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Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
Kidney International Reports Nov 2022Women and girls with X-linked Alport syndrome have a risk of disease progression that is difficult to predict. This systematic review examined whether proteinuria...
INTRODUCTION
Women and girls with X-linked Alport syndrome have a risk of disease progression that is difficult to predict. This systematic review examined whether proteinuria correlated with genotype and disease severity in this population.
METHODS
PubMed and Scopus were searched for manuscripts from the past 20 years with "," "female," "proteinuria" and related terms. Genotypes and clinical data for women and girls with pathogenic heterozygous variants were extracted. Features were then compared between females with proteinuria or without proteinuria; and genotype-phenotype correlations for age at proteinuria and kidney failure determined.
RESULTS
Three-hundred sixty-six women and girls with variants and a median age of 29 years (interquartile range 15-46) were identified. Eighty-eight (24%) had large rearrangements or truncating variants, 63 (17%) had splicing variants, and 215 (59%) had missense changes. In all, 236 (64%) had proteinuria, 56 (16%) had kidney failure, 40 (16%) had a hearing loss, and 15 (7%) had ocular abnormalities. Women and girls with proteinuria were more likely to have large rearrangements or truncating variants ( = 0.005), and less likely to have missense changes ( = 0.0002). Those with proteinuria were also more likely to develop kidney failure ( < 0.0001). Women and girls with truncating, large or splicing variants developed proteinuria earlier than those with missense changes ( = 0.001, < 0.0001 respectively). Those whose proteinuria was detected before the age of 15 progressed to kidney failure sooner ( < 0.0001).
CONCLUSION
Proteinuria correlates with a more severe genotype in women and girls with X-linked Alport syndrome and is an indicator of disease severity and likely progression.
PubMed: 36531881
DOI: 10.1016/j.ekir.2022.08.021 -
European Journal of Anaesthesiology Jul 2021To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up.
BACKGROUND
Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting.
METHODS
We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated.
RESULTS
Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+.
CONCLUSION
Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients.
PROSPERO REGISTRATION
CRD42020190065.
Topics: Acute Kidney Injury; Humans; Postoperative Period; Proteinuria; Renal Replacement Therapy; Risk Factors
PubMed: 34101638
DOI: 10.1097/EJA.0000000000001542 -
BMJ Open Oct 2023The study intended to assess the pooled prevalence of vitamin D deficiency (VDD) and its associated factors among patients with type 2 diabetes mellitus (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The study intended to assess the pooled prevalence of vitamin D deficiency (VDD) and its associated factors among patients with type 2 diabetes mellitus (T2DM).
DESIGN
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were employed to plan and conduct this systematic review and meta-analysis.
DATA SOURCES
PubMed, Medline, Google Scholar, Web of Science, Science Direct and the Worldwide Science database were searched from their inception to 31 January 2023.
METHODS
Data were extracted using a standardised data extraction format prepared in Microsoft Excel. The inverse variance (I) test was used to evaluate the presence of heterogeneity across the included studies. To identify the possible source of heterogeneity, subgroup analysis was carried out. Funnel plot symmetry, Begg's and Egger's tests were used to evaluate the existence of publication bias. In addition, factors associated with VDD among patients with T2DM were examined. All statistical analyses were carried out with STATA V.14 software.
RESULTS
A total of 54 studies with 38 016 study participants were included in the study. The pooled prevalence of VDD among patients with T2DM was found to be 64.2% (95% CI 60.6% to 67.8%) with a substantial level of heterogeneity (I=98.2%; p<0.001). Results of the subgroup analysis indicated that the pooled prevalence of VDD among patients with T2DM was highest (70.9%) in African nations and lowest (57.1%) in Middle East countries. Being female (pooled OR (POR) 1.60, 95% CI 1.29 to 1.97), having poor glycaemic control (POR 2.50; 95% CI 1.74 to 3.59), hypertension (POR 1.21; 95% CI 1.08 to 1.36), obesity (body mass index ≥25) (POR 1.68; 95% CI 1.16 to 2.44), dyslipidaemia (POR 2.54, 95% CI 1.37 to 4.73), albuminuria (POR 2.22, 95% CI 1.71 to 2.95), nephropathy (POR 1.58; 95% CI 1.08 to 2.31) and retinopathy (POR 1.48: 95% CI 1.17 to 1.89) were predictors of VDD among patients with T2DM.
CONCLUSIONS
More than half of patients with T2DM were suffering from VDD. Being female, having poor glycaemic control, hypertension, obesity, dyslipidaemia, albuminuria, nephropathy and retinopathy were the predictors of VDD among patients with T2DM.
Topics: Humans; Female; Male; Diabetes Mellitus, Type 2; Albuminuria; Obesity; Hypertension; Dyslipidemias; Retinal Diseases; Vitamin D Deficiency; Prevalence; Ethiopia
PubMed: 37798019
DOI: 10.1136/bmjopen-2023-075607 -
International Journal of Clinical... 2022Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens.
METHODS
Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions.
RESULTS
Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately).
CONCLUSIONS
Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.
Topics: Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Network Meta-Analysis; Proteinuria; Rituximab; Steroids; Tacrolimus
PubMed: 35685506
DOI: 10.1155/2022/4996239 -
Clinical Nutrition ESPEN Dec 2023Sarcopenic obesity (SO), which refers to the coexistence of sarcopenia and obesity. The aim of this systematic review and meta-analysis was first to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Sarcopenic obesity (SO), which refers to the coexistence of sarcopenia and obesity. The aim of this systematic review and meta-analysis was first to assess the prevalence of SO in patients with diabetes, and second, to evaluate possible adverse outcomes.
METHODS
This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the data were collated by means of meta-analysis and narrative synthesis. We comprehensively and systematically searched PubMed, Embase, Web of Science, CBM, CNKI, Wanfang Database from the establishment of the database to December 2022, and collected related studies on SO in patients with diabetes. Using Stata 16.0 software to pool the estimates for the prevalence of SO in patients with diabetes, and a descriptive systematic review of possible adverse outcomes was performed.
RESULTS
The prevalence of 20 included studies were pooled by a random-effects model, which showed that the prevalence of SO in patients with diabetes was 27%. Subgroup analyses showed that the prevalence of SO was higher among studies using BIA (24%) to assess muscle mass, and those focused on literature of moderate-quality (29%), being published from 2013 to 2016 (29%), female patients with diabetes (17%), North Americans (30%). SO in patients with diabetes can lead to adverse outcomes including decreased glomerular filtration rate, massive proteinuria, cognitive decline, and insulin resistance.
CONCLUSION
The systematic review and meta-analysis revealed a prevalence of 27% for SO in patients with diabetes, and it is associated with potential serious adverse outcomes. Therefore, we should attach importance to the screening of SO in patients with diabetes and early detection of susceptible groups, then selecting appropriate interventions to reduce the occurrence of it and various adverse outcomes in this demographic.
Topics: Humans; Female; Sarcopenia; Prevalence; Obesity; Diabetes Mellitus; Insulin Resistance
PubMed: 38056996
DOI: 10.1016/j.clnesp.2023.09.920 -
Chemotherapy 2014We performed a systematic review and meta-analysis of the risk of proteinuria associated with ramucirumab. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed a systematic review and meta-analysis of the risk of proteinuria associated with ramucirumab.
METHODS
Eligible studies included randomized phase II and III trials of patients with solid tumors on ramucirumab, describing events of all-grade and high-grade proteinuria.
RESULTS
Our search strategy yielded 170 potentially relevant citations from PubMed/Medline, CENTRAL Cochrane database, ASCO and ESMO meeting libraries. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The relative risk (RR) of all-grade proteinuria was 3.31 (95% CI 2.48-4.42; p < 0.00001). Moreover, the RR of high-grade proteinuria was 5.28 (95% CI 2.32-12.01; p < 0.0001).
CONCLUSIONS
Our meta-analysis has demonstrated that ramucirumab use is associated with an increased risk of all-grade and high-grade proteinuria. Early detection strategies should be employed in those patients to prevent the progression to more sinister renal disease.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Clinical Trials as Topic; Humans; Neoplasms; Proteinuria; Treatment Outcome; Ramucirumab
PubMed: 26302785
DOI: 10.1159/000437253 -
Annals of Internal Medicine Apr 2011The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear. (Review)
Review
BACKGROUND
The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear.
PURPOSE
To summarize trials comparing lower versus higher blood pressure targets in adult patients with CKD and focus on proteinuria as an effect modifier.
DATA SOURCES
MEDLINE and the Cochrane Central Register of Controlled Trials (July 2001 through January 2011) were searched for reports from randomized, controlled trials with no language restriction.
STUDY SELECTION
Authors screened abstracts to identify reports from trials comparing blood pressure targets in adults with CKD that had more than 50 participants per group; at least 1-year follow-up; and outcomes of death, kidney failure, cardiovascular events, change in kidney function, number of antihypertensive agents, and adverse events.
DATA EXTRACTION
Reviewers extracted data on study design, methods, sample characteristics, interventions, comparators, outcomes, number of medications, and adverse events and rated study quality and quality of analyses for proteinuria subgroups.
DATA SYNTHESIS
Three trials with a total of 2272 participants were included. Overall, trials did not show that a blood pressure target of less than 125/75 to 130/80 mm Hg is more beneficial than a target of less than 140/90 mm Hg. Lower-quality evidence suggests that a low target may be beneficial in subgroups with proteinuria greater than 300 to 1000 mg/d. Participants in the low target groups needed more antihypertensive medications and had a slightly higher rate of adverse events.
LIMITATIONS
No study included patients with diabetes. Trial duration may have been too short to detect differences in clinically important outcomes, such as death and kidney failure. Ascertainment and reporting of adverse events was not uniform.
CONCLUSION
Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. Whether a lower target benefits patients with proteinuria greater than 300 to 1000 mg/d requires further study.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Kidney Failure, Chronic; Proteinuria; Research Design; Treatment Outcome
PubMed: 21403055
DOI: 10.7326/0003-4819-154-8-201104190-00335 -
Frontiers in Cardiovascular Medicine 2021Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse...
Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse outcomes. To date, no study has synthesized evidence on its role as a prognostic indicator. Thus, the current study aimed to quantitatively assess the prognostic utility of albuminuria as well as dipstick proteinuria in predicting mortality in heart failure patients. PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched up to October 10, 2020. All studies reporting multivariable-adjusted hazard ratios (HR) for albuminuria or dipstick proteinuria for mortality and/or hospitalization in heart failure patients were included. Eleven studies were included. Seven assessed albuminuria and five assessed dipstick proteinuria. Our analysis revealed a statistically significant increased risk of all-cause mortality with microalbuminuria (HR: 1.54; 95% CI, 1.23-1.93; = 79%; = 0.0002) and macroalbuminuria (HR: 1.76; 95% CI, 1.21-2.56; = 88%; = 0.003) in heart failure patients. The risk of all-cause mortality and hospitalization was also significantly increased with macroalbuminuria. Microalbuminuria was associated with significantly increased cardiovascular mortality and combined cardiovascular mortality and hospitalization. Positive dipstick test for proteinuria was significantly associated with mortality in heart failure (HR: 1.54; 95% CI, 1.28-1.84; = 67%; < 0.00001). Both microalbuminuria and macroalbuminuria are predictors of mortality in patients with heart failure. Dipstick proteinuria may be used as a rapid screening test to predict mortality in these patients.
PubMed: 34055938
DOI: 10.3389/fcvm.2021.665831 -
Cerebrovascular Diseases (Basel,... 2015The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure.
METHODS
We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation.
RESULTS
After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the presence of SVD was associated with an increased risk of renal impairment (whether proteinuria or reduced eGFR) OR 2.33 (95% CI 1.80-3.01), when compared to those without SVD. After adjustment for age and hypertension, 15/21 studies still reported a significant association between renal impairment and SVD.
CONCLUSION
We found no specific association between renal impairment and lacunar stroke, but we did find that in individuals who had not had a stroke, having more SVD features on imaging was associated with a worse renal function, which remained significant after controlling for hypertension. However, this finding does not exclude a powerful co-associate effect of age or vascular risk factor exposure. Future research should subtype lacunar stroke sensitively and control for major risk factors.
Topics: Cerebral Small Vessel Diseases; Glomerular Filtration Rate; Humans; Magnetic Resonance Imaging; Renal Insufficiency, Chronic; Stroke, Lacunar; White Matter
PubMed: 25547195
DOI: 10.1159/000369777