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PloS One 2014Vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall incidence and risk of proteinuria associated these drugs is unclear. We performed a systematic review and meta-analysis of published clinical trials to quantify the incidence and risk of proteinuria associated with VEGFR-TKIs.
METHODOLOGY
Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on proteinuria. Statistical analyses were conducted to calculate the summary incidence, Odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.
PRINCIPAL FINDINGS
A total of 6,882 patients with a variety of solid tumors from 33 clinical trials were included in our analysis. The incidence of all-grade and high-grade (grade 3 or higher) proteinuria was 18.7% (95% CI, 13.3%-25.6%) and 2.4% (95% CI, 1.6%-3.7%), respectively. Patients treated with VEGFR-TKIs had a significantly increased risk of all-grade (OR 2.92, 95%CI: 1.09-7.82, p = 0.033) and high-grade proteinuria (OR 1.97, 95%CI: 1.01-3.84, p = 0.046) when compared to patients treated with control medication. No evidence of publication bias was observed.
CONCLUSIONS
The use of VEGFR-TKIs is associated with a significant increased risk of developing proteinuria. Physicians should be aware of this adverse effect and should monitor cancer patients receiving VEGFR-TKIs.
Topics: Humans; Neoplasms; Protein Kinase Inhibitors; Proteinuria; Receptors, Vascular Endothelial Growth Factor; Risk
PubMed: 24621598
DOI: 10.1371/journal.pone.0090135 -
Annals of HepatologyBackground. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease.
AIM
To evaluate the effect of infection with HBV on the risk of chronic kidney disease in the general population.
MATERIAL AND METHODS
We conducted a systematic review of the published medical literature to determine if hepatitis B infection is associated with increased likelihood of chronic kidney disease. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis B virus across the published studies. Meta-regression and stratified analysis were also conducted.
RESULTS
We identified 16 studies (n = 394,664 patients) and separate meta-analyses were performed according to the outcome. The subset of longitudinal studies addressing ESRD (n = 2; n = 91,656) gave a pooled aHR 3.87 (95% CI, 1.48; 6.25, P < 0.0001) among HBV-infected patients and no heterogeneity was recorded. In meta-regression, we noted the impact of male (P = 0.006) and duration of follow- up (P = 0.007) upon the adjusted hazard ratio of incidence of chronic kidney disease (including end-stage renal disease). No relationship occurred between HBV positive status and prevalent chronic disease (n = 7, n = 109,889 unique patients); adjusted odds ratio, were 1.07 (95% CI, 0.89; 1.25) and 0.93 (95% CI, 0.76; 1.10), respectively.
CONCLUSIONS
HBV infection is possibly associated with a risk of developing reduced glomerular filtration rate in the general population; no link between HBV sero-positive status and frequency of chronic kidney disease or proteinuria was noted in cross-sectional surveys.
Topics: Adult; Aged; Chi-Square Distribution; Female; Glomerular Filtration Rate; Hepatitis B; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Observational Studies as Topic; Odds Ratio; Prevalence; Proteinuria; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Time Factors
PubMed: 28051791
DOI: 10.5604/16652681.1226813 -
American Journal of Kidney Diseases :... May 2010Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus.
STUDY DESIGN
Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009).
SETTING & POPULATION
Patients with diabetes mellitus.
SELECTION CRITERIA FOR STUDIES
Randomized controlled trials.
INTERVENTION
Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents.
OUTCOMES
Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups.
RESULTS
Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was -64.8% (95% CI, -75.6 to -53.9) and the WMD of changes in albumin-creatinine ratio was -24.8% (95% CI, -39.6 to -10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.6 units of standard deviation [SD]; 95% CI, -0.8 to -0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, -1.1 units of SD; 95% CI, -1.8 to -0.4).
LIMITATIONS
Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available.
CONCLUSIONS
Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.
Topics: Albuminuria; Diabetic Nephropathies; Disease Progression; Humans; Hypoglycemic Agents; PPAR gamma; Pioglitazone; Proteinuria; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones
PubMed: 20110146
DOI: 10.1053/j.ajkd.2009.11.013 -
American Journal of Kidney Diseases :... Feb 2007Angiogenesis inhibitors have emerged as an effective targeted therapy in the treatment of patients with many cancers. One of the most widely used angiogenesis inhibitors... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiogenesis inhibitors have emerged as an effective targeted therapy in the treatment of patients with many cancers. One of the most widely used angiogenesis inhibitors is bevacizumab, a neutralizing antibody against vascular endothelial growth factor. The overall risk of proteinuria and hypertension in patients with cancer on bevacizumab therapy is unclear. We performed a systematic review and meta-analysis of published clinical trials of bevacizumab to quantify the risk of proteinuria and hypertension.
METHODS
The databases MEDLINE (OVID, 1966 to June 2006) and Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2006 were searched to identify relevant studies. Eligible studies were randomized controlled trials of patients with cancer treated with bevacizumab that described the incidence of proteinuria and hypertension. Relative risk (RR) was calculated by using the fixed-effects model.
RESULTS
A total of 1,850 patients were included in the 7 trials identified from the literature. Bevacizumab was associated with a significant increased risk of proteinuria (RR, 1.4 with low-dose bevacizumab; 95% confidence interval [CI], 1.1 to 1.7; RR, 2.2 with high dose; 95% CI, 1.6 to 2.9). Hypertension also was increased significantly among patients receiving bevacizumab (RR, 3.0 for low dose; 95% CI, 2.2 to 4.2; RR, 7.5 for high dose; 95% CI, 4.2 to 13.4).
CONCLUSION
There was a significant dose-dependent increase in risk of proteinuria and hypertension in patients with cancer who received bevacizumab.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Humans; Hypertension; Proteinuria; Risk Factors; Vascular Endothelial Growth Factor A
PubMed: 17261421
DOI: 10.1053/j.ajkd.2006.11.039 -
Pregnancy Hypertension Mar 2022Dipstick tests are frequently used as bedside proteinuria tests to evaluate women suspected of preeclampsia and may inform diagnosis in low resource settings lacking... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dipstick tests are frequently used as bedside proteinuria tests to evaluate women suspected of preeclampsia and may inform diagnosis in low resource settings lacking laboratory facilities. This systematic review and meta-analysis aimed to (1) estimate the diagnostic accuracy of urine dipsticks in diagnosing proteinuria, (2) compare performance of different dipstick types and (3) estimate their related costs.
METHODS
MEDLINE and EMBASE were searched up to August 1, 2020 for primary studies with cross-sectional diagnostic accuracy data on dipstick test(s) compared to a laboratory reference standard (24-hour protein ≥ 300 mg or protein-creatinine ratio ≥ 30 mg/mmol) in pregnant women ≥ 20 weeks of gestation suspected of preeclampsia. Risk of bias and applicability was assessed with QUADAS-2. Data were analysed using a bivariate model with hierarchical addition of covariates for subgroups.
RESULTS
Nineteen studies were included. Protein-only dipsticks at 1 + threshold had a pooled sensitivity of 0.68 [95%CI: 0.57-0.77] and specificity of 0.85 [95% CI: 0.73-0.93] (n = 3700 urine samples, 18 studies). Higher specificity was found with automatedly (0.93 [95% CI: 0.82-0.98]) compared to visually (0.81 [95% CI: 0.65-0.91]) read dipsticks, whereas sensitivity was similar and costs were higher. The use of albumin-creatinine ratio (ACR) dipsticks was only reported in two studies and did not improve accuracy. Heterogeneity in study design and prevalence of preeclampsia amongst studies complicated interpretation of pooled estimates.
CONCLUSION
Urine dipsticks performed poorly at excluding preeclampsia in hypertensive pregnant women. Further development of accurate and low-cost bedside proteinuria tests is warranted.
Topics: Female; Humans; Point-of-Care Testing; Pre-Eclampsia; Pregnancy; Proteinuria; ROC Curve; Reagent Strips
PubMed: 35051804
DOI: 10.1016/j.preghy.2021.12.015 -
JAMA Apr 2017Preeclampsia is a complex disease of pregnancy with sometimes serious effects on maternal and infant morbidity and mortality. It is defined by hypertension after 20... (Review)
Review
IMPORTANCE
Preeclampsia is a complex disease of pregnancy with sometimes serious effects on maternal and infant morbidity and mortality. It is defined by hypertension after 20 weeks' gestation and proteinuria or other evidence of multisystem involvement.
OBJECTIVE
To systematically review the benefits and harms of preeclampsia screening and risk assessment for the US Preventive Services Task Force.
DATA SOURCES
MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases from 1990 through September 1, 2015. Surveillance for new evidence in targeted publications was conducted through October 5, 2016.
STUDY SELECTION
English-language trials and observational studies, including externally validated prediction models, of screening effectiveness, benefits, and harms from routine preeclampsia screening during pregnancy.
DATA EXTRACTION AND SYNTHESIS
Independent dual review of article abstracts and full texts against a priori inclusion criteria. Meta-analysis was not performed because of clinical and statistical heterogeneity of included studies.
MAIN OUTCOMES AND MEASURES
Maternal and infant health outcomes, including eclampsia, stroke, stillbirth, preterm birth, and low birth weight; screening and risk prediction test performance; harms of screening and risk assessment.
RESULTS
Twenty-one studies (13 982 participants) were included. No studies directly compared the effectiveness of preeclampsia screening in a screened population vs an unscreened population; 1 US trial (n = 2764) found no difference in benefits or harms with fewer prenatal visits but was underpowered for rare, serious outcomes. For harms, a before-after comparison cohort noninferiority study of urine protein screening for specific indications compared with routine screening (n = 1952) did not identify harms with fewer urine screening tests. Four studies (n = 7123) reported external validation performance of 16 risk prediction models, 5 of which had good or better discrimination (c statistic >0.80) for prediction of preeclampsia, and positive predictive values of 4% in the largest, most applicable validation cohorts. Calibration was not reported despite being a key model performance measure. There were no studies of urine screening test performance conducted in asymptomatic primary care populations; 14 studies of protein urine test performance among women being evaluated for suspected preeclampsia (n = 1888) had wide-ranging test accuracy (sensitivity, 22%-100%; specificity, 36%-100%) and high statistical and clinical heterogeneity in tests used, eligibility criteria, and proteinuria prevalence (8.7%-93.8%).
CONCLUSIONS AND RELEVANCE
Evidence to estimate benefits and harms of preeclampsia screening and the test performance of different screening approaches over the course of pregnancy was limited. Externally validated risk prediction models had limited applicability and lacked calibration and clinical implementation data needed to support routine use. Further research is needed to better inform risk-based screening approaches and improve screening strategies, given the complex pathophysiology and clinical unpredictability of preeclampsia.
Topics: Adult; Advisory Committees; Female; Humans; Infant, Newborn; Mass Screening; Middle Aged; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Risk; Sensitivity and Specificity; Young Adult
PubMed: 28444285
DOI: 10.1001/jama.2016.18315 -
International Journal of Rheumatic... Jun 2018Membranous lupus glomerulonephritis (MLN) is associated with morbidities such as thromboembolism, peripheral edema and/or hyperlipidemia. However, treatment of MLN... (Meta-Analysis)
Meta-Analysis Review
AIM
Membranous lupus glomerulonephritis (MLN) is associated with morbidities such as thromboembolism, peripheral edema and/or hyperlipidemia. However, treatment of MLN remains elusive.
METHODS
We performed systematic searches on MEDLINE, EMBASE and Cochrane Library database up to November, 2017. Eligible studies included randomized trials or cohort studies which evaluated different immunosuppressants in adult patients with pathologically proved MLN. No language restrictions were applied. Endpoints included complete remission (CR) as the primary outcome, and CR plus partial remission (PR) and proteinuria-reducing effect as secondary outcomes. Frequentist estimation of a network meta-analysis (NMA) random-effect model was performed.
RESULTS
Eight studies (206 patients) were included with a total of six immunosuppressants as an induction therapy for MLN. NMA results showed that both mycophenolate mofetil (MMF) and calcineurin inhibitors (CNI) are effective in the induction of CR and CR plus PR when compared with corticosteroids (CS) alone, but MMF and CNI are also associated with higher infection rates when compared with CS.
CONCLUSION
Our NMA demonstrated that both MMF and CNI are more effective than CS for induction therapy in MLN patients. However, there are limitations due to intra- and inter-study variability.
Topics: Adult; Female; Glomerulonephritis, Membranous; Humans; Immunocompromised Host; Immunosuppressive Agents; Induction Chemotherapy; Lupus Nephritis; Male; Odds Ratio; Opportunistic Infections; Proteinuria; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 29879319
DOI: 10.1111/1756-185X.13321 -
Autoimmunity Reviews Nov 2022Intravenous immunoglobulin (IVIg) is an anti-inflammatory drug with an unclear role in the treatment of patients with lupus nephritis (LN). This systematic review... (Review)
Review
INTRODUCTION AND OBJECTIVE
Intravenous immunoglobulin (IVIg) is an anti-inflammatory drug with an unclear role in the treatment of patients with lupus nephritis (LN). This systematic review evaluates the evidence for IVIg in the care of patients with LN.
METHODOLOGY
A systematic search was done in the PubMed, EMBASE, BVS and OVID databases - All EBM Reviews following the PRISMA methodology (registration in PROSPERO CRD42021236662). The variables were extracted: indications for use, dosage, partial or complete response, adverse reactions, initiation of renal replacement therapy, reduction of proteinuria, and mortality. The quality assessment was done with the "The Joanna Briggs Institute (JBI) Critical Appraisal tools for use in Systematic Reviews Checklist". In addition, synthesis reports were prepared through the Synthesis Without Meta-analysis - SWiM guide.
RESULTS
A total of 2328 articles were obtained (28 were considered for inclusion). When the studies were evaluated, IVIg therapy was found to be between 60% to 70% effective (except for patients with class V LN) with overall responses (complete + partial) even for patients who are refractory to first line treatment. Normalization (<0.5 g) of nephrotic proteinuria occurred in 24% of cases with infrequent adverse events and a mortality plus dialysis composite of 11.5% and 24.1% (most representative study).
CONCLUSION
In patients with LN refractory to conventional treatment or co-infection situations, the reported data seem to demonstrate effectiveness of IVIg therapy. There are few adverse reactions and caution is exercised when using it on patients with class V NL. However, given the lack of controlled studies with long-term follow-up, these data should be interpreted cautiously thus encouraging the development of high-quality RCTs.
Topics: Humans; Lupus Nephritis; Immunoglobulins, Intravenous; Proteinuria; Remission Induction; Immunosuppressive Agents
PubMed: 36028194
DOI: 10.1016/j.autrev.2022.103182 -
Minerva Urology and Nephrology Jun 2022Proteinuria is considered both a known marker for the severity of chronic kidney disease (CKD) and a robust predictor of future renal function and cardiovascular...
INTRODUCTION
Proteinuria is considered both a known marker for the severity of chronic kidney disease (CKD) and a robust predictor of future renal function and cardiovascular morbidity and mortality in a general population. The urological community has long overlooked proteinuria as a marker of renal function. Recently, the American Urological Association (AUA) clinical practice guideline addressed this issue and suggested introducing proteinuria assessment prior to kidney cancer surgery. The aim of this systematic review was to provide evidence of proteinuria as a predictor of renal function impairment and survival outcomes after kidney surgery for renal tumors.
EVIDENCE ACQUISITION
A systematic search was performed by using three search engines (PubMed, Embase, and Web of Science) from January 2010 to November 2020. Study selection followed the PRISMA guidelines. After screening, ten articles and abstracts fully compatible with the PICOS were included in this systematic review.
EVIDENCE SYNTHESIS
Overall, a total of 11,705 patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) were analyzed. When used as a binomial variable, proteinuria prior to surgery was detected from 10% to 33% of patients. Relying on both proteinuria and estimated glomerular filtration rate (eGFR) in the assessment of renal function yielded up to 33% higher rates of patients with preoperative renal impairment. Moreover, proteinuria increased the risk of long-term renal impairment after PN and RN as well as patients with preoperative proteinuria undergoing PN exhibited a greater risk of postoperative acute kidney injury (AKI). Among eligible studies, proteinuria was associated with diabetes, obesity, metabolic syndrome, hypertension and cardiovascular disease. Finally, proteinuria was an independent predictor of overall mortality, but not of cancer-specific mortality.
CONCLUSIONS
Proteinuria yields a prognostic power beyond that provided by estimated glomerular filtration rate (eGFR) among patients undergoing renal cancer surgery, supporting its introduction in the preoperative assessment of renal function. However, well-designed multicenter prospective studies would be necessary to corroborate these results and provided urological community with high-grade recommendation for clinical practice.
Topics: Humans; Kidney; Kidney Neoplasms; Multicenter Studies as Topic; Nephrectomy; Prospective Studies; Proteinuria
PubMed: 34156198
DOI: 10.23736/S2724-6051.21.04308-1 -
Medicine Mar 2016The risk factors influencing the natural course of chronic kidney disease (CKD) are complex and heterogeneous, and few systematic reviews to date have focused on this... (Meta-Analysis)
Meta-Analysis Review
The risk factors influencing the natural course of chronic kidney disease (CKD) are complex and heterogeneous, and few systematic reviews to date have focused on this issue. The aim of the study is to identify the risk factors for disease development and progression in each stage of CKD. We conducted electronic literature searches of PubMed, MEDLINE, Scopus, and the Cochrane Library up to October 15, 2012, for observational studies evaluating the risk factors on the development or progression of CKD. Eligible studies should have collected repeated information that could evaluate changes in renal function. Extracted information from all the included studies was synthesized narratively. Quality assessments were performed using the Newcastle-Ottawa Scale. An exploratory random-effects meta-analysis was performed where feasible to pool effect sizes across studies for a specific risk factor in a specific outcome. We identified 38 cohort studies and 2 case-control studies from 40 articles, with a total of 318,898 participants from 14 countries. The follow-up duration ranged from 1.5 to 16 years. The majority of the included studies were of high quality. The baseline CKD stages of the included studies ranged from normal to later stages, and only 19 studies could be classified into a specific range of CKD stages during follow-up. Three risk factors from studies of the same baseline and follow-up CKD stages were eligible for the exploratory meta-analysis, including male sex, substantial proteinuria, and diabetes. The hazard ratios for the progression from CKD stages 3-5 to end-stage renal disease (ESRD) were 1.37 (95% confidence interval 1.17-1.62), 1.64 (1.01-2.66), and 1.16 (0.98-1.38) for male sex, substantial proteinuria, and diabetes, respectively. In conclusion, our analyses comprehensively summarize the initiating and perpetuating factors for CKD. Male sex and substantial proteinuria are significant perpetuating factors for the progression from late stage CKD to ESRD, and diabetes may play a minor role for the outcome of ESRD among patients with later stages of CKD.
Topics: Diabetic Nephropathies; Disease Progression; Humans; Proteinuria; Renal Insufficiency, Chronic; Risk Factors
PubMed: 26986114
DOI: 10.1097/MD.0000000000003013