Abstract
BackgroundUrate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain.ObjectiveTo evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables.MethodsLevels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC).ResultsMedian serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: −0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis.ConclusionsOur findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.
Highlights
Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of Multiple Sclerosis (MS) even at the early stage and mainly in females
Uric acid is the main end-product of purine metabolism and circulates in humans at high concentrations, near the limits of its solubility. [2,3] In vitro and in vivo studies showed that urate may protect neurons against oxidative damage caused by reactive nitrogen and oxygen species, by peroxynitrite. [4,5] Peroxynitrite along with other free radicals are believed to be involved in the inflammation, demyelination and axonal injury that occur in MS. [5,6,7] epidemiological studies conducted in US on more than 20 million patient records revealed that MS and gout are almost mutually exclusive
No significant differences were found in median age (MS: 37 years; range: 15–74; neurological controls (NC): 37 years; range: 14–76; Healthy controls (HC): 35 years; range: 15–74; p = 0.6) and sex (p = 0.4) distribution and in median glomerular filtration rate (108 versus 103 and 102 ml/min/ 1.73 m2) between the three groups
Summary
Multiple Sclerosis (MS) is a neurologic disease of unknown aetiology characterized by inflammation, demyelination and diffuse axonal degeneration throughout the central nervous system. [1]Uric acid is the main end-product of purine metabolism and circulates in humans at high concentrations, near the limits of its solubility. [2,3] In vitro and in vivo studies showed that urate may protect neurons against oxidative damage caused by reactive nitrogen and oxygen species, by peroxynitrite. [4,5] Peroxynitrite along with other free radicals are believed to be involved in the inflammation, demyelination and axonal injury that occur in MS. [5,6,7] epidemiological studies conducted in US on more than 20 million patient records revealed that MS and gout are almost mutually exclusive. [8] All these observations raised the possibility that hyperuricemia may play a protective role against MS.In the last ten years several studies evaluated serum urate levels in patients with MS, reporting conflicting results; [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27] some case-control studies found lower, [8,9,10,11,12,13,14,15] but others reported higher [16,17,18] serum urate levels in MS patients than in neurological [16,19,20] and healthy controls [10,16,17,18,19]; other studies found no difference between the MS and neurological, [21,22] and healthy controls. [23,24,25,26,27] A recent metanalysis was in favour of lower serum urate levels in MS than in healthy subjects and neurological controls [28] in a recent clinical trial, the combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone.[29] Based on these observations, the effective contribute of urate to the pathogenesis of MS still remains unclear.In this cross-sectional study we evaluated non-fasting serum levels of uric acid and glomerular filtration rate in MS patients and in age and sex matched healthy (HC) and neurological controls (NC). [23,24,25,26,27] A recent metanalysis was in favour of lower serum urate levels in MS than in healthy subjects and neurological controls [28] in a recent clinical trial, the combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone. [29] Based on these observations, the effective contribute of urate to the pathogenesis of MS still remains unclear. In this cross-sectional study we evaluated non-fasting serum levels of uric acid and glomerular filtration rate in MS patients and in age and sex matched healthy (HC) and neurological controls (NC). Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain
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