Original Article
Modern Pathology (2008) 21, 396–406; doi:10.1038/modpathol.3801011; published online 25 January 2008
Renal pathology in hematopoietic cell transplantation recipients
Megan L Troxell1, Maricel Pilapil2, David B Miklos3, John P Higgins4 and Neeraja Kambham4
- 1Department of Pathology, Oregon Health & Science University, Portland, OR, USA
- 2Division of Nephrology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA
- 3Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA
- 4Department of Pathology, Stanford University Medical Center, Stanford, CA, USA
Correspondence: Dr ML Troxell, Department of Pathology, Oregon Health & Science University, L471, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. E-mail: troxellm@ohsu.edu
Received 8 October 2007; Revised 30 November 2007; Accepted 30 November 2007; Published online 25 January 2008.
Abstract
Hematopoietic cell transplantation-associated renal injury may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease. Renal biopsy specimens from hematopoietic cell transplant recipients at two institutions (Stanford University Medical Center and Oregon Health & Science University) were reviewed in correlation with clinical data. Fifteen cases were identified (post hematopoietic cell transplant time 0.7–14.5 years), including six with autologous hematopoietic cell transplant. Indications for renal biopsy included proteinuria (n=13; nephrotic range in 8), increased serum creatinine (n=10), or both (n=6). Many patients had multiple pathologic findings on renal biopsy. Membranous glomerulonephritis was the most common diagnosis (n=7), including two patients with autologous hematopoietic cell transplant and five with evidence of chronic graft-versus-host disease elsewhere. Four membranous glomerulonephritis patients achieved sustained remission with rituximab therapy. Other glomerular pathology included focal segmental glomerulosclerosis (n=1) and minimal change disease (n=1). Evidence of thrombotic microangiopathy was common (in isolation or combined with other pathology), as was acute tubular necrosis and tubulointerstitial nephritis. Of 14 patients with follow-up (2–64 months, mean 19 months), 6 had chronic renal insufficiency (serum creatinine >1.5 mg/dl), 2 had end stage renal disease, and 6 had essentially normal renal function. Our retrospective study shows that renal dysfunction in hematopoietic cell transplant recipients is often multifactorial, and biopsy may reveal treatable causes. Membranous glomerulonephritis is seen in autologous and allogeneic hematopoietic cell transplant recipients, and may respond to anti-B-cell therapy, which has implications regarding pathogenesis and relationship to graft-versus-host disease.
Keywords:
hematopoietic cell transplantation, graft-versus-host disease, rituximab, calcineurin inhibitor toxicity, membranous glomerulonephritis, thrombotic microangiopathy
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