Logo of ndtLink to Publisher's site
Nephrol Dial Transplant. Nov 2010; 25(11): 3593–3599.
Published online May 25, 2010. doi:  10.1093/ndt/gfq262
PMCID: PMC2980994

The relationship between serum uric acid and chronic kidney disease among Appalachian adults

Abstract

Background. Higher serum uric acid (SUA) levels have been shown to be associated with cardiovascular disease. SUA levels are also associated with hypertension, a strong risk factor for chronic kidney disease (CKD). However, it is unclear whether SUA is independently associated with CKD. We examined the hypothesis that higher SUA levels are positively associated with CKD.

Methods. We analysed data from the C8 Health Study, a population-based study of Appalachian adults aged ≥18 years and free of cardiovascular disease (n = 49,295, 53% women). SUA was examined as gender-specific quartiles. The outcome of interest was CKD (n = 2,980), defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 from serum creatinine.

Results. Overall, we observed a clear positive association between increasing quartiles of SUA and CKD, independent of confounders. Compared with the lowest quartile of SUA (referent), the multivariable odds ratios (95% confidence interval) for quartiles 2–4, respectively, of CKD were 1.53 (1.31, 1.78), 2.16 (1.86 2.50) and 4.67 (4.07, 5.36); P-trend < 0.0001. This observed positive association persisted in separate analysis among men (P-trend < 0.0001) and women (P-trend < 0.0001).

Conclusions. In conclusion, higher SUA levels are positively associated with CKD, suggesting that at least part of the reported association between SUA and cardiovascular disease may be mediated by CKD.

Keywords: Appalachian, chronic kidney disease, creatinine serum, glomerular filtration rate, serum uric acid

Introduction

Chronic kidney disease (CKD) is considered to be an independent risk factor for cardiovascular disease (CVD) and CVD mortality [1]. Studies suggest that elevated serum acid levels are also associated with CVD and CVD mortality [2,3]. Current research shows that higher serum uric acid levels are associated with hypertension [4–8] and diabetes mellitus [9], two major risk factors for chronic kidney disease.

An association between serum uric acid and kidney disease is biologically plausible. A recently developed rat model of mild hyperuricaemia demonstrated that mild elevations in uric acid, even within the normal limits, can cause hypertension and renal microvascular disease without causing urate crystal deposition in kidneys [10]. Studies also suggest that uric acid is an active player in processes related to CVD and kidney disease development such as inflammation, endothelial dysfunction and oxidative stress [11,12].

In spite of these leads, a few epidemiological studies have explored the independent relationship between serum uric acid and CKD, and the results were not consistent. While some studies reported high uric acid to be associated with renal disease [13–16], this finding was not confirmed by others [17,18]. In this context, we examined the association between serum uric acid and chronic kidney disease in a population-based study of Appalachian adults after controlling for the effect of major confounding factors such as body mass index (BMI), diabetes mellitus and hypertension.

Materials and methods

Study population

The C8 Health Study is a population-based study of Appalachian individuals residing in six communities in West Virginia and Ohio. The study was primarily aimed at examining the health effects of environmental exposures among community residents. The study subjects were examined, and the blood samples were collected between August 2005 and August 2006. The study was approved by the Institutional Review Board of the West Virginia University School of Medicine, Morgantown.

We estimated the participation rate among adults aged ≥20 years using the 2005 census data. The overall study participation rate among adults aged ≥20 years was 81%; this ranged from 70.2% to 94.8% in these six communities. Written informed consent was obtained from each subject at the examination.

In the current paper, out of 69,030 subjects who were examined for the C8 Health Study, we excluded subjects who were <18 years of age (n  = 12,476), and those with missing data for variables included in the multivariable analysis, including missing serum creatinine (n = 2,428), smoking status (n = 148), years of school completed (n = 1,346), BMI (n = 13,069), and alcohol intake (n = 2,860). Ninety-six percent of the population was constituted by non-Hispanic whites, 1.24% was non-Hispanic blacks and all other races–ethnicities such as Hispanic and Asian Americans constituted the remaining 2.76%. We additionally excluded subjects with CVD (n = 5931), as that could confound the association between serum uric acid and CKD. This resulted in 49,295 eligible subjects, of whom 2,980 had CKD.

Exposure measurement

The study examination included administering a standardized questionnaire that collected information regarding participants'’ demographic characteristics and details regarding cigarette smoking, alcohol intake, medical histories and medications taken, including diagnosis of diabetes, hypertension or CVD by a physician. Blood specimens were obtained for measurement of plasma glucose, serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. A detailed medical chart review was also performed to verify the accuracy of self-reported diagnoses.

Age was defined as the participant'’s age at the time of examination. Education was categorized as below high school, high school or above high school. BMI was defined as the participant's self-reported weight in kilograms divided by the height in metres squared. Hypertension was defined as self-reported hypertension diagnosis by a physician and use of antihypertensive medications. Persons were defined as having diabetes mellitus if they already had a diabetes diagnosis by a physician and were treated with insulin, oral hypoglycaemic agents or diet (this information was verified by a nurse from physician records), or were newly classified as having diabetes based on the presence of a casual blood sugar value ≥200 mg/dL (11.1 mmol/L) or fasting glucose ≥126 mg/dL (7.0 mmol/L); fasting blood samples were available only on a subset of subjects (30.1% of the whole sample). Uric acid was measured by the enzymatic uricase method. The normal analytical range for the serum uric acid in the labs involved was 0.5–12 mg/dL. The normal range in men is 3.6–8.4 mg/dL and in women is 2.9–7.5 mg/dL [19].

Outcome of interest: chronic kidney disease

Serum creatinine was measured using a kinetic rate Jaffe method consistent with the current National Kidney Disease Education Program (NKEDP) recommendations for serum creatinine measurement [20]. Glomerular filtration rate (GFR) was estimated from serum creatinine using the re-expressed four-variable Modification of Diet in Renal Disease (MDRD) equation defined as follows: eGFR = 175 × serum creatinine (in milligram per decilitre)1.154 × age0.203 × 0.742 (if the individual is female) or × 1.212 (if the individual is black [21]). CKD was defined as an eGFR of <60 mL/min/1.73 m2, based on the US National Kidney Foundation Kidney Disease Outcome Quality Initiative working group definition [22] and the Kidney Disease Improving Global Outcomes (KDIGO) [23].

Statistical analysis

We examined serum uric acid as gender-specific quartiles—quartiles 1–4 in women: <3.8, 3.9–4.6, 4.7–5.5 and >5.5 mg/dL; quartiles 1–4 in men: <5.4, 5.5–6.2, 6.3–7.1 and >7.1 mg/dL. We also analysed serum uric acid as a continuous variable after a logarithmic transformation due to its skewed distribution. The odds ratio (OR) [95% confidence interval (CI)] of CKD was calculated for each serum uric acid quartile, with the lowest quartile as the reference, using multivariable logistic regression models. We used two models: the unadjusted model and the multivariable model adjusted for age (years), race–ethnicity (non-Hispanic whites, non-Hispanic blacks or all others), education categories (<high school, high school or >high school), smoking (never, former or current), alcohol intake (never, former or current), body mass index (normal, overweight or obese), diabetes mellitus (absent or present), hypertension (absent or present) and serum cholesterol (milligram per decilitre). Trends in the OR of CKD across increasing serum uric acid quartiles were determined by modelling serum uric acid as an ordinal variable. Similarly, we examined serum uric acid as a continuous variable using the unadjusted and multivariable-adjusted logistic regression models. We also examined the direct relationship between serum uric acid and estimated glomerular filtration rate using multivariable-adjusted linear regression models.

To examine the consistency of the association between serum uric acid and CKD, we performed subgroup analyses by gender (women and men), age (<60 and ≥60 years) and BMI categories (<25 and ≥25 kg/m2). The observed association between serum uric acid and CKD may be explained by the presence of diabetes mellitus or hypertension, as these are strong risk factors for CKD and are also shown to be related to high uric acid levels. Therefore, we repeated the analysis among study subjects who were free of diabetes mellitus and hypertension (n = 37,398). Finally, to examine whether the observed association between serum uric acid and CKD is due to reverse causality, i.e. hyperuricaemia secondary to severe renal failure, we conducted a sensitivity analysis. We examined the association between serum uric acid and CKD after excluding study subjects with clinical evidence of severe renal failure, defined as a serum creatinine ≥2 mg/dL. Uric acid-lowering medications used to treat gout such as allopurinol may affect the association observed between serum uric acid and chronic kidney disease. Therefore, in a supplementary analysis, we excluded subjects who were taking uric acid lowering medications (n= 335) and repeated the analysis among study subjects who were not taking uric acid lowering medications (n= 48,960). All analyses were performed in SAS version 9.2 (SAS Institute, Cary, NC, USA).

Results

Among 49,295 Appalachian adults ≥18 years of age and without clinical cardiovascular disease included in the current analysis, there were 26,346 women and 22,949 men. Overall, 2,980 subjects had CKD, including 1,977 women and 1,003 men. Among patients with CKD, 71.1% had minor renal damage (eGFR 50–60 mL/min/1.73 m2 range), 23.4% had an eGFR range of 49.9–35 mL/min/1.73 m2, 4.7% had and an eGFR range of 34.9–15 mL/min/1.73 m2 and 0.8% had an eGFR range <15 mL/min/1.73 m2. Also, 65.4% of subjects with CKD were elderly (aged ≥60 years).

Table 1 presents the characteristics of the study population by serum uric acid quartiles. Those individuals who were in higher serum uric acid quartiles were more likely to be high school educated, never and former smokers, and never drinkers, and more likely to have higher BMI and hypertension and higher total cholesterol levels. Also, in a supplementary analysis, we found that the mean serum uric acid level (SE) was 5.6 mg/dL (0.01) among never smokers, 5.8 mg/dL (0.01) among former smokers, 5.3 mg/dL (0.02) among current smokers smoking <1 pack/day, 5.4 mg/dL (0.02) among current smokers smoking 1–2 packs/day and 5.8 mg/dL (0.09) among current smokers smoking >2 packs/day. Similarly, by drinking frequency, the mean serum uric acid level (SE) was 5.5 mg/dL (0.14) among never drinkers, 5.5 mg/dL (0.12) among former drinkers, 5.6 mg/dL (0.1) among current drinkers drinking <1 drink/day, 6.1 mg/dL (0.03) among current drinkers drinking 1–3 drinks/day and 6.3 mg/dL (0.07) among current drinkers drinking >3 drinks/day.

Table 1
Characteristics of the study population by categories of serum uric acid levelsa

Table 2 presents the ORs of CKD by increasing serum uric acid quartiles in the entire cohort. Serum uric acid quartiles were positively associated with CKD in both the unadjusted and the multivariable-adjusted model; models evaluating the trend in this association were also statistically significant. Also, when serum uric acid was analysed as a continuous variable, we observed a positive association with CKD [multivariable OR (95% CI): 1.57 (1.32–1.87)]. Finally, when we examined the direct association between serum uric acid and eGFR in a multivariable linear regression model, we observed a statistically significant, inverse association [beta (standard error): −2.53 (0.06); P-value < 0.0001], consistent with previous results examining categorical CKD as the outcome.

Table 2
Association between serum uric acid levels and CKD in the whole cohort

Table 3 presents the ORs of CKD by increasing serum uric acid quartiles separately in women and men. Among both women and men, there was a clear positive association between increasing serum uric acid quartiles and CKD in both the age-adjusted and the multivariable-adjusted model; models evaluating the trend in this association were statistically significant.

Table 3
Association between serum uric acid levels and CKD, by gender

Table 4 presents the ORs of CKD by increasing serum uric acid quartiles separately in those <60 and ≥60 years. For each age category, there was a clear positive association between increasing serum uric acid quartiles and CKD in both the age-adjusted and the multivariable-adjusted model; models evaluating the trend in this association were statistically significant.

Table 4
Association between serum uric acid levels and CKD, by age category (<60 and ≥60 years)

Table 5 presents the ORs of CKD by increasing serum uric acid quartiles by BMI categories. There was a clear positive association between increasing serum uric acid quartiles and CKD in both the age-adjusted and the multivariable-adjusted model among both normal weight (BMI <25 kg/m2) as well as overweight/obese (BMI ≥25 kg/m2) adults; models evaluating the trend in this association were statistically significant.

Table 5
Association between serum uric acid levels and CKD, by body mass index (BMI)

Table 6 presents the ORs of CKD by increasing serum uric acid quartiles after excluding those with hypertension and diabetes. Consistent with previous results, increasing serum uric acid quartiles were positively associated with CKD in both the unadjusted and multivariable-adjusted model; models evaluating the trend in this association were also statistically significant.

Table 6
Association between serum uric acid levels and CKD among subjects without diabetes or hypertension

Table 7 presents the ORs of CKD by increasing serum uric acid quartiles after excluding those with serum creatinine levels ≥2 mg/dL. Consistent with previous results, increasing serum uric acid quartiles were positively associated with CKD in both the unadjusted and multivariable-adjusted model; models evaluating the trend in this association were also statistically significant.

Table 7
Association between serum uric acid levels and CKD in the whole cohort, excluding those with serum creatinine levels ≥2 mg/dL

A supplementary analysis was conducted excluding individuals who were taking uric acid-lowering medications. Compared with the lowest serum uric acid quartile, the multivariable OR (95% CI) of CKD was 1.56 (1.33, 1.82), 2.17 (1.87, 2.52) and 4.75 (4.13, 5.47); P-trend < 0.0001. In another supplementary analysis, we examined the association between serum uric acid and CVD. In the unadjusted model, we found a strong positive association between increasing serum uric acid quartiles and CVD. Compared with the lowest serum uric acid quartile (referent), the unadjusted OR (95% CI) of CVD was 0.98 (0.90, 1.07), 1.17 (1.07, 1.27) and 1.84 (1.71, 1.99); P-trend < 0.0001. However, the association was attenuated with multivariable adjustment of confounders, including age, race–ethnicity, education, smoking, alcohol intake, body mass index, diabetes, hypertension and serum cholesterol. Compared with the lowest serum uric acid quartile, the multivariable OR (95% CI) of CVD was 1.04 (0.95, 1.15), 1.05 (0.96, 1.16) and 1.13 (1.03, 1.24); P-trend < 0.0001.

Discussion

In a population-based study of Appalachian adults, increasing serum uric acid levels were positively associated with CKD, independent of age, gender, smoking status, alcohol intake, education, diabetes mellitus, hypertension, BMI and total cholesterol. The association between serum uric acid and CKD remained consistent in subgroup analyses by gender, BMI and among subjects without diabetes and hypertension.

Several lines of recent evidence suggest that an association between uric acid and CKD is plausible. In recent rat models, mild hyperuricaemia caused renal microvascular disease without crystal deposition in kidneys [24]. The mechanism for the renal changes in the aforementioned rat model predominantly involves activation of the renin–angiotensin system and inhibition of the endothelial nitric oxide systems [11,12,24].

Hyperuricaemia may also be caused secondarily by renal impairment [25]. Urate handling by the kidneys involves filtration at the glomerulus, reabsorption, secretion and, finally, post-secretory reabsorption at tubules which are handled by multiple organic anion transporters that have been recently identified such as the urate/anion exchanger (URAT1), the human organic anion transporter (hOAT1) and the urate transporter (UAT) [26]. Consequently, elevated serum uric acid levels—as observed in our study—may result secondary to decreased glomerular filtration, decreased tubular secretion or enhanced tubular reabsorption. Decreased urate filtration can contribute to the hyperuricaemia of renal insufficiency. Decreased tubular secretion of urate occurs in patients with acidosis (e.g. diabetic ketoacidosis, ethanol or salicylate intoxication, or starvation ketosis). The organic acids that accumulate in these conditions compete with urate for tubular secretion. Finally, enhanced reabsorption of uric acid distal to the site of secretion is the mechanism thought to be responsible for the hyperuricaemia observed with diuretic therapy and diabetes insipidus.

Our finding of a positive association between higher serum uric acid level and CKD shows high internal validity, as shown by the magnitude of the association, independence from confounding factors such as age, smoking, alcohol intake and other factors, a positive dose–response trend, and consistency of association in subgroup analyses by gender and BMI. As diabetes and hypertension are strong, independent risk factors for CKD and also related to higher uric acid levels, it is possible that the observed association between uric acid and CKD is explained by these CKD risk factors. However, when we examined the association between serum uric acid and CKD among study subjects free of diabetes and hypertension, the results were found to be consistent with the main multivariable findings, suggesting an association independent of diabetes and hypertension. Also, our results of a positive association between uric acid and CKD are consistent with most previous studies [13–16], but not all [17,18,27,28].

Our initial findings showed that subjects in higher serum uric acid quartiles were less likely to be current smokers and more likely to be former smokers. Although these findings are contrary to conventional wisdom, these are consistent with recent research which found that subjects with hyperuricaemia were less likely to be current smokers and more likely to be former smokers [29]. However, in a supplementary analysis, we also found that the mean serum uric acid level was highest in former (5.8 mg/dL) as well as in current smokers who reported smoking >2 packs/day (5.8 mg/dL), suggesting that current heavy smoking was also related to hyperuricaemia in addition to former smoking. Similarly, our initial findings showed that subjects in higher serum uric acid quartiles were less likely to be current drinkers. Although these findings are contrary to conventional wisdom, in a supplementary analysis, we also found that heavy drinkers (>3 drinks/day) had the highest serum uric acid level in our study population, consistent with previous reports [30].

Based on our findings, a corollary observation is that strategies to reduce serum uric acid, including dietary changes such as lower intake of fructose- and sugar-sweetened beverages and red meat [31], and uric acid-lowering drugs such as allopurinol [16], may be useful in preventing or arresting the progression of kidney disease. Reducing levels of serum uric acid may also reduce hypertension [4–8] and diabetes [9], which are strong risk factors of kidney disease. Finally, reduction in kidney disease through uric acid-lowering medication may indirectly help in reducing CVD and CVD mortality. In this context, in a recent randomized controlled trial of 54 hyperuricaemic patients with CKD from China, Siu et al. [16] reported that uric acid-lowering medication with allopurinol was associated with a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Future randomized intervention trials with larger sample sizes (and therefore adequate statistical power) are needed to investigate whether uric acid-lowering medication can, in fact, improve renal function.

The major strengths of our study are its large sample size, standardized methods of data collection, detailed measurement of biomarkers that represent potential confounding pathways such as serum cholesterol, and diabetes status. The internal validity of our results is high, as we stratified by gender, BMI, diabetes and hypertension, and performed multivariable adjustment of confounders. The first major limitation of this study is its cross-sectional design. Therefore, we are unable to draw any conclusions about the temporal association between serum uric acid and chronic kidney disease. Secondly, the large representative sample is primarily comprised of whites, reflecting the typical Appalachian community. Therefore, our results may not be generalized to other populations. Even though we showed that a supplementary analysis (Table 7) excluding those with serum creatinine levels ≥2 mg/dL yielded similar results as the main analysis, the possibility of reverse causality cannot still be definitely ruled out.

In conclusion, in a population-based sample of Appalachian adults, we found that increasing serum uric acid levels were positively associated with CKD. This association appeared to be independent of age, gender, smoking status, alcohol intake, education, diabetes mellitus, hypertension, BMI and total cholesterol levels. If supported by future prospective studies, uric acid-lowering medication may be an effective strategy to prevent and/or arrest CKD.

Acknowledgments

This research is supported in part by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV, USA) between DuPont and Plaintiffs, an American Heart Association National Clinical Research Program grant (AS) from the West Virginia University School of Medicine, and a Predoctoral Fellowship (LC) from the Department of Community Medicine, West Virginia University School of Medicine. This study followed the recommendations of Declaration of Helsinki and was approved by the Institutional Review Board of the West Virginia University School of Medicine, Morgantown, WV, USA. All authors contributed to the intellectual development of this paper. L.C. analysed the data and wrote the first draft of the paper. A.S., A.M.D. and K.S. provided statistical expertise and critical corrections to the manuscript, and were involved in manuscript revisions.

Conflict of interest statement. None declared.

References

1. Shlipak M, Fried L, Cushman M, et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA. 2005;293:1737–1745. [PubMed]
2. Fang J, Alderman M. Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. JAMA. 2000;283:2404–2410. [PubMed]
3. Culleton B, Larson M, Kamel W, et al. Serum uric acid and risk for cardiovascular disease and death: the Framingham Study. Ann Intern Med. 1999;131:7–13. [PubMed]
4. Sundstrom J, Sulliavan L, D’Agostino R, et al. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension. 2005;45:28–33. [PubMed]
5. Shankar A, Klein R, Nieto F, et al. The association between serum uric acid level and long-term incidence of hypertension: population-based cohort study. J Hum Hypertens. 2006;45:937–945. [PubMed]
6. Selby J, Friedman G, Quesenberry C., Jr Precursors of essential hypertension; pulmonary function, heart rate, uric acid and serum cholesterol, and other serum chemistries. Am J Epidemiol. 1990;131:1017–1027. [PubMed]
7. Jossa F, Farinaro E, Panico S, et al. Serum uric acid and hypertension: the Olivetti Heart Study. J Hum Hypertens. 1994;8:677–681. [PubMed]
8. Cannon P, Stason W, Demartini F, et al. Hyperuricemia in primary and renal hypertension. New Engl J Med. 1966;275:457–464. [PubMed]
9. Dehghan A, van Hoe M, Sijbrands E, et al. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31:361–362. [PubMed]
10. Kang D, Nakagawa T, Feng L, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002;13:2888–2897. [PubMed]
11. Bo S, Gambino R, Durazzo M, et al. Associations between serum uric acid and adipokines, markers of inflammation, and endothelial dysfunction. J Endocrinol Invest. 2008;31:499–504. [PubMed]
12. Kang D, Park S, Lee I, et al. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005;16:3553–3562. [PubMed]
13. Chonchol M, Shlipak M, Katz R, et al. Relationship of uric acid with progression of kidney disease. Am J Kidney Dis. 2007;50:239–247. [PubMed]
14. Iseki K, Oshiro S, Tozawa M, et al. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res. 2001;24:691–697. [PubMed]
15. Iseki K, Ikemyia Y, Inoue T, et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44:642–650. [PubMed]
16. Siu Y, Leung K, Tong M, et al. 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. [PubMed]
17. Fessel W. Renal outcomes of gout and hyperuricemia. Am J Med. 1979;67:74–82. [PubMed]
18. Hunsicker L, Alder S, Caggiula A, et al. Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int. 1997;51:1908–1919. [PubMed]
19. Witte D, Angstadt D, Schweitzer J. Chemistry profiles in “wellness programs”: test selection and participant outcomes. Clin Chem. 1988;34:1447–1450. [PubMed]
20. Myers G, Miller W, Coresh J, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem. 2006;52:5–18. [PubMed]
21. Levey A, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–254. [PubMed]
22. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266. [PubMed]
23. Levey A, Eckardt K, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Int. 2005;67:2089–2100. [PubMed]
24. Mazzali M, Hughes J, Kim Y, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38:1101–1106. [PubMed]
25. Madero M, Sarnak M, Wang X, et al. Uric acid and long-term outcomes in CKD. Am J Kidney Dis. 2009;53:796–803. [PMC free article] [PubMed]
26. Eraly S, Vallon V, Rieg T, et al. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol Genomics. 2008;33:180–192. [PMC free article] [PubMed]
27. Hsu C, Iribarren C, McCulloch C, et al. Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med. 2009;169:342–350. [PMC free article] [PubMed]
28. Yu T, Berger L. Impaired renal function in gout: its association with hypertensive vascular disease and intrinsic renal disease. Am J Med. 1982;72:95–100. [PubMed]
29. Villegas R, Xiang Y, Cai Q, et al. Prevalence and determinants of hyperuricemia in middle-aged, urban Chinese men. Metab Syndr Relat Disord. 2010 In press. [PMC free article] [PubMed]
30. Iribarren C, Folsom A, Eckfeldt J, et al. Correlates of uric acid and its association with asymptomatic carotid atherosclerosis: the ARIC Study. Atherosclerosis Risk in Communities. Ann Epidemiol. 1996;6:331–340. [PubMed]
31. Choi H, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum uric acid: the Third National Health and Nutritional Examination Survey. Arthritis Rheum. 2005;52:283–289. [PubMed]

Articles from Nephrology Dialysis Transplantation are provided here courtesy of Oxford University Press
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...