Clinical ScienceUric acid excretion in healthy subjects: a nomogram to assess the mechanisms underlying purine metabolic disorders
Introduction
The reference range for urinary uric acid excretion in male adults has not been precisely defined. The renal excretion of uric acid is a complex process influenced by multiple variables and mediated by several ion transporters [1]. In clinical practice, quantification of uric acid excretion is routinely determined to ascertain whether the kidneys contribute to the purine metabolic disturbance in patients with increased or diminished serum urate levels [2]. Several different variables [3], [4], [5], [6], [7] have been proposed to be in use in determining this information, although precise normal limits have not been established: uric acid excretion in urine over 24 hours, clearance of uric acid, fractional excretion of uric acid, uric acid to creatinine ratio in spot urine, and uric acid excretion per unit of glomerular filtration rate (Simkin index [4]). Most commonly, uric acid excretion in patients with gout has been reported in 24-hour urine, and the results have been compared with those obtained from control subjects with normal serum urate concentrations [1], [8], [9], [10]. On the basis of this comparison, and because most patients with gout have a mean uric acid excretion rate similar to healthy subjects but at significantly increased serum urate levels, it has been concluded that hyperuricemia in gout is mainly due to inefficient uric excretion [8], [9], [10]. To our knowledge, no study has addressed the validity of the different proposed variables to assess normal urinary uric acid excretion. In addition, we are not aware of any previously published nomogram that relates serum urate concentrations to uric acid excretion in healthy subjects for different urate filtered loads. In this study, we assessed which urinary variable best indicates uric acid excretion at different urate filtered loads. We validated the constructed nomogram using data from patients diagnosed with various conditions known to affect the synthesis and/or the renal excretion of uric acid and manifested by hyperuricemia or hypouricemia.
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Subjects and methods
All studies were conducted according to local regulations and the Declaration of Helsinki and were approved by the Institutional Research and Ethics Review Committees of La Paz University Hospital. Control subjects and patients signed a written informed consent form. Ten healthy male subjects were selected among the medical personnel (4), residents (3), and subjects referred to the vascular risk unit for evaluation of cardiovascular risk (3). All subjects proved to be healthy with no risk
Results
The mean age of the 10 control subjects was 33 years (with an SD of 10 years and a range from 26 to 58 years; median age, 34 years). Their mean weight was 65.6 kg, and their (mean ± SD) body mass index was 22.6 ± 2.3 kg/m2 (range, 20.1-26.2 kg/m2; median, 23.0 kg/m2). The median urate filtered load (serum urate multiplied by the glomerular filtration rate determined by the creatinine clearance) was 6.29 mg/(min 1.73m2) (Table 1). This was accompanied by a mean 24-hour urinary uric acid
Discussion
This study aimed to assess the normal limits for uric acid excretion in control subjects over a wide range of serum urate concentrations. The results show that among the 5 urinary variables proposed to determine uric acid excretion in adult healthy subjects [2], [3], [4], [5], [6], [7], the best bilateral correlation coefficient over a wide range of serum urate concentrations was obtained for the 24-hour urinary uric acid excretion. The nomogram drawn, with its 95% confidence limits (Fig. 1),
Funding
Supported by grants from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (FIS, 08/0009), the Red Española de Atención Primaria (2009/70), and RECAVA (RD06/0014/0019).
Conflict of Interest
All authors deny potential conflicts of interest.
Acknowledgment
We are indebted to the Metabolic Vascular Unit research manager Dña Carolina Velasco García and to the nursing staff (Inés Narillos and Arantxa Sánchez) for excellent patient care and follow-up; to Juan J de la Cruz, ScD, for the statistical analysis; and to Almudena Ligos Díaz for assistance in preparing the manuscript. We thank American Journal Experts for their editorial assistance.
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Contributors: JGP, RJT, and EdM contributed to the development and completion of the protocol and the project. RB abstracted the data. AS developed the protocol. JRB supervised the statistical analysis. The writing committee was constituted by JGP, RJT, and EdM; but all authors had contributed to the written document.