-
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 -
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 -
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 -
Frontiers in Immunology 2020Defining the optimal dosage of the immunosuppressive or duration of anti-infective agents is a challenge in solid organ transplant (SOT) recipients. We aimed to... (Meta-Analysis)
Meta-Analysis
Defining the optimal dosage of the immunosuppressive or duration of anti-infective agents is a challenge in solid organ transplant (SOT) recipients. We aimed to systematically review the literature regarding the use of T cell mediated immune functional assays (IFAs) for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. We systematically searched PubMed, Scopus, EMBASE, Web of Science (WOS), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to find human interventional studies or study protocols that used either in-house or commercially available IFAs for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. We included six clinical trials and six study protocols. Four out of the six clinical trials used interferon-γ release assays for cytomegalovirus (IGRA-CMV), and five out of the six registered study protocols planned to use IGRA-CMV for adjustment of anti-CMV antiviral (Valganciclovir) prophylaxis or preemptive therapy in SOT recipients. Primary or secondary anti-CMV prophylaxes were discontinued in SOT recipients who had positive IGRA-CMV results without an increase in the rate of CMV infection or reactivation. Among other IFAs, one clinical trial used interferon-γ release assays for tuberculosis (IGRA-TB), and one study used ImmuKnow for adjustment of the duration and dosage of isoniazid and tacrolimus, respectively. Our systematic review supports a promising role for the IGRA-CMVs for adjustment of the duration of anti-CMV antiviral prophylaxis in SOT recipients. There are limited data to support the use of IFAs other than IGRA-CMVs for adjustment of immunosuppressive or anti-infective agents. Further multicenter randomized clinical trials using IFAs other than IGRA-CMVs may help in personalized immunosuppressive or prophylactic anti-infective therapy in SOT recipients.
Topics: Animals; Anti-Infective Agents; Clinical Decision-Making; Disease Management; Humans; Immunoassay; Immunosuppressive Agents; Infection Control; Infections; Organ Transplantation; T-Lymphocytes; Treatment Outcome
PubMed: 33178194
DOI: 10.3389/fimmu.2020.567715