Four trajectories of 24-hour urine protein levels in real-world lupus nephritis cohorts

OBJECTIVES: A 24-hour urine protein (24hUP) is a key measurement in the management of lupus nephritis (LN); however, trajectories of 24hUP in LN is poorly defined. METHODS: Two LN cohorts that underwent renal biopsies at Renji Hospital were included. Patients received standard of care in a real-world setting and 24hUP data were collected over time. Trajectory patterns of 24hUP were determined using the latent class mixed modelling (LCMM). Baseline characters were compared among trajectories and multinomial logistic regression was used to determine independent risk factors. Optimal combinations of variables were identified for model construction and user-friendly nomograms were developed. RESULTS: The derivation cohort composed of 194 patients with LN with 1479 study visits and a median follow-up of 17.5 (12.2–21.7) months. Four trajectories of 24hUP were identified, that is, Rapid Responders, Good Responders, Suboptimal Responders and Non-Responders, with the KDIGO renal complete remission rates (time to complete remission, months) of 84.2% (4.19), 79.6% (7.94), 40.4% (not applicable) and 9.8% (not applicable), respectively (p<0.001). The ‘Rapid Responders’ distinguish itself from other trajectories and a nomogram, composed of age, systemic lupus erythematosus duration, albumin and 24hUP yielded C-indices >0.85. Another nomogram to predict ‘Good Responders’ yielded C-indices of 0.73~0.78, which composed of gender, new-onset LN, glomerulosclerosis and partial remission within 6 months. When applied to the validation cohort with 117 patients and 500 study visits, nomograms effectively sorted out ‘Rapid Responders’ and ‘Good Responders’. CONCLUSION: Four trajectories of LN shed some light to guide the management of LN and further clinical trials design.