Raised Plasma Levels of Asymmetric Dimethylarginine Are Associated with Pathological Type and Predict the Therapeutic Effect in Lupus Nephritis Patients Treated with Cyclophosphamide

Abstract

Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Asymmetric dimethylarginine (ADMA) has been associated with cardiovascular events in SLE patients and is a strong predictor of the progression of chronic kidney disease. However, whether ADMA can provide a predictive value for the diagnosis and treatment of LN patients remains unclear. This study evaluated the clinical significance of ADMA in LN patients.

Methods: Blood samples of 114 patients with LN, 52 patients with primary glomerular disease, and 20 healthy people were collected. Plasma ADMA was measured via enzyme-linked immunosorbent assay. The relationship between plasma ADMA levels and pathological types and renal function and efficacy in LN patients were further analyzed.

Results: There was no significant difference in plasma ADMA levels between LN and primary glomerular disease, but both were significantly higher than the values in healthy people (p < 0.05). Plasma ADMA levels in LN patients were negatively correlated with baseline estimated glomerular filtration rate (eGFR) and serum superoxide dismutase and positively correlated with serum cystatin C and serum β₂-microglobulin (p < 0.05). The plasma ADMA levels of diffuse proliferative LN patients were significantly higher than those of other histopathological classes of LN. High plasma ADMA levels in LN patients (OR = 1.012; 95% CI 1.003-1.022; p = 0.010) is a risk factor for diffuse proliferative LN. The area under the receiver operating characteristic (ROC) curve of diagnosing diffuse proliferative LN by plasma ADMA was 0.707 (95% CI 0.610-0.805). The area under the ROC curve of combination with plasma ADMA, serum complement C3, and eGFR for diffuse proliferative LN was 0.796 (95% CI 0.713-0.879), which was significantly higher than that of ADMA, complement C3, and eGFR for diffuse proliferative LN alone, respectively (p < 0.05). Low plasma ADMA is an independent protective factor for proliferative LN patients achieving complete remission with cyclophosphamide as induction therapy (OR = 0.978; 95% CI 0.961-0.996; p < 0.05).

Conclusion: High plasma ADMA levels in combination with eGFR and complement C3 may be useful to diagnose diffuse proliferative LN. Low plasma ADMA may help to predict complete remission in proliferative LN patients treated with cyclophosphamide as induction therapy. Plasma ADMA may be a new biomarker to determine the pathological type of LN and predict the therapeutic effect.

Keywords: Asymmetric dimethylarginine; Biomarker; Cyclophosphamide; Lupus nephritis.