Original investigations
Pathogenesis and treatment of kidney disease and hypertension
Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort

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Background: Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. Methods: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level ≥ 7.0 mg/dL [≥416 μmol/L] in men and ≥ 6.0 mg/dL [≥357 μmol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. Results: Mean serum uric acid level was 6.4 ± 1.4 (SD) mg/dL (381 μmol/L) in men and 4.8 ± 1.1 mg/dL (286 μmol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. Conclusion: Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid ≥ 6.0 mg/dL [≥357 μmol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.

Section snippets

Study design

All subjects older than 20 years who participated in the 1993 mass health screening examinations in Okinawa, Japan, were eligible for the study. The population in 1993 was approximately 1.24 million. Screening participants were excluded from the present study if birth date or serum uric acid data were not available from the registry files. Dialysis patients who were among the 1993 screening participants and individuals who had become dialysis patients during the study period through December

Results

Baseline characteristics of screenees with data for serum uric acid level are listed in Table 1. Mean age at screening was 52.2 ± 15.6 years. The distribution of baseline levels of serum uric acid is shown in Fig 1. Mean serum uric acid level was 5.5 ± 1.5 mg/dL (327 μmol/L): 6.4 ± 1.4 mg/dL (381 μmol/L) for men and 4.8 ± 1.1 mg/dL (286 μmol/L) for women. Serum uric acid levels were greater in men than women in all age groups (Fig 2). Levels increased with age in women 51 years and older.

Discussion

The present study aims to investigate the relationship between baseline serum uric acid level and the development of ESRD by using a relatively large screening in a general population in Okinawa, Japan. Results show the significance of hyperuricemia on developing ESRD, particularly in women. Renal outcomes of gout and hyperuricemia have been considered not significant.16, 17 However, it recently was reappraised that hyperuricemia may be directly pathogenic and is not only a marker for other

Acknowledgment

The authors thank the staff of the OGHMA, in particular, M. Itokazu and K. Shiroma, for retrieving data files from the 1993 health check; Dr O. Morita for help with data processing and statistical analysis; and the physicians and co-medical staff of all dialysis units in Okinawa for their collaboration. The following doctors gave invaluable advice, support, and encouragement: T. Minei, T. Kowatari, K. Nishime, H. Ogimi, T. Yonaha, C. Mekaru, K. Kinjo, M. Nakayama, H. Uehara, H. Sunagawa, S.

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    Supported in part by grants from the Ministry of Health and Welfare of Japan.

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