Weinberg JB et al. (2006) Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures. Arthritis Res Ther 8: R140

Although nitric oxide has been implicated in the pathogenesis of joint inflammation, Weinberg and colleagues have demonstrated that serum and urinary levels of nitrates and nitrites (NOx) are difficult to use as measures of whole-body nitric oxide production or as indices of nitric oxide synthase activity and disease activity in patients with rheumatoid arthritis (RA). They found that large variations in dietary NOx intake and reduced urinary clearance of NOx in patients with RA complicate the interpretation of serum and urinary NOx levels.

The authors enrolled 25 patients with established, predominantly severe RA (median duration 9 years) and 20 age-matched and sex-matched healthy control individuals, all with normal creatinine clearance. Participants were hospitalized for 3 days on a low-NOx diet, during which time their serum and urinary NOx levels stabilized. Patients with RA had substantially higher serum NOx levels at all time points, and had higher serum NOx:creatinine ratios on day 3 than controls; however, their urinary NOx levels remained similar to those of controls. Despite comparable glomerular filtration rates, the authors noted 43–75% lower NOx clearances and fractional excretions in RA patients than in controls, which probably explains the differences in serum and urinary NOx levels. The authors speculate that patients with RA have intrinsic renal tubular abnormalities.

The authors recommend that studies of nitric oxide production in patients with RA should focus on specific anatomic or cellular compartments, in order to avoid these difficulties.