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International Urology and Nephrology Oct 2023Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN.
METHODS
A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity.
RESULTS
The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including antibody against phospholipase A2 receptor (PLAR-AB), antibody against thrombospondin type I domain-containing 7A (THSD7A-AB), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLAR-AB for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A-AB for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%.
CONCLUSIONS
This meta-analysis shows that PLAR-AB and THSD7A-AB are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN.
Topics: Humans; Glomerulonephritis, Membranous; RNA, Circular; Autoantibodies; Biomarkers; Polyesters; Receptors, Phospholipase A2
PubMed: 36961513
DOI: 10.1007/s11255-023-03561-w -
Kidney & Blood Pressure Research 2023Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN.
OBJECTIVE
Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients.
METHOD
PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis.
RESULTS
Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer.
CONCLUSION
In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.
Topics: Adult; Humans; Glomerulonephritis, Membranous; Receptors, Phospholipase A2; Remission, Spontaneous; Antibodies; Prognosis; Pathologic Complete Response; Recurrence
PubMed: 36720217
DOI: 10.1159/000529415 -
Liver International : Official Journal... May 2023It is unclear whether the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C-to-G single nucleotide polymorphism, resulting in the substitution...
BACKGROUND
It is unclear whether the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C-to-G single nucleotide polymorphism, resulting in the substitution of isoleucine to methionine at position 148 (I148M), impedes regression of hepatic steatosis when treating non-alcoholic fatty liver disease (NAFLD).
OBJECTIVES
Investigate if carriage of the PNPLA3 148M allele affects the anti-steatotic efficacy of all possible anti-NAFLD interventions, identify gaps in current knowledge and provide guidance for individual treatment.
METHODS
Research available in public databases was searched up to 13 November 2022. Studies were included if a treatment in NAFLD patients decreased hepatic steatosis in the pooled patient group or a PNPLA3 I148M polymorphism subgroup (II/IM/MM). The risk of bias was assessed using the Cochrane Risk-Of-Bias 2 Tool and the Newcastle-Ottawa Scale.
RESULTS
Moderate evidence indicates that NAFLD patients homozygous for the PNPLA3 148M allele benefit less or not at all from omega-3 carboxylic acids to decrease liver fat, while the PNPLA3 148I allele shows moderate benefit. Low evidence suggests that interventions employing lifestyle changes are more effective to reduce liver fat in NAFLD patients homozygous for the PNPLA3 148M allele compared to patients with wild-type PNPLA3.
CONCLUSIONS
NAFLD patients homozygous for the PNPLA3 148M allele might not benefit from omega-3 carboxylic acids to reduce hepatic steatosis in contrast to patients with wild-type PNPLA3. Instead, patients with two PNPLA3 148M alleles should be especially advised to adopt lifestyle changes. Genotyping for PNPLA3 I148M should be encouraged in therapeutic studies for NAFLD.
REGISTRATION NUMBER (PROSPERO)
CRD42022375028.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Homozygote; Carboxylic Acids; Genetic Predisposition to Disease
PubMed: 36719059
DOI: 10.1111/liv.15533 -
Medicina Clinica May 2023To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).
PURPOSE
To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).
PATIENTS AND METHODS
Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up.
RESULTS
Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30-77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8μmol/L. During the follow-up of 33.9±19.1 months (range, 6-73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases.
CONCLUSIONS
Most patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse.
Topics: Humans; Male; Female; Adult; Middle Aged; Glomerulonephritis, Membranous; Remission, Spontaneous; Autoantibodies; Kidney; Prognosis
PubMed: 36690554
DOI: 10.1016/j.medcli.2022.10.014 -
Nutrition Reviews Jul 2023Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic... (Meta-Analysis)
Meta-Analysis
The effects of fatty acid-based dietary interventions on circulating bioactive lipid levels as intermediate biomarkers of health, cardiovascular disease, and cardiovascular disease risk factors: a systematic review and meta-analysis of randomized clinical trials.
CONTEXT
Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic precursor lipoprotein-associated phospholipase A2 (Lp-PLA2) mass; however, the magnitude of this effect remains unclear.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the effect of different dietary FAs on the bioactive lipid profile of healthy participants and those with cardiovascular disease (CVD) and CVD risk factors.
DATA SOURCES
PubMed, SCOPUS and the Cochrane Library databases were searched for relevant articles published between October 2010 and May 2022.
DATA EXTRACTION
Data were screened for relevance and then retrieved in full and evaluated for eligibility by 2 reviewers independently.
DATA ANALYSIS
The net difference in the bioactive lipid mean values between the endpoint and the baseline, and the corresponding SDs or SEs, were used for the qualitative synthesis. For the meta-analysis, a fixed-effects model was used.
RESULTS
Twenty-seven randomized clinical trials (representing >2560 participants) were included. Over 78% of the enrolled participants had ≥1 associated CVD risk factor, whereas <22% were healthy. In the meta-analysis, marine n-3 supplements (dose range, 0.37-1.9 g/d) significantly increased pro-inflammatory lysophosphatidylcholines (lyso-PCs; for lyso-PC(16:0): mean, +0.52 [95% confidence interval (CI), 0.02-1.01] µM; for lyso-PC(18:0): mean, +0.58 [95%CI, 0.09-1.08] µM) in obese participants. Additionally, n-3 supplementation (1-5.56 g/d) decreased plasma Lp-PLA2 mass, a well-known inflammation marker, in healthy (-0.35 [95%CI, -0.59 to -0.10] ng/mL), dyslipidemic (-0.36 [95%CI, -0.47 to -0.25] ng/mL), and stable coronary artery disease participants (-0.52 [95%CI, -0.91 to -0.12] ng/mL).
CONCLUSIONS
Daily n-3 provided as EPA+DHA supplements and consumed from 1 to 6 months reduced plasma Lp-PLA2 mass in healthy participants and those with CVD and CVD risk factors, suggesting an anti-inflammatory effect. However, the saturated lyso-PC response to n-3 was impaired in obese participants.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021218335.
Topics: Humans; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; Cardiovascular Diseases; Fatty Acids; Obesity; Randomized Controlled Trials as Topic; Lipids
PubMed: 36545749
DOI: 10.1093/nutrit/nuac101 -
Journal of Nephrology Mar 2023
Accuracy of serum PLA2R antibody detected by indirect immunofluorescence in diagnosing biopsy-proven primary membranous nephropathy: a single-center experience and a systematic review of the literature.
Topics: Humans; Glomerulonephritis, Membranous; Fluorescent Antibody Technique, Indirect; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Receptors, Phospholipase A2; Biopsy; Biomarkers
PubMed: 36462140
DOI: 10.1007/s40620-022-01528-1 -
Journal of Clinical and Experimental... 2022Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis... (Review)
Review
Lysosomal Acid Lipase Activity in Non-alcoholic Fatty Liver Disease as a Novel Diagnostic and Therapeutic Target: A Systematic Literature Review of Current Evidence and Future Directions.
BACKGROUND AND AIM
Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis.
METHODS
Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies.
RESULTS
A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls.
CONCLUSION
The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.
PubMed: 36340307
DOI: 10.1016/j.jceh.2022.04.011 -
Journal of the Neurological Sciences Nov 2022Animal envenomation in humans is usually accidental or for defensive purposes. Depending on the venom composition and administration, different reactions can be...
Animal envenomation in humans is usually accidental or for defensive purposes. Depending on the venom composition and administration, different reactions can be observed. After reporting the first case of acute polyradiculitis in a 57-year-old healthy male after red lionfish envenomation, we propose to analyze rare similar cases of acute neuritis after animal envenomation published in the medical literature. Including our case, we found 54 patients who developed acute peripheral neuropathy after having been stung or bitten by various animals, mainly hymenoptera (in half of the cases) but also jellyfishes, snakes, corals or nonhooked arthropods. We observed two distinct patterns of peripheral neuropathy: more than half of them were polyneuropathy while the others were focal neuropathy. The prognosis was favorable in most cases. The pathophysiological mechanism associated with these rare complications remain unknown, although some hypotheses may be proposed. A direct action of certain components of the venom, such as phospholipase-A2, could explain the focal forms of peripheral neuropathy trough toxic reactions and/or vasculitis processes. The more diffuse clinical situations could be due to an allergy-triggered immune-mediated reaction (possibly linked to a molecular mimicry mechanism between venom proteins and some myelin proteins of the peripheral nervous system), or to the action of some venom components on membrane ionic channels particularly at the node of Ranvier. Even if acute peripheral neuropathies are rare after envenomation, they may occur after envenomation from various animals, and their usually favorable prognoses should be known by neurologists.
Topics: Animals; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Phospholipases; Vasculitis
PubMed: 36244096
DOI: 10.1016/j.jns.2022.120448 -
Hormone and Metabolic Research =... Oct 2022Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver... (Meta-Analysis)
Meta-Analysis
Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.
Topics: Acyltransferases; Adult; Case-Control Studies; Child; Cholesterol; Genetic Predisposition to Disease; Genotype; Humans; Lipase; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Obesity; Phospholipases; Phospholipases A2, Calcium-Independent; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 36206762
DOI: 10.1055/a-1929-1677 -
Frontiers in Pharmacology 2022Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which is the leading glomerular disease that recurs after kidney...
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which is the leading glomerular disease that recurs after kidney transplantation. Treatment for MN remained controversial and challenging, partly owing to absence of sensitive and specific biomarkers and effective therapy for prediction and diagnosis of disease activity. MN starts with the formation and deposition of circulating immune complexes on the outer area in the glomerular basement membrane, leading to complement activation. The identification of autoantibodies against the phospholipase A receptor (PLAR) and thrombospondin type-1 domain-containing protein 7A (THSD7A) antigens illuminated a distinct pathophysiological rationale for MN treatments. Nowadays, detection of serum anti-PLAR antibodies and deposited glomerular PLAR antigen can be routinely applied to MN. Anti-PLAR antibodies exhibited much high specificity and sensitivity. Measurement of PLAR in immune complex deposition allows for the diagnosis of PLAR-associated MN in patients with renal biopsies. In the review, we critically summarized newer diagnosis biomarkers including PLAR and THSD7A tests and novel promising therapies by using traditional Chinese medicines such as , , and Astragaloside IV for the treatment of MN patients. We also described unresolved questions and future challenges to reveal the diagnosis and treatments of MN. These unprecedented breakthroughs were quickly translated to clinical diagnosis and management. Considerable advances of detection methods played a critical role in diagnosis and monitoring of treatment.
PubMed: 35694252
DOI: 10.3389/fphar.2022.907108