Coronary crystals, such as cholesterol crystals and calcifications, likely exacerbate chronic vascular inflammation via macrophage inflammasome activation, and resultant plaque progression. Likewise, monosodium urate is involved in local inflammation at the culprit site of an acute gouty flare. Relatively, little is known about the evidence of monosodium urate depositions in a human heart because of a lack of imaging that allows to visualize an individual monosodium urate crystal with thickness of 1 to 2 µm. This paper will review recent advances in studies with novel imaging approaches for coronary monosodium urate crystals in human patients.

It remains inconclusive whether urate-lowering therapy for asymptomatic patients with hyperuricemia is effective to prevent chronic kidney diseases (CKD) and atherosclerotic cardiovascular diseases (CVD). Hyperuricemia is caused by reduced renal/extrarenal excretion and overproduction of uric acid. It is affected by the genetic predisposition for uric acid transporters and also by visceral fat accumulation due to overnutrition. Since patients with hyperuricemia comprise a heterogeneous population based on complex pathologies, it may be important to assess whether outcomes are the result of decreasing serum uric acid levels or the inhibitory effect on xanthine oxidoreductase (XOR). This minireview focuses mainly on recent papers investigating the relationship between hyperuricemia and CKD or CVD, and intervention studies involving urate-lowering therapy. Accumulating experimental studies have proposed mechanistic insights into renal damage and atherosclerosis in hyperuricemia, including inflammasome activation, decreased nitric oxide bioavailability and oxidative stress by uric acid, urate crystals, and XOR-mediated reactive oxygen species. Recently, strong positive correlations between plasma XOR activity and liver enzymes have been shown in clinical studies. Especially in the presence of NAFLD, excessive plasma XOR derived from liver accelerates purine catabolism in the circulation, using hypoxanthine secreted from vascular endothelial cells and adipocytes, which can promote the development of vascular remodeling. Furthermore, the XOR inhibitor topiroxostat improved arterial stiffness parameters in hyperuricemic patients with liver dysfunction, which may be related to its inhibitory effect on plasma XOR. In this review, we focused on the significance of liver-derived XOR and XOR inhibition in the development of arteriosclerosis.

Hypouricemia and hyperuricemia in children are important clinical problems. Exercise‑induced acute renal injury (EIAKI) is a major complication in patients with renal hypouricemia and is more common in young patients. Hyperuricemia in children has been linked to obesity, metabolic syndrome, hypertension, glucose intolerance, dyslipidemia, and non‑alcoholic fatty liver disease (NAFLD), and is a risk factor for future development of lifestyle‑related diseases. Recently, we conducted a population‑based cross‑sectional study to measure the prevalences of hypouricemia and hyperuricemia, and identify the associated factors based on the results of pediatric health check‑ups in Kagawa prefecture. Among 31,822 9‑10‑year‑old participants, hypouricemia (serum UA ≤ 2 mg/dL) was detected in 122 [0.38%] participants (57 boys [0.35%] and 65 girls [0.41%]), which is consistent with previously reported prevalences in Japanese adults. The prevalence of hypouricemia was not significantly associated with age, sex, or environmental factors, including overweight. Furthermore, the results indicated that the differential diagnosis of renal hypouricemia is better with serum uric acid levels ≤ 2.0 mg/dL than ≤ 2.5 mg/dL in children as in adults. Hyperuricemia (serum UA ≥ 6.0 mg/dL) was detected in 734 [2.3%] participants (437 boys [2.7%] and 297 girls [1.9%]). The prevalence of hyperuricemia was significantly associated with age, sex, overweight, future diabetes risk, hypertriglyceridemia, low high‑density lipoprotein‑cholesterol, and liver damage, but not with high low‑density lipoprotein cholesterol. Further longitudinal studies are needed to determine the long‑term prognosis of children with hypouricemia and hyperuricemia and the effectiveness of interventions.

As gout is associated with both nephrolithiasis and renal dysfunction, it may be a good research subject for elucidating the relationship between hyperuricemia and renal dysfunction. However, most conventional studies on urolithiasis have focused analysis on urolithiasis history. Our study using CT has provided several novel findings regarding kidney stones and renal damage. They are: (1) one-third of gout patients carry kidney stones, and two-thirds of stone carriers are silent. This means that analysis based on urolithiasis history does not provide an accurate clinical picture. (2) The declined renal function in gout patients was reportedly due to the renal dysfunction in bilateral stone carriers. (3) About 10 percent of gout patients had high-density areas (HDA), with CT values of 60 to 120 HU in renal pyramids. Their renal function was markedly reduced. Many researchers have endeavored to study the relationship between hyperuricemia and renal dysfunction and elucidate the mechanisms underlying inflammation or the immune system as biological effects of hyperuricemia for hypertension and renal dysfunction, but they still remain disputed. Hyperuricemia can simultaneously cause a pathological condition in the collecting ducts, such as uric acid crystallization, which destroys nephrons and induces kidney dysfunction. When hyperuricemia is simply treated as an independent variable in an environment of pH 7.4, other pathologies occurring in the renal pyramid, where the pH fluctuates, might be overlooked. These two pathologies in serum and urine are considered to jointly lead to renal dysfunction by hyperuricemia.

Background and Objective: Fasting decreases urinary urate (UA) excretion by half in uricase (Uox) - knockout (KO) mice, an animal model of hyperuricemia. We speculated that rodents are heavily influenced by dietary purine intake. However, there are no reports on the differences in purine content in animal diets or their effects on UA kinetics. In this study, we measured the purine content in standard and purified diets to investigate the effect of a purified diet on UA kinetics in high hypoxanthine phosphoribosyltransferase (HPRT) - activity Uox - KO mice.

Methods: The purine contents of a standard diet, Charles River Formula-1 (CRF-1), and a purified diet, AIN93M, were measured using a peak-shift assay with xanthine oxidase (XO) treatment and HPLC. Wild-type (WT) and high HPRT-activity Uox - KO mice were fed the CRF-1 or AIN93M diet for seven days to evaluate the effects of dietary purine intake on UA-related parameters.

Results: The purine content of AIN93M was approximately one-seventeenth times lower than that of CRF-1. The WT mice showed no significant variation in UA-related parameters in the AIN93M group compared with that in the CRF-1 group; however, the urinary allantoin/creatinine ratio was decreased. Conversely, the AIN93M group showed significantly decreased plasma UA levels and urinary UA/creatinine ratios than those in the CRF-1 group of high HPRT-activityUox - KO mice.

Conclusion: High HPRT-activity Uox - KO mice were useful for evaluating the variation in UA kinetics induced by dietary therapy. Additionally, a low-purine diet decreased plasma UA levels and urinary UA excretion in a mouse model of hyperuricemia.

Classification of hyperuricemia is important in order to understand its pathology and treat patients effectively. However, classification using 60-minute or 24-hour urine collection in outpatients is not convenient. A straightforward method has been reported for classifying the type of hyperuricemia based on the ratio of the urinary uric acid concentration to urinary creatinine concentration in spot urine. The purpose of this study was to classify hyperuricemia based on spot urine in outpatient cardiology departments and examine the treatment results of dotinurad for the uric acid underexcretion type. This study included 94 consecutive patients with hyperuricemia who had a serum uric acid level greater than 7.0 mg/dL. The patients were classified by spot urine at an outpatient cardiology department between January 2021 and November 2021. A urinary uric acid concentration to urinary creatinine concentration ratio of 0.5 or less was classified as the uric acid underexcretion type, while a ratio of more than 0.5 was classified as the uric acid overproduction type. There were 79 males and 15 females, with a mean age of 69.6 ± 11.8 years. Of the 94 patients, 63 (67%) had the uric acid underexcretion type. Drug therapy was administered to 11 patients with hyperuricemia who met the criteria for drug therapy and provided informed consent. Dotinurad was administered to 8 patients with the underexcretion type of uric acid, and 6 patients (75%) achieved the target control (serum uric acid level ≤ 6.0 mg/dL). Since only 1 mg/day of dotinurad was administered, it was deemed necessary to increase the dosage of dotinurad in order to reach the target level for controlling uric acid.

We previously identified a positive correlation between the uric acid/creatinine ratio and salt intake in both men and women in cases with untreated serum uric acid levels, but a significant positive correlation between urinary pH and potassium excretion only in women, suggesting the presence of sex differences in urinary excretion mechanisms. In this study, we analyzed the relationship between uric acid excretion and changes in electrolyte excretion in men and women. The results showed that the correlations between the urinary UA/Cr ratio and urinary Na/Cr ratio, urinary Na/Cr ratio and urinary pH, and urinary K/Cr ratio and urinary pH changes were significant in both sexes, but the relationship between the urinary Na/Cr ratio and urinary K/Cr ratio changes was significant in female but not male cases. We consider that one possible factor leading to a sex difference in uric acid excretion is a sex difference in the regulation of urinary Na and urinary K.

Xanthine oxidoreductase (XOR) is an enzyme that catalyzes uric acid production by catabolizing hypoxanthine, an intermediate product of the synthesis and degradation of purine nucleotides, including adenosine 5'-triphosphate (ATP). Considering that hypoxanthine is utilized for purine nucleotide synthesis via the salvage pathway, XOR inhibition is expected to increase the hypoxanthine levels and enhance ATP production, leading to the treatment of various diseases. We investigated the effects of NP-1250-HU, a novel potent XOR inhibitor, on the intracellular ATP and purine levels. In the mouse vascular smooth muscle-derived cell line, NP-1250-HU decreased the uric acid levels and increased the hypoxanthine levels at concentrations of 0.3–3.0 µM. The addition of 2.0 µM NP-1250-HU to the medium significantly increased the intracellular ATP levels under hypoxic conditions and recovered cell viability upon respiratory chain inhibition. Compared to other XOR inhibitors, 2.0 µM NP-1250-HU and 10 µM febuxostat showed similar increases in the ATP levels under hypoxic conditions, but 50 µM allopurinol did not. These results suggest that NP-1250-HU contributes to increasing the ATP levels via the salvage pathway by increasing the intracellular hypoxanthine levels. This paper briefly describes a high-performance liquid chromatography method for analyzing purine compounds using caffeine as an internal standard.