitors as urate-lowering treatment, although these drugs inhibit other substrates, so that attributing their effects only to HU is problematic. In this review, we provide new mechanistic insights on the biological effects of soluble and crystalline UA, and discuss clinical evidence on the role of asymptomatic HU in CKD, cardiovascular disease, and sterile inflammation. We identify research areas with gaps in experimental and clinical evidence, specifically on infectious complications that represent the second common cause of death in CKD patients, referred to as secondary immunodeficiency related to kidney disease (SIDKD). In addition, we address potential therapeutic approaches on how and when to treat asymptomatic HU in patients with kidney disease and where further interventional studies are required.

Increased risk of chronic kidney disease in uric acid stone formers with high neutrophil-to-lymphocyte ratio

“…An acidic environment facilitates uric acid crystallization in the kidney 20 , which is a pro-inflammatory and cytotoxic event. The crystalline uric acid not only cause renal tubular obstruction, microhematuria and proteinuria, but also trigger M1-like macrophage-related interstitial inflammation, fibrosis, and subsequently granulomatous interstitial nephritis 21 , 22 , which contribute to CKD progression.…”

Comorbidity of upper urinary tract stones and cardiovascular pathology: risk factors and common pathophysiological mechanisms

“…Підвищений вміст сечової кислоти може спричинити окислювальний стрес і активацію запальних механізмів, що призводить до дисфункції ендотелію судин та розвитку атеросклерозу. Крім того, гіперурикемія може сприяти активації ренін-ангіотензинальдостеронової системи, що сприяє збільшенню кров'яного тиску та розвитку серцево-судинних захворювань і їх ускладнень [18].…”

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease

“…On one side, both disorders coexist inside the metabolic-cardiovascular complex. In addition, CKD predisposes to hyperuricemia, an effect mediated by different mechanisms, which include a reduced glomerular filtration rate (GFR), genetic predisposition and the side effects of different medications for the management of CKD [ 9 ]. On the other side, UA crystal deposition is a well-known determinant of acute and persistent kidney injury [ 10 , 11 ].…”

“…On the other side, UA crystal deposition is a well-known determinant of acute and persistent kidney injury [ 10 , 11 ]. However, it is presently unclear if asymptomatic hyperuricemia can contribute to the generation and progression of CKD [ 9 ]. This controversial association could be a direct consequence of the above mentioned pathogenic effects of UA, and also be indirectly mediated by other factors (high blood pressure, medications).…”