Urine macrophage migration inhibitory factor (MIF) in children with urinary tract infection: a possible predictor of acute pyelonephritis

Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine expressed at sites of inflammation. We have assessed this factor (MIF) in urinary tract infections with the aim of determining a non-invasive and sensitive method to differentiate upper and lower renal involvement. Thirty-three pediatric patients with urinary track infection (25 with acute pyelonephritis, eight with acute cystitis) and 40 healthy subjects were recruited for this prospective case-control study. Pyelonephritis was differentiated from cystitis by dimercaptosuccinic acid (DMSA) scan. Urinary MIF concentration was determined using an enzyme-linked immunosorbent assay method. The urine MIF/creatinine (Cr) ratio was significantly higher in pyelonephritis patients than in those with acute cystitis and the control group (P < 0.001). The optimal cut-point of 4.90 pg/micromol Cr for the urine MIF/Cr ratio has the potential to be a biomarker for distinguishing patients with acute pyelonephritis from those with acute cystitis. Determination of the urinary MIF was also useful in selecting the patients at risk of permanent renal damage. Of those patients with pyelonephritis, based on the DMSA scan at the time of infection, scarring on follow-up DMSA scan 9-12 months later occurred in patients with the highest urinary MIF/Cr ratios. We conclude that the urine MIF/Cr ratio is a sensitive test for differentiating acute pyelonephritis from acute cystitis and also for detecting children with acute pyelonephritis who are at a higher risk for permanent renal scars in the future.