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Scientific Reports Feb 2023To quantify the association between maternal uric acid levels and pre-eclampsia risk in a large collection of primigravid women. A case-control study (1365 cases of... (Meta-Analysis)
Meta-Analysis
To quantify the association between maternal uric acid levels and pre-eclampsia risk in a large collection of primigravid women. A case-control study (1365 cases of pre-eclampsia and 1886 normotensive controls) was conducted. Pre-eclampsia was defined as blood pressure ≥ 140/90 mmHg and proteinuria ≥ 300 mg/24 h. Sub-outcome analysis included early, intermediate, and late pre-eclampsia. Multivariable analysis for pre-eclampsia and its sub-outcomes was conducted using binary and multinomial logistic regression, respectively. Additionally, a systematic review and meta-analysis of cohort studies measuring uric acid levels < 20 weeks of gestation was performed to rule out reverse causation. There was a positive linear association between increasing uric acid levels and presence of pre-eclampsia. Adjusted odds ratio of pre-eclampsia was 1.21 (95%CI 1.11-1.33) for every one standard deviation increase in uric acid levels. No differences in the magnitude of association were observed between early and late pre-eclampsia. Three studies with uric acid measured < 20 weeks' gestation were identified, with a pooled OR for pre-eclampsia of 1.46 (95%CI 1.22-1.75) for a top vs. bottom quartile comparison. Maternal uric acid levels are associated with risk of pre-eclampsia. Mendelian randomisation studies would be helpful to further explore the causal role of uric acid in pre-eclampsia.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Prospective Studies; Uric Acid; Case-Control Studies; Blood Pressure
PubMed: 36810371
DOI: 10.1038/s41598-023-29651-4 -
Frontiers in Pharmacology 2023Apatinib is a novel tyrosine kinase inhibitor used in the treatment of advanced hepatocellular carcinoma (HCC). For decades, sorafenib has been a classic first-line... (Review)
Review
Efficacy and safety of apatinib versus sorafenib/placebo in first-line treatment for intermediate and advanced primary liver cancer: A systematic review and meta-analysis.
Apatinib is a novel tyrosine kinase inhibitor used in the treatment of advanced hepatocellular carcinoma (HCC). For decades, sorafenib has been a classic first-line treatment option for patients with HCC. This meta-analysis aimed to assess the efficacy and safety of apatinib versus sorafenib/placebo as first-line treatment for intermediate and advanced primary liver cancer (PLC). A literature search was performed PubMed, Web of Science, CENTRAL, Embase, CNKI, VIP, and CBM. Data extraction from databases of other languages is not restricted. The Cochrane risk of bias tool, modified Jadad scale, Newcastle-Ottawa scale (NOS), and non-randomized studies of interventions (ROBINS-I) tool were employed to evaluate methodological qualities in original studies. Influence analysis was applied to assess the reliability of pooled results. Publication bias was evaluated using the funnel plot with Begg's test and Egger's test. Seven studies were included in the systematic review and meta-analysis. Four randomized controlled trials (RCTs) and one clinical controlled trial (CCT) were used for comparing apatinib with placebo, and two retrospective clinical studies (RCSs) were used for comparing apatinib with sorafenib. Apatinib led to higher overall effects in objective response rate (ORR), disease control rate (DCR), and mean survival time (MST) over placebo (RR = 2.03, 95% CI = 1.46-2.81, < 0.0001, I = 0%; RR = 1.17, 95% CI = 1.04-1.33, = 0.009, I = 45.8%; SMD = 2.63; 95% CI = 1.47-3.78, < 0.0001, I = 92.7%, respectively). Compared to sorafenib, apatinib showed no superiority in ORR and DCR but was inferior in the 6-month and 1-year survival rate (RR = 1.99, 95% CI = 0.85-4.65, = 0.111, I = 68.3%; RR = 1.04, 95% CI = 0.73-1.47, = 0.840, I = 0.0%; RR = 0.63, 95% CI = 0.42-0.97, = 0.036, I = 0.0%; RR = 0.47, 95% CI = 0.29-0.79, < 0.0001, I = 0.0%, respectively). Apatinib had similar adverse effects over placebo but possessed a greater incidence rate of proteinuria and hypertension over sorafenib. In the first-line setting, apatinib might be an alternative treatment approach for patients with intermediate and advanced PLC. Sorafenib alone showed a better survival rate within 1 year and a lower incidence rate in hypertension and proteinuria than apatinib monotherapy.
PubMed: 37153777
DOI: 10.3389/fphar.2023.1101063 -
Frontiers in Medicine 2020Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary...
Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.
PubMed: 33344486
DOI: 10.3389/fmed.2020.611317 -
PloS One 2015To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis.
METHODS
A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model.
RESULTS
Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster infection.
CONCLUSIONS
Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. Larger RCTs with longer duration of observation are necessary to provide strong evidence of the efficacy and safety of leflunomide in LN patients.
Topics: Adult; Asian People; Cyclophosphamide; Female; Humans; Isoxazoles; Leflunomide; Lupus Nephritis; Male; Odds Ratio; Remission Induction; Treatment Outcome
PubMed: 26670616
DOI: 10.1371/journal.pone.0144548 -
Journal of Lipid Research Mar 2022Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe... (Review)
Review
Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe and characterized by early and progressive chronic kidney disease (CKD). No treatment is currently available for FLD, but novel therapeutics are under development. Furthermore, although biomarkers of LCAT deficiency have been identified, their suitability to monitor disease progression and therapeutic efficacy is unclear, as little data exist on the rate of progression of renal disease. Here, we systematically review observational studies of FLD, FED, and heterozygous subjects, which summarize available evidence on the natural history and biomarkers of LCAT deficiency, in order to guide the development of novel therapeutics. We identified 146 FLD and 53 FED patients from 219 publications, showing that both syndromes are characterized by early corneal opacity and markedly reduced HDL-C levels. Proteinuria/hematuria were the first signs of renal impairment in FLD, followed by rapid decline of renal function. Furthermore, LCAT activity toward endogenous substrates and the percentage of circulating esterified cholesterol (EC%) were the best discriminators between these two syndromes. In FLD, higher levels of total, non-HDL, and unesterified cholesterol were associated with severe CKD. We reveal a nonlinear association between LCAT activity and EC% levels, in which subnormal levels of LCAT activity were associated with normal EC%. This review provides the first step toward the identification of disease biomarkers to be used in clinical trials and suggests that restoring LCAT activity to subnormal levels may be sufficient to prevent renal disease progression.
Topics: Humans; Biomarkers; Heterozygote; Lecithin Cholesterol Acyltransferase Deficiency; Mutation; Phosphatidylcholine-Sterol O-Acyltransferase
PubMed: 35065092
DOI: 10.1016/j.jlr.2022.100169 -
Children (Basel, Switzerland) Dec 2021Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature... (Review)
Review
Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature review was conducted on the United States National Library of Medicine, Excerpta Medica, and Web of Science databases. Twenty-three reports describing 57 individual cases could be included. The majority ( = 35) of the 57 patients were ≤18 years of age and affected by thalassemia ( = 46). Abnormal urinary findings were noted in 54, electrolyte or acid-base abnormalities in 46, and acute kidney injury in 9 patients. Latent tubular damage was diagnosed in 11 (19%), overt kidney tubular damage in 37 (65%), and an acute kidney injury in the remaining nine (16%) patients. Out of the 117 acid-base and electrolyte disorders reported in 48 patients, normal-gap metabolic acidosis and hypophosphatemia were the most frequent. Further abnormalities were, in decreasing order of frequency, hypokalemia, hypouricemia, hypocalcemia, and hyponatremia. Out of the 81 abnormal urinary findings, renal glucosuria was the most frequent, followed by tubular proteinuria, total proteinuria, and aminoaciduria. In conclusion, a proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose.
PubMed: 34943300
DOI: 10.3390/children8121104 -
Oxidative Medicine and Cellular... 2022Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic nephropathy (DN), one of the commonest diabetic microangiopathies, with artemisinins. Here, we aimed to evaluate preclinical evidence for the efficacy and possible mechanisms of artemisinins in reducing diabetic renal injury.
METHODS
We conducted an electronic literature search in fourteen databases from their inception to November 2021. All animal studies assessing the efficacy and safety of artemisinins in DN were included, regardless of publication or language. Overall, 178 articles were screened according to predefined inclusion and exclusion criteria. Finally, 18 eligible articles were included in this systematic review. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool was used to assess the risk of bias in the included studies. The primary outcomes were kidney function, proteinuria, and renal pathology. Secondary endpoints included changes in fasting plasma glucose (FPG) levels, body weight, and relevant mechanisms.
RESULTS
Of the 18 included articles involving 418 animal models of DN, 1, 2, 6, and 9 used dihydroartemisinin, artemether, artesunate, and artemisinin, respectively. Overall, artemisinins reduced indicators of renal function, including blood urea nitrogen ( < 0.00001), serum creatinine ( < 0.00001), and kidney index ( = 0.0001) compared with control group treatment. Measurements of proteinuria ( < 0.00001), microalbuminuria ( < 0.05), and protein excretion ( = 0.0002) suggested that treatment with artemisinins reduced protein loss in animals with DN. Artemisinins may lower blood glucose levels ( = 0.01), but there is a risk of weight gain ( < 0.00001). Possible mechanisms of action of artemisinins include delaying renal fibrosis, reducing oxidative stress, and exerting antiapoptotic and anti-inflammatory effects.
CONCLUSION
Available evidence suggests that artemisinins may be protective against renal injury secondary to diabetes in preclinical studies; however, high-quality and long-term trials are needed to reliably determine the balance of benefits and harms.
Topics: Animals; Artemisinins; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Male; Models, Animal; Proteinuria
PubMed: 35528521
DOI: 10.1155/2022/5401760 -
Kidney International Reports Nov 2018Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series...
INTRODUCTION
Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy.
METHODS
Electronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018.
RESULTS
Fifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died.
CONCLUSION
Secondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.
PubMed: 30450463
DOI: 10.1016/j.ekir.2018.07.020 -
Endocrine Nov 2023The prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are prone to infectious diseases, and urinary tract infections are also widespread. Despite a comprehensive understanding of urinary tract infection (UTI), there is a lack of research regarding primary prevention strategies for asymptomatic bacteriuria (ASB).
OBJECTIVE
To clarify the incidence and risk factors of asymptomatic urinary tract infection in patients with T2DM by meta-analysis to provide evidence for preventing UTI. Help patients, their families, and caregivers to identify the risk factors of patients in time and intervene to reduce the incidence of ASB in patients with T2DM. Fill in the gaps in existing research.
STUDY DESIGN
Meta-analyses were conducted in line with PRISMA guidelines.
METHODS
Eleven databases were systematically searched for articles about ASB in T2DM, and the retrieval time was selected from the establishment of the database to February 5, 2023. Literature screening, quality evaluation, and meta-analysis were independently performed by two researchers according to the inclusion and exclusion criteria, and a meta-analysis was performed using Stata 17.0.
RESULTS
Fourteen articles were included, including cohort and case-control studies. A meta-analysis of 4044 patients with T2DM was included. The incidence of ASB in patients with T2DM was 23.7%(95% CI (0.183, 0.291); P < 0.001). After controlling for confounding variables, the following risk factors were associated with ASB in patients with T2DM: age (WMD = 3.18, 95% CI (1.91, 4.45), I = 75.5%, P < 0.001), female sex (OR = 1.07, 95% CI(1.02, 1.12), I = 79.3%, P = 0.002), duration of type 2 diabetes (WMD = 2.54, 95% CI (1.53, 5.43), I = 80.7%, P < 0.001), HbA1c (WMD = 0.63, 95% CI (0.43, 0.84), I = 62.6,%. P < 0.001), hypertension (OR = 1.59, 95% CI (1.24, 2.04), I = 0%, <0.001), hyperlipidemia (OR = 1.66, 95% CI (1.27, 2.18), I = 0%, P < 0.001), Neuropathy (OR = 1.81, 95% CI (1.38, 2.37), I = 0%, P < 0.001), proteinuria (OR = 3.00, 95% CI (1.82, 4.95), I = 62.7%, P < 0.001).
CONCLUSION
The overall prevalence of ASB in T2DM is 23.7%. Age, female sex, course of T2DM, HbA1C, hypertension, hyperlipidemia, neuropathy, and proteinuria were identified as related risk factors for ASB in T2DM. These findings can provide a robust theoretical basis for preventing and managing ASB in T2DM.
Topics: Humans; Female; Bacteriuria; Diabetes Mellitus, Type 2; Incidence; Glycated Hemoglobin; Risk Factors; Urinary Tract Infections; Proteinuria; Hyperlipidemias; Hypertension
PubMed: 37599328
DOI: 10.1007/s12020-023-03469-6 -
Diseases (Basel, Switzerland) Oct 2023The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone... (Review)
Review
Comparing Efficacy of Erlotinib and Bevacizumab Combination with Erlotinib Monotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-Analysis.
The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors searched databases such as PubMed, Medline, Scopus, and Cochrane Central Register of Controlled Trials for randomized control trials (RCTs) comparing erlotinib plus bevacizumab with erlotinib in NSCLC patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were the outcomes of interest. The pooled hazard ratio (HR) and relative risk (RR) were estimated utilizing both fixed- and random-effect models. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Nine studies comprising 1698 patients with NSCLC were included in this meta-analysis, of whom 850 were treated with erlotinib plus bevacizumab, and 848 with erlotinib. The erlotinib plus bevacizumab combination significantly prolonged PFS (HR, 0.62, 95% CI: 0.56, 0.70, < 0.00001) but did not show any significant improvement in OS (HR, 0.95; 95% CI: 0.83, 1.07, = 0.39) and ORR (HR, 1.10; 95% CI: 0.98, 1.24, = 0.09). Increased risks of hypertension (RR, 5.15; 95% CI: 3.59, 7.39; < 0.00001), proteinuria (RR, 10.54; 95% CI: 3.80, 29.20; < 0.00001) and grade 3 and higher AEs (RR, 2.09; 95% CI: 1.47, 2.97; < 0.00001) were observed with the erlotinib-plus-bevacizumab combination compared to erlotinib monotherapy. On subgroup analyses, the erlotinib plus bevacizumab combination improved PFS only. Combining erlotinib and bevacizumab has been shown to improve PFS in advanced NSCLC patients but did not show any significant OS and ORR benefits. Furthermore, risks of hypertension, proteinuria, and grade 3 or higher AEs were greater with the erlotinib-and-bevacizumab combination.
PubMed: 37873790
DOI: 10.3390/diseases11040146