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Frontiers in Immunology 2023IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence.
METHODS
We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included.
RESULTS
Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19).
CONCLUSIONS
This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.
Topics: Humans; Male; Glomerulonephritis, IGA; Kidney Transplantation; Risk Factors; Kidney Failure, Chronic; Mycophenolic Acid
PubMed: 38090563
DOI: 10.3389/fimmu.2023.1277017 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Zeitschrift Fur Rheumatologie Nov 2023The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment for lupus nephritis (LN).
METHODS
Meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of tacrolimus and MMF as induction therapy for LN. We systematically reviewed RCTs and prospective cohort studies with a tacrolimus dose of 3 mg daily and performed a meta-analysis of the efficacy and safety of tacrolimus as an induction treatment for LN in comparison to MMF.
RESULTS
The inclusion criteria were satisfied by eight studies (five RCTs and three prospective cohort studies) with a total of 408 individuals (289 for tacrolimus vs. MMF and 119 for low-dose tacrolimus). Tacrolimus and MMF had similar complete remission rates (odds ratio [OR] 1.028; 95% confidence interval [CI] 0.589-1.796; p = 0.922). The partial remission rate did not differ between the tacrolimus and MMF groups (OR 1.400; 95% CI 0.741-2.646; p = 0.300). Tacrolimus and MMF showed no differences in proteinuria, serum albumin, serum creatinine, creatinine clearance, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or extra-renal SLEDAI. The incidence of infection, severe infection, leukopenia, and hyperglycemia did not differ between the tacrolimus and MMF groups. However, herpes zoster infection was significantly less common in the tacrolimus group (OR 0.137; 95% CI 0.034-0.546; p = 0.005), whereas serum creatinine elevation was significantly higher in the tacrolimus group than in the MMF group (OR 8.148; 95% CI 1.369-48.50; p = 0.021). At 3 mg/d, tacrolimus was shown to be safe, well tolerated, and offered therapeutic benefits in all investigations.
CONCLUSION
Tacrolimus was comparable to MMF in terms of effectiveness and safety as an induction therapy for LN, with the exception of a reduced risk of herpes zoster infection and a rise in serum creatinine. In individuals with LN, 3 mg/d tacrolimus was proven to be efficacious and safe.
Topics: Humans; Tacrolimus; Lupus Nephritis; Mycophenolic Acid; Immunosuppressive Agents; Cyclophosphamide; Creatinine; Treatment Outcome; Herpes Zoster
PubMed: 36607421
DOI: 10.1007/s00393-022-01313-2 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
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 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364 -
Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
The Cochrane Database of Systematic... Jun 2024IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years.
OBJECTIVES
To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children.
SEARCH METHODS
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
MAIN RESULTS
This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data.
AUTHORS' CONCLUSIONS
There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.
Topics: Adolescent; Child; Humans; Bias; Disease Progression; Glomerular Filtration Rate; Glomerulonephritis, IGA; Immunosuppressive Agents; Mycophenolic Acid; Placebos; Proteinuria; Randomized Controlled Trials as Topic; Young Adult
PubMed: 38864363
DOI: 10.1002/14651858.CD015060.pub2 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
Transplantation Proceedings Jun 2024This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney...
Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies.
INTRODUCTION
This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy.
METHODS
A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events.
RESULTS
Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138).
CONCLUSION
Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.
PubMed: 38853029
DOI: 10.1016/j.transproceed.2024.05.014