-
Transplantation Direct Aug 2023The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior...
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.
UNLABELLED
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 ( > 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.
PubMed: 37456587
DOI: 10.1097/TXD.0000000000001514 -
American Journal of Transplantation :... Oct 2008The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies... (Review)
Review
The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (
valganciclovir prophylaxis, the incidence of late-onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy. Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Diseases; Kidney Transplantation; Liver Diseases; Liver Transplantation; Risk; Time Factors; Transplantation Immunology; Treatment Outcome; Valganciclovir; Virology
PubMed: 18828771
DOI: 10.1111/j.1600-6143.2008.02369.x -
Journal of Pharmacy & Pharmaceutical... 2017Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety of low-dose versus high-dose valganciclovir prophylaxis in renal transplantation recipients.
METHODS
An electronic search was conducted up to November 29, 2016. The primary outcomes were incidences of CMV, CMV disease, mortality and opportunistic infection. The second outcomes were acute rejection, allograft loss, adverse drug reaction (ADR).
RESULTS
7 cohort studies, all with high quality involving (1431 patients) were included. There was no significant difference of the incidence of following CMV disease (1271 patients, odds ratio [OR] 0.74, 95% confidence interval [CI], 0.38-1.43, p=0.36), acute rejection (1343 patients, OR 0.77, 95%CI 0.53-1.14, p=0.19), allograft loss (1271 patients, OR 0.64, 95%CI 0.31-1.35, p=0.24), mortality (1271 patients, OR 0.55, 95%CI 0.20-1.47, p=0.23) and opportunistic infections (OI) (985 patients, OR 0.76, 95%CI 0.52-1.10, p=0.14) between the low-dose and the high-dose valganciclovir prophylaxis. And no significant difference was observed for premature valganciclovir discontinuation (1010 patients, OR 0.81, 95%CI 0.52-1.25, p=0.33) and the incidence of leukopenia (1082 patients, OR 0.65, 95%CI 0.34-1.22, p=0.18) between the two regimens.
CONCLUSION
450 mg and 900 mg doses of valganciclovir are equipotent for CMV universal prophylaxis. CMV 450 mg prophylaxis should be used for renal transplant recipients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Ganciclovir; Humans; Kidney Transplantation; Valganciclovir
PubMed: 28719361
DOI: 10.18433/J3805B -
Clinical Transplantation Jan 2024Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients... (Review)
Review
BACKGROUND
Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID).
METHODS
We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs.
RESULTS
Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).
CONCLUSIONS
The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
Topics: Humans; Kidney Transplantation; Cytomegalovirus; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases
PubMed: 38063324
DOI: 10.1111/ctr.15218 -
Liver Transplantation : Official... Dec 2012Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of... (Meta-Analysis)
Meta-Analysis Review
Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Humans; Leukopenia; Liver Transplantation; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir
PubMed: 22887929
DOI: 10.1002/lt.23530 -
Frontiers in Cellular and Infection... 2022Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Antiviral Agents in Preventing Allograft Rejection Following CMV Prophylaxis in High-Risk Kidney Transplantation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant patients. However, data on the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank CMV prophylaxis agents for allograft rejection prevention following CMV prophylaxis in high-risk kidney transplant patients according to their efficacy and safety. We conducted searches on the MEDLINE, Embase, SCOPUS, and CENTRAL databases, as well as the reference lists of selected studies up to December 2021, for published and peer-reviewed randomized controlled trials assessing the efficacy of CMV prophylaxis agents in high-risk kidney transplant patients. Thirteen studies were independently selected by three reviewers and included post-kidney transplant patients indicated for CMV prophylaxis who had been randomized to receive prophylactic antiviral agents or standard of care. The reviewers independently extracted data from the included studies, and direct and network meta-analyses were applied to assess the study outcomes. The probability of efficacy and safety was evaluated, and the drugs were assigned a numerical ranking. We evaluated the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome was an incidence of biopsy-proven acute rejection, whereas the secondary outcome was a composite of major adverse drug reactions. Each outcome referred to the definition provided in the original studies. Valganciclovir, valacyclovir, and ganciclovir were identified to significantly decrease the incidence of biopsy-proven acute rejection with pooled risk differences (RDs) of -20.53% (95% confidence interval [CI] = -36.09% to -4.98%), -19.3% (95% CI = -32.7% to -5.93%), and -10.4% (95% CI = -19.7% to -0.12%), respectively. The overall major adverse drug reaction was 5.7% without a significant difference when compared with placebo. Valganciclovir had the best combined efficacy and safety among the examined antiviral agents and was the most effective and safest antiviral agent overall for allograft rejection prevention following CMV prophylaxis. Valacyclovir was the optimal alternative antiviral agent for patients who were unable to tolerate intravenous ganciclovir or access oral valganciclovir as financial problem. However, compliance and dose-related toxicities should be closely monitored.
Topics: Allografts; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir
PubMed: 35433502
DOI: 10.3389/fcimb.2022.865735 -
Microorganisms Jun 2021Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term... (Review)
Review
BACKGROUND
Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients.
OBJECTIVE
We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels.
METHODS
A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible.
RESULTS
Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established.
CONCLUSIONS
Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.
PubMed: 34203932
DOI: 10.3390/microorganisms9061304 -
Transplant International : Official... Dec 2021Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta-analysis.
Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral-agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral-agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of -0.36 (-0.54, -0.18) and -0.28 (-0.48, -0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of -0.25 (-0.32, -0.19) and -0.30 (-0.37, -0.22) for CMV infection and -0.26 (-0.40, -0.12) and -0.22 (-0.31, -0.12) for CMV disease. For subgroup analysis by seropositive-donor and seronegative-recipient (D+/R-), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of -0.42 (-0.84, -0.01) and -0.35 (-0.60, -0.12). For pre-emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of -0.33 (-0.47, -0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis
PubMed: 34580930
DOI: 10.1111/tri.14122 -
Annals of Internal Medicine Jun 2015Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States.
PURPOSE
To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs.
DATA SOURCES
MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information.
STUDY SELECTION
English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments.
DATA EXTRACTION
Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus.
DATA SYNTHESIS
Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence).
LIMITATION
Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality.
CONCLUSION
Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.
Topics: Adult; Antiviral Agents; Cognitive Behavioral Therapy; Complementary Therapies; Counseling; Encephalomyelitis; Exercise Therapy; Fatigue Syndrome, Chronic; Humans; Immunologic Factors; Myalgia; Poly I-C; Poly U; Quality of Life
PubMed: 26075755
DOI: 10.7326/M15-0114 -
American Journal of Transplantation :... Feb 2015We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing... (Comparative Study)
Comparative Study Meta-Analysis Review
We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I(2) = 87%; 16 studies, n = 1581) and 7% with PE (95% CI: 3-10; I(2) = 84%; 16 studies, n = 875) (mean difference 2.6; 95% CI: -3.25 to 8.45, p = 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.
Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Liver Diseases; Liver Transplantation; Male; Middle Aged; Risk Assessment; Survival Rate; Valganciclovir
PubMed: 25522141
DOI: 10.1111/ajt.13044