New findings suggest nitric oxide production could be pathogenic in proliferative lupus nephritis.
Systemic nitric oxide (NO) levels are elevated in patients with proliferative lupus nephritis, researchers found. The association is independent of renal elimination of nitrate and nitrite (NOx), a measure of NO production.
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The findings come from a study of 81 patients with systemic lupus erythematosus (SLE)—including 22 with biopsy-documented lupus nephritis—and 41 control subjects. Researchers examined patients at the time of biopsy and compared NO measures to the World Health Organization classification of lupus nephritis. Serum NOx levels were determined by chemiluminescence.
“We found that those patients with proliferative disease had significantly higher levels of nitric oxide production than those patients with class II and V (not proliferative) nephritis,” said lead investigator Jim Oates, MD, associate professor of medicine at the Medical University of South Carolina in Charleston. “It is important to note that we did have the patients on a low nitrate diet prior to measuring the serum nitrate and nitrite levels to eliminate dietary contamination.”
Dr. Oates noted that pharmacologic inhibition of inducible NO synthase has been shown to prevent and treat lupus nephritis in mice.
At the first clinic visit, NOx was greater in the SLE patients than controls (34.6 vs. 19.0 µmol). Among the SLE patients, NOx correlated positively with urine protein/creatinine ratio and negatively with serum C3 and creatinine clearance. Among pa-tients with lupus nephritis, the pa-tients who had proliferative lesions had a trend toward greater NOx levels (class III, 59.5 µmol; class IV, 87.5 µmol) than those with mesangial (class II, 37.3 µmol) or membranous (class V, 23.4 µmol) lesions.
In the lupus nephritis patients, NOx was associated with serum C3 and creatinine levels and urine protein/creatinine ratios. Among those with active lupus nephritis, levels were greater in those with proliferative disease. NO production could be pathogenic in proliferative lupus nephritis in humans, as described previously in mice, Dr. Oates said.
