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1
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Wang X, Patel SA, Haddadin M, Cerny J. Post-allogeneic hematopoietic stem cell transplantation viral reactivations and viremias: a focused review on human herpesvirus-6, BK virus and adenovirus. Ther Adv Infect Dis 2021; 8:20499361211018027. [PMID: 34104434 PMCID: PMC8155777 DOI: 10.1177/20499361211018027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 04/27/2021] [Indexed: 12/30/2022] Open
Abstract
Human cytomegalovirus and Epstein-Barr virus have been recognized as potential drivers of morbidity and mortality of patients undergoing allogeneic stem cell transplantation for years. Specific protocols for monitoring, prophylaxis and pre-emptive therapy are in place in many transplant settings. In this review, we focus on the next three most frequent viruses, human herpesvirus-6, BK virus and adenovirus, causing reactivation and/or viremia after allogeneic transplant, which are increasingly detected in patients in the post-transplant period owing to emerging techniques of molecular biology, recipients' characteristics, treatment modalities used for conditioning and factors related donors or stem cell source. Given the less frequent detection of an illness related to these viruses, there are often no specific protocols in place for the management of affected patients. While some patients develop significant morbidity (generally older), others may not need therapy at all (generally younger or children). Furthermore, some of the antiviral therapies used are potentially toxic. With the addition of increased risk of secondary infections, risk of graft failure or increased risk of graft-versus-host disease as well as the relationship with other post-transplant complications, the outcomes of patients with these viremias remain unsatisfactory and even long-term survivors experience increased morbidity.
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Affiliation(s)
- Xin Wang
- Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Shyam A Patel
- Division of Hematology-Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Michael Haddadin
- Division of Hematology-Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Jan Cerny
- Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA, 01655, USA
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2
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Martínez-Valenzuela L, Draibe J, Fulladosa X, Gomà M, Gómez F, Antón P, Cruzado JM, Torras J. Acute Tubulointerstitial Nephritis in Clinical Oncology: A Comprehensive Review. Int J Mol Sci 2021; 22:2326. [PMID: 33652638 PMCID: PMC7956739 DOI: 10.3390/ijms22052326] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/12/2021] [Accepted: 02/22/2021] [Indexed: 01/01/2023] Open
Abstract
Acute kidney injury in patients who suffer a malignancy is a common complication. Due to its high prevalence and effective treatment, one of the most frequent causes that both oncologists and nephrologists must be aware of is acute tubulointerstitial nephritis (ATIN). ATIN is an immunomediated condition and the hallmark of the disease, with the presence of a tubulointerstitial inflammatory infiltrate in the renal parenchyma. This infiltrate is composed mainly of T lymphocytes that can be accompanied by macrophages, neutrophils, or eosinophils among other cells. One of the major causes is drug-related ATIN, and some antineoplastic treatments have been related to this condition. Worthy of note are the novel immunotherapy treatments aimed at enhancing natural immunity in order to defeat cancer cells. In the context of the immunosuppression status affecting ATIN patients, some pathogen antigens can trigger the development of the disease. Finally, hematological malignancies can also manifest in the kidney leading to ATIN, even at the debut of the disease. In this review, we aim to comprehensively examine differential diagnosis of ATIN in the setting of a neoplastic patient.
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Affiliation(s)
- Laura Martínez-Valenzuela
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
- IDIBELL Biomedical Research Institute, Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Juliana Draibe
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
- IDIBELL Biomedical Research Institute, Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Xavier Fulladosa
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
- IDIBELL Biomedical Research Institute, Hospitalet de Llobregat, 08907 Barcelona, Spain
- Clinical Science Department, Campus de Bellvitge, Barcelona University, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Montserrat Gomà
- Pathology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain;
| | - Francisco Gómez
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
| | - Paula Antón
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
| | - Josep María Cruzado
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
- IDIBELL Biomedical Research Institute, Hospitalet de Llobregat, 08907 Barcelona, Spain
- Clinical Science Department, Campus de Bellvitge, Barcelona University, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Joan Torras
- Nephrology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain; (L.M.-V.); (X.F.); (F.G.); (P.A.); (J.M.C.)
- IDIBELL Biomedical Research Institute, Hospitalet de Llobregat, 08907 Barcelona, Spain
- Clinical Science Department, Campus de Bellvitge, Barcelona University, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
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3
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Lee YJ, Glezerman IG, Tamari R, Sauter CS, Prockop SE, Boulad F, Salvatore SP, Seshan SV, Jaimes EA, Giralt SA, Papadopoulos EB, Jakubowski AA, Papanicolaou GA. BK polyoma virus nephropathy in hematopoietic cell transplant recipients. ACTA ACUST UNITED AC 2019. [DOI: 10.1177/2399369319858362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background: The epidemiology of BK polyoma virus nephropathy in hematopoietic cell transplant recipients is poorly characterized. Kidney dysfunction after hematopoietic cell transplant is often attributed to treatment toxicities and kidney biopsies are rarely performed. Methods: We reviewed pathology-confirmed BK polyoma virus nephropathy cases in adult and pediatric patients who had undergone a hematopoietic cell transplant between 1 January 2015 and 31 December 2017 at our institution. Plasma and urine BK polyoma virus was assessed by a quantitative polymerase chain reaction assay and were obtained at the clinician discretion. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. BK polyoma virus nephropathy was scored by the Banff Working Group Proposal. Results: Eight (7 adult and 1 pediatric) cases of BK polyoma virus nephropathy were identified among 685 hematopoietic cell transplant recipients, 14 of whom had undergone a kidney biopsy. Five patients (62.5%) had received a CD34+-selected peripheral blood hematopoietic cell transplant; two had received a cord blood allograft and one an unmodified peripheral blood hematopoietic cell transplant. Two patients developed acute graft-versus-host disease grade II. Early post–hematopoietic cell transplant BK polyoma viruria was documented with onset at a median of 54 days (range, 6–91) post–hematopoietic cell transplant and median urine BK polyoma viral load was 9.6 log10 copies/mL (range, 8.6–10.0). BK polyoma virus nephropathy was diagnosed at a median of 267 days after hematopoietic cell transplant (range, 133–637). At BK polyoma virus nephropathy diagnosis, all patients had decreased renal function with glomerular filtration rate (median 29 mL/min/1.73 m2; range, 9–98 ) and creatinine (median 2.4 mg/dL; range, 0.8–7.5) ; median plasma BK polyoma viral load was 6.3 log10 copies/mL (range, 5.5–7.1) and median CD4+ lymphocyte count was 82 cell/mcL (range, 21–172). Conclusions: We report eight biopsy-proven BK polyoma virus nephropathies in hematopoietic cell transplant recipients from a single center. BK polyoma virus nephropathy should be considered in hematopoietic cell transplant recipients with worsening kidney function and high BK polyoma viremia.
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Affiliation(s)
- Yeon Joo Lee
- Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
| | - Ilya G Glezerman
- Weill Cornell Medical College, New York, NY, USA
- Renal Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Roni Tamari
- Weill Cornell Medical College, New York, NY, USA
- Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Craig S Sauter
- Weill Cornell Medical College, New York, NY, USA
- Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Susan E Prockop
- Weill Cornell Medical College, New York, NY, USA
- Pediatric Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Farid Boulad
- Weill Cornell Medical College, New York, NY, USA
- Pediatric Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | | | - Edgar A Jaimes
- Weill Cornell Medical College, New York, NY, USA
- Renal Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sergio A Giralt
- Weill Cornell Medical College, New York, NY, USA
- Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Esperanza B Papadopoulos
- Weill Cornell Medical College, New York, NY, USA
- Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ann A Jakubowski
- Weill Cornell Medical College, New York, NY, USA
- Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Genovefa A Papanicolaou
- Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
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4
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Shah A, Kumar V, Palmer MB, Trofe-Clark J, Laskin B, Sawinski D, Hogan JJ. Native kidney BK virus nephropathy, a systematic review. Transpl Infect Dis 2019; 21:e13083. [PMID: 30907978 DOI: 10.1111/tid.13083] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 02/10/2019] [Accepted: 02/15/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the literature have been limited by methodology or by the scope of patients included. STUDY DESIGN AND METHODS Systematic Review (Prospero # CRD42018088524). SETTING & POPULATION Patients without kidney transplant who had biopsy-proven BKVN. SELECTION CRITERIA FOR STUDIES Full-text articles that describe native BKVN patient cases. ANALYTICAL APPROACH Descriptive synthesis. RESULTS The search identified 630 unique articles of which 51 were included in the final review. Sixty-five cases (including two new cases presented in this review) were identified, all but one occurred in the setting of known immunosuppression. LIMITATIONS The primary limitation was the exclusion of studies that did not fulfill the stringent review criteria. We excluded reports with only a clinical diagnosis of BKVN, such as those with viruria and/or viremia without biopsy. CONCLUSIONS As of May 2018, there are 65 reported cases of BKVN in native kidneys. This represents the most comprehensive description of biopsy-proven BKVN in native kidneys to date. Evaluation for BK nephropathy should be considered in immunocompromised patients who exhibit unexplained renal failure.
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Affiliation(s)
- Ankur Shah
- Division of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Vinayak Kumar
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Matthew B Palmer
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jennifer Trofe-Clark
- Division of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania.,Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,Department of Pharmacy Services, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Benjamin Laskin
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,Division of Nephrology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Deirdre Sawinski
- Division of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania.,Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jonathan J Hogan
- Division of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania.,Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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5
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Vigil D, Konstantinov NK, Barry M, Harford AM, Servilla KS, Kim YH, Sun Y, Ganta K, Tzamaloukas AH. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection. World J Transplant 2016; 6:472-504. [PMID: 27683628 PMCID: PMC5036119 DOI: 10.5500/wjt.v6.i3.472] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/25/2016] [Accepted: 09/08/2016] [Indexed: 02/05/2023] Open
Abstract
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
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6
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Gagneux-Brunon A, Pillet S, Laurent B, Mariat C, Michalet M, Lucht F, Botelho-Nevers E. A case of BK virus nephropathy in a stem cell transplant recipient: a rare or under-recognized cause for Acute Kidney injury. Med Mal Infect 2015; 45:331-4. [PMID: 26144286 DOI: 10.1016/j.medmal.2015.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 05/18/2015] [Accepted: 06/03/2015] [Indexed: 11/29/2022]
Affiliation(s)
- A Gagneux-Brunon
- Service de Maladies Infectieuses et Tropicales, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France; Groupe Immunité des Muqueuses et Agents Pathogènes, EA 3064, Université Jean-Monnet, Université de Lyon, CHU de Saint-Étienne, 42000 Saint-Étienne, France.
| | - S Pillet
- Groupe Immunité des Muqueuses et Agents Pathogènes, EA 3064, Université Jean-Monnet, Université de Lyon, CHU de Saint-Étienne, 42000 Saint-Étienne, France; Laboratoire de Bactériologie et Virologie, CHU de Saint-Étienne, 42055 Saint-Étienne, France
| | - B Laurent
- Laboratoire de Cytologie et Histologie rénale, CHU de Saint-Étienne, 42055 Saint-Étienne, France
| | - C Mariat
- Groupe Immunité des Muqueuses et Agents Pathogènes, EA 3064, Université Jean-Monnet, Université de Lyon, CHU de Saint-Étienne, 42000 Saint-Étienne, France; Service de Néphrologie, Dialyse, Transplantation et Hypertension, CHU de Saint-Étienne, 42055 Saint-Étienne, France
| | - M Michalet
- Service d'Hématologie, Hôpitaux Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France
| | - F Lucht
- Service de Maladies Infectieuses et Tropicales, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France; Groupe Immunité des Muqueuses et Agents Pathogènes, EA 3064, Université Jean-Monnet, Université de Lyon, CHU de Saint-Étienne, 42000 Saint-Étienne, France
| | - E Botelho-Nevers
- Service de Maladies Infectieuses et Tropicales, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France; Groupe Immunité des Muqueuses et Agents Pathogènes, EA 3064, Université Jean-Monnet, Université de Lyon, CHU de Saint-Étienne, 42000 Saint-Étienne, France
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7
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Aksenova M, Tsetlina V, Gutovskaya E, Mitrofanova A, Balashov D, Maschan A. BK virus nephropathy in a pediatric patient after hematopoietic stem cell transplantation. Pediatr Transplant 2015; 19:E29-32. [PMID: 25484248 DOI: 10.1111/petr.12411] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/17/2014] [Indexed: 12/17/2022]
Abstract
We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration of renal function 13 months after HSCT for myelodysplastic syndrome. BK virus nephropathy was suspected and confirmed. After reduction of immunosuppression and treatment with IVIG, leflunomide, ciprofloxacin, and cidofovir, clearance of BK virus from blood was achieved, and further progression or renal failure was prevented. We believe that BK virus nephropathy should be considered in cases of renal function deterioration in all immunocompromised patients.
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Affiliation(s)
- M Aksenova
- Nephrology Department, Research and Clinical Institute for Pediatrics, the Pirogov Russian National Research Medical University, Moscow, Russia; Department of Clinical Diagnostics, the Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia
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8
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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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9
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BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a Pathogen. Curr Infect Dis Rep 2014; 16:417. [PMID: 24942378 DOI: 10.1007/s11908-014-0417-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
We reviewed the literature regarding disease induced by BK virus (BKV) in the hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic cystitis (HC) and nephritis. The association between BKV and HC has been reported over the past four decades. BKV has been clinically implicated and widely accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in renal transplant patients. We discuss the potential benefit of early initiation of therapy in patients who fail supportive care alone as well as the different treatment strategies for HC induced by BKV. Treatments that have been used such as cidofovir and leflunomide are accompanied by risks, and the benefits are not as concrete as with other viral illness in the HSCT population.
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10
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Satyanarayana G, Marty FM, Tan CS. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion? Transpl Infect Dis 2014; 16:521-31. [PMID: 24834968 DOI: 10.1111/tid.12233] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 01/22/2014] [Accepted: 02/08/2014] [Indexed: 12/14/2022]
Abstract
BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.
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Affiliation(s)
- G Satyanarayana
- Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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11
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Sharma SG, Nickeleit V, Herlitz LC, de Gonzalez AK, Stokes MB, Singh HK, Markowitz GS, D'Agati VD. BK polyoma virus nephropathy in the native kidney. Nephrol Dial Transplant 2012; 28:620-31. [PMID: 23249622 DOI: 10.1093/ndt/gfs537] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND While BK polyoma virus nephropathy (PVN) is a well-recognized cause of renal allograft dysfunction, PVN of native kidneys is likely under-recognized. METHODS We present the pathologic features, risk factors and outcomes of eight cases of PVN in native kidneys. RESULTS The cohort included eight males aged 16-73 years (mean 47.4) with an immunocompromised state (mean duration 3.15 years) attributable to: hematologic malignancies (n = 6), for which three had undergone bone marrow transplant; lung transplant (n = 1) and combined tuberculosis and diabetes (n = 1). Seven patients were receiving specific immunosuppressive therapies. Patients were biopsied for acute kidney injury (AKI) with rise in mean creatinine levels from baseline 1.6 to 2.8 mg/dL. Pathology showed BK PVN with characteristic intranuclear inclusions staining positive for SV40 T antigen and negative for JC virus (JCV), with positive serum and/or urine PCR for BK virus. One patient had focal medullary JCV co-infection. Two patients also had renal infiltration by chronic lymphocytic leukemia (CLL). Six patients received specific therapy directed to PVN (cidofovir or leflunomide). Follow-up ranged from 2 to 20 (mean 10) months. Despite marked decrease in serum BK viral copy numbers, creatinine continued to rise in six cases (mean 3.7 mg/dL in four, requiring dialysis in two) and three patients died of malignancy, opportunistic infection or renal failure. Advanced histologic stage of PVN, ineffective antiviral therapy, co-morbidities and persistent immunocompromised state likely contributed to the poor outcomes. CONCLUSION A high level of suspicion in immunocompromised patients is needed to diagnose PVN in an early stage that may respond more favorably to antiviral therapy.
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Affiliation(s)
- Shree G Sharma
- Department of Pathology, ColumbiaUniversity Medical Center, New York, NY, USA.
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12
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Abboud I, Peraldi MN, Hingorani S. Chronic kidney diseases in long-term survivors after allogeneic hematopoietic stem cell transplantation: monitoring and management guidelines. Semin Hematol 2012; 49:73-82. [PMID: 22221787 DOI: 10.1053/j.seminhematol.2011.10.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Chronic kidney disease (CKD) occurs commonly (prevalence of approximately 20% in a large series) after allogeneic hematopoietic stem cell transplantation (HSCT). There are three distinct clinical entities that occur after HSCT: thrombotic microangiopathy (TMA), nephrotic syndrome (NS), and idiopathic or graft-versus-host disease (GVHD)-related CKD. Acute renal function decline occurs in the majority of patients in the first months after transplantation. This acute kidney injury can persist and is a risk factor for the later development of CKD. However, the potentially independent role of GVHD, chronic inflammation, and chronic exposure to calcineurin inhibitors in the development and progression of CKD warrants further investigation. Careful monitoring of blood pressure, renal function, and proteinuria is mandatory in patients undergoing HSCT, especially older patients with pre-existent renal impairment. Renal function should be evaluated before HSCT and monitoring should occur at least every 6 to 12 months in these patients. Renal biopsies are indicated in patients with proteinuria and persistent or progressive rises in serum creatinine to determine etiology and prevent progression to end-stage renal disease (ESRD).
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Affiliation(s)
- Imad Abboud
- Saint Louis Hospital (Assistance Publique-Hôpitaux de Paris), Nephrology, Paris, France.
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13
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Khan H, Oberoi S, Mahvash A, Sharma M, Rondon G, Alousi A, Shpall EJ, Kontoyiannis DP, Champlin RE, Ciurea SO. Reversible ureteral obstruction due to polyomavirus infection after percutaneous nephrostomy catheter placement. Biol Blood Marrow Transplant 2011; 17:1551-5. [PMID: 21396475 DOI: 10.1016/j.bbmt.2011.03.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Accepted: 03/01/2011] [Indexed: 10/18/2022]
Abstract
BK virus (BKV) is a human polyomavirus that remains latent in the urinary tract epithelium in most individuals. However, in immunocompromised states, including after hematopoietic stem cell transplantation (HSCT), BKV may reactivate and cause infection predominantly affecting the bladder, commonly manifested as hemorrhagic cystitis. Renal insufficiency, occasionally requiring hemodialysis, is not uncommon and was previously attributed to medications or the development of tubulointestitial nephritis. We report a series of 6 HSCT recipients who developed obstructive uropathy of the upper urinary tract system secondary to inflammation and hemorrhage involving the upper uroepithelium, causing ureteral stenosis. Temporary placement of a percutaneous nephrostomy catheter relieved the obstruction and significantly improved kidney function, successfully preventing progression to more advanced renal disease in these patients.
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Affiliation(s)
- Hassan Khan
- Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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14
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Verghese PS, Finn LS, Englund JA, Sanders JE, Hingorani S. BK nephropathy in pediatric hematopoietic stem cell transplant recipients. Pediatr Transplant 2009; 13:913-8. [PMID: 19067914 PMCID: PMC2802860 DOI: 10.1111/j.1399-3046.2008.01069.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BK nephropathy is a known cause of renal insufficiency in kidney transplant recipients. Activation of the polyoma virus may also occur in the native kidneys of non-renal allograft recipients. BK nephropathy has only been reported in a few patients after HCT, most being adult patients, and the single reported pediatric case had evidence of hemorrhagic cystitis. The response to antiviral therapy also seems to differ widely. Here, we describe two cases of BK nephropathy in the native kidneys of HCT recipients exposed to high levels of immunosuppression because of GVHD. Neither of our patients had any evidence of hemorrhagic cystitis. We present definitive renal pathology and detailed chronological evidence of the rising serum creatinine with simultaneous serum and urine BK PCR titers. In one of our cases, antiviral therapy did not seem beneficial as documented by continued renal dysfunction and elevated serum/urine BK PCR titers. Based on our report, intense immunosuppression in pediatric HCT recipients seems to be involved in the activation of BK virus and BK nephropathy should be suspected even in the absence of hematuria in HCT recipients with unexplained renal dysfunction.
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Affiliation(s)
- Priya S Verghese
- Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA 98105, USA.
| | - Laura S Finn
- Department of laboratory & pathology, University of Washington and Children’s Hospital & Regional Medical Center, Seattle, WA
| | - Janet A Englund
- Department of pediatrics, University of Washington and Children’s Hospital & Regional Medical Center, Seattle, WA, Fred Hutchinson Cancer Research Center and Children’s Hospital and Regional Medical Center
| | - Jean E Sanders
- Department of pediatrics, University of Washington and Children’s Hospital & Regional Medical Center, Seattle, WA, Fred Hutchinson Cancer Research Center and Children’s Hospital and Regional Medical Center
| | - Sangeeta Hingorani
- Department of pediatrics, University of Washington and Children’s Hospital & Regional Medical Center, Seattle, WA, Fred Hutchinson Cancer Research Center and Children’s Hospital and Regional Medical Center
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15
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Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JAH, Boeckh MJ, Boeckh MA. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15:1143-238. [PMID: 19747629 PMCID: PMC3103296 DOI: 10.1016/j.bbmt.2009.06.019] [Citation(s) in RCA: 1195] [Impact Index Per Article: 74.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Accepted: 06/23/2009] [Indexed: 02/07/2023]
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16
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17
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O'Donnell PH, Swanson K, Josephson MA, Artz AS, Parsad SD, Ramaprasad C, Pursell K, Rich E, Stock W, van Besien K. BK virus infection is associated with hematuria and renal impairment in recipients of allogeneic hematopoetic stem cell transplants. Biol Blood Marrow Transplant 2009; 15:1038-1048.e1. [PMID: 19660716 DOI: 10.1016/j.bbmt.2009.04.016] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 04/27/2009] [Indexed: 12/21/2022]
Abstract
BK virus (BKV) is an important pathogen and cause of nephropathy in renal transplant recipients, but its significance following hematopoetic stem cell transplantation (HSCT) is less well described. We measured blood and urine BKV in 124 allogeneic HSCT patients (67 had undergone prior HSCT [surveillance cohort]; 57 were monitored from transplant day 0 [prospective cohort]). BK viruria was manifest in 64.8% of the patients; 16.9% developed viremia. In the prospective cohort, the median time from transplantation to BK viremia development (128 days) was longer than for viruria (24 days; P < .0001). Among clinical factors (sex, disease, transplant type, alemtuzumab use, cytomegalovirus [CMV] viremia, graft-versus-host disease [GVHD], donor HLA C7 allele), only CMV viremia was more common in patients with BKV infection (P < or = .04). There was a direct relationship between blood and urine BKV levels and the occurrence, and degree, of hematuria (P < or = .03). Finally, BKV infection was analyzed along with other clinical factors in relation to the development of post-HSCT renal impairment. On multivariate analysis, only BK viremia (P=.000002) and alternative-donor transplantation (P=.002) were independent predictors of development of post-HSCT renal impairment, with BK viremia associated with a median 1.62mg/dL rise in creatinine from the pretransplant baseline. Among 8 patients in the surveillance cohort with BK viremia, 2 developed biopsy-proven BKV nephropathy requiring hemodialysis. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation.
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Affiliation(s)
- Peter H O'Donnell
- Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA
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18
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Lekakis LJ, Macrinici V, Baraboutis IG, Mitchell B, Howard DS. BK virus nephropathy after allogeneic stem cell transplantation: a case report and literature review. Am J Hematol 2009; 84:243-6. [PMID: 19208419 DOI: 10.1002/ajh.21358] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Polyomaviruses are increasingly recognized as important human pathogens. Among those, BK virus has been identified as the main cause of polyomavirus-associated nephropathy (PVAN), a major cause of renal allograft failure. PVAN has also been well described in the setting of non-renal solid organ transplantation. The reports of PVAN after hematopoietic stem cell transplantation (HCT) are surprisingly very few. Here, we describe a patient with treatment-related myelodysplastic syndrome who received an unrelated donor HCT after ablative conditioning and in vivo T cell depletion with alemtuzumab. He developed a biopsy-proven BK nephropathy, which contributed to his renal failure. Leflunomide as well as cidofovir were given at different times, both in combination with intravenous immunoglobulin. Both treatments were effective in reducing the BK viral load, the cystitis symptoms and both stabilized but did not really improved the renal function. The patient was still dialysis-dependent when he died from Pseudomonas sepsis 13 months after HCT. A critical review of the literature and the treatment modalities for post-HCT PVAN are provided.
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MESH Headings
- Antiviral Agents/therapeutic use
- BK Virus/pathogenicity
- Cystitis/etiology
- Cystitis/virology
- Cytomegalovirus Infections/complications
- Fatal Outcome
- Graft vs Host Disease/complications
- Hematopoietic Stem Cell Transplantation/adverse effects
- Hepatorenal Syndrome/etiology
- Humans
- Immunoglobulins, Intravenous
- Immunosuppressive Agents/adverse effects
- Immunosuppressive Agents/therapeutic use
- Kidney Failure, Chronic/etiology
- Kidney Failure, Chronic/therapy
- Lymphoma, Follicular/complications
- Lymphoma, Follicular/drug therapy
- Lymphoma, Follicular/surgery
- Male
- Middle Aged
- Myelodysplastic Syndromes/etiology
- Myelodysplastic Syndromes/surgery
- Nephritis, Interstitial/etiology
- Nephritis, Interstitial/virology
- Polyomavirus Infections/complications
- Polyomavirus Infections/transmission
- Postoperative Complications
- Reoperation
- Tacrolimus/adverse effects
- Transplantation Conditioning/adverse effects
- Transplantation, Autologous
- Transplantation, Homologous/adverse effects
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Affiliation(s)
- Lazaros J Lekakis
- Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.
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19
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Hoefele J, Rüssmann D, Klein B, Weber LT, Führer M. BK virus induced nephritis in a boy with acute myeloid leukaemia undergoing bone marrow transplantation. NDT Plus 2008; 1:336-9. [PMID: 25983928 PMCID: PMC4421277 DOI: 10.1093/ndtplus/sfn077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2008] [Accepted: 05/30/2008] [Indexed: 02/06/2023] Open
Abstract
BK virus (BKV) is a human polyomavirus. The primary infection occurs typically without specific signs or symptoms. Almost 80% of adults are seropositive. Clinically relevant infections are usually limited to individuals who are immunosuppressed. After primary infection, BKV remains latent in the kidneys and can be reactivated in the setting of immunosuppression. BKV is associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients. Furthermore, BKV-induced haemorrhagic cystitis (HC) is a severe complication of bone marrow transplantation (BMT) in children and adults. A combination of HC and tubulointerstitial nephritis in a patient has not been reported so far. We report on an 11-year-old boy with acute myeloid leukaemia undergoing BMT. BKV infection was reactivated during post-transplant immunosuppressive therapy causing HC associated with tubulointerstitial nephritis.
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Affiliation(s)
| | | | - Barbara Klein
- Department of Transplantation , University Children's Hospital , Dr. von Haunersches Kinderspital , Ludwig-Maximilians-University of Munich , Munich , Germany
| | | | - Monika Führer
- Department of Transplantation , University Children's Hospital , Dr. von Haunersches Kinderspital , Ludwig-Maximilians-University of Munich , Munich , Germany
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20
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HAYAT ASHIK, MUKHOPADHYAY RATNA, RADHIKA SRINIVASAN, SACHDEVA MANUPDESHS, NADA RITAMBHRA, JOSHI KUSUM, SAKHUJA VINAY, JHA VIVEKANAND. Adverse impact of pretransplant polyoma virus infection on renal allograft function. Nephrology (Carlton) 2008; 13:157-63. [DOI: 10.1111/j.1440-1797.2007.00861.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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21
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Dropulic LK, Jones RJ. Polyomavirus BK infection in blood and marrow transplant recipients. Bone Marrow Transplant 2007; 41:11-8. [PMID: 17952131 DOI: 10.1038/sj.bmt.1705886] [Citation(s) in RCA: 148] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population.
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Affiliation(s)
- L K Dropulic
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
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22
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Dropulic LK, Jones RJ. Polyomavirus BK infection in blood and marrow transplant recipients. Bone Marrow Transplant 2007. [PMID: 17952131 DOI: 10.1038/j.bmt.1705886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population.
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Affiliation(s)
- L K Dropulic
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
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23
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Chang A, Hingorani S, Kowalewska J, Flowers MED, Aneja T, Smith KD, Meehan SM, Nicosia RF, Alpers CE. Spectrum of renal pathology in hematopoietic cell transplantation: a series of 20 patients and review of the literature. Clin J Am Soc Nephrol 2007; 2:1014-23. [PMID: 17702721 DOI: 10.2215/cjn.01700407] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
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.
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Affiliation(s)
- Anthony Chang
- University of Chicago Medical Center, Department of Pathology, 5841 S. Maryland Avenue, Room S-628 (MC6101), Chicago, IL 60637, USA.
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24
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Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and renal allografts: an update on an escalating threat. Transpl Int 2006; 19:960-73. [PMID: 17081225 DOI: 10.1111/j.1432-2277.2006.00360.x] [Citation(s) in RCA: 90] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Polyomavirus nephropathy, also termed BK-virus nephropathy (BKN) after the main causative agent, the polyoma-BK-virus strain, is a significant complication after kidney transplantation. BKN is the most common viral infection that affects renal allografts with a prevalence of 1-9% on average 8-13 months post surgery. It can also occur sporadically in native kidneys. Viral nephropathy is caused by the (re)activation of latent BK viruses that enter into a replicative cycle under sustained and intensive immunosuppression. Pure productive kidney infections with JC- and SV-40 polyomaviruses are exceptionally rare. BKN is morphologically defined by the presence of intranuclear viral inclusion bodies in epithelial cells and tubular injury, which is the morphological correlate for renal dysfunction. Renal disease can progress through different histologic stages (from early BKN stage A to late fibrotic stage C) that carry prognostic significance; disease stages B and C often result in chronic kidney (allograft) dysfunction and end-stage renal disease. The clinical goal is to diagnose viral nephropathy in disease stage A and to limit chronic renal injury. Strategies to recognize, classify, and manage BKN are critically discussed including ancillary techniques for risk assessment and patient monitoring: (i) urine cytology and the search for so-called 'decoy cells'; (ii) PCR analyses for viral load measurements in the plasma and urine; and (iii) negative staining urine electron microscopy to identify viral particles.
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Affiliation(s)
- Volker Nickeleit
- Nephropathology Laboratory, Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
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25
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Shapiro S, Robin M, Espérou H, Devergie A, Rocha V, Garnier F, Gluckman E, Socié G, Ribaud P, Oudot C, Scieux C, Cherot J, Mougenot B, Ulinski T. Polyomavirus nephropathy in the native kidneys of an unrelated cord blood transplant recipient followed by a disseminated polyomavirus infection. Transplantation 2006; 82:292-3. [PMID: 16858298 DOI: 10.1097/01.tp.0000226172.68372.f9] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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26
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Barber CEH, Hewlett TJC, Geldenhuys L, Kiberd BA, Acott PD, Hatchette TF. BK virus nephropathy in a heart transplant recipient: case report and review of the literature. Transpl Infect Dis 2006; 8:113-21. [PMID: 16734635 DOI: 10.1111/j.1399-3062.2006.00163.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The human polyomavirus BK virus (BKV) remains latent in the urinary tract and may be reactivated in immunocompromised states. BKV is noted to be the etiologic agent of polyomavirus-associated nephropathy (PVAN), which is a significant cause of allograft failure in renal transplant patients. Renal dysfunction following non-renal solid organ transplantation is common and is typically attributed to drug toxicity or patient comorbidities. In this article we describe a case of PVAN in the native kidneys of a heart transplant recipient and review the literature. Although this is only the fourth case reported, BKV nephropathy should be considered in the differential diagnosis of new renal failure following non-kidney solid organ transplantation, as early diagnosis of PVAN is necessary to prevent irreversible renal damage.
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Affiliation(s)
- C E H Barber
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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27
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Schwarz A, Mengel M, Haller H, Niedermeyer J. Polyoma virus nephropathy in native kidneys after lung transplantation. Am J Transplant 2005; 5:2582-5. [PMID: 16162212 DOI: 10.1111/j.1600-6143.2005.01043.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Polyoma virus nephropathy is recognized as an emerging clinical problem in renal transplantation; however, polyoma in native kidneys is unusual. We report a patient who developed polyoma nephropathy in his native kidneys 15 months after successful lung transplantation. His immunosuppression consisted of tacrolimus, mycophenolate mofetil, and large doses of steroids because of three rejection episodes. When the condition was recognized, cidofovir was an effective treatment (3 doses of 2-3mg/kg); however, his renal function deteriorated nonetheless. Tubulitis and interstitial cell infiltration in his native kidneys were evidence that the changes were in response to viral injury. Polyoma nephropathy of native kidneys is unusual. An earlier course of cisplatin treatment because of metastatic seminoma prior to lung transplantation may have been contributory to pre-existing renal injury. After cidofovir was begun, the polyoma viral load in serum and urine decreased substantially; however, after high-dose steroid treatment of two rejection episodes, each time a significant increase in viral load was seen. We stained biopsies of native kidneys from 30 recipients of other organs. The biopsies were done for various reasons but not because polymoma virus was suspected. We found no additional cases.
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Affiliation(s)
- Anke Schwarz
- Department of Nephrology, Hannover Medical School, Hannover, Germany.
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28
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Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault-Keener M, Schnitzler MA, Major EO, Brennan DC. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant 2005; 5:2213-21. [PMID: 16095500 DOI: 10.1111/j.1600-6143.2005.01000.x] [Citation(s) in RCA: 225] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
In a previous study, we performed serial BK virus (BKV), polymerase chain reaction (PCR) and detected active BKV infection in 70 (35.4%) of 198 renal transplant recipients. In the current study, pre-transplant donor and recipient samples were analyzed for BKV antibody titer and HLA alleles. Donor antibody titer was inversely proportional to onset of viruria, p<0.001, directly proportional to duration of viruria, p=0.014 and directly proportional to peak urine viral titer p=0.005. Recipient pairs receiving kidneys from the same donor were concordant for BKV infection, p=0.017, and had matched sequences of segments of the NCCR and VP1 genes that tended to vary among recipients of kidneys from different donors. We did not see an association of HLA A, B, or DR, HLA allele mismatches or total HLA mismatches and BK infection. However, all 11 recipients with sustained BK viremia received kidneys from donors lacking HLA C7, and 10 recipients also lacked C7. These findings derive from the largest and most comprehensive prospective study of BKV infection in renal transplant recipients performed to date. Our data support donor origin for early BKV infection in kidney transplant recipients, and suggest that a specific HLA C locus may be associated with failure to control BKV infection.
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Affiliation(s)
- Daniel L Bohl
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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29
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Schmid H, Burg M, Kretzler M, Banas B, Gröne HJ, Kliem V. BK virus associated nephropathy in native kidneys of a heart allograft recipient. Am J Transplant 2005; 5:1562-8. [PMID: 15888070 DOI: 10.1111/j.1600-6143.2005.00883.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Polyomavirus-mediated nephropathy is an increasingly recognized complication in renal transplant recipients, but data on the status of viral activity in the native kidneys of non-renal solid organ recipients are limited. Thirteen native kidney biopsies of heart transplant recipients with significant renal impairment were evaluated for the evidence of polyomavirus reactivation by immunohistochemistry and PCR. One case of BK virus-mediated nephropathy in a cardiac transplant recipient exposed to high levels of immunosuppressive drugs was identified. Clinical and histopathological findings of this patient progressing to terminal renal failure are discussed in detail. In conclusion, polyomavirus reactivation in native kidneys of heart transplant recipients can cause significant renal impairment and should be considered in the differential diagnosis in this patient cohort.
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Affiliation(s)
- Holger Schmid
- Nephrologisches Zentrum Niedersachsen, Hann. Münden, Germany
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30
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Abstract
Viruses are among the most common causes of opportunistic infection after transplantation and the most important. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Viral infection, both symptomatic and asymptomatic, causes the "direct effects" of invasive disease and "indirect effects," including immune suppression predisposing to other opportunistic infections and oncogenesis. Rapid and sensitive microbiologic assays for many of the common viruses after transplantation have replaced, for the most part, serologic testing and in vitro cultures for the diagnosis of infection. Furthermore, quantitative molecular tests allow the individualization of antiviral therapies for prevention and treatment of infection. This advance is most prominent in the management of cytomegalovirus, Epstein-Barr, hepatitis B, and hepatitis C viruses. Diagnostic advances have not been accompanied by the development of specific and nontoxic anti-viral agents or effective antiviral vaccines. Vaccines, where available, should be given to patients as early as possible and well in advance of transplantation to optimize the immune response. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections.
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Affiliation(s)
- Camille N Kotton
- Transplant Infectious Disease and Compromised Host Service, Infectious Disease Division, Massachusetts General Hospital, 55 Fruit Street; GRJ 504, Boston, MA 02114, USA
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31
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Limaye AP, Smith KD, Cook L, Groom DA, Hunt NC, Jerome KR, Boeckh M. Polyomavirus Nephropathy in Native Kidneys of Non‐Renal Transplant Recipients. Am J Transplant 2005. [DOI: 10.1034/j.1600-6143.2003.00126.x-i1] [Citation(s) in RCA: 91] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
| | | | - Linda Cook
- Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Debra A. Groom
- Department of Pathology, Providence Alaska Medical Center, Anchorage, AL
| | | | - Keith R. Jerome
- Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Michael Boeckh
- Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA
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