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Naik ND, Elliott J. Mycophenolate Mofetil-Induced Cytomegalovirus Colitis in a Patient With Polymyositis. Cureus 2022; 14:e28848. [PMID: 36225471 PMCID: PMC9536758 DOI: 10.7759/cureus.28848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2022] [Indexed: 11/20/2022] Open
Abstract
As the rate of autoimmune conditions and cancers is increasing in the United States, a larger number of patients are being managed with immunosuppressive medications. Diarrhea is a common problem in immunocompromised patients. A feared complication of immunosuppression is infection with opportunistic pathogens. Cytomegalovirus is an opportunistic infection that can cause infection in a variety of different organ systems, including affecting the gastrointestinal system. Severe infection is most commonly seen as a complication of acquired immunodeficiency syndrome (AIDS), organ transplant, hematological malignancy, or cancer therapy. This case report describes a case of cytomegalovirus colitis in an immunosuppressed patient following mycophenolate mofetil (CellCept) therapy.
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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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Czarnecka P, Czarnecka K, Tronina O, Durlik M. Cytomegalovirus Disease After Liver Transplant-A Description of a Treatment-Resistant Case: A Case Report and Literature Review. Transplant Proc 2018; 50:4015-4022. [PMID: 30577306 DOI: 10.1016/j.transproceed.2018.05.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 05/23/2018] [Indexed: 12/18/2022]
Abstract
Cytomegalovirus (CMV) infection is a common complication in solid organ transplant recipients. In patients receiving immunosuppressive treatment, CMV may lead to life-threatening organ complications or graft loss. We describe a case of 31-year-old CMV-seronegative patient who underwent liver transplant from a CMV-seropositive donor with an early acute resistant rejection of the transplanted organ followed by primary CMV infection, despite prophylaxis, and its severe organ complications. Routine treatment of acute allograft rejection through increasing the base immunosuppression and then administering methylprednisolone infusions did not yield significant therapeutic effect. This resulted in anti-thymocyte globulin and ultimately proteasome inhibitor introduction. The cholestasis remitted and liver parameters improved. But 4 weeks later the patient was admitted again due to incorrect liver function tests. Blood tests revealed high CMV viral load, and primary CMV infection was diagnosed. On diagnosis the patient was treated with ganciclovir (GCV) intravenously. As GCV resistance was suspected based on clinical premises, foscarnet (FOS) and leflunomide (LFM) were implemented with concomitant cautious immunosuppression reduction due to the history of recent graft rejection. Despite aggressive treatment introduction, viral clearance was not obtained. Ultimately the patient died due to respiratory distress resulting from lung fibrosis, most probably owing to CMV diseases with Pneumocystis jiroveci coinfection. The presented case proves the importance of strictly following the rules of prophylaxis, especially in patients with a high risk factor of CMV infection development. A quick diagnosis, implementation of appropriate treatment, and fast reaction to the lack of satisfying therapeutic effect can be the key to a successful treatment.
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Affiliation(s)
- P Czarnecka
- Department of Transplantation Medicine, Nephrology, and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - K Czarnecka
- Department of Transplantation Medicine, Nephrology, and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - O Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - M Durlik
- Department of Transplantation Medicine, Nephrology, and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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Kizilbash SJ, Rheault MN, Bangdiwala A, Matas A, Chinnakotla S, Chavers BM. Infection rates in tacrolimus versus cyclosporine-treated pediatric kidney transplant recipients on a rapid discontinuation of prednisone protocol: 1-year analysis. Pediatr Transplant 2017; 21:10.1111/petr.12919. [PMID: 28371243 PMCID: PMC5423828 DOI: 10.1111/petr.12919] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/17/2017] [Indexed: 12/16/2022]
Abstract
AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients.
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Affiliation(s)
- Sarah J Kizilbash
- Department of Pediatric Nephrology, University of Minnesota, Minneapolis, MN, United States
| | - Michelle N Rheault
- Department of Pediatric Nephrology, University of Minnesota, Minneapolis, MN, United States
| | - Ananta Bangdiwala
- Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States
| | - Arthur Matas
- Department of Transplant Surgery, University of Minnesota, Minneapolis, MN, United States
| | - Srinath Chinnakotla
- Department of Transplant Surgery, University of Minnesota, Minneapolis, MN, United States
| | - Blanche M Chavers
- Department of Pediatric Nephrology, University of Minnesota, Minneapolis, MN, United States
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Efficacy and Safety of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroids in Renal Transplantation: A Japanese Multicenter Study. Transplant Proc 2016; 48:794-8. [DOI: 10.1016/j.transproceed.2015.12.117] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Accepted: 12/30/2015] [Indexed: 11/21/2022]
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Ascha MS, Ascha ML, Hanouneh IA. Management of immunosuppressant agents following liver transplantation: Less is more. World J Hepatol 2016; 8:148-161. [PMID: 26839639 PMCID: PMC4724578 DOI: 10.4254/wjh.v8.i3.148] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/12/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.
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Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus. Case Rep Nephrol 2016; 2016:2736805. [PMID: 26942027 PMCID: PMC4752979 DOI: 10.1155/2016/2736805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 01/17/2016] [Indexed: 11/18/2022] Open
Abstract
Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection.
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Pavlopoulou ID, Poulopoulou S, Melexopoulou C, Papazaharia I, Zavos G, Boletis IN. Incidence and risk factors of herpes zoster among adult renal transplant recipients receiving universal antiviral prophylaxis. BMC Infect Dis 2015. [PMID: 26204926 PMCID: PMC4513398 DOI: 10.1186/s12879-015-1038-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Herpes zoster (HZ) is a significant cause of morbidity and complications in adult renal transplant recipients. We determined the incidence, complications and risk factors for the development of HZ after renal transplantation in a setting using universal antiviral prophylaxis. Methods The medical files of all adult renal transplants, performed between 2004 and 2008, were retrospectively reviewed to assess the clinical characteristics and risk factors of HZ. Incident cases of HZ were determined and the probability of developing post-transplant HZ for all subjects was calculated using the Kaplan Meier method. A multivariable Cox proportional hazards model was applied to assess the risk factors associated with the development of HZ. Results A total of 450 patients were eligible with a median follow up of 38 months. Twenty nine subjects (6.4 %) developed HZ, the median time to onset was 18 months, only three of them (10.3 %) required hospitalization, and none developed disseminated or visceral disease and death directly attributed to zoster. However, high rates of post-herpetic neuralgia (48.7 %) were observed. Overall incidence was calculated at 20.6 cases per 1000 patient-years of follow-up. Following multivariate analysis, increased age ≥ 60 years old, positive pre-transplant history of varicella related disease and administration of rejection treatment conferred an increased risk of 4.00-fold (CI: 1.79- 8.92), 16.00-fold (CI: 4.62- 55.52), and 5.57-fold (CI: 1.56- 19.84) respectively, for the development of post-transplant zoster. Conclusions HZ remains a common complication after renal transplantation in adults under current immunosuppession protocols and universal antiviral prophylaxis. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1038-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ioanna D Pavlopoulou
- Paediatric Research Laboratory, National and Kapodistrian University of Athens, Faculty of Nursing, Athens, Greece.
| | | | - Christina Melexopoulou
- Renal Transplant Unit, "Laiko" General Hospital, National and Kapodistrian University, Faculty of Medicine, Athens, Greece.
| | - Ioanna Papazaharia
- Postgraduate Program, National and Kapodistrian University of Athens, Faculty of Nursing, Athens, Greece.
| | - George Zavos
- Renal Transplant Unit, "Laiko" General Hospital, National and Kapodistrian University, Faculty of Medicine, Athens, Greece.
| | - Ioannis N Boletis
- Renal Transplant Unit, "Laiko" General Hospital, National and Kapodistrian University, Faculty of Medicine, Athens, Greece.
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Yoshimura N, Ushigome H, Akioka K, Nobori S, Suzuki T, Sakai K, Okamoto M. The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients. Clin Exp Nephrol 2012; 17:127-33. [PMID: 23011290 DOI: 10.1007/s10157-012-0669-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Accepted: 07/12/2012] [Indexed: 11/27/2022]
Abstract
BACKGROUND Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore, we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and safe for kidney transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. METHODS A total of 40 living related patients were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and corticosteroids was also employed in this study. RESULTS The 2-year graft survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The rejection rate in the MZR group (25 %) was not significantly higher than that in the MMF group (16 %). Serum creatinine level was not significant between the two groups. The number of patients who developed cytomegalovirus (CMV) disease was 0 (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P < 0.05). The number of patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P < 0.05), respectively. CONCLUSIONS The combination of high-dose MZR with CsA, basiliximab, and corticosteroids can establish not only satisfactory immunosuppression but also a low rate of CMV infection in vivo.
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Affiliation(s)
- Norio Yoshimura
- Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, 465 Hirokoji, Kawaramachi, Kamikyo-ku, Kyoto 602-8566, Japan.
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Florescu DF, Langnas AN, Grant W, Mercer DF, Botha J, Qiu F, Shafer L, Kalil AC. Incidence, risk factors, and outcomes associated with cytomegalovirus disease in small bowel transplant recipients. Pediatr Transplant 2012; 16:294-301. [PMID: 22212495 DOI: 10.1111/j.1399-3046.2011.01628.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Despite improved prophylaxis, monitoring, and more efficient immunosuppression, CMV infection remains a common opportunistic infection in transplant recipients. We assessed the incidence of CMV disease in pediatric SBT recipients, the timing of CMV disease after transplantation, and its impact on patient outcome. The medical records of 98 SBT recipients were reviewed. We performed descriptive analysis, regression analysis, and Kaplan-Meier curves to determine the time-to-event after transplantation. Fifty-three percent patients were male and 47% female, with a mean age of 38.3 months. Thirty-five percent of patients received prophylactic VGC, 55% GCV, 10% a combination of GCV/VGC, and 99% CMV immunoglobulins. A total of 24.5% recipients were CMV D+/R- (CMV serostatus donor positive/recipient negative). Seven (c. 7%) patients developed CMV disease. CMV disease was associated with 2.5 times (0.52-12.1; p = 0.25) higher rate of CMV mismatch and 11.1 times (1.3-95.9; p = 0.03) higher risk of death. CMV prophylaxis increased time-to-death (p = 0.074). Time-to-CMV disease was shorter in patients with enteritis (p < 0.0001), and CMV disease was associated with shorter time-to-death after transplantation (p = 0.001). CMV disease in SBT recipients was associated with an 11-fold mortality increase and a fourfold faster time-to-death. Time-to-death was significantly shorter with CMV enteritis.
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Affiliation(s)
- D F Florescu
- Infectious Diseases Division, Transplant Infectious Diseases Program, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5400, USA.
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Bhadauria D, Sharma RK, Kaul A, Prasad N, Gupta A, Gupta A, Srivastava A. Cytomegalovirus disease in renal transplant recipients: a single-center experience. Indian J Microbiol 2012; 52:510-5. [PMID: 23997350 DOI: 10.1007/s12088-012-0268-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Accepted: 03/17/2012] [Indexed: 12/19/2022] Open
Abstract
Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively reviewed 521 live related kidney transplant recipients at our institute. 74 (14.2 %) live related allograft recipients developed CMV disease after a median interval of 7.18 ± 4.35 months from transplantation. The mean age was 36.15 ± 10.7 years. 63 of the patients were male. Malaise, fever and diarrhea were among most common symptoms. 20 (27.02 %) of the 74 recipients developed transaminitis, 13 (17.2 %) developed CMV gastritis, 5 (9.13 %) recipients developed pneumonia, and 3 (4.05 %) patient developed colitis. 59 (80 %) patients had leucopenia and 41 (56.5 %) developed thrombocytopenia. Mean serum creatinine level was 1.5 ± 0.4 (0.9-2.4) mg/dl before the disease, 1.9 ± 0.6 (1.3-3.6) mg/dl at the time of the diagnosis, and 1.7 ± 0.06 (0.8-4.2) mg/dl at the end of the treatment. CMV disease developed in 9 (36 %) of recipients who received basiliximab as induction therapy and 13 (30.24 %) of recipients who received ATG (p > 0.05). The incidence of CMV disease was similar in cyclosporine based regimen (13.2 %) and Tacrolimus based regimen 27 (16.16 %) (p = 0.137) and was also similar in Azathioprine 41 (9.5 %) and MMF group 33 (14.3 %) (p = 0.163). There was no significant difference in severity of CMV disease in both groups, except a higher incidence of leucopenia in Azathioprine group (86 vs. 74 %, p < 0.05) as compared to MMF group. 51 (68.91 %) patient developed graft dysfunction during CMV disease. In conclusion we report a low incidence (14.2 %) and milder form of cytomegalovirus disease at our center. Use of universal cytomegalovirus prophylaxis was associated with a low incidence and milder form of the disease. Incidence of CMV disease was similar between Azathioprine and MMF groups.
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Affiliation(s)
- Dharmendra Bhadauria
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, India
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Pantanelli SM, Khalifa YM. Cytomegalovirus colitis and viremia from mycophenolate mofetil monotherapy in birdshot chorioretinopathy. Ocul Immunol Inflamm 2011; 19:450-2. [PMID: 22106917 DOI: 10.3109/09273948.2011.611961] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To describe a case of cytomegalovirus (CMV) viremia and colitis in a patient on mycophenolate mofetil (MMF) monotherapy for birdshot chorioretinopathy. DESIGN Case report. METHODS Retrospective chart review. RESULTS Treatment with MMF 1.5 g twice daily for 5 years led to leucopenia and a CD4 count of 299, which resulted in active CMV infection. CONCLUSIONS Treatment with MMF alone may put otherwise immune-competent individuals at risk for opportunistic CMV infection. Greater awareness of this association may allow for better monitoring, earlier detection, and treatment of future cases.
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Chacko B, John GT. Leflunomide for cytomegalovirus: bench to bedside. Transpl Infect Dis 2011; 14:111-20. [PMID: 22093814 DOI: 10.1111/j.1399-3062.2011.00682.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Revised: 05/02/2011] [Accepted: 08/04/2011] [Indexed: 11/27/2022]
Abstract
Cytomegalovirus (CMV) remains a major cause of morbidity and mortality among transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo. Data are emerging about its potential role in ganciclovir-sensitive and -resistant CMV, primarily by virtue of a unique mechanism inhibiting virion assembly, as opposed to inhibition of viral DNA synthesis by current agents. This review aims to put in perspective, the knowledge acquired in the last decade or so on leflunomide for CMV. Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource-poor setting, is economical. Although the data presented here are not from randomized trials, several relevant observations have been made that could influence future, more structured assessments of the drug. An immune suppressive compound with antiviral features and experimental activity in chronic rejection is an attractive combination for organ transplantation, and it appears that leflunomide may just fit that niche.
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Affiliation(s)
- B Chacko
- Department of Nephrology, St. Johns Medical College Hospital, Bangalore, India.
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Erdbruegger U, Scheffner I, Mengel M, Schwarz A, Verhagen W, Haller H, Gwinner W. Impact of CMV infection on acute rejection and long-term renal allograft function: a systematic analysis in patients with protocol biopsies and indicated biopsies. Nephrol Dial Transplant 2011; 27:435-43. [PMID: 21712490 DOI: 10.1093/ndt/gfr306] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Higher rates of acute rejection (AR) and reduced graft survival have been reported in patients with cytomegalovirus (CMV) infection, but an association between these factors remains controversial. METHODS In this study, serial protocol biopsies (PBs) and clinically indicated biopsies (IBs) from a large cohort of renal allograft recipients (n ¼ 594) were analyzed to examine the relation between CMV and AR. RESULTS Patients with CMV were more likely to receive IB (85 of the 153 patients; 56%) compared to patients without CMV (138 of 441 patients; 32%; P = 0.003). However, this did not translate into a greater number of patients with episodes of acute cellular rejection on histopathology in IBs. Analysis of PBs revealed a significantly higher number of episodes of rejection per patient with CMV infection (P = 0.04), but only in a subgroup of patients with triple immunosuppression. Long-term graft function post-transplantation was analyzed in four different subgroups according to CMV infection and/or AR. Differences in renal function were apparent within the first 6 weeks after transplantation and persisted during follow-up, with the best renal function in patients without AR or CMV, whereas patients with both AR and CMV had the worst (P < 0.012 at 1 year; P < 0.001 at 2 years). On average, the latter group had significantly older donors and more often delayed graft function. CONCLUSIONS Our data suggests that the link between CMV and AR is far less significant than previously thought. Outcome in patients with CMV may be more determined by coexisting conditions like high donor age and delayed graft function.
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Affiliation(s)
- Uta Erdbruegger
- Division of Nephrology and Hypertension, University of Virginia, Charlottesville, VA, USA.
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15
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Mustapic Z, Basic-Jukic N, Kes P, Lovcic V, Bubic-Filipi L, Mokos I, Kastelan Z, Zekan S. Varicella zoster infection in renal transplant recipients: prevalence, complications and outcome. Kidney Blood Press Res 2011; 34:382-6. [PMID: 21654179 DOI: 10.1159/000328730] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2010] [Accepted: 04/13/2011] [Indexed: 01/20/2023] Open
Abstract
Varicella zoster virus (VZV) is an important pathogen after renal transplantation. In the present study, we examined the prevalence, clinical presentation and outcome of VZV infections in renal transplant recipients. Charts and medical records of adult renal allotransplant recipients were investigated to find patients with VZV infection. From December 1972 until July 2010, 1,139 patients received kidney allograft at our institution. VZV infection was diagnosed in 40 patients (3.51%). 28 patients (70%) had intensified immunosuppression prior to VZV infection occurrence. Median time of onset was 2.13 years after transplantation (range 9 days to 19.2 years). 35 patients developed VZV during the first post-transplant year (median 0.61 years). Four patients developed VZV infection more than 12 years after transplantation. 33 patients (82.5%) had dermatomal distribution, 5 (12.5%) disseminated herpes zoster (HZ), and 2 patients (5%) who were VZV IgG-negative before transplantation, developed chickenpox. Immunosuppression was reduced and patients received acyclovir. Cutaneous scarring was recorded in 7 cases (17.5%). Two patients developed post-herpetic neuralgia, which was accompanied by scarring and skin depigmentation in 1 of them. Five patients (12.5%) experienced relapse of HZ. Timely initiation of therapy may prevent development of complications and the visceral form of disease. Based on our experience with development of chickenpox, we suggest active immunization for all seronegative patients before organ transplantation.
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Affiliation(s)
- Z Mustapic
- Department of Nephrology, Arterial Hypertension and Dialysis, Clinical Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia
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Ponticelli C. Herpes viruses and tumours in kidney transplant recipients. The role of immunosuppression. Nephrol Dial Transplant 2011; 26:1769-75. [DOI: 10.1093/ndt/gfr157] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Weclawiak H, Kamar N, Mengelle C, Esposito L, Mohamed AO, Lavayssiere L, Ribes D, Cointault O, Nogier MB, Cardeau-Desangles I, Izopet J, Rostaing L. Pre-emptive intravenous ganciclovir versus valganciclovir prophylaxis for de novo cytomegalovirus-seropositive kidney-transplant recipients. Transpl Int 2010; 23:1056-64. [DOI: 10.1111/j.1432-2277.2010.01101.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Fortun J, Martin-Davila P, Pascual J, Cervera C, Moreno A, Gavalda J, Aguado J, Pereira P, Gurguí M, Carratala J, Fogueda M, Montejo M, Blasco F, Bou G, Torre-Cisneros J. Immunosuppressive therapy and infection after kidney transplantation. Transpl Infect Dis 2010; 12:397-405. [DOI: 10.1111/j.1399-3062.2010.00526.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Ritter ML, Pirofski L. Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity. Transpl Infect Dis 2009; 11:290-7. [PMID: 19497072 DOI: 10.1111/j.1399-3062.2009.00407.x] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Mycophenolate mofetil (MMF) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. MMF is an inhibitor of inosine-5'-monophosphate, and is able to preferentially inhibit B-cell and T-cell function. The immunosuppressive abilities of MMF have made it one of the most successful anti-rejection drugs in transplant patients, but patients also appear to have increased susceptibility to infections, specifically cytomegalovirus and BK virus. Despite its association with an increased risk of infection, MMF has also exhibited antimicrobial activity against pathogens including hepatitis C, Pneumocystis jirovecii, and human immunodeficiency virus. A thorough understanding of the functions of MMF on the immune system and interaction with infectious pathogens could be helpful in implementing preventative strategies against opportunistic infections in transplant patients.
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Affiliation(s)
- M L Ritter
- Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA
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Swaminathan S, Kelley P, Ahern M, Gordon D. Acute cytomegalovirus infection presenting with severe vulvar swelling. Int J Gynaecol Obstet 2007; 99:133-4. [PMID: 17612541 DOI: 10.1016/j.ijgo.2007.04.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2007] [Revised: 04/24/2007] [Accepted: 04/24/2007] [Indexed: 11/28/2022]
Affiliation(s)
- S Swaminathan
- Department of Immunology, Allergy and Arthritis, Flinders Medical Centre, Adelaide, Australia
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