Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome produced by dysregulated activation of the immune system. Acute kidney injury (AKI) and proteinuria have been infrequently described in the setting of HLH, and investigations of underlying histopathologic changes...

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Main Authors: Miroslav Sekulic, Ibrahim Batal, Satoru Kudose, Dominick Santoriello, M. Barry Stokes, Belinda Jim, Hans-Peter Marti, Øystein Eikrem, Jai Radhakrishnan, Vivette D. D’Agati, Glen S. Markowitz
Format: Article
Language:English
Published: Elsevier 2024-02-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024923015759
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author Miroslav Sekulic
Ibrahim Batal
Satoru Kudose
Dominick Santoriello
M. Barry Stokes
Belinda Jim
Hans-Peter Marti
Øystein Eikrem
Jai Radhakrishnan
Vivette D. D’Agati
Glen S. Markowitz
author_facet Miroslav Sekulic
Ibrahim Batal
Satoru Kudose
Dominick Santoriello
M. Barry Stokes
Belinda Jim
Hans-Peter Marti
Øystein Eikrem
Jai Radhakrishnan
Vivette D. D’Agati
Glen S. Markowitz
author_sort Miroslav Sekulic
collection DOAJ
description Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome produced by dysregulated activation of the immune system. Acute kidney injury (AKI) and proteinuria have been infrequently described in the setting of HLH, and investigations of underlying histopathologic changes in the kidney are limited. Methods: To characterize kidney pathology in HLH, a retrospective review of 30 patients’ clinical and laboratory data, and kidney tissue was performed (18 from autopsy, and 12 biopsied patients). Results: HLH was associated with infection (83%), autoimmune disease (37%), and malignancy (20%), including 30% with concurrent autoimmune disease and infection. Nephrological presentations included subnephrotic range proteinuria (63%), AKI (63%), hematuria (33%), chronic kidney disease (CKD, 20%), nephrotic range proteinuria (13%), and nephrotic syndrome (7%); and 40% of patients required hemodialysis (HD). Among the 12 patients who underwent kidney biopsy, 6 subsequently showed improved kidney function and the remainder had progressive CKD with most progressing to end-stage kidney disease. Autopsy patients had a median terminal admission of 1 month, and 33% of the biopsied patients died (ranging from 0.3–5 months post-biopsy). Variable pathologies were identified, including acute tubular injury (ATI, 43%), lupus nephritis (LN, 23%), collapsing glomerulopathy (17%), thrombotic microangiopathy (TMA, 17%), and cortical necrosis (10%). Most autopsied patients had significant kidney pathology other than ATI that likely contributed to kidney function decline. A majority of patients with HLH exhibited kidney dysfunction that likely contributed to the poor prognosis. Conclusion: Kidney dysfunction in HLH should not be assumed to be solely attributable to ATI, and in certain scenarios a kidney biopsy may be warranted.
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spelling doaj-art-6f8d99fddaca4735bd435abbbda4a2752025-08-20T03:45:06ZengElsevierKidney International Reports2468-02492024-02-019241042210.1016/j.ekir.2023.10.033Kidney Dysfunction and Pathology in the Setting of Hemophagocytic LymphohistiocytosisMiroslav Sekulic0Ibrahim Batal1Satoru Kudose2Dominick Santoriello3M. Barry Stokes4Belinda Jim5Hans-Peter Marti6Øystein Eikrem7Jai Radhakrishnan8Vivette D. D’Agati9Glen S. Markowitz10Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA; Correspondence: Miroslav Sekulic, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, VC14-238C, New York, New York 10032, USA.Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Medicine, Division of Nephrology, Jacobi Medical Center at Albert Einstein College of Medicine, New York, New York, USADepartment of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, NorwayDepartment of Internal Medicine, Nephrology Division, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USAIntroduction: Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome produced by dysregulated activation of the immune system. Acute kidney injury (AKI) and proteinuria have been infrequently described in the setting of HLH, and investigations of underlying histopathologic changes in the kidney are limited. Methods: To characterize kidney pathology in HLH, a retrospective review of 30 patients’ clinical and laboratory data, and kidney tissue was performed (18 from autopsy, and 12 biopsied patients). Results: HLH was associated with infection (83%), autoimmune disease (37%), and malignancy (20%), including 30% with concurrent autoimmune disease and infection. Nephrological presentations included subnephrotic range proteinuria (63%), AKI (63%), hematuria (33%), chronic kidney disease (CKD, 20%), nephrotic range proteinuria (13%), and nephrotic syndrome (7%); and 40% of patients required hemodialysis (HD). Among the 12 patients who underwent kidney biopsy, 6 subsequently showed improved kidney function and the remainder had progressive CKD with most progressing to end-stage kidney disease. Autopsy patients had a median terminal admission of 1 month, and 33% of the biopsied patients died (ranging from 0.3–5 months post-biopsy). Variable pathologies were identified, including acute tubular injury (ATI, 43%), lupus nephritis (LN, 23%), collapsing glomerulopathy (17%), thrombotic microangiopathy (TMA, 17%), and cortical necrosis (10%). Most autopsied patients had significant kidney pathology other than ATI that likely contributed to kidney function decline. A majority of patients with HLH exhibited kidney dysfunction that likely contributed to the poor prognosis. Conclusion: Kidney dysfunction in HLH should not be assumed to be solely attributable to ATI, and in certain scenarios a kidney biopsy may be warranted.http://www.sciencedirect.com/science/article/pii/S2468024923015759autoimmune diseasehemophagocytic lymphohistiocytosishistopathologyinfectionmalignancy
spellingShingle Miroslav Sekulic
Ibrahim Batal
Satoru Kudose
Dominick Santoriello
M. Barry Stokes
Belinda Jim
Hans-Peter Marti
Øystein Eikrem
Jai Radhakrishnan
Vivette D. D’Agati
Glen S. Markowitz
Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
Kidney International Reports
autoimmune disease
hemophagocytic lymphohistiocytosis
histopathology
infection
malignancy
title Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
title_full Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
title_fullStr Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
title_full_unstemmed Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
title_short Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis
title_sort kidney dysfunction and pathology in the setting of hemophagocytic lymphohistiocytosis
topic autoimmune disease
hemophagocytic lymphohistiocytosis
histopathology
infection
malignancy
url http://www.sciencedirect.com/science/article/pii/S2468024923015759
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