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Kidney Week

Abstract: FR-PO672

Renal Microangiopathy and Tubulitis Following Haploidentical Stem Cell Transplant with α/β T Cell and CD19 B Cell Depletion

Session Information

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Hertz-Tang, Amber, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Kenkre, Vaishalee P., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Zhong, Weixiong, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Yang, David, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Djamali, Arjang, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Bhutani, Gauri, University of Wisconsin Madison, Madison, Wisconsin, United States
Introduction

Selective depletion of α/β T-cells and CD19 B-cells in haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) is being investigated as a strategy to avoid graft versus host disease (GVHD) while preserving immune reconstitution. We describe 4 cases of renal dysfunction following haplo-HSCT.

Case Description

All cases were Caucasian males who underwent non-myeloablative peripheral blood haplo-HSCT using fludarabine, cyclophosphamide and total nodal irradiation (7Gy). All reached engraftment and received mycophenolate (MMF) for GVHD prophylaxis (30 days). All are living at last follow up. The table summarizes their presentations.

Discussion

All patients had endothelial injury and most (3/4) had inflammatory tubular pathology. Given the setting of haplo-HSCT with selective T-cell depletion, timeline and degree of renal insult, as well as response to IS, renal complications were most concerning for alloimmune response (GVHD). Chemotherapy and pre-IS infections may also have contributed to endothelial/tubular injury in early post-HSCT period. Our series highlights (1) GVHD is likely an important factor in post haplo-HSCT endothelial injury and direct/indirect tubular injury; (2) This condition is difficult to treat due to high risk of infections post-HSCT. Renal risks in haplo-HSCT need further investigation.

 Case 1Case 2Case 3Case 4
DiagnosisChronic Lymphocytic LeukemiaMarginal Zone LymphomaPeripheral T-Cell LymphomaMantle Cell Lymphoma
Age at HSCT52575565
Baseline serum creatinine (mg/dl) (eGFR mL/min/1.73sqm) pre-HSCT1.06 (85)1.63 (46)0.89 (93)1.03 (72)
Total follow up post-HSCT (days)1021491315301
Time to 50% GFR loss (days)127199277155
Renal pathologyThrombotic microangiopathy (TMA) and active tubulointerstitial nephritis (TIN)Severe chronic active TIN and TMAMild chronic and active TMA and acute tubular necrosis (ATN)ATN, TIN, TIN and chronic active TMA
Infections [pre-immuno-suppression (IS)]CMVNone●CMV
●C.diff
C.diff
Other organ dysfunction (days post-HSCT)Skin-GVHD confirmed (29)None●Skin-GVHD presumed (33)
●Gut-GVHD confirmed (176)
●Pulmonary hypertension (308)
●Skin-GVHD confirmed (45)
●Lung-GVHD presumed (129)
●Pulmonary hypertension (82)
GVHD treatment●Prednisone
●MMF
●Rituximab
●Eculizumab
-Renal indication
●Prednisone
●MMF
●Etanercept
-Renal indication
Prednisone
-GI indication
●Prednisone
●Sirolimus
-Pulmonary indication
Infections (post-IS)●Aspergillus
●Pseudomonas
●Influenza A
●Strep pneumo
●C.diff
●Parapertusis
●Adenovirus
●H.influenza
●RSV
●MSSA
●Pseudomonas
●E.coli sepsis
Renal responsePartial response (PR) to IS. Progressed to ESRD with infections.PR to IS. Progressed to ESRD with infections.PR to IS. Last known serum creatinine:2.36 eGFR:29No IS given for renal disease. Progressed to ESRD in setting of infections and cardiac disease