Previous clinical studies have indicated that hyperuricemia is a potentially modifiable risk factor for the development and progression of chronic kidney disease (CKD).¹ x 1 Bose, B., Badve, S.V., Hiremath, S.S. et al. Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2014; 29: 406–413 Crossref | PubMed | Scopus (90) | Google Scholar See all References ^{, 2} x 2 Badve, S.V., Brown, F., Hawley, C.M. et al. Challenges of conducting a trial of uric-acid-lowering therapy in CKD. Nat Rev Nephrol. 2011; 7: 295–300 Crossref | PubMed | Scopus (28) | Google Scholar See all References ^{, 3} x 3 Jalal, D.I., Chonchol, M., Chen, W., and Targher, G. Uric acid as a target of therapy in CKD. Am J Kidney Dis. 2013; 61: 134–146 Abstract | Full Text | Full Text PDF | PubMed | Scopus (102) | Google Scholar See all References ^{, 4} x 4 Iseki, K., Ikemiya, Y., Inoue, T., Iseki, C., Kinjo, K., and Takishita, S. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004; 44: 642–650 Abstract | Full Text | Full Text PDF | PubMed | Scopus (327) | Google Scholar See all References Some small controlled clinical studies have shown that urate-lowering therapy with allopurinol can retard CKD progression.⁵ x 5 Gibson, T., Rodgers, V., Potter, C., and Simmonds, H.A. Allopurinol treatment and its effect on renal function in gout: a controlled study. Ann Rheum Dis. 1982; 41: 59–65 Crossref | PubMed | Scopus (52) | Google Scholar See all References ^{, 6} x 6 Siu, Y.P., Leung, K.T., Tong, M.L.K., and Kwan, T.H. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006; 47: 51–59 Abstract | Full Text | Full Text PDF | PubMed | Scopus (506) | Google Scholar See all References ^{, 7} x 7 Goicoechea, M., de Vinuesa, S.G., Verdalles, U. et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010; 5: 1388–1393 Crossref | PubMed | Scopus (449) | Google Scholar See all References ^{, 8} x 8 Goicoechea, M., Garcia de Vinuesa, S., Verdalles, U. et al. Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis. 2015; 65: 543–549 Abstract | Full Text | Full Text PDF | PubMed | Scopus (98) | Google Scholar See all References Nevertheless, sufficient clinical evidence to support widespread use of the therapy to slow CKD progression is not available.¹ x 1 Bose, B., Badve, S.V., Hiremath, S.S. et al. Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2014; 29: 406–413 Crossref | PubMed | Scopus (90) | Google Scholar See all References Furthermore, information for the effects of xanthine oxidase inhibitors on early kidney damage is sparse or lacking.⁹ x 9 Pisano, A., Cernaro, V., Gembillo, G., D'Arrigo, G., Buemi, M., and Bolignano, D. Xanthine oxidase inhibitors for improving renal function in chronic kidney disease patients: an updated systematic review and meta-analysis. Int J Mol Sci. 2017; 18 (pii:E2283) Crossref | PubMed | Scopus (2) | Google Scholar See all References

Significance: High salt intake is common in Western diets and likely contributes to hypertension and cardiovascular disease. Recently high salt intake has also been found to both be associated and predict the development of obesity, insulin resistance, and metabolic syndrome. Here we show that high-salt diet activates the aldose reductase (polyol) pathway in the liver, resulting in endogenous fructose production that then induces leptin resistance and the development of metabolic syndrome and fatty liver. Blocking fructose metabolism blocks the effects of high-salt diet. High salt intake also predicts diabetes and nonalcoholic fatty liver disease in Japanese adults. Thus, high-salt diet, an essential micronutrient with no intrinsic caloric value, may have a contributory role in driving obesity and diabetes.

Whether asymptomatic hyperuricemia in the absence of comorbidities increases the risk for cardiometabolic disorders and chronic kidney disease remains controversial. This study was conducted to clarify the association between asymptomatic hyperuricemia and cardiometabolic conditions. Subjects consisting of Japanese adults between 30 and 85 years of age were enrolled in the study at Center for Preventive Medicine, St Luke’s International Hospital, Tokyo, and were available at enrollment (2004) and at 5-year follow-up (2009). Subjects were excluded if they were overweight or obese, hypertensive, diabetic, and dyslipidemic, had a history of gout or hyperuricemia on medications, or had chronic kidney disease as estimated glomerular filtration rate 7 mg/dL in men and ≥6 mg/dL in women) was associated with increased cumulative incidence of hypertension (14.9% versus 6.1%; P <0.001), dyslipidemia (23.1% versus 15.5%; P <0.001), chronic kidney disease (19.0% versus 10.7%; P <0.001), and overweight/obesity (8.9% versus 3.0%; P <0.001), while diabetes mellitus (1.7% versus 0.9%; P =0.087) showed a trend but did not reach statistical significance. In conclusion, asymptomatic hyperuricemia carries a significant risk for developing cardiometabolic conditions in Japanese individual without comorbidities.

Background: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C–lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. Methods: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. Results: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50–0.86; P =0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37–0.98; P =0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18–0.79; P =0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. Conclusions: LDL-C–lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp . Unique identifier: UMIN000001988.

Prehypertension frequently progresses to hypertension, a condition associated with high morbidity and mortality from cardiovascular diseases and stroke. However, the risk factors for developing hypertension from prehypertension remain poorly understood. We conducted a retrospective cohort study using the data from 3584 prehypertensive Japanese adults (52.1±11.0 years, 2081 men) found to be prehypertensive in 2004 and reexamined in 2009. We calculated the cumulative incidences of hypertension over 5 years, examined risk factors, and calculated odds ratios (ORs) for developing hypertension after adjustments for age, sex, body mass index, smoking and drinking habits, baseline systolic and diastolic blood pressure, pulse rate, diabetes mellitus, dyslipidemia, chronic kidney disease, and serum uric acid levels. The additional analysis evaluated whether serum uric acid (hyperuricemia) constituted an independent risk factor for developing hypertension. The cumulative incidence of hypertension from prehypertension over 5 years was 25.3%. There were no significant differences between women and men (24.4% versus 26.0%; P =0.28). The cumulative incidence of hypertension in subjects with hyperuricemia (n=726) was significantly higher than those without hyperuricemia (n=2858; 30.7% versus 24.0%; P <0.001). After multivariable adjustments, the risk factors for developing hypertension from prehypertension were age (OR, 1.023; P <0.001), female sex (OR, 1.595; P <0.001), higher body mass index (OR, 1.051; P <0.001), higher baseline systolic (OR, 1.072; P <0.001) and diastolic blood pressure (OR, 1.085; P <0.001), and higher serum uric acid (OR, 1.149; P <0.001). Increased serum uric acid is a strong risk marker for developing hypertension from prehypertension. Further studies are needed to determine whether treatment of hyperuricemia in prehypertensive subjects could impede the onset of hypertension.