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1
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Leuzinger K, Hirsch HH. Amplicon size and non-encapsidated DNA fragments define plasma cytomegalovirus DNA loads by automated nucleic acid testing platforms: A marker of viral cytopathology? J Med Virol 2023; 95:e29139. [PMID: 37804497 DOI: 10.1002/jmv.29139] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/31/2023] [Accepted: 09/20/2023] [Indexed: 10/09/2023]
Abstract
Management of cytomegalovirus (CMV) in transplant patients relies on measuring plasma CMV-loads using quantitative nucleic acid testing (QNAT). We prospectively compared the automated Roche-cobas®6800-CMV and Roche-CAP/CTM-CMV with laboratory-developed Basel-CMV-UL54-95bp, and Basel-CMV-UL111a-77bp. Roche-cobas®6800-CMV and Roche-CAP/CTM-CMV were qualitatively concordant in 142/150 cases (95%). In-depth comparison revealed higher CMV-loads of the laboratory-developed assay and correlated with smaller amplicon size. After calibration to the 1.WHO-approved CMV international standard, differences were reduced but remained significant. DNase-I pretreatment significantly reduced CMV-loads for both automated Roche-CAP/CTM-CMV and Roche-cobas®6800-CMV assays, whereby 90% and 95% of samples became undetectable. DNase-I pretreatment also reduced CMV-loads quantified by Basel-CMV-UL54-95bp and Basel-CMV-UL111a-77bp, but remaining detectable in 20% and 35%, respectively. Differences were largest for 110 samples with low-level CMV-DNAemia being detectable but not-quantifiable by Roche-cobas®6800-CMV, whereby the smaller amplicon sizes yielded higher viral loads for concordant positives. We conclude that non-encapsidated fragmented CMV-DNA is the major form of plasma CMV-loads also measured by fully-automated platforms. Amplicons of <150 bp and calibrators are needed for reliable and commutable QNAT-results. We hypothesize that non-encapsidated fragmented CMV-DNA results from lysis of CMV-replicating cells and represent a direct marker of viral cell damage, which contribute to delayed viral load responses despite effective antivirals.
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Affiliation(s)
- Karoline Leuzinger
- Clinical Virology, University Hospital Basel, Basel, Switzerland
- Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland
| | - Hans H Hirsch
- Clinical Virology, University Hospital Basel, Basel, Switzerland
- Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland
- Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
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2
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Kumar L, Murray-Krezan C, Singh N, Brennan DC, Rakita RM, Dasgupta S, Fisher CE, Limaye AP. A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients. Transplant Direct 2023; 9:e1514. [PMID: 37456587 PMCID: PMC10348730 DOI: 10.1097/txd.0000000000001514] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 06/02/2023] [Indexed: 07/18/2023] Open
Abstract
The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior meta-analyses that CMV disease rates with preemptive therapy (PET) and universal prophylaxis (UP) were comparable may have been affected by inclusion of studies lacking key determinants of efficacy of the respective strategies. Methods We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir. PubMed and Embase databases were reviewed from January 1, 2010, to April 1, 2022. Risk of bias was assessed with 3 instruments (Cochrane RoB, Cochrane RoBINS-I, and an instrument for assessing risk in observational studies). The primary outcome was CMV disease incidence by 1-y posttransplant. Secondary outcomes by 1-y were graft loss, acute allograft rejection, and mortality. Results were synthesized using generalized linear mixed model meta-analysis. PET studies were stratified into low-threshold (LT) and high-threshold (HT) PET based on the viral load threshold for initiation of antiviral therapy. Results Twenty-five studies met inclusion criteria (6 PET, 19 UP). CMV disease incidence was significantly higher in HT (0.30 [95% confidence interval (CI), 0.22-0.39]) versus LT PET (0.06 [95% CI, 0.03-0.12]). LT PET was associated with a significantly lower CMV disease incidence (0.06 [95% CI, 0.03-0.12]) versus UP (0.21 [95% CI, 0.17-0.27]). Incidence of graft loss, acute allograft rejection, or mortality was not significantly different between LT PET and UP (P > 0.05 for all comparisons). Receipt of lymphocyte-depleting antibodies was not associated with a significant difference in CMV disease incidence (odds ratio = 1.34 [95% CI, 0.80-2.25]). Conclusions LT PET is associated with a significantly lower incidence of CMV disease compared to UP with similar rates of other clinical outcomes. These findings provide rationale and preliminary data for a randomized superiority trial of optimized LT-PET versus UP in donor seropositive recipient seronegative kidney transplant recipients.
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Affiliation(s)
- Lakshin Kumar
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA
| | - Cristina Murray-Krezan
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Nina Singh
- Department of Medicine, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, PA
| | - Daniel C. Brennan
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Robert M. Rakita
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA
| | - Sayan Dasgupta
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA
| | - Cynthia E. Fisher
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA
| | - Ajit P. Limaye
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA
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Montero C, Yomayusa N, Torres R, Cortes J, Alvarez C, Gallo J, Aldana G, Acevedo A, Rios M, Echeverri J, Yepes Z, Silva A, Gayon D, Perez J, Ibanez M. Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy. Nefrologia 2022:S2013-2514(22)00143-2. [PMID: 36437203 DOI: 10.1016/j.nefroe.2022.11.018] [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: 02/18/2021] [Accepted: 10/06/2021] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. METHODS Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/μl, they received valganciclovir adjusted for their renal function. RESULTS 132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation. CONCLUSIONS Due to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series.
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Affiliation(s)
- Camilo Montero
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia.
| | - Nancy Yomayusa
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia; Infectious Diseases Department, Clinica Colsanitas, Bogota, Colombia
| | - Rodolfo Torres
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia
| | - Jorge Cortes
- Facultad de Medicina, Universidad Nacional de Colombia
| | - Carlos Alvarez
- Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia; Infectious Diseases Department, Clinica Colsanitas, Bogota, Colombia
| | - Juan Gallo
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia
| | - Guillermo Aldana
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia
| | - Andres Acevedo
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia
| | - Maria Rios
- Molecular Biology and Immunology Laboratory, Clinica Colsanitas, Bogota, Colombia
| | - Johana Echeverri
- Molecular Biology and Immunology Laboratory, Clinica Colsanitas, Bogota, Colombia
| | - Zuly Yepes
- Molecular Biology and Immunology Laboratory, Clinica Colsanitas, Bogota, Colombia
| | - Adriana Silva
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia
| | - Diana Gayon
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia
| | - Jorge Perez
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia; Infectious Diseases Department, Clinica Colsanitas, Bogota, Colombia; Molecular Biology and Immunology Laboratory, Clinica Colsanitas, Bogota, Colombia
| | - Milciades Ibanez
- Renal Transplantation Group, Clinica Reina Sofia, University Clinic, Bogota, Colombia; Translational Investigation Group, Sanitas University, Clinica Colsanitas, Bogota, Colombia
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Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy. Nefrologia 2021. [DOI: 10.1016/j.nefro.2021.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Raval AD, Kistler KD, Tang Y, Murata Y, Snydman DR. Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real-world evidence. Transpl Infect Dis 2021; 23:e13483. [PMID: 33012092 DOI: 10.1111/tid.13483] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 12/21/2022]
Abstract
Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A comprehensive review of published literature reporting real-world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real-world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R- and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one-fourth of KTR developed CMV infection. Age and D+/R- CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management.
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Good-Weber M, Roos M, Mueller TF, Rüsi B, Fehr T. Tailored immunosuppression after kidney transplantation - a single center real-life experience. BMC Nephrol 2020; 21:501. [PMID: 33228545 PMCID: PMC7686677 DOI: 10.1186/s12882-020-02137-5] [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: 03/04/2020] [Accepted: 10/29/2020] [Indexed: 11/30/2022] Open
Abstract
Background Kidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group incompatibility and sensitized recipients) increase. Between 2006 and 2008, a new tailored immunosuppression scheme for kidney transplantation was implemented at the University Hospital in Zurich, together with an ABO-incompatible transplant program and systematic pre- and posttransplant anti-human leukocyte antigen (HLA) antibody screening by Luminex technology. This study retrospectively evaluated the results of this tailored immunosuppression approach with a particular focus on immunologically higher risk transplants. Methods A total of 204 consecutive kidney transplantations were analyzed, of whom 14 were ABO-incompatible and 35 recipients were donor-specific anti-HLA antibodies (DSA) positive, but complement-dependent cytotoxicity crossmatch (CDC-XM) negative. We analyzed patient and graft survival, acute rejection rates and infectious complications in ABO-compatible versus -incompatible and in DSA positive versus negative patients and compared those with a historical control group. Results Overall patient, death-censored allograft survival and non-death-censored allograft survival at 4 years were 92, 91 and 87%, respectively. We found that (1) there were no differences between ABO-compatible and -incompatible and between DSA positive and DSA negative patients concerning acute rejection rate and graft survival; (2) compared with the historical control group there was a significant decrease of acute rejection rates in sensitized patients who received an induction with thymoglobulin; (3) there was no increased rate of infection among the patients who received induction with thymoglobulin compared to no induction therapy. Conclusions We observed excellent overall mid-term patient and graft survival rates with our tailored immunosuppression approach. Induction with thymoglobulin was efficient and safe in keeping rejection rates low in DSA positive patients with a negative CDC-XM. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-020-02137-5.
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Affiliation(s)
- Miriam Good-Weber
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Malgorzata Roos
- Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University Zurich, Zurich, Switzerland
| | - Thomas F Mueller
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Barbara Rüsi
- HLA Typing Laboratory, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Fehr
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland. .,Department of Internal Medicine, Cantonal Hospital Graubünden, Loestrasse 170, 7000, Chur, Switzerland.
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Pretagostini R, Poli L, Lai Q, Russo G, Nudo F, Garofalo M, Melandro F, Gaeta A, Nazzari C, Fazio C, Di Simone E, Vullo V, Berloco PB. Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation. Transplant Proc 2017; 49:638-641. [PMID: 28457362 DOI: 10.1016/j.transproceed.2017.02.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.
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Affiliation(s)
- R Pretagostini
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy.
| | - L Poli
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - Q Lai
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - G Russo
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - F Nudo
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - M Garofalo
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - F Melandro
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - A Gaeta
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - C Nazzari
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - C Fazio
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - E Di Simone
- Biomedicina e Prevenzione, Università di Roma Tor Vergata, Rome, Italy
| | - V Vullo
- Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
| | - P B Berloco
- UOC Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Policlinico Umberto I Roma, Rome, Italy
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8
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Cortés JA, Yomayusa N, Arias YR, Arroyave IH, Cataño JC, García P, Guevara FO, Mesa L, Montero C, Rios MF, Robayo A, Rosso F, Torres R, Uribe LG, González L, Alvarez CA. Consenso colombiano para la estratificación, diagnóstico, tratamiento y prevención de la infección por citomegalovirus en pacientes adultos con trasplante renal. INFECTIO 2016. [DOI: 10.1016/j.infect.2015.10.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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Kim T, Lee YM, Lee SO, Choi SH, Kim YS, Woo JH, Sung H, Jung JH, Shin S, Kim YH, Kang YA, Lee YS, Lee JH, Lee JH, Lee KH, Park SK, Han DJ, Kim SH. Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy. Korean J Intern Med 2016; 31:961-70. [PMID: 27055664 PMCID: PMC5016278 DOI: 10.3904/kjim.2015.079] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/22/2015] [Accepted: 06/30/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.
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Affiliation(s)
- Tark Kim
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu-Mi Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Inje University Busan Paik Hospital, Busan, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Hee Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Ah Kang
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Shin Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Hee Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Je-Hwan Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Kil Park
- Department of Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Prophylactic CMV therapy does not improve three-yr patient and graft survival compared to preemptive therapy. Clin Transplant 2015; 29:1230-8. [DOI: 10.1111/ctr.12657] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/07/2015] [Indexed: 11/26/2022]
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Fehr T, Cippà PE, Mueller NJ. Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy? Transpl Int 2015; 28:1351-6. [PMID: 26138458 DOI: 10.1111/tri.12629] [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: 02/22/2015] [Revised: 03/13/2015] [Accepted: 06/18/2015] [Indexed: 01/15/2023]
Abstract
Cytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre-emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre-emptive therapy and anti-CMV prophylaxis are both equally potent in preventing CMV-associated complications; however, the pre-emptive approach may have distinct advantages in allowing for development of long-term anti-CMV immunity. We propose a risk-adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre.
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Affiliation(s)
- Thomas Fehr
- Department of Internal Medicine, Cantonal Hospital Graubuenden, Chur, Switzerland.,Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Pietro E Cippà
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Nicolas J Mueller
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
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Cytomegalovirus: Why Viral Dynamics Matter. EBioMedicine 2015; 2:631. [PMID: 26288831 PMCID: PMC4534701 DOI: 10.1016/j.ebiom.2015.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Accepted: 06/01/2015] [Indexed: 11/20/2022] Open
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13
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Matter-Walstra KW, Greiner M, Cusini A, Schiesser M, Ledergerber B, Fehr T, Mueller NJ. Stringent adherence to a cytomegalovirus-prevention protocol is associated with reduced overall costs in the first 6 months after kidney transplantation. Transpl Infect Dis 2015; 17:342-9. [PMID: 25816700 DOI: 10.1111/tid.12379] [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: 08/21/2014] [Revised: 11/20/2014] [Accepted: 02/16/2015] [Indexed: 11/29/2022]
Abstract
BACKGROUND We previously documented that a stringent implementation of a preemptive cytomegalovirus (CMV) prevention protocol reduced the number of CMV disease episodes after kidney transplantation, when compared with a routine preemptive protocol. The impact on overall costs was assessed. METHODS Cost comparisons were made for inpatient and outpatient costs and overall costs, using costs provided by the financial department. Variables were analyzed using the Wilcoxon rank-sum test. A multivariable global linear model evaluated the effect of all co-variables on cost differences. In Cohort 1 (n = 84), 74% were followed with a standard CMV preemptive protocol, and 26% received prophylaxis. In Cohort 2 (n = 74), an intensified CMV surveillance protocol was applied in 74% of patients, and 26% were given prophylaxis. RESULTS Overall, Cohort 1 had significantly higher treatment costs as compared with Cohort 2 (mean Swiss francs [CHF] 104,548 and CHF 76,983, respectively, P = 0.0005). Excluding patients who received prophylaxis reduced these costs to CHF 89,318 in Cohort 1 and CHF 73,652 in Cohort 2. Outcome between Cohort 1 and 2 was comparable. CONCLUSION A stringent adherence to the CMV prevention protocol was associated with a significant reduction in overall costs. Whether this benefit is because of the demonstrated reduction in the rate of CMV disease needs to be assessed in a randomized trial.
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Affiliation(s)
- K W Matter-Walstra
- Institute of Pharmaceutical Medicine/ECPM, University Basel, Basel, Switzerland
| | - M Greiner
- Division of Infectious Disease and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland
| | - A Cusini
- Division of Infectious Disease and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland
| | - M Schiesser
- Division of Visceral and Transplantation Surgery, University Hospital Zürich, Zürich, Switzerland
| | - B Ledergerber
- Division of Infectious Disease and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland
| | - T Fehr
- Division of Nephrology, University Hospital Zürich, Zürich, Switzerland
| | - N J Mueller
- Division of Infectious Disease and Hospital Epidemiology, University Hospital Zürich, Zürich, Switzerland
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Salvadori M, Bertoni E. What's new in clinical solid organ transplantation by 2013. World J Transplant 2014; 4:243-266. [PMID: 25540734 PMCID: PMC4274595 DOI: 10.5500/wjt.v4.i4.243] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 07/11/2014] [Accepted: 07/27/2014] [Indexed: 02/05/2023] Open
Abstract
Innovative and exciting advances in the clinical science in solid organ transplantation continuously realize as the results of studies, clinical trials, international conferences, consensus conferences, new technologies and discoveries. This review will address to the full spectrum of news in transplantation, that verified by 2013. The key areas covered are the transplantation activity, with particular regards to the donors, the news for solid organs such as kidney, pancreas, liver, heart and lung, the news in immunosuppressive therapies, the news in the field of tolerance and some of the main complications following transplantation as infections and cancers. The period of time covered by the study starts from the international meetings held in 2012, whose results were published in 2013, up to the 2013 meetings, conferences and consensus published in the first months of 2014. In particular for every organ, the trends in numbers and survival have been reviewed as well as the most relevant problems such as organ preservation, ischemia reperfusion injuries, and rejections with particular regards to the antibody mediated rejection that involves all solid organs. The new drugs and strategies applied in organ transplantation have been divided into new way of using old drugs or strategies and drugs new not yet on the market, but on phase Ito III of clinical studies and trials.
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15
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Beam E, Dioverti V, Razonable RR. Emerging cytomegalovirus management strategies after solid organ transplantation: challenges and opportunities. Curr Infect Dis Rep 2014; 16:419. [PMID: 24986636 DOI: 10.1007/s11908-014-0419-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cytomegalovirus (CMV) remains as one of the most common pathogens after solid organ transplantation (SOT). During the past year, management guidelines were updated, and numerous studies were published-all collectively emphasizing the ongoing efforts to improve management of CMV after SOT. Improvement in laboratory diagnostics was aided by the WHO international calibration standard for nucleic acid testing, which allows for meaningful comparison of viral load values among laboratories. The potential translation of methods for assessing CMV-specific cellular immunity could provide tools for CMV risk assessment and management. Efforts continue to optimize antiviral strategies for CMV disease prevention and treatment. CMV vaccines continue to be tested in various stages of clinical trials. Novel anti-CMV drugs are being developed, including agents that have been used as compassionate therapy for treatment of drug-resistant CMV. In this article, the authors review recent developments on CMV and discuss their implications in CMV management after transplantation.
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Affiliation(s)
- E Beam
- Division of Infectious Diseases, Department of Medicine, and the William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA
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16
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Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, Berger C, Boggian K, Cusini A, Koller MT, Weisser M, Pascual M, Meylan PR. Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2013; 13:2402-10. [PMID: 23914796 DOI: 10.1111/ajt.12388] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 05/28/2013] [Accepted: 06/15/2013] [Indexed: 01/25/2023]
Abstract
We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox regression models. One thousand two hundred thirty-nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R- vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14-9.14], p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63-2.17], p = 0.63). CMV disease was not associated with a lower graft failure-free survival (HR 1.27 [95% CI 0.64-2.53], p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63 [95% CI 1.01-2.64], p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.
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Affiliation(s)
- O Manuel
- Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
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17
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Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L, Humar A. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 2013; 96:333-60. [PMID: 23896556 DOI: 10.1097/tp.0b013e31829df29d] [Citation(s) in RCA: 562] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cytomegalovirus (CMV) continues to be one of the most common infections after solid-organ transplantation, resulting in significant morbidity, graft loss, and adverse outcomes. Management of CMV varies considerably among transplant centers but has been become more standardized by publication of consensus guidelines by the Infectious Diseases Section of The Transplantation Society. An international panel of experts was reconvened in October 2012 to revise and expand evidence and expert opinion-based consensus guidelines on CMV management, including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues. The following report summarizes the recommendations.
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Affiliation(s)
- Camille N Kotton
- Transplant and Immunocompromised Host Infectious Diseases, Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
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