Abstract: TH-PO193

Thrombotic Microangiopathy and AKI Associated with MT-3724

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports


  • Shaban, Mona, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Kshirsagar, Abhijit V., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Mikhailov, Alexei V., University of North Carolina, Chapel Hill, North Carolina, United States

Study drug MT-3724 is a CD20-targeting immunotoxin consisting of a recombinant fusion protein with a CD20 binding variable fragment fused to the enzymatically active Shiga-like toxin-I A1 subunit (SLT-I A1). Upon binding to the surface of CD20, SLT-I A1 leads to MT-3724 internalization, which inactivates cell ribosomes and causes cell death. MT-3724 is currently being studied in relapsed diffuse B cell lymphoma (DLBCL). Here, we report a case of acute kidney injury (AKI) secondary to thrombotic microangiopathy after administration of MT-3724 and leading to dialysis dependence.


A 70-year-old female with relapsed DLBCL presented with lower extremity swelling during the second cycle of study drug, MT-3724. Each cycle of MT-3724 is 75 mg/kg dosed on days 1,3,5,8,10, and 12. Exam was remarkable for significant peripheral edema. Serum creatinine (SCr) was 3.2 mg/dL from a baseline of 1.0-1.2 mg/dL. Urine protein to creatinine ratio (U P/C) was 20 g/g. Urine sediment revealed multiple oval fat bodies, hyalofatty casts, and dysmorphic red blood cells. Renal biopsy was performed and revealed thrombotic microangiopathy with evidence of fragmented red blood cells in the mesangium and interstitium. Glomeruli had signs of low flow and 1 fibrocellular crescent was observed. There was moderate to severe interstitial fibrosis and tubular atrophy (Figure 1, Panel A-D). 22 days after last dose of MT-3724, SCr continued to rise to 10 mg/dL associated with uremic symptoms and oliguria. Hemodialysis was initiated and patient continues to require outpatient dialysis.


The pathogenesis of this acute kidney injury is currently unclear, however we can speculate on the role of Shiga-like toxin given the clear association between Shiga toxin and hemolytic uremic syndrome (HUS). Novel targeted therapies in the treatment of DLBCL can potentially be nephrotoxic and early recognition and cessation of offending agent may prevent progression of kidney injury.