Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –

Takae, Keita; Nagata, Michio; Hata, Jun; Mukai, Naoko; Hirakawa, Yoichiro; Yoshida, Daigo; Kishimoto, Hiro; Tsuruya, Kazuhiko; Kitazono, Takanari; Kiyohara, Yutaka; Ninomiya, Toshiharu

doi:10.1253/circj.cj-16-0030

Cited by 50 publications

(45 citation statements)

References 30 publications

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“…Comprehensive surveys of cognitive impairment in the elderly of this town have been conducted since 1985 11. In 2002 and 2003, 1760 residents aged 60 and older (participation rate 83.4%) underwent a screening examination for the present study 12. After excluding 122 subjects who already had dementia at baseline, 31 for whom no urine sample was obtained, 1 for whom no blood sample was obtained, and 44 for whom no educational information was obtained, the remaining 1562 subjects (672 men, 890 women) were enrolled in this study.…”

Section: Methodsmentioning

confidence: 99%

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Takae

Hata

Ohara

et al. 2018

JAHA

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BackgroundEpidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD).Methods and ResultsA total of 1562 community‐dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all‐cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin–creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow‐up, 358 subjects developed all‐cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable‐adjusted risks of all‐cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78–1.60], 1.65 [1.18–2.30], and 1.56 [1.11–2.19] for UACR of ≤6.9, 7.0–12.7, 12.8–29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77–1.86], 1.75 [1.16–2.64], and 1.58 [1.03–2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46–2.29], 1.94 [0.96–3.95], and 2.19 [1.09–4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of <60 mL/min per 1.73 m2 had 3.3‐fold greater risk of VaD than those with UACR <12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m2.ConclusionsAlbuminuria is a significant risk factor for the development of both AD and VaD in community‐dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.

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Section: Methodsmentioning

confidence: 99%

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Takae

Hata

Ohara

et al. 2018

JAHA

Self Cite

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“…Previous epidemiological studies have reported that elevated serum uric acid level was associated with an increased risk of CKD [11][12][13][14][15][16], but moderate alcohol consumption was associated with decreased risk of CKD [17][18][19][20]. The comparative importance and joint relationship of elevated serum uric acid and alcohol consumption to the risk of CKD has not been confirmed well.…”

Section: Introductionmentioning

confidence: 94%

“…The comparative importance and joint relationship of elevated serum uric acid and alcohol consumption to the risk of CKD has not been confirmed well. Only 4 prospective studies of healthy middle-aged adults are available on relating serum uric acid to the risk of incident CKD after adjustment for alcohol consumption [13][14][15][16]. Of them, 3 studies used alcohol consumption levels as a dichotomous variable and did not describe its definition clearly [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Only 4 prospective studies of healthy middle-aged adults are available on relating serum uric acid to the risk of incident CKD after adjustment for alcohol consumption [13][14][15][16]. Of them, 3 studies used alcohol consumption levels as a dichotomous variable and did not describe its definition clearly [14][15][16]. The other in the Netherlands used alcohol consumption levels as a continuous variable, but did not show the results of alcohol consumption in association with the risk of CKD [13].…”

Section: Introductionmentioning

confidence: 99%

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Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

et al. 2019

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Background: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. Methods: A prospective cohort study of 9,116 middle-aged nondiabetic Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1–23.0 g ethanol/day), moderate drinkers (23.1–46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. Results: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11–1.70), 1.58 (95% CI 1.28–1.95), 2.27 (95% CI 1.86–2.77), and 3.12 (95% CI 2.56–3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46–0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. Conclusions: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.

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“…Meanwhile, on the basis of the well-known relationship between serum uric acid (SUA) level and renal function deterioration [4,5], hyperuricemia is an independent risk factor [6] that impairs each of renal functions, i.e. glomerular filtration rate and albuminuria.…”

Section: Introductionmentioning

confidence: 99%

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

et al. 2018

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Background Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. Methods The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level. Results At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-tocreatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the estimated glomerular filtration rate (− 0.2 vs. − 4.0 mL/min/1.73 m 2 , p = 0.0303) and the serum uric acid level (− 2.94 vs. − 0.20 mg/ dL, p < 0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group. Conclusion These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients.

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Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –

Cited by 50 publications

References 30 publications

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

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Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community – The Hisayama Study –

Cited by 50 publications

References 30 publications

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia in Community‐Dwelling Japanese Elderly: The Hisayama Study

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

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Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –