Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study

Background. Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). Methods. We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), alpha 1-microglobulin (alpha 1M), albumin, immunoglobulin IgG and IgM and/or anti-phospholipase 2 receptor (PLA(2)R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA(2)R with these urinary biomarkers. Results. Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m(2) x 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (A urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (U alpha 1M) (mg/24 h) and URBP (mu g/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA(2)R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. Conclusions. The results suggest that in patients with MN, quantification of low-, medium- and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes.