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Spectrum of Renal Pathology in Hematopoietic Cell Transplantation: A Series of 20 Patients and Review of the Literature

Anthony Chang^*, Sangeeta Hingorani, Jolanta Kowalewska, Mary E.D. Flowers^,||, Tia Aneja^||, Kelly D. Smith, Shane M. Meehan^*, Roberto F. Nicosia, and Charles E. Alpers^,

^* Department of Pathology, University of Chicago Medical Center, Chicago, Illinois; and Department of Pediatrics, Children's Hospital & Regional Medical Center, Departments of Pathology and Medicine, University of Washington Medical Center, and ^|| Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

Address correspondence to: Dr. Anthony Chang, University of Chicago Medical Center, Department of Pathology, 5841 S. Maryland Avenue, Room S-628 (MC6101), Chicago, IL 60637. Phone: 773-834-3426; Fax: 773-834-7644; E-mail: anthony.chang{at}uchospitals.edu

Background and Objectives: Hematopoietic cell transplantation is a common treatment option for a variety of hematopoietic malignancies. As a result of the use of total body irradiation and/or chemotherapeutic agents, renal dysfunction often ensues. Many pharmacologic agents, such as cyclosporine and high-intensity conditioning regimens, have been linked with thrombotic microangiopathy. In addition, an association between membranous nephropathy and graft-versus-host disease has been reported in this clinical setting.

Design, Setting, Participants, and Measurements: A study of autologous and allogeneic hematopoietic cell transplantation patients with renal dysfunction was conducted to document the spectrum of renal manifestations. The pathology files at the University of Washington and University of Chicago Medical Centers were reviewed, and 20 patients with a kidney biopsy after hematopoietic cell transplantation were identified. The histologic findings were correlated with relevant clinical information.

Results: A wide spectrum of renal diseases could be classified into four categories: (1) Complications related to hematopoietic cell transplantation (conditioning regimen, immunosuppression, or posttransplantation complications), (2) podocytopathy, (3) membranous nephropathy, or (4) recurrence or persistence of original hematologic disease. Pathologic diagnoses included thrombotic microangiopathy, polyoma virus nephropathy, acute kidney injury/acute tubular necrosis, acute and chronic interstitial nephritis, minimal-change disease, "tip" variant of focal segmental glomerulosclerosis, membranous nephropathy, amyloidosis, and myeloma cast nephropathy. Membranous nephropathy, minimal-change disease, and amyloidosis were common causes of severe proteinuria. Because of the conditioning regimens, posttransplantation complications, and potential nephrotoxic agents used during hematopoietic cell transplantation, it was difficult to attribute the subsequent renal dysfunction to specific factors.

Conclusions: The renal biopsy remains essential for diagnosing the underlying injury that can affect one or more compartments of the kidney in this unique clinical setting.