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Leung P, Pianta T, Langsford D, Tay HS, Cooke R. Minimal change disease following autologous stem cell transplant for Hodgkin lymphoma. BMJ Case Rep 2025; 18:e259306. [PMID: 39848788 DOI: 10.1136/bcr-2023-259306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025] Open
Abstract
Nephrotic syndrome is characterised by heavy proteinuria secondary to glomerular injury. It is an uncommon but serious complication of allogeneic haematopoietic stem cell transplant (HSCT), but rarely reported after autologous HSCT. Here, we report the case of a man in his mid-20s who presented with significant peripheral oedema 2 months after autologous HSCT for Hodgkin lymphoma. Investigations demonstrated nephrotic range proteinuria and hypoalbuminaemia. Renal biopsy demonstrated minimal change disease. Initial treatment with glucocorticoids was complicated by toxicity without remission. However, the clinical and biochemical resolution of his nephrotic syndrome promptly followed administration of rituximab. This case highlights nephrotic syndrome as a complication after autologous HSCT and suggests potential effectiveness of rituximab in minimal change disease in the presence of steroid toxicity or other contraindications.
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Affiliation(s)
- Patrick Leung
- Department of Haematology, Northern Health, Epping, Victoria, Australia
| | - Timothy Pianta
- Department of Nephrology, Northern Health, Epping, Victoria, Australia
| | - David Langsford
- Department of Nephrology, Northern Health, Epping, Victoria, Australia
| | - Hui Sien Tay
- Department of Anatomical Pathology, Alfred Health, Melbourne, Victoria, Australia
| | - Rachel Cooke
- Department of Haematology, Northern Health, Epping, Victoria, Australia
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Jin Y, Zhao P, Zhang YY, Ye YS, Zhou F, Wan DM, Chen Y, Zhou J, Li X, Wang Y, Liu Y, Bian ZL, Yang KQ, Li Z, Zhang J, Xu WW, Zhou JY, An ZY, Fu HX, Chen YH, Chen Q, Wu J, Wang JZ, Mo XD, Chen H, Chen Y, Wang Y, Chang YJ, Huang H, Huang XJ, Zhang XH. Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study. Ann Hematol 2024; 103:4261-4270. [PMID: 38990296 DOI: 10.1007/s00277-024-05875-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 07/01/2024] [Indexed: 07/12/2024]
Abstract
Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.
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Affiliation(s)
- Yue Jin
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Peng Zhao
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yuan-Yuan Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yi-Shan Ye
- Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Fang Zhou
- Department of Hematology, Hospital of People's Liberation Army, Jinan, China
| | - Ding-Ming Wan
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi Chen
- Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jian Zhou
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Xin Li
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yan Wang
- Hematology Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China
| | - Yue Liu
- Department of Hematology, Hospital of People's Liberation Army, Jinan, China
| | - Zhi-Lei Bian
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kai-Qian Yang
- Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhen Li
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Jian Zhang
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Wen-Wei Xu
- Hematology Department, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China
| | - Jian-Ying Zhou
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Zhuo-Yu An
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Hai-Xia Fu
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yu-Hong Chen
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Qi Chen
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Jin Wu
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Jing-Zhi Wang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Dong Mo
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Huan Chen
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yao Chen
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Ying-Jun Chang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - He Huang
- Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao-Jun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiao-Hui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
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Bosnić Kovačić I, Matošević M, Laganović M, Dika Ž, Fištrek Prlić M, Ivandić E, Ćorić M, Bulimbašić S, Duraković N, Perić Z, Desnica L, Vrhovac R, Jelaković B, Sethi S, Vuković Brinar I. Specific antigen-based stratification of membranous nephropathy in patients after haematopoietic stem cell allotransplantation - a case series and literature review. BMC Nephrol 2024; 25:254. [PMID: 39118046 PMCID: PMC11312175 DOI: 10.1186/s12882-024-03675-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 07/16/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
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Affiliation(s)
- Ines Bosnić Kovačić
- Department of Nephrology and Dialysis, Clinical Hospital Sveti Duh, Zagreb, Croatia
| | - Matija Matošević
- Institute of Emergency Medicine of Zagreb County, Velika Gorica, Croatia
| | - Mario Laganović
- Department of Nephrology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Živka Dika
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Margareta Fištrek Prlić
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Ema Ivandić
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Marijana Ćorić
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Stela Bulimbašić
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Nadira Duraković
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Haematology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb, Croatia
| | - Zinaida Perić
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Haematology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb, Croatia
| | - Lana Desnica
- Department of Haematology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb, Croatia
| | - Radovan Vrhovac
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Haematology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb, Croatia
| | - Bojan Jelaković
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Ivana Vuković Brinar
- School of Medicine, University of Zagreb, Zagreb, Croatia.
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia.
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Mongera N, Passler W, Sethi S, Kozakowski N, Tabbì MG. A case of protocadherin FAT1-positive membranous nephropathy secondary to hematopoietic stem-cell transplantation. J Nephrol 2024; 37:1153-1156. [PMID: 37815750 DOI: 10.1007/s40620-023-01786-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2023] [Indexed: 10/11/2023]
Affiliation(s)
- Nicola Mongera
- Nephrology Department, Bolzano Hospital, Bolzano, Italy.
| | | | - Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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Gudsoorkar P, Abudayyeh A, Tchakarov A, Hanna R. Onconephrology and Thrombotic Microangiopathy: Looking Beyond the Horizon. Semin Nephrol 2023; 42:151345. [PMID: 37196461 DOI: 10.1016/j.semnephrol.2023.151345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Thrombotic microangiopathies (TMAs) represent a complex interaction of endothelial and podocyte biology, nephron physiology, complement genetics, and oncologic therapies with host immunology. The complexity of various factors, such as molecular causes, genetic expressions, and immune system mimicking, along with incomplete penetrance, make it difficult to find a straightforward solution. As a result, there may be variations in diagnosis, study, and treatment approaches, and achieving a consensus can be challenging. Here, we review the molecular biology, pharmacology, immunology, molecular genetics, and pathology of the various TMA syndromes in the setting of cancer. Controversies in etiology, nomenclature, and points requiring further clinical, translational, and bench research are discussed. Complement-mediated TMAs, chemotherapy drug-mediated TMAs, TMAs in monoclonal gammopathy, and other TMAs central to onconephrology practice are reviewed in detail. In addition, established and emerging therapies within the US Food and Drug Administration pipeline subsequently are discussed. Finally, a comprehensive review of critical areas of onconephrology clinical practice is presented as practical value to the clinical practitioner and seeds of investigation to be sown among the community of atypical hemolytic uremic syndrome researchers.
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Affiliation(s)
- Prakash Gudsoorkar
- Division of Nephrology, Kidney C.A.R.E. Program, University of Cincinnati, Cincinnati, OH
| | - Ala Abudayyeh
- Section of Nephrology, The University of Texas, MD Anderson Cancer Center, Houston, TX
| | - Amanda Tchakarov
- Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, TX
| | - Ramy Hanna
- Division of Nephrology, Department of Medicine, University of California Irvine Medical Center, Orange, CA.
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Sakai T, Uchida T, Iwama S, Sugisaki K, Yamada M, Inamoto Y, Oda T. Chronic Graft-versus-host Disease-associated Membranous Nephropathy Following Bone Marrow Transplantation, Successfully Treated with Rituximab. Intern Med 2023; 62:269-273. [PMID: 35732451 PMCID: PMC9908386 DOI: 10.2169/internalmedicine.9655-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
A 67-year-old woman who had undergone bone marrow transplantation 2 years previously for acute myeloid leukemia (AML) developed complications of chronic graft-versus-host disease (cGVHD). She thereafter also developed nephrotic syndrome, and membranous nephropathy (MN) was diagnosed by a renal biopsy. Although the causative antigens of the MN were not detected, immunofluorescence staining showed codominant deposition of immunoglobulins G2 and G3, a finding indicating secondary MN, thereby suggesting an association between MN and cGVHD. Rituximab treatment was initiated, and her nephrotic syndrome gradually improved without relapse of AML. Our present case suggests that rituximab is a safe and effective therapeutic option for cGVHD-associated MN.
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Affiliation(s)
- Takashi Sakai
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
| | - Takahiro Uchida
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
| | - Sachiko Iwama
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
| | - Kentaro Sugisaki
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
| | - Muneharu Yamada
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
| | - Yoshihiro Inamoto
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Japan
| | - Takashi Oda
- Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, Japan
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John EE, Roy S, Devasia AJ, Karuppusami R, Jose N, Mani SSR, Eapen JJ, Yusuf S, Thomas A, Valson AT, David VG, Mathews V, Biju George, Varughese S, Alexander S. Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients. GLOMERULAR DISEASES 2023; 3:98-115. [PMID: 37064012 PMCID: PMC10098275 DOI: 10.1159/000529699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/09/2023] [Indexed: 03/16/2023]
Abstract
Introduction Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.
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Affiliation(s)
| | - Sanjeet Roy
- Department of Pathology, Christian Medical College, Vellore, India
| | - Anup J. Devasia
- Department of Hematology, Christian Medical College, Vellore, India
| | - Reka Karuppusami
- Department of Biostatistics, Christian Medical College, Vellore, India
| | - Nisha Jose
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | | | - Sabina Yusuf
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Athul Thomas
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T. Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Vikram Mathews
- Department of Hematology, Christian Medical College, Vellore, India
| | - Biju George
- Department of Hematology, Christian Medical College, Vellore, India
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A case of membranous nephropathy as a manifestation of graft-versus-host disease accompanied by BK nephropathy in the native kidney. Int Urol Nephrol 2023; 55:165-166. [PMID: 35851674 DOI: 10.1007/s11255-022-03270-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 06/02/2022] [Indexed: 01/05/2023]
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Nasr SH, Leung N, Said SM, Alkhateeb HB, Madden BJ, Charlesworth MC, Beck LH, Larsen CP, Sethi S. Membranous Nephropathy With Extensive Tubular Basement Membrane Deposits Following Allogeneic Hematopoietic Cell Transplant: A Report of 5 Cases. Am J Kidney Dis 2022; 79:904-908. [PMID: 34508832 DOI: 10.1053/j.ajkd.2021.07.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/20/2021] [Indexed: 12/24/2022]
Abstract
Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4). Proteomic analysis of glomeruli in 4 cases identified PLA2R in 1, with no significant protein spectra for PLA2R, THSD7A, EX1/2, NELL-1, PCDH7, NCAM1, or SEMA3B detected in the remaining 3. On follow-up (for a mean 42 months), 4 patients had complete and 1 partial remission following prednisone and/or rituximab therapy. We propose that membranous nephropathy with extensive TBM deposits is a distinctive clinicopathologic lesion associated with allogeneic hematopoietic cell transplant. Pathogenesis likely involves cGVHD-driven antibodies against glomerular and TBM components, the identity of which remains to be elucidated.
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Affiliation(s)
- Samih H Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Division of Hematology, Mayo Clinic, Rochester, Minnesota.
| | - Samar M Said
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | - Benjamin J Madden
- Medical Genome Facility, Proteomics Core, Mayo Clinic, Rochester, Minnesota
| | | | | | | | - Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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Sethi S, Madden B, Casal Moura M, Nasr SH, Klomjit N, Gross L, Negron V, Charlesworth MC, Alexander MP, Leung N, Specks U, Fervenza FC, Haas M. Hematopoietic Stem Cell Transplant-Membranous Nephropathy Is Associated with Protocadherin FAT1. J Am Soc Nephrol 2022; 33:1033-1044. [PMID: 35321939 PMCID: PMC9063902 DOI: 10.1681/asn.2021111488] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 02/25/2022] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Membranous nephropathy (MN) is a common cause of proteinuria in patients receiving a hematopoietic stem cell transplant (HSCT). The target antigen in HSCT-associated MN is unknown. METHODS We performed laser microdissection and tandem mass spectrometry (MS/MS) of glomeruli from 250 patients with PLA2R-negative MN to detect novel antigens in MN. This was followed by immunohistochemical (IHC)/immunofluorescence (IF) microscopy studies to localize the novel antigen. Western blot analyses using serum and IgG eluted from frozen biopsy specimen to detect binding of IgG to new 'antigen'. RESULTS MS/MS detected a novel protein, protocadherin FAT1 (FAT1), in nine patients with PLA2R-negative MN. In all nine patients, MN developed after allogeneic HSCT (Mayo Clinic discovery cohort). Next, we performed MS/MS in five patients known to have allogeneic HSCT-associated MN (Cedar Sinai validation cohort). FAT1 was detected in all five patients by MS/MS. The total spectral counts for FAT1 ranged from 8 to 39 (mean±SD, 20.9±10.1). All 14 patients were negative for known antigens of MN, including PLA2R, THSD7A, NELL1, PCDH7, NCAM1, SEMA3B, and HTRA1. Kidney biopsy specimens showed IgG (2 to 3+) with mild C3 (0 to 1+) along the GBM; IgG4 was the dominant IgG subclass. IHC after protease digestion and confocal IF confirmed granular FAT1 deposits along the GBM. Lastly, Western blot analyses detected anti-FAT1 IgG and IgG4 in the eluate obtained from pooled frozen kidney biopsy tissue and in the serum of those with FAT1-asssociated MN, but not from those with PLA2R-associated MN. CONCLUSIONS FAT1-associated MN appears to be a unique type of MN associated with HSCT. FAT1-associated MN represents a majority of MN associated with HSCT.
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Affiliation(s)
- Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Benjamin Madden
- Medical Genome Facility, Proteomics Core, Mayo Clinic, Rochester, Minnesota
| | - Marta Casal Moura
- Division of Pulmonary and Critical Care, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Samih H. Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Nattawat Klomjit
- Division of Nephrology and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - LouAnn Gross
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Vivian Negron
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | - Mariam P. Alexander
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Ulrich Specks
- Division of Pulmonary and Critical Care, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Mark Haas
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
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Abudayyeh A, Wanchoo R. Kidney Disease Following Hematopoietic Stem Cell Transplantation. Adv Chronic Kidney Dis 2022; 29:103-115.e1. [PMID: 35817518 DOI: 10.1053/j.ackd.2021.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 10/07/2021] [Accepted: 11/15/2021] [Indexed: 11/11/2022]
Abstract
Hematopoietic stem cell transplantation (SCT) provides a curative option for the treatment of several malignancies. Its growing use is associated with an increased burden of kidney disease. Acute kidney injury is usually seen within the first 100 days of transplantation and has an incidence ranging between 12 and 73%, with the highest rate in myeloablative allogeneic SCT. A large subset of patients after SCT develop chronic kidney disease. They can be broadly classified into thrombotic microangiopathy, nephrotic syndrome, and calcineurin toxicity. Dialysis requirement after SCT is associated with mortality exceeding 80%. Given the higher morbidity and mortality related to development kidney disease, nephrologists need to be aware of the various causes and best treatment options.
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Affiliation(s)
- Ala Abudayyeh
- Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rimda Wanchoo
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY.
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12
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Bai MC, Wu JJ, Miao KR, Zhu JF, Mao HJ. Nephrotic syndrome in syngeneic hematopoietic stem cell transplantation recipients: A case report. World J Clin Cases 2021; 9:614-622. [PMID: 33553399 PMCID: PMC7829719 DOI: 10.12998/wjcc.v9.i3.614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 11/25/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is widely used in the treatment of hematological diseases. However, complications after transplantation, such as acute and chronic graft-vs-host disease (GVHD), still seriously affect the quality of life and even threaten the lives of patients. There is evidence that glomerular diseases can manifest as GVHD. However, GVHD should not occur as a result of syngeneic HSCT.
CASE SUMMARY A 20-year-old male diagnosed with T lymphoblastic lymphoma (stage IIIA, aaIPI 1) in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission. He underwent syngeneic HSCT in June 2014, and had no kidney disease history before the transplant. However, nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT. Renal biopsy was performed, which led to a diagnosis of atypical membranous nephropathy. After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine, the nephrotic syndrome was completely relieved.
CONCLUSION We report a case of delayed nephrotic syndrome after syngeneic HSCT. Antibody-mediated autoimmune glomerular disease may be the underlying mechanism. After treatment with immunosuppressive agents, the nephrotic syndrome was completely relieved but further long-term follow-up is still needed.
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Affiliation(s)
- Ming-Chuan Bai
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Jing-Jing Wu
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Kou-Rong Miao
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Jing-Feng Zhu
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Hui-Juan Mao
- Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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13
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Rosner MH, Jhaveri KD, McMahon BA, Perazella MA. Onconephrology: The intersections between the kidney and cancer. CA Cancer J Clin 2021; 71:47-77. [PMID: 32853404 DOI: 10.3322/caac.21636] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 07/17/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022] Open
Abstract
Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug-induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.
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Affiliation(s)
- Mitchell H Rosner
- Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Kenar D Jhaveri
- Division of Kidney Disease and Hypertension, Zucker School of Medicine at Hofstra University, Great Neck, New York
| | - Blaithin A McMahon
- Division of Nephrology. Medical, University of South Carolina, Charleston, South Carolina
| | - Mark A Perazella
- Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut
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14
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Hogan JJ. A Case of Nephrotic Syndrome after Allogeneic Stem Cell Transplantation. Clin J Am Soc Nephrol 2020; 15:873-875. [PMID: 32144100 PMCID: PMC7274296 DOI: 10.2215/cjn.00100120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Jonathan J Hogan
- Division of Nephrology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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15
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Mrabet S, Aicha NB, Abdessayed N, Mokni M, Achour A. Membranous nephropathy succeeding autologous hematopoietic stem cell transplant: a case report. BMC Nephrol 2018. [PMID: 29523091 PMCID: PMC5845168 DOI: 10.1186/s12882-018-0855-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits. Most of the cases are primary, while only approximately 25% of the cases are secondary to some known diseases. Recently, MN has been considered to be a possible presentation of chronic graft-versus-host disease (GVHD) of the kidney in allogeneic hematopoietic stem cell transplantation (HSCT) patients. In autologous HSCT populations, there have been scarce reports of associated MN, as a result of immune dysregulation leading to systemic autoimmunity and miming chronic GVHD. Case presentation We report an exceptional case of MN associated to an acute renal failure occurring within days following an autologous HSCT indicated by multiple myeloma. There was no evidence of GVHD or myeloma relapse. A complete remission of nephrotic syndrome with normalization of renal function were rapidly obtained by corticosteroid therapy. Conclusion This is the first published case of acute renal failure due to MN occurring in the acute phase of an autologous HSCT. These findings support the antibodymediated autoimmune glomerular disease.
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Affiliation(s)
- Sanda Mrabet
- Department of Nephrology, Dialysis and transplantation. Sahloul university Hospital, Sousse, Tunisia.
| | - Narjess Ben Aicha
- Department of Nephrology, Dialysis and transplantation. Sahloul university Hospital, Sousse, Tunisia
| | - Nihed Abdessayed
- Department of Pathology, Farhat Hached University Hospital, Sousse, Tunisia
| | - Moncef Mokni
- Department of Pathology, Farhat Hached University Hospital, Sousse, Tunisia
| | - Abdellatif Achour
- Department of Nephrology, Dialysis and transplantation. Sahloul university Hospital, Sousse, Tunisia
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16
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Brinkerhoff BT, Houghton DC, Troxell ML. Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series. Mod Pathol 2016; 29:637-52. [PMID: 27015134 DOI: 10.1038/modpathol.2016.61] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 02/14/2016] [Accepted: 02/15/2016] [Indexed: 12/29/2022]
Abstract
Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury.
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Affiliation(s)
- Brian T Brinkerhoff
- Oregon Health & Science University, Department of Pathology, Portland, OR, USA
| | - Donald C Houghton
- Oregon Health & Science University, Department of Pathology, Portland, OR, USA
| | - Megan L Troxell
- Oregon Health & Science University, Department of Pathology, Portland, OR, USA.,Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA
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17
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Beyar-Katz O, Davila EK, Zuckerman T, Fineman R, Haddad N, Okasha D, Henig I, Leiba R, Rowe JM, Ofran Y. Adult Nephrotic Syndrome after Hematopoietic Stem Cell Transplantation: Renal Pathology is the Best Predictor of Response to Therapy. Biol Blood Marrow Transplant 2015; 22:975-981. [PMID: 26740372 DOI: 10.1016/j.bbmt.2015.12.014] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 12/16/2015] [Indexed: 01/28/2023]
Abstract
Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HSCT) is a rare phenomenon usually associated with graft-versus-host disease (GVHD). This systematic review of post-HSCT NS cases reported in the literature aimed to identify risk factors and unique features of the disease in this clinical setting. One hundred sixteen cases of post-HSCT NS published in the English literature between 1988 and 2015 were revealed and analyzed. The median onset of NS was 20.5 months (range, 3 to 174) post-HSCT. NS development was associated with acute or chronic GVHD in 87.2% of cases. Membranous nephropathy (MGN) was the most frequent pathology (65.5%), followed by minimal change disease (MCD) (19%). Complete remission of the NS was achieved in 63.5% of patients (59.1% of MGN cases and 81.3% of MCD cases; P = .15). Patients presenting with MCD recovered at a median of 1.75 months (range, 1 to 12) and with MGN a median of 7 months (range, 1 to 53) (P = .001). NS was treated with corticosteroids alone in 16.8% of patients and with a combination of corticosteroids and other immunosuppressive agents in 73.5% of patients. Univariate analysis failed to identify a single predictive factor of response to therapy. In conclusion, post-HSCT NS usually develops concomitant to GVHD and is associated with high rates of response to therapy. Although most patients were treated with a combination of immunosuppressive drugs, single-agent therapy with steroids may be sufficient in some cases.
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Affiliation(s)
- Ofrat Beyar-Katz
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
| | | | - Tsila Zuckerman
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
| | - Riva Fineman
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
| | - Nuhad Haddad
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
| | - Doaa Okasha
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
| | - Israel Henig
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
| | - Ronit Leiba
- Department of Statistics, Rambam Health Care Campus, Haifa, Israel
| | - Jacob M Rowe
- Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel; Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Yishai Ofran
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
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18
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Chanswangphuwana C, Townamchai N, Intragumtornchai T, Bunworasate U. Glomerular diseases associated with chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation: case reports. Transplant Proc 2015; 46:3616-9. [PMID: 25498099 DOI: 10.1016/j.transproceed.2014.07.076] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 06/24/2014] [Accepted: 07/15/2014] [Indexed: 02/03/2023]
Abstract
Chronic graft-versus-host disease (cGVHD) is the major complication following allogeneic stem cell transplantation (allo-SCT). Nephrotic syndrome (NS) and other types of glomerulonephritis have been proposed to be the very rare forms of renal cGVHD. From 1991 to 2011, 253 patients underwent allo-SCT at our center. We report here 4 cases (1.6%) presenting with varieties of glomerular manifestations associated with cGVHD. The first case was typical NS. The renal pathology showed membranous nephropathy (MN). The second case was also MN, but this patient also had the pathology of focal segmental glomerulosclrosis (FSGS) and acute tubular necrosis (ATN). The third case showed lupus nephritis-like glomerular lesions with a high anti-nuclear antibody (ANA) titer. The fourth case presented with rapidly progressive glomerulonephritis (RPGN)-like symptoms. The kidney histology in this case was not available. The patient responded well to immunosuppressive therapy, but NS later recurred. Therefore, overt glomerular diseases after allo-SCT in Thai patients are not very rare. Monitoring urinalysis during withdrawal of immunosuppressive drugs and also during follow-up of patients with cGVHD may be considered.
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Affiliation(s)
- C Chanswangphuwana
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
| | - N Townamchai
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - T Intragumtornchai
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - U Bunworasate
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
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19
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Abudayyeh A, Truong LD, Beck LH, Weber DM, Rezvani K, Abdelrahim M. Membranous nephropathy in autologous hematopoietic stem cell transplant: autologous graft-versus-host disease or autoimmunity induction? Clin Kidney J 2015; 8:440-4. [PMID: 26251713 PMCID: PMC4515891 DOI: 10.1093/ckj/sfv036] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 03/02/2015] [Accepted: 04/27/2015] [Indexed: 12/04/2022] Open
Abstract
With the increasing utility of hematopoietic stem cell transplantation (SCT) as a treatment for cancer and noncancerous disorders, more challenges and complications associated with SCT have emerged. Renal injury immediately after transplant is common and well understood, but long-term renal injury is becoming more evident. Chronic graft-versus-host disease (GVHD) is a known long-term complication of SCT, and membranous nephropathy (MN) is emerging as the most common cause of SCT-associated glomerular pathology. In this case report, we present a patient who developed features of anti-PLA2R antibody-negative MN following autologous SCT. The renal injury responded well to steroids and further response to rituximab therapy was noted, suggesting antibody-mediated autoimmune glomerular disease. We also present a review of the literature on autologous GVHD and the role of T and B cells in induction of autoimmunity by SCT.
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Affiliation(s)
- Ala Abudayyeh
- Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston , TX , USA
| | - Luan D Truong
- Department of Pathology and Genomic Medicine , The Houston Methodist Hospital, Houston , TX , USA
| | - Laurence H Beck
- Department of Medicine, Section of Nephrology , Boston University School of Medicine, Boston , MA , USA
| | - Donna M Weber
- Department of Lymphoma/Myeloma , The University of Texas MD Anderson Cancer Center, Houston , TX , USA
| | - Katy Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center , Houston , TX , USA
| | - Maen Abdelrahim
- Division of Medical Oncology, Duke University Medical Center , Durham, North Carolina , USA
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20
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Byrne-Dugan CJ, Collins AB, Lam AQ, Batal I. Membranous nephropathy as a manifestation of graft-versus-host disease: association with HLA antigen typing, phospholipase A2 receptor, and C4d. Am J Kidney Dis 2014; 64:987-93. [PMID: 25304985 DOI: 10.1053/j.ajkd.2014.09.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Accepted: 07/29/2014] [Indexed: 12/31/2022]
Abstract
Glomerulopathy is an uncommon but increasingly recognized complication of hematopoietic cell transplantation. It typically manifests as membranous nephropathy, less commonly as minimal change disease, and rarely as proliferative glomerulonephritis. There is evidence to suggest that these glomerulopathies might represent manifestations of chronic graft-versus-host disease. In this report, we focus on membranous nephropathy as the most common form of glomerulopathy after hematopoietic cell transplantation. We present a case of membranous nephropathy that developed 483 days post-allogeneic hematopoietic stem cell transplantation in a patient with a history of acute graft-versus-host disease. We also share our experience with 4 other cases of membranous nephropathy occurring after allogeneic hematopoietic stem cell transplantation. Clinicopathologic correlates, including the association with graft-versus-host-disease, HLA antigen typing, glomerular deposition of immunoglobulin G (IgG) subclasses, subepithelial colocalization of IgG deposits with phospholipase A2 receptor staining, C4d deposition along the peritubular capillaries, and treatment, are discussed with references to the literature.
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Affiliation(s)
- Cathryn J Byrne-Dugan
- Renal Pathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - A Bernard Collins
- Renal Pathology, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Albert Q Lam
- Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Ibrahim Batal
- Renal Pathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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21
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Abstract
The kidney is subject to a large variety of injurious factors before, during, and after hematopoietic stem cell transplantation (HCT), leading to a high incidence of acute kidney injury in the peritransplant period. Chronic kidney disease is estimated to impact 15% to 20% of HCT recipients. Although renal biopsies may be deferred in the setting of thrombotic microangiopathy, acute self-limited impairment, or slowly progressive functional decline, in many patients renal biopsy yields important diagnostic insight to guide treatment. Light microscopic, immunofluorescence, and ultrastructural analysis often reveals a number of concurrent abnormalities in glomeruli, tubules, interstitium, and vessels. Meta-analysis of the literature reveals that membranous nephropathy is the most commonly reported glomerular lesion in the setting of HCT, followed by minimal change disease. Autopsy and biopsy studies show that clinical criteria lack sensitivity and specificity for renal acute and chronic thrombotic microangiopathy. Viral infection and other causes of interstitial nephritis and tubular injury are important findings in HCT renal biopsies, which in many instances may not be clinically suspected. Given the complexity and variability of HCT protocols, clinicopathologic correlation is needed.
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22
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Jhaveri KD, Shah HH, Patel C, Kadiyala A, Stokes MB, Radhakrishnan J. Glomerular diseases associated with cancer, chemotherapy, and hematopoietic stem cell transplantation. Adv Chronic Kidney Dis 2014; 21:48-55. [PMID: 24359986 DOI: 10.1053/j.ackd.2013.08.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 08/16/2013] [Accepted: 08/20/2013] [Indexed: 02/07/2023]
Abstract
Many solid and hematological malignancies have been associated with different glomerular diseases. Several case reports and case series of cancer-associated glomerular diseases have shown that treating the cancer may lead to resolution of the glomerular process. Hence, knowledge and approach to cancer-associated glomerular diseases is important for both the caring nephrologists and the cancer specialists. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies, especially non-Hodgkin's lymphoma. Membranoproliferative glomerulonephritis is increasingly being recognized to be associated with chronic hematologic malignancies such as chronic lymphocytic leukemia. In this article, we review various cancer-associated glomerular diseases and their pathogenesis as well as principles of treatment. In addition, we also review glomerular diseases seen after chemotherapy and hematopoietic stem cell transplantation.
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23
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Detection of anti-PLA2R autoantibodies and IgG subclasses in post-allogeneic hematopoietic stem cell transplantation membranous nephropathy. Am J Med Sci 2013; 346:32-7. [PMID: 23103439 DOI: 10.1097/maj.0b013e318267b5cd] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Membranous nephropathy (MN) is the most common glomerular disease of post-allogeneic hematopoietic stem cell transplantation (HSCT). Although this condition is now considered a renal complication of chronic graft-versus-host disease (cGVHD), the pathogenesis of this disease is not well established. METHODS Five patients with post-HSCT MN diagnosed by renal biopsy were selected for this study. The clinical and renal pathological data of these patients were analyzed, and anti-PLA2R (M-type phospholipase A2 receptor) autoantibodies and IgG subclasses were detected in the serum samples from the patients. RESULTS None of the 5 patients had a history of kidney disease. All the patients had a combination of cGVHD and proteinuria, which was in remission after an effective anti-graft-versus-host disease treatment. The immunofluorescent detection showed that IgG4 was the predominant IgG subclass, and the distribution of IgG4 was the same as that of nephrin. The anti-PLA2R autoantibodies were negative in 4 patients and positive in 1 patient. The levels of IgG2, IgG3 and IgG4 increased in the majority of the patients. CONCLUSIONS Our data showed that the clinical course of post-HSCT MN patients was closely related to that of cGVHD. Although the renal pathology was similar to idiopathic MN, the negative result for the anti-PLA2R autoantibodies in the majority of the patients suggested that the formation of an immune complex occurs differently between these 2 diseases.
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24
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Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney Int 2013; 84:34-44. [DOI: 10.1038/ki.2012.484] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 12/14/2012] [Accepted: 12/21/2012] [Indexed: 01/01/2023]
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25
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Han JH, Kim HR, Kim GJ, Lim BJ, Jeong HJ, Oh HJ, Yoo TH, Kang SW, Choi KH, Han SH. A case of membranous nephropathy as a manifestation of graft-versus-host disease. Kidney Res Clin Pract 2012; 32:39-42. [PMID: 26889436 PMCID: PMC4716117 DOI: 10.1016/j.krcp.2012.09.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Revised: 07/05/2012] [Accepted: 07/28/2012] [Indexed: 11/24/2022] Open
Abstract
Nephrotic syndrome (NS) rarely occurs after hematopoietic stem cell transplantation (HSCT) as a late manifestation of graft-versus-host disease (GVHD). Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.
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Affiliation(s)
- Jae Hyun Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyoung Rae Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Jeong Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Jin Lim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Hyeon Joo Jeong
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Hyung Jung Oh
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Shin-Wook Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 for Medical Science, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea
| | - Kyu Hun Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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26
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Denker B, Robles-Osorio ML, Sabath E. Recent advances in diagnosis and treatment of acute kidney injury in patients with cancer. Eur J Intern Med 2011; 22:348-354. [PMID: 21767751 DOI: 10.1016/j.ejim.2011.02.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 01/30/2011] [Accepted: 02/03/2011] [Indexed: 02/06/2023]
Abstract
Acute Kidney Injury (AKI) is a common complication in patients with cancer and even though there are many causes of renal failure in this population the classical classification of prerenal, renal, and postrenal is useful as a diagnostic guide. Important risk factors for AKI are dehydration, use of nephrotoxic drugs, preexisting renal impairment and large tumor burden. The development of AKI is associated with poor prognosis but early recognition and treatment initiation are associated with better outcomes in this population.
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Affiliation(s)
- Bradley Denker
- Renal Division, Brigham and Women's Hospital, United States
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