Contribution of Renal and Non-Renal Clearance on Increased Total Clearance of Adalimumab in Glomerular Disease

The contribution of renal and non-renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collected from seven patients treated with adalimumab. Renal clearance (Cl-R) was measured and non-renal clearance (Cl-NR) was calculated as the difference between total clearance and Cl-R. Differences in cumulative amount in urine, Cl-R, and Cl-NR between study weeks 1 and 16 and relationships between proteinuria (protein: creatinine ratio (Up/c)), and Cl-R and Cl-NR were evaluated. Up to 13% of the adalimumab dose was lost in urine. Cl-NR contributed more than Cl-R to enhanced total clearance. There was a nonlinear relationship between Up/c and Cl-R (R-2 0.7059); an increase in Cl-R beginning at Up/c of 12 mg/mg [slope 1.755, (C. I. -7.825 to 11.34)]. There was a linear relationship between Up/c and Cl-NR (R-2 0.5039); for every one unit increase in Up/c, Cl-NR would increase by 3.5 mL/hr (P = 0.01). Both Cl-R and Cl-NR contribute to enhanced total clearance of adalimumab in glomerular disease secondary to FSGS. Additional research is needed to identify mechanisms for the increased Cl-NR pathways.