Macrophage migration inhibitory factor urinary excretion revisited – MIF a potent predictor of the immunosuppressive treatment outcomes in patients with proliferative primary glomerulonephritis

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine that shares many activities with other pro-inflammatory cytokines in primary glomerulonephritis (GN). This study assesses the influence of immunosuppressive treatment on serum and urine MIF in patients with proliferative (PGN) and non-proliferative (NPGN) glomerulonephritis, and evaluates the potential of MIF in predicting outcomes. METHODS: Eighty-four patients (45 males and 39 females) with primary GN were included. Urinary excretion of MIF (ng/mg of urinary creatinine) was measured both pre- and post-treatment with combined steroids and cyclophosphamide. After a 12-month follow-up, the patients were retrospectively divided into four subgroups: responders of proliferative GN (R-PGN), non-responders of proliferative GN (NR-PGN), responders of non-proliferative GN (R-NPGN) and non-responders of non-proliferative GN (NR-NPGN). RESULTS: The median pre-treatment urinary MIF values were higher in PGN than in NPGN (3.6 versus 2.2; ANOVA P = 0.039). The highest pre-treatment urinary excretion of MIF was observed in NR-PGN (median 6.1), which was significantly higher than other subgroups (ANOVA P < 0.05). The treatment significantly reduced MIF urinary excretion only in R-PGN (P < 0.01). In NR-PGN, pre- (5.9 ± 2.9 pg/mgCr) and post-treatment mean MIF excretion (4.9 ± 2.3 pg/mgCr) exceeded the calculated cut off value (3.3 pg/mgCr). CONCLUSION: MIF urinary excretion appears to be a prognostic marker of therapy outcomes only in proliferative glomerulonephritis, in which lower urinary MIF may be linked with good prognosis, whereas a higher MIF urinary excretion value was a marker of unfavorable therapy outcomes. In Non-Responders, urinary MIF measurements may help to reconsider the choice of the immunosuppressive regimen at early stages of the treatment and act as an impulse to search for new therapeutic strategies.