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Clinical Journal of the American... Aug 2017The objective of this meta-analysis is to compare the incidences of cytomegalovirus and BK polyoma virus infections in renal transplant recipients receiving a mammalian... (Meta-Analysis)
Meta-Analysis Review
CMV and BKPyV Infections in Renal Transplant Recipients Receiving an mTOR Inhibitor-Based Regimen Versus a CNI-Based Regimen: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials.
BACKGROUND AND OBJECTIVES
The objective of this meta-analysis is to compare the incidences of cytomegalovirus and BK polyoma virus infections in renal transplant recipients receiving a mammalian target of rapamycin inhibitor (mTOR)-based regimen compared with a calcineurin inhibitor-based regimen.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a comprehensive search for randomized, controlled trials up to January of 2016 addressing our objective. Other outcomes included acute rejection, graft loss, serious adverse events, proteinuria, wound-healing complications, and eGFR. Two review authors selected eligible studies, abstracted data, and assessed risk of bias. We assessed quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology.
RESULTS
We included 28 randomized, controlled trials with 6211 participants classified into comparison 1: mTOR inhibitor versus calcineurin inhibitor and comparison 2: mTOR inhibitor plus reduced dose of calcineurin inhibitor versus regular dose of calcineurin inhibitor. Results showed decreased incidence of cytomegalovirus infection in mTOR inhibitor-based group in both comparison 1 (risk ratio, 0.54; 95% confidence interval, 0.41 to 0.72), with high quality of evidence, and comparison 2 (risk ratio, 0.43; 95% confidence interval, 0.24 to 0.80), with moderate quality of evidence. The available evidence neither confirmed nor ruled out a reduction of BK polyoma virus infection in mTOR inhibitor-based group in both comparisons. Secondary outcomes revealed more serious adverse events and acute rejections in mTOR inhibitor-based group in comparison 1 and no difference in comparison 2. There was no difference in graft loss in both comparisons. eGFR was higher in the mTOR inhibitor-based group in comparison 1 (mean difference =4.07 ml/min per 1.73 m; 95% confidence interval, 1.34 to 6.80) and similar to the calcineurin inhibitor-based group in comparison 2. More proteinuria and wound-healing complications occurred in the mTOR inhibitor-based groups.
CONCLUSIONS
We found moderate- to high-quality evidence of reduced risk of cytomegalovirus infection in renal transplant recipients in the mTOR inhibitor-based compared with the calcineurin inhibitor-based regimen. Our review also suggested that a combination of a mTOR inhibitor and a reduced dose of calcineurin inhibitor may be associated with similar eGFR and rates of acute rejections and serious adverse events compared with a standard calcineurin inhibitor-based regimen at the expense of higher incidence of proteinuria and wound-healing complications.
Topics: Adult; BK Virus; Calcineurin Inhibitors; Chi-Square Distribution; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Odds Ratio; Opportunistic Infections; Polyomavirus Infections; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; TOR Serine-Threonine Kinases; Time Factors; Treatment Outcome; Tumor Virus Infections
PubMed: 28576905
DOI: 10.2215/CJN.13221216 -
Transplant Infectious Disease : An... Aug 2019There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the...
BACKGROUND
There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the literature have been limited by methodology or by the scope of patients included.
STUDY DESIGN AND METHODS
Systematic Review (Prospero # CRD42018088524).
SETTING & POPULATION
Patients without kidney transplant who had biopsy-proven BKVN.
SELECTION CRITERIA FOR STUDIES
Full-text articles that describe native BKVN patient cases.
ANALYTICAL APPROACH
Descriptive synthesis.
RESULTS
The search identified 630 unique articles of which 51 were included in the final review. Sixty-five cases (including two new cases presented in this review) were identified, all but one occurred in the setting of known immunosuppression.
LIMITATIONS
The primary limitation was the exclusion of studies that did not fulfill the stringent review criteria. We excluded reports with only a clinical diagnosis of BKVN, such as those with viruria and/or viremia without biopsy.
CONCLUSIONS
As of May 2018, there are 65 reported cases of BKVN in native kidneys. This represents the most comprehensive description of biopsy-proven BKVN in native kidneys to date. Evaluation for BK nephropathy should be considered in immunocompromised patients who exhibit unexplained renal failure.
Topics: Adult; Aged; BK Virus; Biopsy; Humans; Immunocompromised Host; Immunosuppression Therapy; Kidney; Kidney Diseases; Kidney Transplantation; Male; Polyomavirus Infections; Tumor Virus Infections; Viremia
PubMed: 30907978
DOI: 10.1111/tid.13083 -
Exercise Immunology Review 2022There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public... (Meta-Analysis)
Meta-Analysis
There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public health advice on the potential benefits of physical activity for immunity. Here, we carried out a meta-analysis of studies of the effects of moderate exercise (ME) and exercise until fatigue (EF) on symptom severity, morbidity and mortality during viral infection in animal models. The systematic review on PubMed, Scopus, Embase, Web of Science, Cochrane and EBSCOhost (CINAHL and SPORT Discus) identified 8 controlled studies, with 15 subgroups within them. The studies exposed the animals (mice [7 studies] and monkeys [1 study]) to exercise immediately before or after viral inoculation (HSV-1, H1N1 influenza and B.K. virus) with follow-up for 21 days. ME significantly reduced morbidity (OR 0.43 [0.19; 0.98], P = 0.04) with no change for symptom severity (SMD -3.37 [-9.01; 2.28], P = 0.24) or mortality (OR 0.48 [0.08;3.03], P = 0.43). In contrast, EF gave a trend towards increased symptom severity (SMD 0.96 [-0.06; 1.98], P = 0.07) and mortality (OR 1.47 [0.96;2.28], P =0.08) with no change in morbidity (OR 1.22 [0.60;2.5], P = 0.58). We conclude that in animals moderate exercise during infection is advantageous, whilst exercise until fatigue should be avoided. Further research is required to determine if moderate exercise may also be beneficial in humans during infection.
Topics: Animals; Exercise Therapy; Fatigue; Humans; Influenza A Virus, H1N1 Subtype; Mice; Morbidity; Virus Diseases
PubMed: 35913495
DOI: No ID Found -
Journal of Clinical Virology : the... Jul 2021BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is... (Meta-Analysis)
Meta-Analysis
BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is reduction of the immunosuppressive load which increases the risk of kidney transplant rejection. There is no biomarker to monitor BKV activity besides BK viral load. The value of the Enzyme-Linked Immunosorbent Spot (ELISPOT) assay as a tool to monitor the recipient's anti-BKV immune response after transplantation was investigated systematically. Electronic databases, including MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for studies of ELISPOT evaluating the immune response against BKV. BKV status was categorized as "active BKV infection" and as "resolving BKV infection". Random-effects model meta-analysis was performed to determine the diagnostic performance of the ELISPOT assay, after stratifying patients into groups based on positive and negative ELISPOT results. One-hundred twenty-seven articles were identified of which nine were included. Patients with negative ELISPOT had an increased risk of having active BKV replication (odds ratio of 71.9 (95%-CI 31.0-167.1). Pooled sensitivity was 0.95 (95%-CI 0.89-0.98) and specificity was 0.88 (95%-CI 0.78-0.94). The standardized mean difference of the number of IFN-γ producing cells between patients with active BKV infection compared with patients who had resolving BKV infection was -2.09 (95%-CI -2.50, -1.68). The ELISPOT assay is a useful tool for BKV risk assessment and in combination with BKV load may support clinicians in guiding immunosuppressive therapy in patients with BKV replication.
Topics: BK Virus; Enzyme-Linked Immunospot Assay; Humans; Immunity; Immunosorbents; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 33979739
DOI: 10.1016/j.jcv.2021.104848 -
The Cochrane Database of Systematic... Sep 2014Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after transplantation is associated with complications. Steroids have adverse effects on cardiovascular risk factors such as hypertension, hyperglycaemia or hyperlipidaemia, increase risk of infection, obesity, cataracts, myopathy, bone metabolism alterations, dermatologic problems and cushingoid appearance. Whether avoiding steroids changes outcomes is unclear.
OBJECTIVES
We aimed to assess the safety and efficacy of steroid early withdrawal (treatment for less than 14 days after transplantation), late withdrawal (after 14 days after transplantation) or steroid avoidance in patients receiving a pancreas (including a vascularized organ) alone (PTA), simultaneous with a kidney (SPK) or after kidney transplantation (PAK).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (to 18 June 2014) through contact with the Trials' Search Co-ordinator. We handsearched: reference lists of nephrology textbooks, relevant studies, recent publications and clinical practice guidelines; abstracts from international transplantation society scientific meetings; and sent emails and letters seeking information about unpublished or incomplete studies to known investigators.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or cohort studies of steroid avoidance (including early withdrawal) versus steroid maintenance or versus late withdrawal in pancreas or pancreas with kidney transplant recipients. We defined steroid avoidance as complete avoidance of steroid immunosuppression, early steroid withdrawal as steroid treatment for less than 14 days after transplantation and late withdrawal as steroid withdrawal after 14 days after transplantation.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the retrieved titles and abstracts, and where necessary the full text reports to determine which studies satisfied the inclusion criteria. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Cohort studies were not meta-analysed, but their findings summarised descriptively.
MAIN RESULTS
Three RCTs enrolling 144 participants met our inclusion criteria. Two compared steroid avoidance versus late steroid withdrawal and one compared late steroid withdrawal versus steroid maintenance. All studies included SPK and only one also included PTA. All studies had an overall moderate risk of bias and presented only short-term results (six to 12 months). Two studies (89 participants) compared steroid avoidance or early steroid withdrawal versus late steroid withdrawal. There was no clear evidence of an impact on mortality (2 studies, 89 participants: RR 1.64, 95% CI 0.21 to 12.75), risk of kidney loss censored for death (2 studies, 89 participants: RR 0.35, 95% CI 0.04 to 3.09), risk of pancreas loss censored for death (2 studies, 89 participants: RR 1.05, 95% CI 0.36 to 3.04), or acute kidney rejection (1 study, 49 participants: RR 2.08, 95% CI 0.20 to 21.50), however results were uncertain and consistent with no difference or important benefit or harm of steroid avoidance/early steroid withdrawal. The study that compared late steroid withdrawal versus steroid maintenance observed no deaths, no graft loss or acute kidney rejection at six months in either group and reported uncertain effects on acute pancreas rejection (RR 0.88, 95% CI 0.06 to 13.35). Of the possible adverse effects only infection was reported by one study. There were significantly more UTIs reported in the late withdrawal group compared to the steroid avoidance group (1 study, 25 patients: RR 0.41, 95% CI 0.26 to 0.66).We also identified 13 cohort studies and one RCT which randomised tacrolimus versus cyclosporin. These studies in general showed that steroid-sparing and withdrawal strategies had benefits in lowering HbAc1 and risk of infections (BK virus and CMV disease) and improved blood pressure control without increasing the risk of rejection. However, two studies found an increased incidence of acute pancreas rejection (HR 2.8, 95% CI 0.89 to 8.81, P = 0.066 in one study and 43.3% in the steroid withdrawal group versus 9.3% in the steroid maintenance, P < 0.05 at three years in the other) and one study found an increased incidence of acute kidney rejection (18.7% in the steroid withdrawal group versus 2.8% in the steroid maintenance, P < 0.05) at three years.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence for the benefits and harms of steroid withdrawal in pancreas transplantation in the three RCTs (144 patients) identified. The results showed uncertain results for short-term risk of rejection, mortality, or graft survival in steroid-sparing strategies in a very small number of patients over a short period of follow-up. Overall the data was sparse, so no firm conclusions are possible. Moreover, the 13 observational studies findings generally concur with the evidence found in the RCTs.
Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Middle Aged; Pancreas Transplantation; Randomized Controlled Trials as Topic; Steroids; Withholding Treatment
PubMed: 25220222
DOI: 10.1002/14651858.CD007669.pub2 -
Hepatology Communications Jul 2022Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have... (Meta-Analysis)
Meta-Analysis
Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
Topics: Adult; Carcinoma, Hepatocellular; Hepatectomy; Hepatitis B; Hepatitis C; Humans; Liver Neoplasms; Survival Analysis
PubMed: 35234371
DOI: 10.1002/hep4.1923 -
JHEP Reports : Innovation in Hepatology Jan 2023The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This...
BACKGROUND & AIMS
The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.
METHODS
We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.
RESULTS
The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity ( = 54%, <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity ( = 0.00%, = 1.00).
CONCLUSIONS
Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.
IMPACT AND IMPLICATIONS
Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
PubMed: 36466989
DOI: 10.1016/j.jhepr.2022.100617 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
The Cochrane Database of Systematic... Jan 2017Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non-depleting interleukin-2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte-depleting antibodies but the relative benefits and harms of the available agents are uncertain.
OBJECTIVES
We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e.g. children and sensitised recipients).
SEARCH METHODS
Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI).
MAIN RESULTS
We included 99 studies (269 records; 8956 participants; 33 with contemporary agents). Methodology was incompletely reported in most studies leading to lower confidence in the treatment estimates.Antithymocyte globulin (ATG) prevented acute graft rejection (17 studies: RR 0.63, 95% CI 0.51 to 0.78). The benefits of ATG on graft rejection were similar when used with (12 studies: RR 0.61, 0.49 to 0.76) or without (5 studies: RR 0.65, 0.43 to 0.98) calcineurin inhibitor (CNI) treatment. ATG (with CNI therapy) had uncertain effects on death (3 to 6 months, 3 studies: RR 0.41, 0.13 to 1.22; 1 to 2 years, 5 studies: RR 0.75, 0.27 to 2.06; 5 years, 2 studies: RR 0.94, 0.11 to 7.81) and graft loss (3 to 6 months, 4 studies: RR 0.60, 0.34 to 1.05; 1 to 2 years, 3 studies: RR 0.65, 0.36 to 1.19). The effect of ATG on death-censored graft loss was uncertain at 1 to 2 years and 5 years. In non-CNI studies, ATG had uncertain effects on death but reduced death-censored graft loss (6 studies: RR 0.55, 0.38 to 0.78). When CNI and older non-CNI studies were combined, a benefit was seen with ATG at 1 to 2 years for both all-cause graft loss (7 studies: RR 0.71, 0.53 to 0.95) and death-censored graft loss (8 studies: RR 0.55, 0.39 to 0.77) but not sustained longer term. ATG increased cytomegalovirus (CMV) infection (6 studies: RR 1.55, 1.24 to 1.95), leucopenia (4 studies: RR 3.86, 2.79 to 5.34) and thrombocytopenia (4 studies: RR 2.41, 1.61 to 3.61) but had uncertain effects on delayed graft function, malignancy, post-transplant lymphoproliferative disorder (PTLD), and new onset diabetes after transplantation (NODAT).Alemtuzumab was compared to ATG in six studies (446 patients) with early steroid withdrawal (ESW) or steroid minimisation. Alemtuzumab plus steroid minimisation reduced acute rejection compared to ATG at one year (4 studies: RR 0.57, 0.35 to 0.93). In the two studies with ESW only in the alemtuzumab arm, the effect of alemtuzumab on acute rejection at 1 year was uncertain compared to ATG (RR 1.27, 0.50 to 3.19). Alemtuzumab had uncertain effects on death (1 year, 2 studies: RR 0.39, 0.06 to 2.42; 2 to 3 years, 3 studies: RR 0.67, 95% CI 0.15 to 2.95), graft loss (1 year, 2 studies: RR 0.39, 0.13 to 1.30; 2 to 3 years, 3 studies: RR 0.98, 95% CI 0.47 to 2.06), and death-censored graft loss (1 year, 2 studies: RR 0.38, 0.08 to 1.81; 2 to 3 years, 3 studies: RR 2.45, 95% CI 0.67 to 8.97) compared to ATG. Creatinine clearance was lower with alemtuzumab plus ESW at 6 months (2 studies: MD -13.35 mL/min, -23.91 to -2.80) and 2 years (2 studies: MD -12.86 mL/min, -23.73 to -2.00) compared to ATG plus triple maintenance. Across all 6 studies, the effect of alemtuzumab versus ATG was uncertain on all-cause infection, CMV infection, BK virus infection, malignancy, and PTLD. The effect of alemtuzumab with steroid minimisation on NODAT was uncertain, compared to ATG with steroid maintenance.Alemtuzumab plus ESW compared with triple maintenance without induction therapy had uncertain effects on death and all-cause graft loss at 1 year, acute rejection at 6 months and 1 year. CMV infection was increased (2 studies: RR 2.28, 1.18 to 4.40). Treatment effects were uncertain for NODAT, thrombocytopenia, and malignancy or PTLD.Rituximab had uncertain effects on death, graft loss, acute rejection and all other adverse outcomes compared to placebo.
AUTHORS' CONCLUSIONS
ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non-CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection.In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes (reduced death or lower toxicity) do not appear to be improved.
Topics: Acute Disease; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Calcineurin Inhibitors; Cytomegalovirus Infections; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Muromonab-CD3; Randomized Controlled Trials as Topic; Receptors, Interleukin-2; Steroids
PubMed: 28073178
DOI: 10.1002/14651858.CD004759.pub2 -
International Journal of Organ... 2011The standard treatment of antibody-mediated rejection (AMR) consists of antilymphocyte antibody, intravenous immunoglobulin, and plasmapheresis. This treatment is...
BACKGROUND
The standard treatment of antibody-mediated rejection (AMR) consists of antilymphocyte antibody, intravenous immunoglobulin, and plasmapheresis. This treatment is associated with a high rate of resistance and refractory AMR. Recent interest has focused on use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody.
OBJECTIVE
We conducted a systematic review and meta-analysis of studies of RTX in AMR of the renal allograft.
METHODS
Combining two comprehensive search themes (AMR and RTX), we searched electronic databases from 1969 through 2010, supplemented by a manual review of abstracts from nephrology and transplant meetings, and reference lists of review articles. All studies evaluating explicit response of patients with AMR to RTX were included. The outcome was pooled odds ratio (OR) of response to RTX.
RESULTS
A total of 114 studies were identified, 94 of which were excluded on initial screening. Analysis of the 10 studies (249 patients) showed an OR of 3.16 (95% CI: 1.75-5.70) for response to RTX. Reported adverse effects included BK virus nephropathy, cytomegalovirus (CMV) viremia, pneumonia, herpes zoster, and septic shock.
CONCLUSION
This study suggests that RTX is a reasonable therapeutic option in the treatment of AMR. Further randomized studies are necessary to establish its efficacy and safety.
PubMed: 25013595
DOI: No ID Found