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Abstract: SA-PO208

Renal-Limited TMA (Thrombotic Microangiopathy) in Patients with HSCT (Hematopoietic Stem Cell Transplant): An Endothelial Variant of Graft vs Host Disease (GVHD)

Session Information

  • Trainee Case Reports - V
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 103 AKI: Mechanisms

Authors

  • Hasan, Alia, Northwell Health, Briarwood, New York, United States
  • Wanchoo, Rimda, Zucker School of Medicine at Hofstra Northwell, GREAT NECK, New York, United States
  • Pullman, James M., Montefiore Medical Center, Bronx, New York, United States
  • Jhaveri, Kenar D., Northwell Health Sys, Great Neck, New York, United States
  • Uppal, Nupur N., Hofstra Northwell School of Medicine, Great Neck, New York, United States
Introduction

Thrombotic microangiopathy (TMA) and graft versus host disease (GVHD) are well-recognized complications of hematopoietic stem cell transplantation (HSCT). TMA in HSCT (TA-TMA) is characterized by endothelial injury triggered by chemo-radiotherapy, infections or immunosuppressive drugs. Recent data suggests that GVHD itself may be a trigger of TA-TMA. We report 2 cases where GVHD in HSCT was associated with renal-limited TMA.

Case Description

A 58-year-old female with history of HSCT one year ago, was admitted with sub-acute acute kidney injury (AKI), worsening hypertension (HTN), nephrotic range proteinuria and anemia. Patient was on cyclosporine treatment for gastrointestinal GVHD at the time of admission. During the hospitalization, cyclosporine was discontinued. However, kidney function continued to worsen and she eventually required dialysis. A kidney biopsy confirmed acute on chronic TMA with minimal fibrosis. She received 2 doses of rituximab which led to the resolution of her AKI over 6 weeks. The patient eventually died due to sepsis. Our other patient, a 58-year-old-female with a second HSCT on tacrolimus therapy for skin GVHD, developed AKI 1 year after transplant along with worsening HTN, new onset proteinuria, and anemia. Her SCr worsened from 1.1mg/dl to 3.8mg/dl despite discontinuation of tacrolimus. A kidney biopsy revealed chronic TMA, with tubular reticular inclusion bodies (TRIs) without any viral etiology demonstrable by serology or immunohistochemistry.

Discussion

A relationship between GVHD and TA-TMA has been previously described but was confounded by calcineurin inhibitor use, infections, heterogeneous study populations, and retrospective study designs. Our findings suggest a possible link between GVHD and TA-TMA since both our patients presented with active GVHD in another organ concomitant with renal HSCT-TMA. Our first patient’s gastrointestinal GVHD and TA-TMA improved following anti-B cell therapy (rituximab). Our second patient showed evidence of a high interferon state (TRIs) in the kidney which is also seen in GVHD. Our findings suggest that TA-TMA represents a form of “renal GVHD” or “endothelial GVHD”. However, more research is needed to understand the exact mechanism of development of GVHD associated TA-TMA.