Urinary macrophage migration inhibitory factor predicts kidney failure in advanced CKD patients

Urinary macrophage migration inhibitory factor (uMIF) was reported as a promising biomarker for kidney inflammation and injury. The purpose of this study was to investigate the value of uMIF for predicting the progression to kidney failure in patients with advanced CKD. In this prospective cohort study, a total of 584 patients with advanced CKD (eGFR 10-59 ml/min/1.73m2) were enrolled and followed at least 12 months. Levels of uMIF were measured at baseline. CKD progression was defined as developing kidney failure, that was need for kidney replacement treatment (maintenance dialysis or kidney transplantation). The restricted cubic spline (RCS) fitting cox regression was used to find the optimal cut-off point of uMIF for predicting CKD progression. The propensity score matching (PSM) and the standardized mortality ratio weighting (SMRW) analysis were also used to explore the independent association between urinary MIF and CKD progression. Finally, urinary MIF was added to KFRE to assess the improvement of risk prediction using C statistics. Of the 584 advanced CKD patients identified from between 2014 and 2019, 181 (30.9%) developed kidney failure during a mean follow-up of 3 years. The RCS model showed a linear relationship between urinary MIF and CKD progression with an optimal cut-off of 4. 2ng/g creatinine. Higher levels (> 4. 2ng/g creatinine) of urinary MIF were associated with 1.57, 1.51-fold higher risk for CKD progression in PSM and SMRW analysis (both P < 0.05). Survival analysis showed that higher level of uMIF offered faster kidney disease progression and the results were consistent when stratified by age, sex, CKD stage, UACR. Adding uMIF to the 4-variable KFRE enhanced the 5-years overall performance with the C-statistics increased from 0.78 to 0.80, 0.86 to 0.90 and 0.78 to 0.80 by Cox regression, PSM, and SMRW analysis separately. uMIF provided independent predictive value for CKD progression and could further improve the performance of KFRE for predicting kidney failure in advanced CKD.