Prediction of steroid responsiveness in the idiopathic nephrotic syndrome using urinary retinol-binding protein and beta-2-microglobulin

Objectives: To determine the prevalence of early proximal tubular dysfunction, measured by urinary excretion of retinol-binding protein (RBP) and beta-2-microglobulin (B2M), in patients with the idiopathic nephrotic syndrome and to investigate the value of these tests in predicting steroid responsiveness. Design: Before-after trial with 8-week treatment period. Setting: Tertiary referral center. Patients: Sequential sample of 37 patients with the idiopathic nephrotic syndrome caused by minimal change disease, focal segmental glomerulosclerosis, or mesangial proliferative glomerulonephritis. Intervention: All patients were treated with prednisone as one dose of 1 to 1.5 mg/kg body weight per day for 8 weeks. Measurements: Urinary RBP was measured by an immunoenzymometric assay and B2M, by an enzyme-linked immunosorbent assay. Remission of the nephrotic syndrome after steroid treatment was the main outcome variable. Results: Elevated levels of urinary RBP and B2M before treatment were detected in 65% and 75% of the patients, respectively. Median urinary RBP and B2M, before treatment, were significantly higher in the steroid-unresponsive group than in the responsive group (P < 0.01). In the steroid-responsive group, urinary RBP and B2M levels decreased significantly after remission (P < 0.01). In the steroid-unresponsive group, the likelihood ratios for urinary RBP greater than 4000 μg/g creatinine and for B2M greater than 3000 μg/g creatinine were 3.8 and 3.0, respectively. The probability was 100% that values of RBP of less than 1300 μg/g creatinine and B2M of less than 130 μg/g creatinine were from steroid-responsive patients. Multivariate analysis confirmed that higher urinary levels of RBP and B2M were associated with a lower likelihood of steroid responsiveness, independent of age and histologic diagnosis. Conclusions: Proximal tubular dysfunction is frequent in patients with the idiopathic nephrotic syndrome. Pretreatment urinary RBP and B2M levels may be helpful in identifying nephrotic patients who are more likely to be responsive to steroids.