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Kraivisitkul N, Noppakun K, Sakuludomkan C, Jirawattanapong S, Kwangsukstith S, Dukaew N, Suyayai N, Na Takuathung M, Koonrungsesomboon N. The association between serum tacrolimus concentrations and BK viruria in kidney transplant recipients. Sci Rep 2025; 15:2872. [PMID: 39843551 PMCID: PMC11754913 DOI: 10.1038/s41598-025-86465-2] [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: 04/20/2024] [Accepted: 01/10/2025] [Indexed: 01/24/2025] Open
Abstract
The objective of this study was to examine the association between serum tacrolimus trough levels and the detection of BK viruria in kidney transplant recipients. We conducted a retrospective study and included kidney transplant recipients who underwent BK viruria screening during 2018-2021. Serum tacrolimus trough levels, urine BK viral load, and potential risk factors were collected. Statistical analysis was performed to identify the association between the serum tacrolimus trough levels and the detection of BK virus in urine (defined as positive BK viruria), as well as to determine the cumulative incidence and risk factors for BK viruria. Out of 243 recipients, 76 had positive BK viruria. The average serum tacrolimus trough level was significantly higher among the positive BK viruria group compared to the BK viruria-negative group. High HLA mismatch was identified as a risk factor for BK viruria. Approximately half of the recipients with average serum tacrolimus trough levels exceeding 10 ng/mL would develop BK viruria early. This study found an association between the average serum tacrolimus trough level and the detection of BK viruria. High HLA mismatch and an average serum tacrolimus trough level exceeding 10 ng/mL should be regarded as a risk for BK viruria.
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Affiliation(s)
| | - Kajohnsak Noppakun
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Chotiwit Sakuludomkan
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | | | | | - Nahathai Dukaew
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Naruemon Suyayai
- Transplant and Dialysis Unit, Medical Nursing Division, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, 50200, Thailand
| | - Mingkwan Na Takuathung
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Nut Koonrungsesomboon
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
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Kotton CN, Kamar N, Wojciechowski D, Eder M, Hopfer H, Randhawa P, Sester M, Comoli P, Tedesco Silva H, Knoll G, Brennan DC, Trofe-Clark J, Pape L, Axelrod D, Kiberd B, Wong G, Hirsch HH. The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation. Transplantation 2024; 108:1834-1866. [PMID: 38605438 PMCID: PMC11335089 DOI: 10.1097/tp.0000000000004976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 04/13/2024]
Abstract
BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.
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Affiliation(s)
- Camille N. Kotton
- Transplant and Immunocompromised Host Infectious Diseases Unit, Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
| | - David Wojciechowski
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Michael Eder
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Helmut Hopfer
- Division of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Parmjeet Randhawa
- Division of Transplantation Pathology, The Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
| | - Martina Sester
- Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany
| | - Patrizia Comoli
- Cell Factory and Pediatric Hematology/Oncology Unit, Department of Mother and Child Health, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Helio Tedesco Silva
- Division of Nephrology, Hospital do Rim, Fundação Oswaldo Ramos, Paulista School of Medicine, Federal University of São Paulo, Brazil
| | - Greg Knoll
- Department of Medicine (Nephrology), University of Ottawa and The Ottawa Hospital, Ottawa, ON, Canada
| | | | - Jennifer Trofe-Clark
- Renal-Electrolyte Hypertension Division, Associated Faculty of the Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA
- Transplantation Division, Associated Faculty of the Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA
| | - Lars Pape
- Pediatrics II, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - David Axelrod
- Kidney, Pancreas, and Living Donor Transplant Programs at University of Iowa, Iowa City, IA
| | - Bryce Kiberd
- Division of Nephrology, Dalhousie University, Halifax, NS, Canada
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, NSW, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - Hans H. Hirsch
- Division of Transplantation and Clinical Virology, Department of Biomedicine, Faculty of Medicine, University of Basel, Basel, Switzerland
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
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ALTUN E, ULU S, APAYDIN S, GÜVEN B. Biopsy-proven BK virus nephropathy in kidney transplant patients: risk factors, prevalence and treatment approach. CUKUROVA MEDICAL JOURNAL 2022. [DOI: 10.17826/cumj.1133550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Purpose: BK virus nephropathy (BKVN) is a latent infection and it is closely associated with immunsuppressive therapy. We aimed in this study to evaluate biopsy-proven BKVN and investigate frequency, risk factors and treatment management.
Materials and Methods: In this study, 422 kidney transplant recipients were analysed retrospectively between April 2014 and April 2020 for biopsy-proven BK virus nephropathy. Group I included 16 kidney transplant patients with biopsy-proven BK nephropathy and group II included 36 kidney transplant patients with negative BK virus nephropathy. We aimed demographic, clinical features of kidney transplant recipients with BKVN (group I, n: 16 ) and non-BKVN (group II, n:36) were compared and the factors affecting of BKVN.
Results: The mean age of grup I and group II were were 41±14.8 years and 39±15.2 respectively. The patients mean follow-up period of 43±11.2 months. Serum creatinine and proteinuria degree were significantly higher in the group with BKVN. In order to reduce the dose of immunosuppression in patients with BKVN, tacrolimus treatment was discontinued in 8 patients, and they were switched to everolimus + MMF + prednisone treatment, leflunamide + MMF + prednisone treatment in 4 patients, and sirolimus + MMF + prednisone treatment in 4 patients. The mean serum creatinine level of the patients who were followed up were observed as 1.78±0.98 mg/dl in group I.
Conclusion: In our center, the prevalance of BKVN was found 3.92% during the study period. Reduction of dose immunosuppressive therapy is the most effective treatment. It is thought that there was no differences between Leflunamide and other approaches for treatment. Early diagnosis and screening (frequently intervals) seems to be most effective way for BKVN.
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Affiliation(s)
- Eda ALTUN
- Bahçeşehir Üniversitesi Tıp Fakültesi İç Hastalıkları Nefroloji
| | - Sena ULU
- Bahçeşehir Üniversitesi Tıp Fakültesi, Nefroloji Bilim Dalı
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Prevalence of JC and BK Polyomavirus Infection in Patients with Chronic Kidney Disease in the State of Pará, Brazil. Trop Med Infect Dis 2022; 8:tropicalmed8010009. [PMID: 36668916 PMCID: PMC9861779 DOI: 10.3390/tropicalmed8010009] [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: 10/25/2022] [Revised: 11/12/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
The polyomaviruses that infect humans, JC virus (JCV) and BK virus (BKV), can establish persistent infections in the cells that make up the renal system, causing nephritis and BKV-associated nephropathy in up to 10% of renal transplant patients, and of these, 90% lose the graft and return for hemodialysis. This study aimed to determine the prevalence of polyomaviruses (PyV) in the population with chronic kidney disease (CKD), classified into three groups (conservative, dialysis, and transplanted) and a control group. Urine samples were collected from 290 individuals, including 202 patients with CKD and 88 from the control group. PyV screening was performed by PCR amplification of a fragment of the VP1 region, and the JCV and BKV species were distinguished through enzymatic digestion with the restriction endonuclease BamHI from the amplification of a TAg region. All amplification products were visualized on a 3% agarose gel. The prevalence of PyV infection was correlated with clinical-epidemiological variables using the chi-squared and Fisher's exact tests. In the group with CKD, the prevalence of PyV was 30.2%, a higher rate being observed in conservative patients (36.66%; 22/60), followed by dialysis patients (30.48%; 25/82), and transplanted patients (20%; 12/60). In the control group, the prevalence was 46.59% (41/88). The differentiation between species revealed that JCV was present in 77.8% and BKV in 22.2% of the group with CKD. The prevalence of infection was higher in male patients (59.32%), whose most common pathology was systemic arterial hypertension (35.59%). In the group of transplanted patients, there was a statistically significant association between infection and the use of the immunosuppressant azathioprine (p = 0.015). The prevalence of PyV infection was higher in the control group than in the group with CKD, being predominant in males and in patients with systemic arterial hypertension.
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Peitz T, Möhlendick B, Eisenberger U, Siffert W, Heinemann FM, Kribben A, Friebus-Kardash J. CC Genotype of GNAS c.393C>T (rs7121) Polymorphism Has a Protective Effect against Development of BK Viremia and BKV-Associated Nephropathy after Renal Transplant. Pathogens 2022; 11:pathogens11101138. [PMID: 36297195 PMCID: PMC9609707 DOI: 10.3390/pathogens11101138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/23/2022] [Accepted: 09/28/2022] [Indexed: 11/07/2022] Open
Abstract
The GNAS gene encodes the alpha-subunit of the stimulatory G-protein (Gαs) in humans and mice. The single-nucleotide polymorphism of GNAS, c.393C>T, is associated with an elevated production of Gαs and an increased formation of cyclic adenosine monophosphate (cAMP). In the present study, we analyzed the effect of this GNAS polymorphism on a renal allograft outcome. We screened a cohort of 436 renal allograft recipients, who were retrospectively followed up for up to 5 years after transplant. GNAS genotypes were determined with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays. The 393T allele was detected in 319 (73%) recipients (113 recipients with TT and 206 with CT genotype) and the CC genotype in 117 (27%). The CC genotype was associated with a significantly lower frequency of BK viremia (CC, 17 recipients (15%); T 84 (26%)); p = 0.01; TT, 27 vs. CC, 17, p = 0.07; TT, 27 vs. CT, 57, p = 0. 46; CT, 57 vs. CC, 17, p = 0.01) and BKV-associated nephropathy (CC, 3 recipients (3%); T, 27 (8%); p = 0.03; TT,10 vs. CC, 3, p = 0.04; TT, 10 vs. CT,17, p = 0.85; CT, 17 vs. CC,3, p = 0.04) after transplant. BKV-associated nephropathy-free survival was significantly better among CC genotype carriers than among T allele carriers (p = 0.043; TT vs. CC, p = 0.03; CT vs. CC, p = 0.04; TT vs. CT, p = 0.83). Multivariate analysis indicated an independent protective effect of the CC genotype against the development of both BK viremia (relative risk. 0.54; p = 0.04) and BKV-associated nephropathy after renal transplant (relative risk. 0.27; p = 0.036). The GNAS 393 CC genotype seems to protect renal allograft recipients against the development of BK viremia and BKV-associated nephropathy.
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Affiliation(s)
- Tobias Peitz
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Birte Möhlendick
- Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Ute Eisenberger
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Winfried Siffert
- Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Falko Markus Heinemann
- Institute for Transfusion Medicine, Transplantation Diagnostics, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Andreas Kribben
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Justa Friebus-Kardash
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Correspondence: ; Tel.: +49-(0)-201-7236559; Fax: +49-(0)-201-7236907
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AY N. Comparison of BK virus nephropathy risk between double-J-stent with anti-reflux mechanism and standart double-J-stent: single-center experience. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1141455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Aim: Ureteral stend use is a risk factor for BK nephropathy (BKVN). In 2015, we compared the patients with anti-reflux mechanism DJS (ARD-DJS) and those used standard DJS (st-DJS) in terms of BKV and BKVN frequency in 90 kidney transplant patients in two centers. With the increase in the number of our patients over time and lengthening of the follow-up duration, we needed to re-evaluate the data in one center.
Material and Method: We retrospectively evaluated 211 patients who underwent kidney transplantation at Gazi Yaşargil Training and Research Hospital between September 2012 and September 2019. The following parameters were recorded, demographic data, immunosuppression protocols, presence of rejection, graft loss, plasma BKV levels, and presence of BKVN.
Median and IQR follow-up time for ARD-DJS and St-DJS patients was 72 months (62,5-80,3 months) and 27,8 months (17,4-39,6 months) respectively.
Results: Thirteen patients (6,1%) had BKV viremia. BKVN was revealed by kidney biopsy in 3 of 13 patients. However, graft loss due to BKVN was observed in only one patient. ARD-DJS was used in 4 of these cases and standard DJS was used in 9 of these cases. Patients in whom BKV revealed in the first 3 months were compared in the aspect of DJS technique, BKV was significantly less observed in the ARD-DJS group (ARD-DJS: 2 patients; St-DJS:9 patients), (p=0,046).
Conclusion: In our study, BKV was observed less in patients with ARD-DJS that were clinically significant but not statistically significant. Therefore, prospective randomized studies with high patient numbers are needed to determine the effectiveness of ARD-DJS.
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Affiliation(s)
- Nurettin AY
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, DİYARBAKIR GAZİ YAŞARGİL SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
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BK Virus Nephropathy in Kidney Transplantation: A State-of-the-Art Review. Viruses 2022; 14:v14081616. [PMID: 35893681 PMCID: PMC9330039 DOI: 10.3390/v14081616] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/10/2022] [Accepted: 07/22/2022] [Indexed: 11/16/2022] Open
Abstract
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing progression to nephropathy and graft loss. However, it can be a diagnostic and therapeutic challenge. In this in-depth state-of-the-art review, we will discuss the history of the virus, virology, epidemiology, cellular response, pathogenesis, methods of screening and diagnosis, evidence-based treatment strategies, and upcoming therapeutics, along with the issue of re-transplantation in patients.
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8
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Gately R, Chong CH, Scholes-Robertson N, Teixeira-Pinto A, Isbel NM, Johnson DW, Hawley CM, Campbell SB, Wong G. Predictive factors for BK polyomavirus infection in solid organ transplant recipients. Hippokratia 2022. [DOI: 10.1002/14651858.cd015174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Ryan Gately
- Department of Nephrology; Princess Alexandra Hospital; Woolloongabba Australia
| | - Chanel H Chong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
| | | | | | - Nicole M Isbel
- Department of Nephrology; Princess Alexandra Hospital; Woolloongabba Australia
| | - David W Johnson
- Department of Nephrology; Princess Alexandra Hospital; Woolloongabba Australia
| | - Carmel M Hawley
- Department of Nephrology; Princess Alexandra Hospital; Woolloongabba Australia
| | - Scott B Campbell
- Department of Nephrology; Princess Alexandra Hospital; Woolloongabba Australia
| | - Germaine Wong
- Sydney School of Public Health; The University of Sydney; Sydney Australia
- Centre for Kidney Research; The Children's Hospital at Westmead; Westmead Australia
- Centre for Transplant and Renal Research; Westmead Hospital; Westmead Australia
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Zhao J, You X, Zeng X. Research progress of BK virus and systemic lupus erythematosus. Lupus 2022; 31:522-531. [PMID: 35264023 DOI: 10.1177/09612033221084259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients are often infected by viruses due to deficient immunity or immunosuppressant use. BK virus (BKV)mainly affects the kidney and can also cause multiple organ involvement throughout the body, which is similar to SLE. BKV is mostly a latent infection in vivo. The incidence of virus reactivation is higher in SLE patients. Reactivation of BKV can induce the production of autoantibodies, thereby promoting the occurrence and development of SLE.Purpose: Aim of this article is to review the prevalence and pathegenesis of BKV infection in SLE patients.Method: The literature search was conducted using four different databases including PubMed, Cochrane Library, Scopus and Web of Science.Results: BK virus is higher infection and reactivation in SLE patients. The "hapten carrier" mechanism may lead to the production of autoantibodies. Some immunosuppressive drugs, like leflumide and hydroxychloroquine, may show a protective effect.Conclusions: BKV infection plays a role in the occurrence and development of SLE, and its significance deserves further exploration.
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Affiliation(s)
- Jiawei Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
| | - Xin You
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
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Uppin M, Veduruvada R, Madireddy N, Koyya S, Guditi S, Taduri G, Raju S. Clinicopathologic features of polyomavirus nephropathy: Our experience - A retrospective observational study. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_115_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Handley G, Hand J. Adverse Effects of Immunosuppression: Infections. Handb Exp Pharmacol 2021; 272:287-314. [PMID: 34671868 DOI: 10.1007/164_2021_550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Immunosuppressive therapies are currently indicated for a wide range of diseases. As new agents emerge and indications evolve the landscape grows increasingly complex. Therapies can target pathologic immune system over-activation in rheumatologic or autoimmune disease, or conditioning and graft versus host disease (GVHD) prophylactic regimens may eliminate or inhibit host immune function to improve graft survival and risk of complication in solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT). With immunosuppressive therapy, infections occur. Complex disease states, host factors, and concomitant therapies contribute to a "net state" of immunosuppression that must be considered and may confound perceived increased infection risks in patients receiving treatment.
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Affiliation(s)
- Guy Handley
- Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Jonathan Hand
- Department of Infectious Diseases, Ochsner Health, The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA, USA.
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Mallavarapu RK, Sanoff SL, Howell DN, Roberts JK. BK virus nephropathy in non-renal solid organ transplant recipients: Are we looking hard enough? Clin Transplant 2021; 35:e14265. [PMID: 33615555 DOI: 10.1111/ctr.14265] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/06/2021] [Accepted: 02/11/2021] [Indexed: 01/02/2023]
Abstract
We retrospectively examined the clinical characteristics, pathological features, and outcomes of BK viremia and nephropathy in a population of non-renal solid organ transplant patients (NRSOT) referred for outpatient nephrology consultation over a period of 5 years. In the entire cohort of liver, heart, and lung transplant recipients referred to this clinic, 14% percent were found to have BK viremia with a median peak serum BK viral load of 35 500 copies/ml (range 250 to 21 100 000 copies/ml). BK viremia resolved in six of the seventeen patients (35%). Four out of five patients biopsied showed BK virus (BKV) nephropathy. Eleven out of seventeen patients with BK viremia developed advanced (stage 4 or 5) chronic kidney disease. Four patients developed rejection of their solid organ transplant within the first year post detection of BK viremia after immunosuppression reduction. We conclude that a multi-center study is required to evaluate whether implementation of a systematic BK screening program would be effective in early detection and management of this problem in the NRSOT population.
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Affiliation(s)
- Ravi K Mallavarapu
- Division of Transplant Nephrology, Augusta University-Medical College of Georgia, Augusta, GA, USA
| | - Scott L Sanoff
- Division of Nephrology, Duke University School of Medicine, Durham, NC, USA
| | - David N Howell
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
| | - John K Roberts
- Division of Nephrology, Duke University School of Medicine, Durham, NC, USA
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Nickeleit V, Davis VG, Thompson B, Singh HK. The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish "Presumptive" from "Definitive" Polyomavirus Nephropathy: How to Use It-When to Use It-How Does It Compare to PCR Based Assays? Viruses 2021; 13:135. [PMID: 33477927 PMCID: PMC7833404 DOI: 10.3390/v13010135] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/12/2021] [Accepted: 01/13/2021] [Indexed: 12/17/2022] Open
Abstract
"Definitive" biopsy proven polyomavirus nephropathy (PyVN), usually caused by BK polyomavirus (BKPyV), remains a significant infection of kidney transplants. Diagnosis depends upon an allograft biopsy and outcome depends upon early intervention. Here, we report data on a non-invasive biomarker for PyVN, the urinary PyV-Haufen test. Test results were compared to those of conventional laboratory assays targeting PyV replication, i.e., BKPy-viremia, -viruria and urinary decoy cell shedding. Of 809 kidney transplant recipients, 228 (28%) showed PyV replication with decoy cell shedding and/or BKPy-viremia by quantitative PCR; only a subset of 81/228 (36%) showed "definitive" PyVN. Sensitivity and specificity for identifying patients with PyVN was: 100% and 98%, respectively, urinary PyV-Haufen test; 50% and 54%, respectively, urinary decoy cell shedding; 97% and 32%, respectively, BKPy-viremia with cut-off of ≥250 viral copies/mL; 66% and 80%, respectively, for BKPy-viremia ≥104 viral copies/mL. The PyV-Haufen test showed a very strong correlation with the severity of PyVN (Spearman's ρ = 0.84) and the Banff PyVN disease classes (p < 0.001). In comparison, BKPy-viremia and -viruria levels by PCR displayed modest correlations with PyVN severity (Spearman's ρ = 0.35 and 0.36, respectively) and were not significantly associated with disease classes. No association was found between decoy cell shedding and PyVN severity or disease classes. Pilot data demonstrated that PyVN resolution with decreasing Banff pvl-scores was reflected by a gradual decrease in PyV-Haufen shedding; such a tight association was not noted for BKPy-viremia. In conclusion, urinary PyV-Haufen testing is a highly specific, non-invasive method to accurately diagnose patients with "definitive" PyVN and to optimize patient management. Assay specifics are discussed.
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Affiliation(s)
| | | | | | - Harsharan K. Singh
- Division of Nephropathology, UNC-School of Medicine, Brinkhous-Bullitt Bldg., Room 409, Campus Box 7525, 160 Medical Drive, Chapel Hill, NC 27599-7525, USA; (V.N.); (V.G.D.); (B.T.)
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14
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Korneffel K, Gehring B, Rospert D, Rees M, Ortiz J. BK Virus in Renal Transplant Patients Using Alemtuzumab for Induction Immunosuppression. EXP CLIN TRANSPLANT 2020; 18:557-563. [DOI: 10.6002/ect.2019.0041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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15
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Höcker B, Schneble L, Murer L, Carraro A, Pape L, Kranz B, Oh J, Zirngibl M, Dello Strologo L, Büscher A, Weber LT, Awan A, Pohl M, Bald M, Printza N, Rusai K, Peruzzi L, Topaloglu R, Fichtner A, Krupka K, Köster L, Bruckner T, Schnitzler P, Hirsch HH, Tönshoff B. Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study. Transplantation 2020; 103:1224-1233. [PMID: 30130322 DOI: 10.1097/tp.0000000000002414] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. METHODS We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. RESULTS Presumptive BKPyVAN (defined as sustained [>3 wk] high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P < 0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P < 0.01) but also with younger recipient age (OR, 1.1 per y younger; P < 0.001) and obstructive uropathy (OR, 12.4; P < 0.01) as primary renal disease. CONCLUSIONS Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.
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Affiliation(s)
- Britta Höcker
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany
| | - Lukas Schneble
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany
| | - Luisa Murer
- Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padua, Italy
| | - Andrea Carraro
- Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padua, Italy
| | - Lars Pape
- Hanover Medical School, Hanover, Germany
| | - Birgitta Kranz
- Department of General Pediatrics, University Children's Hospital Münster, Münster, Germany
| | - Jun Oh
- Department of Pediatric Nephrology, University Children's Hospital, Hamburg, Germany
| | | | - Luca Dello Strologo
- Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Anja Büscher
- Pediatric Nephrology, Pediatrics II, University Children's Hospital Essen, Essen, Germany
| | - Lutz T Weber
- Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany
| | - Atif Awan
- Temple Street Children's University Hospital, Dublin, Ireland
| | - Martin Pohl
- Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Martin Bald
- Olga Children's Hospital, Clinic of Stuttgart, Stuttgart, Germany
| | - Nikoleta Printza
- 1st Pediatric Department, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Krisztina Rusai
- Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
| | - Licia Peruzzi
- Pediatric Nephrology Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Rezan Topaloglu
- Hacettepe University Faculty of Medicine, Department of Pediatric Nephrology, Ankara, Turkey
| | - Alexander Fichtner
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany
| | - Kai Krupka
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany
| | - Lennart Köster
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.,Institute of Medical Biometry and Informatics, University of Heidelberg, Germany
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Germany
| | - Paul Schnitzler
- Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany
| | - Hans H Hirsch
- Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.,Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Burkhard Tönshoff
- Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany
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16
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Gomes RM, Barbosa WB, Godman B, Costa JDO, Ribeiro Junior NG, Simão Filho C, Cherchiglia ML, Acurcio FDA, Guerra Júnior AA. Effectiveness of Maintenance Immunosuppression Therapies in a Matched-Pair Analysis Cohort of 16 Years of Renal Transplant in the Brazilian National Health System. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E1974. [PMID: 32192172 PMCID: PMC7142921 DOI: 10.3390/ijerph17061974] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 03/09/2020] [Accepted: 03/11/2020] [Indexed: 12/11/2022]
Abstract
The maintenance of patients with renal transplant typically involves two or more drugs to prevent rejection and prolong graft survival. The calcineurin inhibitors (CNI) are the most commonly recommended medicines in combinations with others. While immunosuppressive treatment regimens are well established, there is insufficient long-term effectiveness data to help guide future management decisions. The study analyzes the effectiveness of treatment regimens containing CNI after renal transplantation during 16 years of follow-up with real-world data from the Brazilian National Health System (SUS). This was a retrospective study of 2318 SUS patients after renal transplantion. Patients were propensity score-matched (1:1) by sex, age, type and year of transplantation. Kaplan-Meier analysis was used to estimate the cumulative probabilities of survival. A Cox proportional hazard model was used to evaluate factors associated with progression to graft loss. Multivariable analysis, adjusted for diabetes mellitus and race/color, showed a greater risk of graft loss for patients using tacrolimus plus mycophenolate compared to patients treated with cyclosporine plus azathioprine. In conclusion, this Brazilian real-world study, with a long follow-up period using matched analysis for relevant clinical features and the representativeness of the sample, demonstrated improved long-term effectiveness for therapeutic regimens containing cyclosporine plus azathioprine. Consequently, we recommend that protocols and clinical guidelines for renal transplantation should consider the cyclosporine plus azathioprine regimen as a potential first line option, along with others.
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Affiliation(s)
- Rosângela Maria Gomes
- Department of Social Pharmacy, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- Programa de Pós-graduação em Medicamentos e Assistência Farmacêutica, Departamento de Farmácia Social, Faculdade de Farmácia, Universidade Federal de Minas Gerais—UFMG. Av. Presidente Antônio Carlos, 6627 Campus Pampulha, Belo Horizonte, MG 31270-901 Brazil
| | - Wallace Breno Barbosa
- Department of Social Pharmacy, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Brian Godman
- Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, Glasgow G4 ORE, UK
- Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
- Health Economics Centre, Liverpool University Management School, Chatham Street, Liverpool L69 7ZH, UK
- School of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, South Africa
| | - Juliana de Oliveira Costa
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- Department of Preventive and Social Medicine, College of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Nélio Gomes Ribeiro Junior
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Charles Simão Filho
- Department of Surgery, College of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Mariângela Leal Cherchiglia
- Department of Preventive and Social Medicine, College of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Francisco de Assis Acurcio
- Department of Social Pharmacy, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Augusto Afonso Guerra Júnior
- Department of Social Pharmacy, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
- SUS Collaborating Centre—Technology Assessment & Excellence in Health, College of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
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17
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Mühlbacher T, Beck R, Nadalin S, Heyne N, Guthoff M. Low-dose cidofovir and conversion to mTOR-based immunosuppression in polyomavirus-associated nephropathy. Transpl Infect Dis 2019; 22:e13228. [PMID: 31797495 DOI: 10.1111/tid.13228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 11/08/2019] [Accepted: 12/01/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Polyomavirus-associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%. Reduction in overall immunosuppression is a cornerstone of therapy, whereas no specific antiviral regimen has shown conclusive benefit to date. The present case series demonstrates the efficacy of a dual therapeutic approach with low-dose cidofovir and conversion to mTOR-based immunosuppression in PVAN. METHODS Patients with biopsy-proven PVAN having received low-dose cidofovir (0.25 mg/kg) according to the Tübingen Cidofovir Protocol and been converted to mTOR-based immunosuppression were analyzed retrospectively. RESULTS Twenty-three patients with a median follow-up of 2.24 [IQR 1.55-5.01] years were included in the analysis. Median time to PVAN diagnosis was 268 [IQR 153-869] days after transplantation. Polyomavirus clearance from plasma was achieved in 78% of patients after a median of 118 [IQR 76-293] days. Of the 23 patients, nine patients (39%) lost their allograft function during follow-up, but only three of these (13%) due to PVAN. Fourteen patients (61%) stabilized or improved allograft function. The cidofovir protocol allowed for specific antiviral therapy without adverse nephrotoxicity, even in patients with low allograft function. CONCLUSIONS Low-dose cidofovir and conversion to mTOR-based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients.
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Affiliation(s)
- Thomas Mühlbacher
- Section of Nephrology and Hypertension, Dept. of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Robert Beck
- Institute of Medical Virology and Epidemiology of Viral Diseases, University of Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Dept. of General-, Visceral- and Transplant Surgery, University of Tübingen, Tübingen, Germany
| | - Nils Heyne
- Section of Nephrology and Hypertension, Dept. of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Martina Guthoff
- Section of Nephrology and Hypertension, Dept. of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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18
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Alcendor DJ. BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression. J Clin Med 2019; 8:jcm8091477. [PMID: 31533282 PMCID: PMC6780320 DOI: 10.3390/jcm8091477] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/16/2019] [Accepted: 09/16/2019] [Indexed: 12/12/2022] Open
Abstract
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80–90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and nephropathy. BKV infection is less commonly associated with pneumonitis, retinitis, liver disease, and meningoencephalitis. BKV is known to replicate, establish latency, undergo reactivation, and induce clinical pathology in renal tubular epithelial cells. However, recent in vitro studies support the notion that BKV has expanded tropism-targeting glomerular parenchymal cells of the human kidney, which could impact glomerular function, enhance inflammation, and serve as viral reservoirs for reactivation from latency during immunosuppression. The implications of BKV expanded tropism in the glomerulus, and how specific host and viral factors that would contribute to glomerular inflammation, cytolysis, and renal fibrosis are related to BKV associated nephropathy (BKVAN), have not been explored. The pathogenesis of BKV in human glomerular parenchymal cells is poorly understood. In this review, I examine target cell populations for BKV infectivity in the human glomerulus. Specifically, I explore the implications of BKV expanded tropism in the glomerulus with regard viral entry, replication, and dissemination via cell types exposed to BKV trafficking in glomerulus. I also describe cellular targets shown to be permissive in vitro and in vivo for BKV infection and lytic replication, the potential role that glomerular parenchymal cells play in BKV latency and/or reactivation after immunosuppression, and the rare occurrence of BKV pathology in glomerular parenchymal cells in patients with BKVAN.
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Affiliation(s)
- Donald J Alcendor
- Center for AIDS Health Disparities Research, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd., Hubbard Hospital, 5th Floor, Rm. 5025, Nashville, TN 37208, USA.
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19
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Chong S, Antoni M, Macdonald A, Reeves M, Harber M, Magee CN. BK virus: Current understanding of pathogenicity and clinical disease in transplantation. Rev Med Virol 2019; 29:e2044. [PMID: 30958614 DOI: 10.1002/rmv.2044] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/28/2019] [Accepted: 03/01/2019] [Indexed: 12/19/2022]
Abstract
BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its frequently unpredictable onset, persistence, and the lack of effective antiviral agents or prevention strategies. This review covers our current understanding of epidemiology, viral transmission and disease progression, and treatment and prevention strategies that have been used to manage this disease.
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Affiliation(s)
- Stephanie Chong
- Department of Renal Medicine, Royal Free Hospital, University College London, London, UK
| | - Michelle Antoni
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, London, UK
| | - Andrew Macdonald
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, London, UK
| | - Matthew Reeves
- Institute of Immunity and Transplantation, Royal Free Hospital, University College London, London, UK
| | - Mark Harber
- Department of Renal Medicine, Royal Free Hospital, University College London, London, UK
| | - Ciara N Magee
- Department of Renal Medicine, Royal Free Hospital, University College London, London, UK
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20
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Favi E, Puliatti C, Sivaprakasam R, Ferraresso M, Ambrogi F, Delbue S, Gervasi F, Salzillo I, Raison N, Cacciola R. Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation. World J Clin Cases 2019; 7:270-290. [PMID: 30746369 PMCID: PMC6369392 DOI: 10.12998/wjcc.v7.i3.270] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 12/08/2018] [Accepted: 12/12/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless, long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear. AIM To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation. METHODS This single-centre observational study with a median follow up of 57 (31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasma quantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment, rejection, renal function, urologic complications, opportunistic infections, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy. RESULTS BK-viremia was detected in 9.5% recipients. Initial viral load was high (≥ 10000 copies/mL) in 66.7% and low (< 10000 copies/mL) in 33.3% of these patients. Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia (95% vs 25%, P < 0.00001), nephropathy (92.5% vs 15%, P < 0.00001), and polyomavirus-related graft loss (27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity (33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50% (30% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, P = 0.0110), and rejection within thirty days of transplant (21.7% vs 9.5%; P = 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However, viremic recipients showed higher 5-year crude cumulative (22.5% vs 12.2%, P = 0.0270) and 30-d-event-censored (22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27% (P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in 55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1% (P = 0.008) and 29.1% vs 7.2% (P < 0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective. CONCLUSION Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.
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Affiliation(s)
- Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Carmelo Puliatti
- Renal Transplantation, Barts Health NHS Trust, Royal London Hospital, London E1 1BB, United Kingdom
| | - Rajesh Sivaprakasam
- Renal Transplantation, Barts Health NHS Trust, Royal London Hospital, London E1 1BB, United Kingdom
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Federico Ambrogi
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Serena Delbue
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20100, Italy
| | - Federico Gervasi
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Ilaria Salzillo
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Nicholas Raison
- MRC Centre for Transplantation, King’s College London, London WC2R 2LS, United Kingdom
| | - Roberto Cacciola
- Renal Transplantation, Barts Health NHS Trust, Royal London Hospital, London E1 1BB, United Kingdom
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21
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Fan Y, Bai H, Qian Y, Sun Z, Shi B. CD4+ T Cell Immune Response to VP1 and VP3 in BK Virus Infected Recipients of Renal Transplantation. Surg Infect (Larchmt) 2019; 20:236-243. [PMID: 30707648 DOI: 10.1089/sur.2018.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To investigate the characteristics of BK virus (BKV) specific cellular immune response in the recipients who have early infection with BKV after renal transplantation. METHODS The recipients of renal allografts (n = 30) were divided into groups of BK virus nephropathy (BKVN), viruria, and viremia. The BKV load was observed with real-time fluorescence quantitative polymerase chain reaction in urine and blood every three months. The values of serum creatinine (SCr) were detected. The peripheral blood mononuclear cells (PBMCs) were cultivated with overlapping peptide pool containing BKV structural proteins VP1, VP2, and VP3, and regulatory proteins large tumor antigen (LT-Ag) and small tumor antigen (st-Ag), to stimulate in vitro specific cellular immunoresponse. Flow cytometry was used to measure the proliferation of CD3+/CD4+/CD8+ T and interferon [INF]-γ/interleukin [IL]-2/tumor necrosis factor [TNF]-α T cell subsets. RESULTS The BKV infection increased SCr values in recipients of renal transplantation. CD4+ T cells were dominant (>90%) in the in vitro cellular immunoresponse to VP1, VP2, VP3, LT-Ag, and st-Ag. At the presence of viremia and BKVN, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly decreased in vitro cellular immunoresponse to VP1, VP2, and VP3 (p < 0.05), but insignificantly changed to LT-Ag and st-Ag (p > 0.05). For the cases of viruria and viremia, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly higher in vitro cellular immunoresponse to VP1, VP2, and VP3 than to LT-Ag and st-Ag (p < 0.05). The immunogenicity of VP1 and VP3 was significantly higher than that of VP2 (p < 0.05). CONCLUSIONS The BKV infection increases SCr values, and CD4+ T cells are dominant in the in vitro BKV specific cellular immunoresponse in the recipients of renal transplantation. Viremia significantly decreased the immunoresponse to VP1, VP2, and VP3. There is the significantly stronger immunoresponse to VP1 and VP3 when compared with that to VP2, LT-Ag, and st-Ag, suggesting that VP1 and VP3 may be the major targets for the BKV specific immune response.
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Affiliation(s)
- Yu Fan
- Department of Transplantation Surgery, The 309th Hospital of Chinese People's Liberation Army, Beijing, China
| | - Hongwei Bai
- Department of Transplantation Surgery, The 309th Hospital of Chinese People's Liberation Army, Beijing, China
| | - Yeyong Qian
- Department of Transplantation Surgery, The 309th Hospital of Chinese People's Liberation Army, Beijing, China
| | - Zhongwei Sun
- Department of Transplantation Surgery, The 309th Hospital of Chinese People's Liberation Army, Beijing, China
| | - Bingyi Shi
- Department of Transplantation Surgery, The 309th Hospital of Chinese People's Liberation Army, Beijing, China
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22
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周 易, 姚 雷, 于 哲, 崔 乃, 符 芳, 叶 悦, 邓 文, 徐 健, 付 绍, 刘 如, 于 立, 苗 芸. [Characteristics of BK polymavirus infection in kidney transplant recipients]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2019; 39:120-124. [PMID: 30692077 PMCID: PMC6765578 DOI: 10.12122/j.issn.1673-4254.2019.01.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs). METHODS We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×104 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×104 copy/mL (control group). RESULTS Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group (P < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (r2=0.351, P < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min-1·1.73 m-2) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention. CONCLUSIONS Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.
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Affiliation(s)
- 易 周
- 南方医科大学第一临床医学院，广东 广州 510515First Clinical Medical School, Southern Medical University, Guangzhou 510515, China
| | - 雷雨 姚
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 哲 于
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 乃千 崔
- 南方医科大学第一临床医学院，广东 广州 510515First Clinical Medical School, Southern Medical University, Guangzhou 510515, China
| | - 芳翔 符
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 悦典 叶
- 南方医科大学第一临床医学院，广东 广州 510515First Clinical Medical School, Southern Medical University, Guangzhou 510515, China
| | - 文锋 邓
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 健 徐
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 绍杰 付
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 如敏 刘
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 立新 于
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 芸 苗
- 南方医科大学南方医院器官移植科，广东 广州 510515Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Zakaria ZE, Elokely AM, Ghorab AA, Bakr AI, Halim MA, Gheith OA, Nagib AM, Makkeyah Y, Balaha MA, Magdy MM, Al-Otaibi T. Screening for BK Viremia/Viruria and the Impact of Management of BK Virus Nephropathy in Renal Transplant Recipients. EXP CLIN TRANSPLANT 2019; 17:83-91. [PMID: 30777529 DOI: 10.6002/ect.mesot2018.o17] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this study to evaluate screening of BK virus in blood and/or urine among renal transplant recipients and to assess the effects of different therapeutic modalities in renal transplant recipients with BK nephropathy. MATERIALS AND METHODS Kidney transplant recipients were screened at the time of transplant and then at 1, 2, 3, 6, 9, 12, 18, and 24 months posttransplant. Fiftynine patients were diagnosed with BK virus viremia. Patients were divided into 2 groups according to treatment: group 1 (n = 29) received an active treatment and group 2 (n = 30) received minimized immunosuppression. RESULTS Most patients required graft biopsies to confirm diagnosis (86.2% in group 1 vs 50% in group 2; P = .03). Both groups were comparable regarding demographic data. Initial posttransplant graft function was significantly better in group 1 (P = .017); ultimately, there was no significant difference between both groups regarding graft survival (P= .51). Fifty percent of patients had biopsy-proven acute T-cell-mediated rejection before BK virus-associated nephropathy diagnosis (significantly higher in group 1). Serum creatinine levels were significantly better in group 2 at 3, 4, and 5 years after BK nephropathy (P = .001, .017, and .003, respectively). CONCLUSIONS The prevalence of BK nephropathy in our renal transplant recipients was 5.9% with a rate of graft loss ranging from 43% to 51%. Regular screening, less intensive immunosuppressive therapy, and early intervention by reduction of immunosuppressive medications are advisable to obtain early diagnosis and to have better outcomes of BK virus-associated nephropathy with antiviral agents.
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24
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The clinical significance of BK viremia and the effect of cyclosporine and/or mizoribine on BK virus infection. TRANSPLANTATION REPORTS 2018. [DOI: 10.1016/j.tpr.2018.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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25
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El Hennawy HM. BK Polyomavirus Immune Response With Stress on BK-Specific T Cells. EXP CLIN TRANSPLANT 2018; 16:376-385. [PMID: 29766776 DOI: 10.6002/ect.2017.0354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Polyomavirus-associated nephropathy is a pertinent cause of poor renal allograft survival. Absence of defensive immunity toward BK polyomavirus may favor the occurrence of BK polyomavirus-active infection and influence the progression to polyomavirus-associated nephropathy. Humoral immune responses may offer incomplete protection. In this review, available data on both humoral and cellular immunity were examined, with a concentration on BK polyomavirus-specific T cells; in addition, their roles in BK polyomavirus cellular immune response and immunotherapy were discussed. This traditional narrative review used PubMed and Medline searches for English language reports on BK polyomavirus immune response and BK-specific T cells published between January 1990 and November 2017. The search included the key words BK virus, BK polyomavirus, immune and response, and specific T cells. Monitoring BK polyomavirus-specific T cells has both therapeutic and prognostic value. Innovative cellular immunotherapy approaches, including development of vaccinations and infectious recombinant BK polyomavirus, could further contribute to the prevention of BK polyomavirus infection and related diseases.
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Affiliation(s)
- Hany M El Hennawy
- From the Transplant Surgery Section, Department of General Surgery, Armed Forces Hospital, Southern Region, Khamis Mushate, KSA
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26
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Scadden JRW, Sharif A, Skordilis K, Borrows R. Polyoma virus nephropathy in kidney transplantation. World J Transplant 2017; 7:329-338. [PMID: 29312862 PMCID: PMC5743870 DOI: 10.5500/wjt.v7.i6.329] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 11/17/2017] [Accepted: 12/01/2017] [Indexed: 02/05/2023] Open
Abstract
BK virus (BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts via BK virus-associated nephritis (BKVAN). This condition was mis-diagnosed in the past due to clinical and histopthological similarities with acute rejection. Due to the prevalence of the virus in the population, it is an important pathogen in this context, and so it is important to understand how this virus functions and its' relationship with the pathogenesis of BKVN. Screening for BKV often reveals viruria and/or viremia, which then manifests as BKVN, which can be asymptomatic or result in clinical features namely renal dysfunction. The pathogenesis of BKV infection is still unclear and needs to be further investigated; nevertheless there are a variety of hypotheses that indicate that there are a host of factors that play important roles. Treatments for BKVAN include a reduction in immunosuppression, the use of antiviral therapy or the combination of both treatment options.
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Affiliation(s)
- Jacob RW Scadden
- University of Birmingham, Edgbaston, Birmingham B15 2TH, United Kingdom
| | - Adnan Sharif
- Department of Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Kassi Skordilis
- Department of Renal Histopathology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Richard Borrows
- Department of Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
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27
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Abstract
BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications.
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28
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Verghese PS, Schmeling DO, Filtz EA, Matas AJ, Balfour HH. The impact of recipient BKV shedding before transplant on BKV viruria, DNAemia, and nephropathy post-transplant: A prospective study. Pediatr Transplant 2017; 21:10.1111/petr.12942. [PMID: 28557148 PMCID: PMC5511090 DOI: 10.1111/petr.12942] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/20/2017] [Indexed: 12/20/2022]
Abstract
We previously demonstrated that detectable BKV replication in donor urine pretransplant was significantly associated with post-transplant recipient BKV viremia. In this 4-year prospective study, we assessed whether recipient BKV replication pretransplant was associated with post-transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person-years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and two children; and viremia in none pretransplant. Post-transplant viruria occurred in all recipients with pretransplant BKV viruria, significantly more than in recipients without pretransplant viruria on univariate (P<.005) and multivariate analysis including type of organ transplanted and immunosuppression type (P .008). Time to post-transplant viruria was significantly shorter in recipients with pretransplant viruria (P .01). By univariate and multivariate analysis, BKV viruria in recipients pretransplant did not impact post-transplant BKV viremia (P=.97 and .97, respectively) even when stratified by type of organ transplant (kidney P=.6; liver P=.5). The peak serum and urine BKV PCR post-transplant were not significantly different in patients with pretransplant BKV viruria and no one developed BK nephropathy. In conclusion, recipient BKV viruria prior to transplant predicts post-transplant viruria but not viremia or BKV nephropathy.
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Affiliation(s)
- PS Verghese
- Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, MN 55454, US
| | - DO Schmeling
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN 55454, US
| | - EA Filtz
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN 55454, US
| | - AJ Matas
- Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN 55454, US
| | - HH Balfour
- Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, MN 55454, US,Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN 55454, US
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Dvir R, Paloschi V, Canducci F, Dell'Antonio G, Racca S, Caldara R, Pantaleo G, Clementi M, Secchi A. IL28B rs12979860 genotype as a predictor marker of progression to BKVirus Associated nephropathy, after kidney transplantation. Sci Rep 2017; 7:6746. [PMID: 28751760 PMCID: PMC5532253 DOI: 10.1038/s41598-017-06915-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 06/05/2017] [Indexed: 12/22/2022] Open
Abstract
BK virus (BKV) associated nephropathy (BKVAN) is still an important cause of allograft dysfunction after kidney transplantation (KT). Recent data have shown that the new interferon (IFN)-λ family has been ascribed antiviral properties similar to IFNα, and that the response to IFNλ in kidney is restricted to epithelial cells, suggesting that the IFNλ system evolves as specific protection of the epithelia. We aimed to test the hypothesis of correlation between a single nucleotide polymorphism (C/T dimorphism rs12979860) in the genomic region of IL28B and BKVAN, in patients after KT. Fifty kidney-transplanted patients were included as follow: Group 1 (BKV+/BKVAN+): 11 patients with active BKV- replication and biopsy-proven BKVAN; Group 2 (BKV+/BKVAN-): 22 patients with active BKV- replication but without evidence of BKVAN; Group 3 (BKV-/BKVAN-): 17 patients without evidence of BKV- replication (control group). Here we show that the C/C genotype was statistically higher in group 2 than in group 1 and BKVAN was detected significantly more frequently in patients with C/T and T/T genotypes than in patients with C/C genotype. We therefore propose IL28B polymorphism (rs12979860), as a predictor-marker to differentiate between patients with self-limited, even if persistent, BKV- reactivation and patients with a high risk of progression towards BKVAN, and to modulate the clinical management of these patients accordingly.
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Affiliation(s)
- Roee Dvir
- Laboratory of Clinical Microbiology & Virology, San Raffaele Hospital IRCCS, Milan, Italy
| | - Vera Paloschi
- Transplant Unit, Department of Internal Medicine, San Raffaele Hospital IRCCS, Milan, Italy
| | - Filippo Canducci
- Laboratory of Clinical Microbiology & Virology, San Raffaele Hospital IRCCS, Milan, Italy
- University of Insubria, Dept. of Biotechnology and Life Sciences, Varese, Italy
| | | | - Sara Racca
- Laboratory of Clinical Microbiology & Virology, San Raffaele Hospital IRCCS, Milan, Italy
| | - Rossana Caldara
- Transplant Unit, Department of Internal Medicine, San Raffaele Hospital IRCCS, Milan, Italy
| | - Giuseppe Pantaleo
- UniSR-Social.Lab [Research Methods], Faculty of Psychology, Vita Salute San Raffaele University, Milan, Italy
| | - Massimo Clementi
- Laboratory of Clinical Microbiology & Virology, San Raffaele Hospital IRCCS, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Antonio Secchi
- Transplant Unit, Department of Internal Medicine, San Raffaele Hospital IRCCS, Milan, Italy.
- Vita-Salute San Raffaele University, Milan, Italy.
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30
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Abstract
Similarly to the general population, genitourinary tract infections are common conditions in theimmunocompromised host. They can be furthermore divided into infections of the urinary tract and genital tract infections. Transplant recipients are more likely to have infections of the urinary tract infections while persons with human immunodeficiency virus (HIV) are at higher risk for the second group of infections, especially sexually transmitted infections (STIs). Manifestations of these diseases can be associated with more complications and can be more severe. We provide an overview of manifestations, diagnosis, and management of these disorders.
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31
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Gard L, van Doesum W, Niesters HGM, van Son WJ, Diepstra A, Stegeman CA, Groen H, Riezebos-Brilman A, Sanders JS. A delicate balance between rejection and BK polyomavirus associated nephropathy; A retrospective cohort study in renal transplant recipients. PLoS One 2017; 12:e0178801. [PMID: 28609473 PMCID: PMC5469458 DOI: 10.1371/journal.pone.0178801] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 05/18/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN). In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied. METHODS 358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included. RESULTS Incidence of BKPyV-viremia was not significantly different between the CsAM (n = 42/191) (22.0%) and the TacM (n = 36/167) (21.6%) group. Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03). Longitudinal data analysis showed a significant earlier decline of viral load in plasma in the CsAM group compared to the TacM group (p = 0.005). The incidence of biopsy proven acute rejection (BPAR) was significantly higher in the CsAM (19.9%) compared to the TacM (10.8%) (p = 0.02) group. Graft loss, estimated glomerular filtration rate and mortality rate did not differ in both treatment groups. CONCLUSION In conclusion, this study shows that immunosuppressive treatment with Tac and MPA compared to CsA and MPA is associated with a lower incidence of BPAR, but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant.
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Affiliation(s)
- Lilli Gard
- Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- * E-mail:
| | - Willem van Doesum
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Hubert G. M. Niesters
- Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Willem J. van Son
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Arjan Diepstra
- Department of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Coen A. Stegeman
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Henk Groen
- Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Annelies Riezebos-Brilman
- Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Jan Stephan Sanders
- Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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Alagoz S, Kuskucu M, Gulcicek S, Yalin SF, Oruc M, Midilli K, Yılmaz E, Altiparmak MR, Seyahi N. The Frequency and Associated Factors for BK Virus Infection in a Center Performing Mainly Living Kidney Transplantations. Prog Transplant 2017; 27:152-159. [PMID: 28617169 DOI: 10.1177/1526924817699969] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE BK virus (BKV) nephropathy has increasingly become an important cause of morbidity in renal transplant recipients. We evaluated the frequency and associated factors for BKV infection in a center performing mainly living donor transplantations over a long time period. METHODS One hundred consecutive renal transplant patients were included. Quarterly visits were planned to examine urine for decoy cells and to measure the BKV DNA in the blood and urine. Renal biopsy was performed in case of deteriorated allograft function. Serological examinations for BKV immunoglobulin G (IgG) were performed in donors. RESULTS Throughout the entire follow-up period, the rates of viruria, viremia, and the positivity of decoy cells were 12%, 6%, and 13%, respectively. The negative and positive predictive values of decoy cells were 93.1% and 69.2%, respectively, for viruria, and 99.2% and 45.5%, respectively, for viremia. Biopsy-proven BKV nephropathy was observed in 1 patient. The BKV IgG was positive in all living donors. Viruria and viremia were associated with deceased donor transplantation, acute rejection, and pulse steroid therapy. In addition, viremia was associated with antithymocyte globulin therapy and a short duration of the posttransplant period. CONCLUSIONS The frequency of BKV infection was lower in our transplant unit compared to previous reports. Reduced doses of immunosuppression seem to be the main factor that may explain the reduced frequency. However, an active screening strategy is still of importance for this patient group.
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Affiliation(s)
- Selma Alagoz
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Mert Kuskucu
- 2 Department of Clinical Microbiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Sibel Gulcicek
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Serkan Feyyaz Yalin
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Meric Oruc
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Kenan Midilli
- 2 Department of Clinical Microbiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Erkan Yılmaz
- 3 Tissue Typing Laboratory, Department of Organ Transplantation, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Mehmet Riza Altiparmak
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Nurhan Seyahi
- 1 Division of Nephrology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
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Hu J, Li S, Yang M, Xu L, Zhang X, Zhao H, Dong H, Huang Y, Fan J, Li L. Incidence, risk factors and the effect of polyomavirus infection in hematopoietic stem cell transplant recipients. J Int Med Res 2017; 45:762-770. [PMID: 28415933 PMCID: PMC5536654 DOI: 10.1177/0300060517691795] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Objective The effect of polyomavirus infection in HSCT recipients is poorly understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by nested qualitative polymerase chain reaction (PCR) assays of urine. The risk factors for BK virus and JC virus were analysed. The kidney and liver functions of infected and uninfected patients were compared. Results BK virus, JC virus, and simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients respectively. HCMV infection was found to be an independent risk factor for JC virus infection (odds ratio (OR): 8.528), while transplants with mismatched HLA are more susceptible to BK virus infection (OR: 12.000). Liver function of JC virus-infected subjects was worse than that of uninfected subjects. Conclusion We must be vigilant for opportunistic polyomavirus infections in HSCT recipients, especially those with HCMV co-infection or a mismatched HLA transplant. When unexplained liver function deterioration is observed, JC virus infection should be considered.
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Affiliation(s)
- Jianhua Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Siying Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Meifang Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Lichen Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Xuan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Hong Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Huihui Dong
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Yaping Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Jun Fan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
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Liu LS, Li J, Chen XT, Zhang HX, Fu Q, Wang HY, Xiong YY, Liu S, Liu XM, Li JL, Huang M, Wang CX. Comparison of tacrolimus and cyclosporin A in CYP3A5 expressing Chinese de novo kidney transplant recipients: a 2-year prospective study. Int J Clin Pract 2016:43-52. [PMID: 26177348 DOI: 10.1111/ijcp.12666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
AIMS To assess the efficacy and safety of tacrolimus and cyclosporin A (CsA)-based immunosuppressive regimens in Chinese de novo kidney transplant recipients who are CYP3A5 expressers. METHODS The CYP3A5 (6986 A>G, rs776746) polymorphism of eligible patients was determined before transplantation. De novo kidney transplant recipients enrolled in this study were assigned to tacrolimus (Tac group) or CsA (CsA group) based therapy. The follow-up period was 2 years. The incidence of acute rejection, patient and graft survival rates, renal allograft function and post-transplant complications were compared. The intra-individual variability (IIV) of Tac and CsA blood concentrations was analysed. Medication costs were also compared. The analysis was conducted on the intention-to-treat principle. RESULTS A total of 72 CYP3A5 expressers were enrolled, with 36 patients in each group. AR incidence was higher in the Tac group (11.1% vs. 5.6%), but there was no significant difference (p > 0.05). The 2-year patient and graft survival was comparable, and renal function was comparable in the two groups. Notably, the Tac group presented a significantly higher incidence of BK viremia (22.2% vs. 5.6%, p < 0.05) and BK viruria (38.9% vs. 16.7%, p < 0.05) than the CsA group. The CsA IIV at 1 and 3 months post-transplant was significantly lower than the Tac IIV (p < 0.05). The medical costs of both immunosuppressive drugs and management of complications was significantly lower in the CsA group. CONCLUSIONS Cyclosporin A-based maintenance therapy is safe for Chinese de novo kidney transplant recipients who are CYP3A5 expressers. CsA significantly reduced medication costs and decreased BKV infection, suggesting that it is more beneficial for this specific population.
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Affiliation(s)
- L-S Liu
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - J Li
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - X-T Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - H-X Zhang
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Q Fu
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - H-Y Wang
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Y-Y Xiong
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - S Liu
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - X-M Liu
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - J-L Li
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - M Huang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - C-X Wang
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Radtke J, Dietze N, Fischer L, Achilles EG, Li J, Scheidat S, Thaiss F, Nashan B, Koch M. Incidence of BK polyomavirus infection after kidney transplantation is independent of type of immunosuppressive therapy. Transpl Infect Dis 2016; 18:850-855. [PMID: 27639176 DOI: 10.1111/tid.12611] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 05/06/2016] [Accepted: 07/04/2016] [Indexed: 01/03/2023]
Abstract
BACKGROUND BK polyomavirus (BKV) infection and BKV nephropathy (BKVN) are risk factors for allograft function and survival. METHODS We retrospectively analyzed BK viremia and BKVN in 348 patients who received a kidney transplantation donated after brain death (n=232) or living donation (n=116) between 2008 and 2013. A total of 266 patients were treated with standard immunosuppression consisting of basiliximab induction, calcineurin inhibitor (CNI), and mycophenolic acid (MPA, n=219) or everolimus (n=47); 82 patients received more intense immunosuppression with lymphocyte depletion, CNI and MPA (n=38) or everolimus (n=44). RESULTS BK viremia occurred in 33 (9.5%) patients in the first year and in 7 (2.0%) recipients in the second year after transplantation. BKVN occurred in 4 (1.1%) patients in the first year. Donor and recipient age, diabetes, previous transplantation, and type of transplantation (donated after brain death vs living donation) were not risk factors (P>.05). BK incidence did not differ depending on induction or maintenance immunosuppression. CONCLUSION Incidence of BK viremia is independent of recipient characteristics, type of transplantation as well as induction and maintenance immunosuppression.
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Affiliation(s)
- Josephine Radtke
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Nina Dietze
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Lutz Fischer
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Eike-Gert Achilles
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Jun Li
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Silke Scheidat
- Department of Internal Medicine III, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Friedrich Thaiss
- Department of Internal Medicine III, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Bjoern Nashan
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
| | - Martina Koch
- Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf UKE, University Transplantation-Center UTC, Hamburg, Germany
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Broeders EN, Hamade A, El Mountahi F, Racapé J, Hougardy JM, Le Moine A, Vereerstraeten P. Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function. Transpl Infect Dis 2016; 18:872-880. [PMID: 27615506 DOI: 10.1111/tid.12603] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 04/16/2016] [Accepted: 06/29/2016] [Indexed: 01/02/2023]
Abstract
BACKGROUND Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus. MATERIAL AND METHODS From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv <104 copies (cp)/mL (n=573), (B) ≥104 Upv <107 cp/mL (n=100), and (C) Upv ≥107 cp/mL (n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only, as 14 patients (subgroup Cb) were at risk for graft rejection. RESULTS The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P<.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome. CONCLUSION The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.
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Affiliation(s)
- Emine Nilufer Broeders
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
| | - Anwar Hamade
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
| | - Fadoua El Mountahi
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
| | - Judith Racapé
- Research Center of Biostatistics, Epidemiology and Clinical Research, School of Public Health, Université Libre de Bruxelles, Brussels, Belgium
| | - Jean-Michel Hougardy
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
| | - Alain Le Moine
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
| | - Pierre Vereerstraeten
- Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
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Trofe J, Gordon J, Roy-Chaudhury P, Koralnik IJ, Atwood WJ, Alloway RR, Khalili K, Woodle ES. Polyomavirus Nephropathy in Kidney Transplantation. Prog Transplant 2016; 14:130-40; quiz 141-2. [PMID: 15264457 DOI: 10.1177/152692480401400207] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Polyomavirus nephropathy has become an important complication in kidney transplantation, with a prevalence of 1% to 8%. Unfortunately, the risk factors for polyomavirus nephropathy and renal allograft loss are not well defined. The definitive diagnosis is made through assessment of a kidney transplant biopsy. Recently, noninvasive urine and serum markers have been used to assist in polyomavirus nephropathy diagnosis and monitoring. Primary treatment is immunosuppression reduction, but must be balanced with the risks of rejection. No antiviral treatments for polyomavirus nephropathy have been approved by the Food and Drug Administration. Although cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Graft loss due to polyomavirus nephropathy should not be a contraindication to retransplantation; however, experience is limited. This review presents potential risk factors, screening, diagnostic and monitoring methods, therapeutic management, and retransplantation experience for polyomavirus nephropathy.
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Affiliation(s)
- Jennifer Trofe
- University of Cincinnati, Division of Transplantation, Ohio, USA
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38
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Thölking G, Schmidt C, Koch R, Schuette-Nuetgen K, Pabst D, Wolters H, Kabar I, Hüsing A, Pavenstädt H, Reuter S, Suwelack B. Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation. Sci Rep 2016; 6:32273. [PMID: 27573493 PMCID: PMC5004181 DOI: 10.1038/srep32273] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 08/04/2016] [Indexed: 02/08/2023] Open
Abstract
Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.
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Affiliation(s)
- Gerold Thölking
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Christina Schmidt
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Raphael Koch
- Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany
| | - Katharina Schuette-Nuetgen
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Dirk Pabst
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Heiner Wolters
- Department of General Surgery, University Hospital of Münster, Münster, Germany
| | - Iyad Kabar
- Department of Transplant Medicine, University Hospital of Münster, Münster, Germany
| | - Anna Hüsing
- Department of Transplant Medicine, University Hospital of Münster, Münster, Germany
| | - Hermann Pavenstädt
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Stefan Reuter
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
| | - Barbara Suwelack
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany
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Sharma R, Tzetzo S, Patel S, Zachariah M, Sharma S, Melendy T. BK Virus in Kidney Transplant: Current Concepts, Recent Advances, and Future Directions. EXP CLIN TRANSPLANT 2016; 14:377-84. [PMID: 27267780 DOI: 10.6002/ect.2016.0030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BK virus nephropathy is a challenging clinical problem in kidney transplant recipients with wide range of surveillance and management practices, based on individual experience. BK virus reactivation in kidney transplant recipients can result in BK virus nephropathy and graft loss. The most effective strategy for early diagnosis and treatment of BK virus nephropathy is regular monitoring for BK virus, currently achieved by quantification of viral DNA in blood by quantitative polymerase chain reaction. Immunosuppression reduction remains the mainstay of treatment; however, viral clearance is often followed by acute rejection, likely secondary to a delay between immune reconstitution and viral clearance. Impaired cell-mediated immune response to BK virus has been shown to correlate with progression to BK virus nephropathy, while reconstitution of this response correlates with resolution of nephropathy. There is recent research to support monitoring BK virus-specific cell-mediated immune response as a predictor of disease progression and resolution. In this article, we review the current concepts and recent developments in understanding BK virus-associated disease in the context of kidney transplant and outline areas for future research.
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Affiliation(s)
- Rajeev Sharma
- From the Department of Surgery, State University of New York, Buffalo, New York, USA
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40
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Mohamed M, Parajuli S, Muth B, Astor BC, Panzer SE, Mandelbrot D, Zhong W, Djamali A. In kidney transplant recipients with BK polyomavirus infection, early BK nephropathy, microvascular inflammation, and serum creatinine are risk factors for graft loss. Transpl Infect Dis 2016; 18:361-371. [PMID: 26998753 DOI: 10.1111/tid.12530] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 12/28/2015] [Accepted: 01/20/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Little information is available on the risk factors for graft loss in kidney transplant recipients with BK polyomavirus (BKPyV) nephropathy (BKVN) in the presence or absence of antibody-mediated rejection (AMR). METHODS We examined the risk factors for graft loss in consecutive kidney allograft recipients with biopsy-confirmed BKVN, with or without concomitant AMR. RESULTS A total of 1904 kidney transplants were performed at our institution during 2005-2011. Of these, 330 (17.33%) were diagnosed with BKPyV viremia, and 69 were diagnosed with BKVN (3.6%). Eleven patients had a concomitant diagnosis of AMR. Patients with AMR were characterized by significantly higher peak panel-reactive antibody, retransplant rates, and desensitization preconditioning at the time of transplantation, as well as microvascular inflammation (MVI = glomerulitis + peritubular capillaritis), C4d score, and donor-specific antibody at the time of diagnosis (P ≤ 0.01). Treatment with plasma exchange, intravenous immunoglobulin, and cidofovir was more prevalent in this group (P ≤ 0.02). Univariate analyses assessing the risk factors for graft loss in all patients with BKVN, identified an independent association of African-American race, deceased-donor transplantation, serum creatinine (Scr), MVI, and early disease (BKVN within 6 months of transplant) with poor outcomes. Multivariate analyses retained only 3 variables: Scr >2 mg/dL (hazard ratio [HR] = 4.3, 95% confidence interval [CI] 1.9-9.7, P = 0.0004), early BKVN (HR = 2.7, 95% CI 1.3-5.3, P = 0.004), and MVI (HR = 1.8, 95% CI 1.2-2.8, P = 0.008). CONCLUSIONS These observations suggest that, in patients with BK infection, early BKVN, Scr >2, and MVI are predictors of poor outcomes. Further studies are needed to determine effective treatment strategies for BKVN, with or without AMR.
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Affiliation(s)
- M Mohamed
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - S Parajuli
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - B Muth
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - B C Astor
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - S E Panzer
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - D Mandelbrot
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - W Zhong
- Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - A Djamali
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
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Conversion to mTOR-inhibitors with calcineurin inhibitor elimination or minimization reduces urinary polyomavirus BK load in kidney transplant recipients. J Formos Med Assoc 2016; 115:539-46. [PMID: 26994751 DOI: 10.1016/j.jfma.2016.01.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 01/05/2016] [Accepted: 01/20/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND/PURPOSE Polyomavirus BK (BKV) reactivation causes allograft dysfunction in some kidney transplant recipients. The use of mammalian target of rapamycin (mTOR) inhibitor-based immunotherapy is associated with a lower incidence of polyomavirus-associated nephropathy compared with other immunosuppressants. This retrospective study assessed whether conversion to mTOR inhibitor-based immunotherapy directly reduced urinary BKV load. METHODS A total of 63 kidney recipients were divided into mTOR inhibitor-conversion (21 patients) and nonconversion (42 patients) groups. Urinary BKV loads were determined before and at least 6 months after the conversion. RESULTS The results demonstrated that urinary BKV titer was significantly reduced in the conversion group (3.94 ± 0.43 copies (log)/mL to 2.49 ± 0.19 copies (log)/mL) and remained unaltered in the nonconversion group (3.19 ± 0.20 copies (log)/mL to 2.90 ± 0.20 copies (log)/mL). In addition, the percentage of patients with reduced urinary BKV load was significantly higher in the conversion group (76.2% vs. 42.9%). The estimated glomerular filtration rate after 24 months mTOR inhibitor conversion was significantly increased compared with that in the nonconversion group. Conversion to mTOR-inhibitor-based immunotherapy was the only factor associated with an increase in estimated glomerular filtration rate. CONCLUSION This study reveals an association of conversion to mTOR-inhibitor-based immunotherapy with the reduction of urinary BKV load.
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Toptan T, Yousem SA, Ho J, Matsushima Y, Stabile LP, Fernández-Figueras MT, Bhargava R, Ryo A, Moore PS, Chang Y. Survey for human polyomaviruses in cancer. JCI Insight 2016; 1. [PMID: 27034991 DOI: 10.1172/jci.insight.85562] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Over the past 8 years, the discovery of 11 new human polyomaviruses (HPyVs) has revived interest in this DNA tumor virus family. Although HPyV infection is widespread and largely asymptomatic, one of these HPyVs, Merkel cell polyomavirus (MCV), is a bona fide human tumor virus. JC virus (JCV), BK virus, HPyV7, and trichodysplasia-spinulosa virus (TSV) can cause nonneoplastic diseases in the setting of immunosuppression. Few specific reagents are available to study the biology of the newly discovered HPyVs. We developed a pan-HPyV-screening method using a cocktail of 3 antibodies that, when combined, recognize T antigen proteins of all HPyVs. We validated detection characteristics of the antibody cocktail by immunoblotting and immunohistochemistry and screened 1,184 cases, including well-defined diseases and tumor tissue microarrays. This assay robustly detected MCV, TSV, JCV, and HPyV7 in etiologically related diseases. We further identified WU polyomavirus in a case of chronic lymphocytic lymphoma-associated bronchitis. Except for scattered, incidentally infected cells in 5% of lung squamous cell carcinomas and colon adenocarcinomas, a broad panel of tumor tissues was largely negative for infection by any HPyV. This method eliminates known HPyVs as suspected causes of cancers investigated in this study. Pan-HPyV survey can be applied to identify diseases associated with recently discovered polyomaviruses.
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Affiliation(s)
- Tuna Toptan
- Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
| | - Samuel A Yousem
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jonhan Ho
- Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Yuki Matsushima
- Division of Virology, Kawasaki City Institute for Public Health, Kanagawa, Japan
| | - Laura P Stabile
- Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | | | - Rohit Bhargava
- Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Akihide Ryo
- Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, Japan
| | - Patrick S Moore
- Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
| | - Yuan Chang
- Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
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Schachtner T, Zaks M, Kahl A, Reinke P. Simultaneous pancreas/kidney transplant recipients present with late-onset BK polyomavirus-associated nephropathy. Nephrol Dial Transplant 2016; 31:1174-82. [PMID: 26758790 DOI: 10.1093/ndt/gfv441] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 11/29/2015] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Infections have increased in simultaneous pancreas/kidney transplant recipients (SPKTRs) with BK polyomavirus (BKV)-associated nephropathy (BKVN) being the most important infectious cause of allograft loss. Comparisons of BKVN with kidney transplant recipients (KTRs), however, are lacking. METHODS We studied all SPKTRs and KTRs at our transplant centre between 2003 and 2012. Eleven of 106 SPKTs (10.4%) and 21 of 1062 KTRs (2.0%) were diagnosed with BKVN with allograft loss in 1 SPKTR (9.1%) and 2 KTRs (9.5%). A control of 95 SPKTRs without BKVN was used for comparison. RESULTS SPKTRs showed an increased incidence of BKVN compared with KTRs (P < 0.001). Onset of BKVN in SPKTRs was significantly later compared with KTRs (P = 0.033). While 67% of KTRs showed early-onset BKVN, 64% of SPKTRs developed late-onset BKVN. Older recipient age and male gender increased the risk of BKVN in SPKTRs (P < 0.05). No differences were observed for patient and allograft survival (P > 0.05). However, SPKTRs with BKVN showed inferior estimated glomerular filtration rate and a higher incidence of de novo donor-specific antibodies compared with SPKTRs without BKVN in long-term follow-up (P < 0.05). SPKTRs showed higher peak BKV loads, a need for more intense therapeutic intervention and were more likely not to recover to baseline creatinine after BKVN (P < 0.05). CONCLUSIONS Our results suggest a higher incidence, more severe course and inferior outcome of BKVN in SPKTRs. An increased vulnerability of the allograft kidney due to inferior organ quality may predispose KTRs to early-onset BKVN. In contrast, SPKTRs present with late-onset BKVN in the presence of high-dose immunosuppression.
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Affiliation(s)
- Thomas Schachtner
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
| | - Marina Zaks
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany
| | - Andreas Kahl
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
| | - Petra Reinke
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
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Kauke T, Klimaschewski S, Schoenermarck U, Fischereder M, Dick A, Guba M, Stangl M, Werner J, Meiser B, Habicht A. Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience. PLoS One 2016; 11:e0146075. [PMID: 26730981 PMCID: PMC4711576 DOI: 10.1371/journal.pone.0146075] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Accepted: 12/11/2015] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND The shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols. METHODS We herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups. RESULTS 1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 ± 0.5 vs 1.78 ± 0.6 vs 1.64 ± 0.5 vs 1.6 ± 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03). CONCLUSION We demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN.
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Affiliation(s)
- Teresa Kauke
- Laboratory for Immunogenetics, University Hospital LMU, Munich, Germany
- Clinic for General, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University Hospital LMU, Munich, Germany
| | | | - Ulf Schoenermarck
- Department of Internal Medicine IV, Renal Division, University Hospital LMU, Munich, Germany
| | - Michael Fischereder
- Department of Internal Medicine IV, Renal Division, University Hospital LMU, Munich, Germany
| | - Andrea Dick
- Laboratory for Immunogenetics, University Hospital LMU, Munich, Germany
| | - Markus Guba
- Clinic for General, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University Hospital LMU, Munich, Germany
| | - Manfred Stangl
- Clinic for General, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University Hospital LMU, Munich, Germany
| | - Jens Werner
- Clinic for General, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University Hospital LMU, Munich, Germany
| | - Bruno Meiser
- Transplant Center, University Hospital LMU, Munich, Germany
| | - Antje Habicht
- Transplant Center, University Hospital LMU, Munich, Germany
- * E-mail:
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Lee HM, Jang IA, Lee D, Kang EJ, Choi BS, Park CW, Choi YJ, Yang CW, Kim YS, Chung BH. Risk factors in the progression of BK virus-associated nephropathy in renal transplant recipients. Korean J Intern Med 2015; 30:865-72. [PMID: 26552462 PMCID: PMC4642016 DOI: 10.3904/kjim.2015.30.6.865] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 05/16/2014] [Accepted: 07/22/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS BK virus-associated nephropathy (BKVAN) is an important cause of allograft dysfunction in kidney transplant recipients. It has an unfavorable clinical course, and no definite treatment guidelines have yet been established. Here, we report our center's experience with biopsy-proven BKVAN and investigate factors associated with its progression. METHODS From January 2004 to April 2013, 25 patients with BKVAN were diagnosed by biopsy at Seoul St. Mary's Hospital. Of the 25 patients, 10 were deceased-donor transplant recipients and 15 were living-donor transplant recipients. Three of the patients underwent retransplantation. The primary immunosuppressant used was tacrolimus in 17 patients and cyclosporine in eight patients. RESULTS BKVAN was observed at a mean duration of 22.8 ± 29.1 months after transplantation. The mean serum creatinine level at biopsy was 2.2 ± 0.7 mg/dL. BKVAN occurred with acute rejection in eight patients (28%). Immunosuppression modification was performed in 21 patients (84%). Additionally, leflunomide and intravenous immunoglobulin were administered to 13 patients (52%) and two (8%), respectively. Allograft loss occurred in five patients (27.8%) during the follow- up period at 0.7, 17.1, 21.8, 39.8, and 41.5 months after the BKVAN diagnosis. Advanced stages of BKVAN, increased creatinine levels, and accompanying acute rejection at the time of BKVAN diagnosis increased the risk of allograft failure. CONCLUSIONS The clinical outcomes in patients with biopsy-proven BKVAN were unfavorable in the present study, especially in patients with advanced-stage BKVAN, poor renal function, and acute allograft rejection.
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Affiliation(s)
- Hae Min Lee
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - In-Ae Jang
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Dongjae Lee
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Eun Jin Kang
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Bum Soon Choi
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Cheol Whee Park
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Yeong Jin Choi
- Department of Hospital Pathology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Chul Woo Yang
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Yong-Soo Kim
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Byung Ha Chung
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
- Correspondence to Byung Ha Chung, M.D. Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-6066 Fax: +82-2-599-3589 E-mail :
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T-cell alloreactivity and transplantation outcome: a budding role for heterologous immunity? Curr Opin Organ Transplant 2015; 20:454-60. [PMID: 26126194 DOI: 10.1097/mot.0000000000000218] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Despite the association between alloreactive T cells and poor graft survival, the mechanisms behind T-cell-mediated rejection are still under investigation. In this review, we will discuss the latest insights into the impact of T-cell alloreactivity on solid organ transplantation and hematopoietic stem cell transplantation (HSCT), with special emphasis on the potential impact of heterologous immunity. RECENT FINDINGS A large part of the memory T-cell repertoire is induced upon virus infections, and evidence for a role of T-cell receptor cross-reactivity of virus-induced memory T cells against allogeneic human leukocyte antigen (HLA) is accumulating in experimental and clinical solid organ transplantation studies. In HSCT, strong alloreactive potential of naïve T cells causes concerns for graft-versus-host disease while additional HLA-DP matching is suggested to prevent CD4 alloreactivity. Furthermore, virus-induced memory T cells hamper mixed chimerism induction, pointing once more towards a role for heterologous immunity. SUMMARY Both memory and naïve T cells contribute to the alloimmune response after transplantation. Monitoring for T-cell phenotypes could help predict rejection episodes and/or graft-versus-host disease, allowing timely intervention. Tailoring donor lymphocyte infusions and additional HLA matching could prevent strong alloreactivity in HSCT. Furthermore, the potential role of heterologous immunity in T-cell alloreactivity and transplantation is gaining interest.
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Boran M, Yıldırım T, Boran E, Boran M, Kilic H. Late-Onset BK Viruria in Renal Transplant Recipients. Transplant Proc 2015; 47:1786-9. [PMID: 26293051 DOI: 10.1016/j.transproceed.2015.06.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 05/29/2015] [Accepted: 06/16/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND Most cases of BK virus (BKV) infections emerge within the 1st years of kidney transplantation. We aimed to determine the prevalence of late-onset BKV infection and whether there are any differences between risk factors in early and late BKV infections. METHODS In this single-center retrospective study, we reviewed 300 kidney transplant recipients that were under regular follow-up and selected recipients with BKV infection and recorded associated risk factors, connection with immunosuppression, and responses to modification of treatment. RESULTS BKV was detected within the 1st 5 years after transplantation in 20 patients (6.6%, group 1) and after 5 years in 15 patients (5.0%, group 2). There were no significant differences between the 2 groups regarding age, sex, sex mismatches, donor type, BKV elimination time, serum creatinine, and estimated glomerular filtration rate at the times of BKV detection and last follow-up visit. In group 1, 2 recipients had biopsy-proven BKV-associated nephropathy (BKVAN), 3 recipients had BK viruria and viremia without BKVAN (biopsy proven), and 15 recipients (75%) had only BK viruria. In group 2, all of the patients had only BK viruria. In this group, on detection of BK viruria and immediate modification of immunosuppressive regimens prevented BK viremia. CONCLUSIONS Routine screening of renal transplant recipients for BKV was indicated not only during the 1st 5 years, but also for the full follow-up period after transplantation.
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Affiliation(s)
- Mediha Boran
- Department of Nephrology, Hemodialysis, and Transplantation, Turkiye Higher Education Hospital, Ankara, Turkey.
| | - T Yıldırım
- Department of Nephrology, Ankara Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
| | - E Boran
- Department of Anesthesiology and Reanimation, Duzce University Faculty of Medicine, Duzce, Turkey
| | - Mertay Boran
- Department of Thoracic Surgery, Duzce University Faculty of Medicine, Duzce, Turkey
| | - H Kilic
- Department of Microbiology, Turkiye Higher Education Hospital, Ankara, Turkey
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Gupta N, Lawrence RM, Nguyen C, Modica RF. Review article: BK virus in systemic lupus erythematosus. Pediatr Rheumatol Online J 2015; 13:34. [PMID: 26293687 PMCID: PMC4545992 DOI: 10.1186/s12969-015-0033-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 08/16/2015] [Indexed: 02/08/2023] Open
Abstract
BK virus (BKV) is a human polyomavirus with a seroprevalence of 60-80 % in the general population. In renal transplant patients, it is known to cause renal failure, ureteric stenosis and hemorrhagic cystitis. In bone marrow transplant patients, it is evident that BKV can also cause hemorrhagic cystitis along with BK virus nephropathy (BKVN) in the native kidneys, with subsequent renal failure. However, little is known about BVKN in non-transplanted immune-compromised patients, such as systemic lupus erythematosus (SLE) who may have underlying nephritis and have a compromised immune system due to therapy and/or systemic illness. Thus, this article will focus on the clinical aspects of BKV and its association in patients with SLE.
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Affiliation(s)
- Nirupama Gupta
- Division of Nephrology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
| | - Robert M. Lawrence
| | - Cuong Nguyen
- Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32610, USA.
| | - Renee F. Modica
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Rao N, Schepetiuk S, Choudhry M, Juneja R, Passaris G, Higgins G, Barbara J. JC viraemia in kidney transplant recipients: to act or not to act? Clin Kidney J 2015; 5:471-3. [PMID: 26019830 PMCID: PMC4432428 DOI: 10.1093/ckj/sfs123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2012] [Accepted: 07/27/2012] [Indexed: 11/29/2022] Open
Affiliation(s)
- N Rao
- Department of Nephrology , Flinders Medical Centre and Flinders University , Bedford Park , SA , Australia
| | - S Schepetiuk
- Microbiology and Infectious Diseases , Institute of Medical and Veterinary Sciences , Adelaide, SA , Australia
| | - M Choudhry
- Department of Nephrology , Flinders Medical Centre and Flinders University , Bedford Park , SA , Australia
| | - R Juneja
- Department of Nephrology , Flinders Medical Centre and Flinders University , Bedford Park , SA , Australia
| | - G Passaris
- Department of Nephrology , Flinders Medical Centre and Flinders University , Bedford Park , SA , Australia
| | - G Higgins
- Microbiology and Infectious Diseases , Institute of Medical and Veterinary Sciences , Adelaide, SA , Australia
| | - J Barbara
- Department of Nephrology , Flinders Medical Centre and Flinders University , Bedford Park , SA , Australia
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Schachtner T, Babel N, Reinke P. Different risk factor profiles distinguish early-onset from late-onset BKV-replication. Transpl Int 2015; 28:1081-91. [PMID: 25959355 DOI: 10.1111/tri.12601] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 03/10/2015] [Accepted: 05/04/2015] [Indexed: 01/15/2023]
Abstract
Two of three reactivations of latent BKV-infection occur within the first 6 months after renal transplantation. However, a clear differentiation between early-onset and late-onset BKV-replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV-associated nephropathy (BKVN). Sixty-seven KTRs with early-onset BKV-replication (65%) and 36 KTRs with late-onset BKV-replication (35%) were identified. A control group of 598 KTRs without BKV-replication was used for comparison. Lymphocyte-depleting induction, CMV-reactivation, and acute rejection increased the risk of early-onset BKV-replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late-onset BKV-replication (P < 0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft function (P < 0.05). KTRs with late-onset BK viremia were more likely not to recover to baseline creatinine after BKV-replication (P = 0.018). Our data suggest different risk factors in the pathogenesis of early-onset and late-onset BKV-reactivation. While a more intensified immunosuppression is associated with early-onset BKV-replication, a chronic inflammatory state in presensitized KTRs may contribute to late-onset BKV-replication.
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Affiliation(s)
- Thomas Schachtner
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.,Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
| | - Nina Babel
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.,Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
| | - Petra Reinke
- Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.,Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany
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