Bortezomib for Reduction of Proteinuria in IgA Nephropathy

Abstract

Introduction: IgA nephropathy is the most common glomerulonephritis in the world. We conducted a pilot trial (NCT01103778) to test the effect of bortezomib in patients with IgA nephropathy and significant proteinuria.

Methods: We treated 8 consecutive subjects from July 2011 until March 2016 with 4 doses of bortezomib. All subjects had biopsy-proven IgA nephropathy and proteinuria of greater than 1 g per day. They were given 4 doses of bortezomib i.v. at 1.3 mg/m² of body surface area per dose. Changes in proteinuria and renal function were followed for 1 year after enrollment. The primary endpoint was full remission defined as proteinuria of less than 300 mg per day.

Results: All 8 subjects received and tolerated 4 doses of bortezomib over a 2-week period during enrollment. The median baseline daily proteinuria was 2.46 g (interquartile range: 2.29-3.16 g). At 1-year follow-up, 3 subjects (38%) had achieved the primary endpoint. The 3 subjects who had complete remission had Oxford classification T scores of 0 before enrollment. Of the remaining 5 subjects, 1 was lost to follow-up within 1 month of enrollment and 4 (50%) did not have any response or had progression of disease.

Conclusion: Proteasome inhibition by bortezomib may reduce significant proteinuria in select cases of IgA nephropathy. Subjects who responded to bortezomib had Oxford classification T score of 0 and normal renal function.

Keywords: IgA nephropathy; bortezomib; proteinuria.

Figure S1

Treatment course and laboratory results before and after bortezomib for subject 6. Patient first noticed leg edema, foamy urine, and weight gain 2 months before kidney biopsy. A timed 24-hour urine collection revealed protein excretion at study screening of 4.96 g, which was obtained 17 days before the first dose of bortezomib. The timed 24-hour proteinuria was 0.04 g at 6 months and 0.10 g at 1 year after bortezomib.