[in Japanese]

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Uric acid is considered to be one of the risk factors for atherosclerotic disorders. The suggested mechanisms include renin angiotensin system (RAS) activation. It is well-known that RAS plays a pivotal role in atherosclerotic disorders. However, evidence that uric acid is involved in RAS activation is still not sufficient. We therefore tested the hypothesis that a genetic variant of a uric acid transporter, SLC2A9 (GLUT9), was significantly correlated with the prevalence of a hyper-reninemic state. We enrolled 804 consecutive patients who had consulted our hospitals for lifestyle-related diseases. We divided them into a hyper-reninemic group as cases and normo-reninemic group as controls based on plasma renin activity (PRA). Genomic DNA was isolated from leukocytes. Genotypes were assayed for C/Tvariants using the real-time PCR system with the TaqMan method. The association between genetic variants and the hyper-reninemic state was tested. Compared with the CC and CT groups, the serum uric acid level of the TT group was significantly higher. Accordingly, the risk of a hyper-reninemic state was around 1.2 for the T allele, with significance on allelic comparison. Armitage’s trend test also revealed that the T allele was the risk allele. The uric acid levels are associated with a genetic variant of GLUT9, and subjects with the high uric acid variant show a hyper-reninemic constitution. Thus, from the viewpoint of the Mendelian randomization theory, a high uric acid state may have a significant impact on RAS activation.

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Tumor lysis syndrome (TLS) is a life-threatening oncological emergency caused by the rapid release of intracellular materials from lysing malignant cells. The outcomes of novel cancer chemotherapies have recently improved. However, their potent anticancer effects have increased the risk of developing TLS with hyperuricemia and/or renal dysfunction. Several new antihyperuricemic agents have also been developed. The present TLS guidance was published in Japan in 2013, but this may not provide optimal management strategies for TLS. We aimed to determine the present status of TLS and acute uric acid nephropathy (UAN) management in daily clinical practice by conducting a questionnaire survey involving 55 doctors in the Hokuriku Hematology Oncology Study Group. Thirty-eight (69%) respondents described their experiences with 612 patients, among whom 286, 167, and 48 were at low, intermediate, and high risk of TLS, respectively. The responses showed that 13 of the 612 patients who were treated with new anticancer drugs developed TLS and three developed acute UAN despite being at low risk of TLS. The responses also showed that 67.5% of doctors tried to prevent TLS using antihyperuricemics agents even for patients at low risk of TLS. Thus, the present findings revealed that the Japanese TLS guidance for managing TLS does not appropriately classify the real-world risk 2019. Thus, the TLS guidance regarding treatment strategies should be revised as soon as possible.

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