Prevalence and Risk Factors for Urolithiasis in Primary Gout: Is a Reappraisal Needed?
JOSÉ ALVAREZ-NEMEGYEI, MARTHA MEDINA-ESCOBEDO, SALHA VILLANUEVA-JORGE, and JANITZIA VAZQUEZ-MELLADO
Objective. To assess the prevalence and risk factors for urolithiasis in primary gout.
Objective. To assess the prevalence and risk factors for urolithiasis in primary gout.
Methods. One hundred forty patients with primary gout were studied. Urolithiasis was defined as a history of urolithiasis, or nephrolithiasis detected via ultrasonography in patients with no previous record of urolithiasis. Patient age, duration of gout, presence of tophi, obesity, alcoholism, high blood pressure, diabetes, hyperlipidemia, family history of urolithiasis, daily urine output, uricemia, urine pH, FeNa, FeUrate, urine pH/FeUrate index, and daily urine excretion of urate, sodium, calcium and potassium were compared between lithiasic and non-lithiasic subjects.
Results. Fifty-five (39%; 95% CI 31–47) patients had urolithiasis, of which 37 (26%) were diagnosed by clinical history and 18 (13%) by ultrasonography. Patients with a silent kidney stone diagnosed by ultrasound tended to have shorter evolution of gout. Aside from urinary H+ ion concentration (lithiasic subjects 5.17 ± 3.9 µM/l; non-lithiasic subjects 3.80 ± 3.01 µM/l; p = 0.02), no difference was found between lithiasic and non-lithiasic subjects for the other variables studied.
Conclusion. Ultrasonography increased the probability of diagnosing urolithiasis by 50%, meaning the prevalence of urolithiasis in gout is likely higher than previously reported. A higher urinary H+ ion concentration was the only variable associated with urolithiasis. Due to advances in diagnosis of gout and urolithiasis, as well as biochemical assays, the prevalence and risk factors for urolithiasis in gout require reassessment. (J Rheumatol 2005;32:2189-91)
Key Indexing Terms:
From the Unidad de Investigación en Epidemiología Clínica, HE CMN "Ignacio García Tellez," Instituto Mexicano del Seguro Social, Mérida, Yucatán; Laboratorio de Investigación, Hospital General "Agustin O'Horan," FUNSALUD Capítulo Peninsular-Secretaria de Salud, Mérida, Yucatán; and Servicio de Reumatología, Hospital General de México, Secretaría de Salud, Mexico City, México.
Supported by grants from FOFOI/IMSS and FUNSALUD Capítulo Peninsular.
J. Alvarez-Nemegyei, MSc, Researcher, Unidad de Investigación en Epidemiología Clínica, HE CMN "Ignacio García Tellez"; M. Medina-Escobedo, MSc, Researcher; S. Villanueva-Jorge, Staff, Laboratorio de Investigación, Hospital General "Agustin O'Horan"; J. Vazquez-Mellado, PhD, Researcher, Servicio de Reumatología, Hospital General de México.
Address reprint requests to Dr. J. Alvarez-Nemegyei, Calle 57 #503 x 50 y 62, Col. Centro, 97000 Mérida, Yucatan, Mexico. E-mail: firstname.lastname@example.org
Accepted for publication June 24, 2005.
Gout is a systemic metabolic disease in which several forms of nephropathy can occur1. The most frequent type of gout-related nephropathy2-5 is urolithiasis (10%–20%), and its prevalence is much higher than observed in the general population6.
Since Yu and Gutman's 1967 study7, the principal accepted risk factors for urolithiasis in gout have been serum uric acid levels, daily urine urate excretion, and urine pH. That study was done using the colorimetric method for uric acid measurement, before validated diagnostic criteria for gout existed, and urolithiasis was diagnosed only from clinical history. Despite all these potential sources of bias, Yu and Gutman's findings have not been reassessed. In response, a study was done to reassess the influence of a set of clinical, biochemical, and sociodemographic variables on the risk of developing urolithiasis in a group of patients with primary gout, all diagnosed based on the criteria of Wallace, et al8 and using ultrasonography and clinical history for diagnosis of urolithiasis.
MATERIALS AND METHODS
Subjects. Between March 2000 and September 2001, patients were recruited from the Rheumatology Service of the Ignacio Garcia Tellez Specialties Hospital of the Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS), Mérida, México, and from the Gout Clinic at the Rheumatology Service of the Mexico General Hospital of the Secretariat of Health (Secretaría de Salud) in Mexico City. The inclusion criterion was a diagnosis of gouty arthritis based on the Wallace criteria8. Presence of primary gout was diagnosed after exclusion of any other pathology or pharmacology-associated cause of hyperuricemia1. All subjects with a serum creatinine > 1.5 mg/dl or a creatinine clearance < 80 ml/min were eliminated from the analysis of biochemical variables, as were those who did not complete the requested questionnaires. A lithiasic subject was defined as one who acknowledged having had a urine stone delivery or previous surgery for urolithiasis; or in whom a kidney stone was identified by ultrasonography. This procedure was performed on all subjects who denied previous stone delivery or urolithiasis-related surgery.
Methods. A researcher blinded to presence of urolithiasis surveyed all relevant clinical and sociodemographic data for the subjects. Samples were analyzed in a quality-certified laboratory. Serum and urine concentrations of uric acid were measured by the uricase-peroxidase spectrophotometry method, calcium levels by the o-cresol complexone method; a Nova 1 CRT device was used for sodium and potassium measurement. All subjects were asked to stop use of all drugs modifying urine and serum uric acid levels 72 h before sampling.
Every subject gave signed informed consent before inclusion, and the protocol was approved by the Research and Ethics Committee of the Ignacio Garcia Téllez Specialties Hospital.
Statistical methods. A chi-square with Yates' correction or Fisher's test was used for comparisons of categorical variables. Numerical variables were compared by unpaired t test. Data were analyzed using SPSS for Windows (v. 7.5) statistical software (SPSS Inc., Chicago, IL, USA).
One hundred forty subjects [138 men (98%), aged 50.4 ± 11.9 years, disease evolution time 9.8 ± 9.3 years] were included in the study. Ninety-seven patients were from Merida and 43 from Mexico City. No significant difference in gout duration (Merida patients 9.1 ± 9.5 yrs, Mexico City patients 11.7 ± 7.4 yrs; p = 0.16) existed between the 2 patient sources.
Fifty-five subjects (39%; 95% CI 31–47) were diagnosed as urolithiasic. Lithiasis was clinically diagnosed in 37 (26%) of these patients, and 18 (13%) were diagnosed with lithiasis solely by ultrasonography. Ultrasonography increased the possibility of diagnosing urolithiasis by 50%. Subjects with lithiasis diagnosed by ultrasonography showed a trend toward shorter disease evolution compared to the clinically-diagnosed subjects (8.1 ± 5.3 vs 11.6 ± 8.9 yrs; p = 0.07). No difference in prevalence of lithiasis was found between the 2 patient sources [Mérida 40/94 subjects (42%); Mexico City 15/43 subjects (33%); p = 0.35], although the Mexico City patients (8/15, 53%) tended to have a higher prevalence of ultrasound-diagnosed lithiasis compared to Merida subjects [10/40 (25%); p = 0.04].
Apart from a higher urinary H+ ion concentration in the lithiasic group, no difference was identified between the lithiasic and the non-lithiasic gout patients for any of the other variables analyzed (Tables 1 and 2).
The prevalence and risk factors associated with urolithiasis in gout were originally studied by Yu and Gutman7. They reported a prevalence of urolithiasis of 24%, and a correlation between urate serum levels, daily urine urate excretion, and lower urine pH and prevalence of urolithiasis. When published, their findings seemed authoritative and the study became a classic5,9-13. For a number of reasons their findings now need reassessment. In their report, diagnosis of urolithiasis was only done clinically, leading to possible misclassification of subjects with a silent stone. As well, the Wallace criteria8 for gouty arthritis had not been published, and at that time uric acid measurement was done by a colorimetric method, now considered inaccurate.
The prevalence of urolithiasis in patients with primary gout in our study was 39%, much higher than in previous reports1-5,9-13. Further, the results suggest that if renal ultrasonography is done for gout patients with no history of stones, the prevalence of urolithiasis may increase significantly.
Of all the results, only a higher urinary H+ ion concentration was associated with the presence of urolithiasis in primary gout. No difference was observed between lithiasic and non-lithiasic gout patients for any of the other variables that have been proposed previously as urolithiasis risk factors5,7,9-13. In addition, the urate excretion anomalies identified by Pak, et al14 in the condition known as "gouty diathesis" were not identified in the urolithiasic gout patients we studied.
A reassessment of prevalence and risk factors for nephrolithiasis in gout is needed because diagnosis methods for gout and lithiasis have improved notably over the last 38 years and more accurate analytical assays have been developed.
2. Rose BR, Becker MA. Uric acid renal disease. In: Rose BD, editor. UpToDate. Wellesley, MA: UpToDate; 2001.
7. Yu TS, Gutman A. Uric acid nephrolithiasis. Predisposing factors. Ann Intern Med 1967;67:1133-48.
8. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895-900.
9. Gutman AB, Yu TS. Uric acid nephrolithiasis. Am J Med 1968;45:756-79.
10. Fessel WJ. Renal outcomes of gout and hyperuricemia. Am J Med 1979;67:74-82.