The epidemiology of uric acid and fructose

During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Correspondingly, the prevalence and incidence of gout have doubled. Potential reasons behind these trends include the increasing prevalence of obesity and metabolic syndrome, Western lifestyle factors, increased prevalence of medical conditions (eg, renal conditions, hypertension, and cardiovascular disorders), and use of medications that increase uric acid levels (eg, diuretics and low-dose aspirin). The substantial increase in sugar-sweetened soft drinks and associated fructose consumption also has coincided with the secular trend of hyperuricemia and gout. Recently, several large-scale epidemiologic studies have clarified a number of these long-suspected risk factors in relation with hyperuricemia and gout. Furthermore, recent studies have illuminated the substantial comorbidities of hyperuricemia and gout, particularly metabolic-cardiovascular-renal conditions. Although many prospective studies have suggested an independent association between serum uric acid levels and the future risk of cardiovascular-metabolic morbidities and mortality, only a limited number of randomized clinical trials and observational studies recently have shown that the use of allopurinol can be beneficial against these outcomes. Because these data are scarce and the effects of allopurinol might not be limited to decreasing serum uric acid levels, the potential causal role of uric acid on these outcomes remains to be clarified with further studies.     

The effects of topiroxostat on vascular function in patients with hyperuricemia

Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol and febuxostat, inhibit the catalysis of serum uric acid (SUA) synthesis. In doing so, they are thought to improve vascular endothelial function in patients with hyperuricemia and cardiovascular risk by reducing increases in SUA and reactive oxygen species levels. We performed a retrospective cohort study to evaluate the effects of topiroxostat, a novel XOR inhibitor, on vascular function measured by flow‐mediated dilation (FMD) on ultrasonography. In total, 23 patients with hyperuricemia were enrolled. After approximately 8 weeks, topiroxostat was associated with a significant increase in the peak percentage change in diameter (∆FMD) from 4.53% ± 2.09% to 5.54% ± 3.08% (P = .045). It also significantly reduced the SUA levels from 7.31 ± 1.43 to 5.44 ± 1.11 mg/dL (P < .001). Although further studies are needed to validate these results, it appears that topiroxostat improves vascular endothelial function in patients with hyperuricemia.     

Spontaneous tumor lysis syndrome in a child with T‐cell acute lymphoblastic leukemia

We report a 5‐year‐old female who presented with unexplained acute renal failure (ARF) and hyperuricemia and who was subsequently diagnosed of T‐cell acute lymphoblastic leukemia (ALL). Peripheral smear was initially unremarkable. She required hemodialysis. Two weeks later, peripheral smear showed 40% blasts and bone marrow demonstrated T‐cell ALL. Our case was the fifth and the youngest case of ALL with spontaneous tumor lysis syndrome. However, in contrast to previous reports in ALL or acute myeloid leukemia, our patient did not have blasts noted on periphereal blood smear and her white blood cell count and serum lactate dehydrogenase level were normal on admission, a time when dialysis‐dependent ARF and severe hyperuricemia were present. Occult hematologic malignancy should be considered in cases of ARF and hyperuricemia of unknown etiology even when peripheral hematologic findings are not informative. Pediatr Blood Cancer 2010;54:773–775. © 2009 Wiley‐Liss, Inc.     

通络止痛合剂对高尿酸血症大鼠血尿酸、黄嘌呤氧化酶的影响

目的：观察通络止痛合剂对高尿酸血症大鼠的治疗作用。方法：将大鼠按照性别、体重随机分为正常组、模型组、通络止痛合剂组、别嘌呤醇组和苯溴马隆组。按照腺嘌呤、氧嗪酸钾连续灌胃复制大鼠高尿酸血症模型。观察各组用药后28d大鼠血清中尿酸含量的变化及黄嘌呤氧化酶（xanthine oxidase,XOD）的活性。结果：用药28d后,药物组血清中尿酸含量明显降低,与模型组比较（P〈0.05）,有统计学意义。各药物组XOD活性较模型组明显降低（P〈0.05）。结论：通络止痛合剂可降低血清尿酸含量及XOD活性,对高尿酸血症有一定的治疗作用。     

Novel urate transporter 1 (URAT1) inhibitors: a review of recent patent literature (2016–2019)

ABSTRACT

Introduction: Human urate transporter 1 (URAT1), which is an influx transporter protein, is located at the apical surface of renal tubular cells and presumed to be the major transporter responsible for the reabsorption of urate from blood. About 90% of patients develop hyperuricemia due to insuf?cient urate excretion; thus, it is important to develop URAT1 inhibitors that could enhance renal urate excretion by blocking the reabsorption of urate anion.

Areas covered: In this review, the authors addressed the patent applications (2016–2019) about URAT1 inhibitors and some medicinal chemistry strategies employed in these patents.

Expert opinion: Substituent decorating, bioisosterism, and scaffold hopping are three common medicinal chemistry strategies used in the discovery of URAT1 inhibitors. Meanwhile, the introduction of sulfonyl group into small molecules has become one of the important strategies for structural optimization of URAT1 inhibitors. Furthermore, developing drug candidates targeting both URAT1 and xanthine oxidase (XOD) has attracted lots of interest and attention.     

Pegloticase and the patient with treatment-failure gout

Gout is an inflammatory arthritis characterized by sudden, painful inflammation. Gout can affect any joint in an asymmetric distribution. Gouty attacks may be isolated or can be followed by years of recurrent flares. Over time, elevated serum urate levels and tophaceous deposits can lead to deformity and disability from underlying bony erosion. The concept of ‘treatment-failure gout’ describes a unique population that has been either unable to tolerate allopurinol or who have not experienced normalization of serum urate levels on allopurinol. It is estimated that approximately 1–1.5% of the estimated 3–8 million people with gout in the USA have treatment-failure gout. Pegloticase is an US FDA-approved intravenous medication that is a mammalian recombinant uricase conjugated to monomethoxy polyethylene glycol. Two recent Phase III trials have found pegloticase to be effective in the management of treatment-failure gout. These studies also highlight safety concerns regarding the drug’s immunogenicity.     

益肾健脾泄浊化瘀方联合西药治疗慢性高尿酸血症肾病随机平行对照研究

[目的]观察益肾健脾泄浊化瘀方联合西药治疗慢性高尿酸血症肾病疗效。[方法]使用随机平行对照方法,将40例住院及门诊患者按随机数字表法分为两组。对照组20例基础西药治疗;嘌呤醇,0.1~0.2g/次,3次/d,口服;至血尿酸降至360umol/L时改为维持量:0.1g/次,1次/d,口服。治疗组20例益肾健脾泄浊化瘀方(山茱萸12g,山药、伏苓各20g,薏苡仁30g,土茯苓、川牛膝、制大黄各15g,丹参30g,萆薢15g,益母草、黄芪、威灵仙各20g),1剂/d,水煎450mL,3次/d,口服;西药治疗同对照组。连续治疗28d为1疗程。观测临床症状、临床表现积分、肾损害指标、不良反应。连续治疗2疗程,判定疗效。[结果]治疗组显效9例,有效9例,无效2例,总有效率90.00%。对照组显效2例,有效10例,无效8例,总有效率60.00%。治疗组疗效优于对照组(P0.05)。生化指标、临床表现积分改善治疗组优于对照组(P0.05)。临床表现积分治疗组改善优于对照组(P0.05)。肾损害指标治疗组改善优于对照组(P0.05)。[结论]益肾健脾泄浊化瘀方联合西药治疗慢性高尿酸血症肾病效果显著,值得推广。     

益肾泄浊方治疗慢性肾脏病伴高尿酸血症临床研究

目的评价益肾泄浊方治疗慢性肾脏病伴高尿酸血症的临床疗效。方法采用前瞻性队列研究方法,将52例患者分为治疗组(27例)和对照组(25例),分别予益肾泄浊方和别嘌呤醇片治疗。两组疗程均为3个月,观察血清肌酐(Scr)、估算肾小球滤过率(eGFR)、血清尿酸(UA)及尿素氮(BUN)等指标的变化情况。结果治疗后治疗组Scr、UA水平显著下降(P0.05),eGFR明显升高(P0.05);对照组UA水平显著下降(P0.05),但Scr及eGFR未见明显改善(P0.05);组间治疗前后差值比较,Scr、eGFR差异有统计学意义(P0.05)。结论益肾泄浊方能够显著改善慢性肾脏病伴高尿酸血症患者的肾功能,其升高eGFR的作用并非依赖UA的降低;对于GFR下降的患者,单独应用别嘌呤醇虽能降低UA水平,但并不能使患者的肾功能受益。     

温肾泄浊汤对中老年男性无症状高尿酸血症血尿酸及性激素的影响

目的观察温肾泄浊汤对中老年男性无症状高尿酸血症患者血尿酸及性激素水平的影响。方法将60例高尿酸血症患者随机分为观察组和对照组,各30例;对照组采用二妙丸治疗,观察组采用温肾泄浊汤治疗,疗程6周。观察两组治疗前后血尿酸(SUA)、睾酮(T)、雌二醇(E2)水平变化。结果治疗后两组SUA均有下降(P0.05,P0.01),但组间比较无统计学差异(P0.05)。治疗后观察组T水平显著升高(P0.05),E2水平显著降低(P0.05),E2/T比值显著降低(P0.01);两组T水平和E2/T比值有显著差异(P0.05,P0.01)。结论温肾泄浊汤治疗高尿酸血症可降低血尿酸及调整性激素水平。