Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series

Brinkerhoff, Brian; Houghton, Donald C.; Troxell, Megan L.

doi:10.1038/modpathol.2016.61

Cited by 23 publications

(27 citation statements)

References 51 publications

(83 reference statements)

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“…Kidney biopsies in HCT patient cohorts are performed in .5% to 4.3% of patients, with the total number of investigated biopsy specimens in published studies ranging between 2 and 20 [16]. Studies of autopsies are even more scarce [17,18] or have focused only on specific issues, such as infections or thrombotic microangiopathy (TMA) [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Kidney Pathology after Hematologic Cell Transplantation—A Single-Center Observation Study of Indication Biopsies and Autopsies

Girsberger

Hopfer

Dickenmann

et al. 2018

Biology of Blood and Marrow Transplantation

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Hematopoietic cell transplantation (HCT) is an increasingly used treatment for hematologic malignancies as well as for nonmalignant diseases. Kidney impairment remains an important early and late post-transplantation complication. Although numerous histopathological changes have been reported, the pathophysiology remains incompletely understood. Furthermore, correlations between clinical findings and morphological changes have not been well studied. Between 2000 and 2016, 17 recipients of allogeneic (n = 12) or autologous (n = 5) HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at our center. The most common biopsy findings were therapy-related changes with thrombotic microangiopathy (n = 5), calcineurin inhibitor toxicity (n = 4), and membranous glomerulonephritis (n = 3), representing the majority of cases in this category. In addition, kidney findings from 137 autopsies performed between 1995 and March 2017 were analyzed. The most common changes were acute kidney injury (n = 55), most likely due to the patients' premortal deteriorated state, and thrombotic microangiopathy (n = 14). Several cases demonstrated involvement by either infectious agents (n = 6) or tumors (n = 9). Distinct kidney diseases, such as glomerulonephritis, were rare (3% of cases). Uncommon and yet rarely described diagnoses for this patient cohort were IgG4-related tubulointerstitial nephritis and fibrillary nephritis. This study provides a comprehensive overview of the histomorphological findings in kidney biopsy specimens from HCT recipients. Along with treatment-related complications, one putative correlate of chronic GVHD of the kidney could be documented: membranous glomerulonephritis. In contrast, no morphological correlate of acute GVHD of the kidney was identified. Findings at the time of autopsy varied greatly, spanning a wider range than those of indication biopsies.

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Section: Introductionmentioning

confidence: 99%

Kidney Pathology after Hematologic Cell Transplantation—A Single-Center Observation Study of Indication Biopsies and Autopsies

Girsberger

Hopfer

Dickenmann

et al. 2018

Biology of Blood and Marrow Transplantation

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“…The most common histological diagnosis is MN followed by minimal change disease . Histological studies of patients with non‐nephrotic presentation, on the other hand, are not so often documented and include TMA and interstitial nephritis . TMA in post‐HSCT patients is known as a multi‐organ disease due to endothelial injury caused by various factors, and investigations have so far become available and focus on clinical data, risk factors, and prognosis without renal biopsy .…”

Section: Discussionmentioning

confidence: 99%

“…In this article, we describe a case of post‐HSCT NS showing simultaneously overlapped glomerular lesions of TMA and MN in the renal biopsy. According to several large retrospective studies of post‐HSCT renal pathology, a combination of glomerular, and non‐glomerular pathologies, for example, TMA or glomerulonephritis with concomitant acute tubular necrosis and/or interstitial nephritis, is not uncommon . Although Troxell et al .…”

Section: Discussionmentioning

confidence: 99%

“…1,10 Histological studies of patients with non-nephrotic presentation, on the other hand, are not so often documented and include TMA and interstitial nephritis. 2,8,11,12 TMA in post-HSCT patients is known as a multi-organ disease due to endothelial injury caused by various factors, and investigations have so far become available and focus on clinical data, risk factors, and prognosis without renal biopsy. 13,14 Recently, clinicopathological analyses of histology-based renal TMA after HSCT were performed, and the patients in those studies often did not fulfill the clinical criteria for TMA.…”

Section: Discussionmentioning

confidence: 99%

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A Case of the nephrotic syndrome in bone marrow transplantation recipient, histologically showing overlapped glomerular lesions of thrombotic microangiopathy and membranous nephropathy

Masuzawa

Nishimura

Kitani

et al. 2017

Pathology International

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Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions. Although both MN and TMA after HSCT are associated with GVHD and immunological abnormalities, these diseases are exceptionally coexistent in renal biopsy specimens. We herein describe a case of post-HSCT NS, histologically showing overlapped lesions of TMA and MN. Renal biopsy specimen after presentation of NS revealed early stage MN and TMA with evidence of chronicity. TMA was thought to have preceded MN, and renal biopsy at the phase of pre-nephrotic proteinuria might reveal earlier histological changes of isolated renal TMA. Detection of subclinical renal TMA earlier by spontaneous renal biopsy can help prevent progression of renal injury or overlapping of other renal pathologies. We also demonstrated Th2 predominant intraglomerular infiltration of lymphocytes by immunohistochemistry.

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“…According to a recent report, kidney-biopsy specimens obtained from patients with TMA showed mesangiolysis and loss of endothelial cells with occlusion of capillary lumens with fibrin, as was the case for our patient [13]. According to one institution's study of 67 patients, kidney specimens often demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, arteriosclerosis, and rarely membranous nephropathy [25]. Another study showed that the most commonly reported pathology was membranous nephropathy, followed by minimal change disease [22].…”

Section: Renal Pathology In Gvhd and Ta-tmamentioning

confidence: 99%

Thrombotic Microangiopathy With Granulomatosis Interstitial Nephritis in an Allogenic Bone Marrow Transplant Patient: A Case Report and Review of the Literature

Mirza

Verma

et al. 2017

J Hematol

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Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation (HSCT) with variable presentations. TA-TMA has often been described as a diagnosis of exclusion but a renal biopsy is rarely pursued to confirm the diagnosis, an essential step for our patient with renally limited TMA. We report a case report from the onconephrology clinic and review the literature associated with TA-TMA as it relates to diagnosis and treatment. A 45-year-old woman with acute myeloid leukemia and stage 3 chronic kidney disease underwent a matched unrelated donor allogenic HSCT. Postoperatively, she developed gastrointestinal graft versus host disease (GvHD) and was treated with tacrolimus, sirolimus, budesonide, and beclomethasone. Following discharge, she developed uncontrolled hypertension and required losartan, amlodipine, carvedilol, clonidine patch, and hydralazine as needed. On day 180 post-transplant, she developed lower extremity edema and acute kidney injury (AKI) with creatinine increasing to 2 mg/dL. On day 480 post-transplant, she developed worsening thrombocytopenia, anemia, new hematuria, left flank pain, and worsening renal function with creatinine peaking to 6 mg/dL. Peripheral smear revealed no schistocytes, lactate dehydrogenase of 265 mg/dL, and urinalysis with 100 mg/dL protein. ADAMTS 13 activity was normal (92%) and no inhibitor was detected. She became anuric and was started on hemodialysis. Renal biopsy revealed glomerular changes consistent with TA-TMA. During HSCT, systemic vascular endothelial injury triggers microangiopathic hemolytic anemia, platelet consumption, injury of glomerular endothelial cells and fibrin occluded renal capillaries. Thus, TA-TMA should be considered in HSCT patients with elevated LDH, proteinuria, hypertension, and AKI. However, a diagnosis is difficult to confirm without a renal biopsy. Treatment involves discontinuing potentially toxic agents such as calcineurin inhibitors and sirolimus, prescribing adequate antimicrobial treatment, and using renal replacement therapy if needed. A renal biopsy early in the course of disease not only confirms the diagnosis, but may limit the extent of disease.

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Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series

Cited by 23 publications

References 51 publications

Kidney Pathology after Hematologic Cell Transplantation—A Single-Center Observation Study of Indication Biopsies and Autopsies

Kidney Pathology after Hematologic Cell Transplantation—A Single-Center Observation Study of Indication Biopsies and Autopsies

A Case of the nephrotic syndrome in bone marrow transplantation recipient, histologically showing overlapped glomerular lesions of thrombotic microangiopathy and membranous nephropathy

Thrombotic Microangiopathy With Granulomatosis Interstitial Nephritis in an Allogenic Bone Marrow Transplant Patient: A Case Report and Review of the Literature

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