Is the Serum Uric Acid Level Independently Associated with Incidental Urolithiasis?

Doo-Ho Lim; Min-ho Kim; Seokchan Hong; Yong-Gil Kim; Chang-Keun Lee; Seung Won Choi; Bin Yoo; Ji Seon Oh

doi:10.4078/jrd.2018.25.2.116

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Lim, Kim, Hong, Kim, Lee, Choi, Yoo, and Oh: Is the Serum Uric Acid Level Independently Associated with Incidental Urolithiasis?

Original Article

J Rheum Dis 2018;25(2):116-121.

Published online: 30 April 2018

DOI: https://doi.org/10.4078/jrd.2018.25.2.116

Is the Serum Uric Acid Level Independently Associated with Incidental Urolithiasis?

Doo-Ho Lim¹, Min-ho Kim², Seokchan Hong³, Yong-Gil Kim³, Chang-Keun Lee³, Seung Won Choi¹, Bin Yoo³, Ji Seon Oh⁴

¹Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

²Ewha Institute of Convergence Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea

³Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea

⁴Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding to: Ji Seon Oh http://orcid.org/0000-0002-0205-6492 Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: mdjsoh@amc.seoul.kr

Received 11 October 20171 January 2017 Accepted 23 January 2017

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Urolithiasis is one of the manifestations of gout and the risk is higher in gouty patients. On the other hand, an independent association between the urinary stone and serum uric acid (UA) level has not been established. This study examined whether the risk of urolithiasis increases with increasing serum UA level.

Methods

Among the people who visited a tertiary hospital from 2010 to 2013, 13,964 individuals who underwent both ultrasonography and a laboratory test were recruited in the study. The risk of urolithiasis on ultrasonography was analyzed in association with the serum UA level by multiple logistic regression analysis with an adjustment for age, sex, body mass index, estimated glomerular filtration rate, and known underlying diseases, including diabetes mellitus and hypertension.

Results

Among the 6,743 men (48.3%) and 7,221 women (51.7%), the age was 51.3±13.5 and the serum UA level was 4.5±2.1 mg/dL. Hyperuricemia (＞7 mg/dL) was observed in 1,381 cases (9.9%). Urolithiasis was detected by ultrasonography in 608 cases (4.4%). The detection rates of urolithiasis in individuals with hyperuricemia and normouricemia were 5.9% and 4.1%, respectively (p=0.001). Multiple logistic regression analysis showed that individuals with hyperuricemia had a significantly higher risk of urolithiasis (adjusted odds ratio [OR]=1.54; 95% confidence interval [CI], 1.20∼1.96; p=0.001). A comparison of the highest with the lowest quartile of serum UA revealed a multi-variable-adjusted OR of 3.17 (95% CI, 1.98∼5.11) for men and 1.79 (1.08∼2.93) for women.

Conclusion

These results suggest that individuals with a higher serum UA level have a higher risk of subclinical and clinical urolithiasis.

Keywords: Uric acid, Hyperuricemia, Urolithiasis, Urinary calculi, Gout

REFERENCES

1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. Eur Urol. 2012; 62:160–5.

2. Parmar MS. Kidney stones. BMJ. 2004; 328:1420–4.

3. Mehta TH, Goldfarb DS. Uric acid stones and hyper-uricosuria. Adv Chronic Kidney Dis. 2012; 19:413–8.

4. Shekarriz B, Stoller ML. Uric acid nephrolithiasis: current concepts and controversies. J Urol. 2002; 168:1307–14.

5. Yü T, Gutman AB. Uric acid nephrolithiasis in gout. Predisposing factors. Ann Intern Med. 1967; 67:1133–48.

6. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994. Am J Kidney Dis. 2002; 40:37–42.

7. Kramer HJ, Choi HK, Atkinson K, Stampfer M, Curhan GC. The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study. Kidney Int. 2003; 64:1022–6.

8. Madore F, Stampfer MJ, Willett WC, Speizer FE, Curhan GC. Nephrolithiasis and risk of hypertension in women. Am J Kidney Dis. 1998; 32:802–7.

9. Roubenoff R, Klag MJ, Mead LA, Liang KY, Seidler AJ, Hochberg MC. Incidence and risk factors for gout in white men. JAMA. 1991; 266:3004–7.

10. Fox J. Effect displays in R for generalised linear models. J Stat Softw. 2003; 8:1–27.

11. Roughley MJ, Belcher J, Mallen CD, Roddy E. Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies. Arthritis Res Ther. 2015; 17:90.

12. Richette P, Bardin T. Gout. Lancet. 2010; 375:318–28.

13. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001; 38:1101–6.

14. Johnson RJ, Nakagawa T, Jalal D, Sánchez-Lozada LG, Kang DH, Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013; 28:2221–8.

15. Brisbane W, Bailey MR, Sorensen MD. An overview of kidney stone imaging techniques. Nat Rev Urol. 2016; 13:654–62.

16. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004; 350:684–93.

17. Coe FL. Uric acid and calcium oxalate nephrolithiasis. Kidney Int. 1983; 24:392–403.

18. Coe FL, Lawton RL, Goldstein RB, Tembe V. Sodium urate accelerates precipitation of calcium oxalate in vitro. Proc Soc Exp Biol Med. 1975; 149:926–9.

Figure 1.

Proportion of urolithiasis according to serum uric acid levels.

Figure 2.

Plots of odds ratios (ORs) for urolithiasis according to serum uric acid level, age, glomerular filtration rate (GFR), presence of diabetes mellitus, presence of hypertension, body mass index, and serum uric acid quartile. Squares and horizontal bars represent ORs and 95% confidence intervals (CIs), respectively. *p＜0.05, **p＜0.01, ***p＜0.001.

Figure 3.

Effect plots showing the predicted probabilities and 95% confidence intervals (represented by shaded areas or error bars) for urolithiasis based on the multivariable logistic regression model.

Table 1.

Clinical characteristics of the study population

Characteristic	Without urolithiasis (n=13,356)	With urolithiasis (n=608)	p-value
Age (yr)	51.2±13.6	53.5±12.9	＜0.001
	51.0 (42.0∼60.0)	54.0 (46.0∼62.0)
Sex, male (%)	6,446 (48.3)	297 (48.8)	0.777
BMI (kg/m²)	24.0±3.5	23.8±3.3	0.561
	23.7 (21.6∼26.0)	23.8 (21.6∼25.6)
Serum creatinine (mg/dL)	2.07±2.17	2.06±2.23	0.151
	1.1 (0.9∼1.7)	1.1 (0.9∼1.6)
GFR (mL/min)	56.3±27.7	55.4±26.2	0.009
	66.0 (39.0∼75.0)	64.0 (44.0∼74.0)
Serum uric acid (mg/dL)	4.5±2.1	4.9±2.2	＜0.001
	4.6 (3.3∼5.8)	4.9 (3.8∼6.2)
Hyperuricemia (uric acid ＞7 mg/dL)	1,296 (9.7)	85 (14.0)	＜0.001
Diabetes mellitus	1,704 (12.8)	95 (15.6)	0.039
Hypertension	1,910 (14.3)	127 (20.9)	＜0.001
Gout	186 (1.4)	18 (3.0)	0.002

Values are presented as mean±standard deviation, median (interquartile range) or number (%). BMI: body mass index, GFR: glomerular filtration rate.

Table 2.

Clinical characteristics of the study population according to gender

Characteristic	Female		p-value	Male		p-value
Characteristic	Without urolithiasis (n=6,910)	With urolithiasis (n=311)	p-value	Without urolithiasis (n=6,446)	With urolithiasis (n=297)	p-value
Age (yr)	51.5±13.5	53.0±12.7	0.015	50.9±13.6	54.0±13.2	＜0.001
Age (yr)	51.0 (43.0∼60.0)	53.0 (46.0∼61.0)	0.015	51.0 (41.0∼60.0)	55.0 (45.0∼63.0)	＜0.001
BMI (kg/m²)	23.9±3.8	23.6±3.3	0.449	24.0±3.3	24.0±3.3	0.985
BMI (kg/m²)	23.5 (21.4∼26.0)	23.7 (21.2∼25.5)	0.449	23.9 (22.0∼26.0)	24.1 (22.0∼25.8)	0.985
Serum creatinine (mg/dL)	1.8±1.9	1.8±2.0	0.699	2.4±2.4	2.4±2.4	0.015
Serum creatinine (mg/dL)	0.9 (0.8∼1.2)	0.9 (0.8∼1.1)	0.699	1.2 (1.0∼2.4)	1.2 (1.1∼1.8)	0.015
GFR (mL/min)	56.1±26.7	56.5±26.2	0.512	56.5±28.7	54.2±26.2	0.003
GFR (mL/min)	65.0 (45.0∼74.0)	65.0 (49.0∼74.0)	0.512	67.0 (28.0∼77.0)	63.0 (42.0∼73.0)	0.003
Serum uric acid (mg/dL)	3.9±1.8	4.2±1.7	0.011	5.0±2.3	5.6±2.3	＜0.001
Serum uric acid (mg/dL)	4.2 (3.2∼4.9)	4.3 (3.4∼5.1)	0.011	5.5 (3.8∼6.6)	5.8 (4.6∼6.8)	＜0.001
Hyperuricemia (uric acid ＞7 mg/dL)	222 (3.2)	19 (6.1)	0.009	1,074 (16.7)	66 (22.2)	0.015
Diabetes mellitus	790 (11.4)	44 (14.1)	0.169	914 (14.2)	51 (17.2)	0.175
Hypertension	959 (13.9)	66 (21.2)	＜0.001	951 (14.8)	61 (20.5)	0.008
Gout	32 (0.5)	1 (0.3)	1.000	154 (2.4)	17 (5.7)	0.001

Values are presented as mean±standard deviation, median (interquartile range) or number (%). BMI: body mass index, GFR: glomerular filtration rate.

Table 3.

Age-adjusted and multivariable-adjusted odds ratio for the presence of urolithiasis by hyperuricemia

Variable	Age-adjusted	p-value	Multivariable-adjusted*	p-value
Variable	Odds ratio (95% CI)	p-value	Odds ratio (95% CI)	p-value
No hyperuricemia	1.00 (Reference)		1.00 (Reference)
Hyperuricemia (serum uric acid ＞7 mg/dL)
Total	1.54 (1.21∼1.94)	＜0.001	1.54 (1.20∼1.96)	0.001
Male	1.50 (1.12∼1.98)	0.005	1.47 (1.09∼1.94)	0.009
Female	1.89 (1.13∼2.99)	0.010	1.89 (1.11∼3.02)	0.012

CI: confidence intervals.

^* Adjusted by age, body mass index, glomerular filtration rate, diabetes mellitus and hypertension.

Table 4.

Age-adjusted and Multivariable-adjusted odds ratio for the presence of urolithiasis by serum uric acid level

Variable	Age-adjusted	p-value	Multivariable-adjusted*	p-value
Variable	Odds ratio (95% CI)^†	p-value	Odds ratio (95% CI)^†	p-value
Total	1.11 (1.07∼1.15)	＜0.001	1.15 (1.09∼1.20)	＜0.001
Male	1.13 (1.08∼1.19)	＜0.001	1.18 (1.11∼1.24)	＜0.001
Female	1.10 (1.03∼1.17)	0.003	1.11 (1.02∼1.19)	0.012

CI: confidence intervals.

^* Adjusted by age, body mass index, glomerular filtration rate, diabetes mellitus and hypertension.

^† Odds ratio and 95% CI was impressed by 1 mg/dL increase of serum uric acid.

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