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European Journal of Clinical... Dec 2022The main objective was to evaluate the clinical efficacy and safety of finerenone in patients with CKD associated with T2D, especially with regard to renal and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The main objective was to evaluate the clinical efficacy and safety of finerenone in patients with CKD associated with T2D, especially with regard to renal and cardiovascular protection.
METHODS
Eight databases were searched. Mean difference (MD) with 95% confidence interval (CI) of the outcomes and risk ratio (RR) were calculated as the effect measure.
RESULTS
Four trials (n = 13,510) were included. Compared to placebo groups, the urinary albumin-to-creatinine ratio (UACR) mean ratio, along with the proportion of patients with a decreased eGFR (≥ 40%) and end-stage kidney disease (ESKD), was significantly lower (MD: -0.30 (95% CI: -0.32, -0.28), p < 0.00001; RR: 0.85 (95% CI: 0.78, 0.93), p = 0.0002; RR: 0.80 (95% CI: 0.65, 0.99), p = 0.04, respectively). Furthermore, the proportion of patients with cardiovascular events (CVs) was significantly lower (RR: 0.88 (95% CI: 0.80, 0.96), p = 0.003). In terms of safety, while the increase in serum potassium concentration and the incidence of hyperkalemia were significantly higher in the finerenone groups (MD: 0.16 (95% CI: 0.07, 0.26), p = 0.00006; RR: 2.03 (95% CI: 1.83, 2.26), p < 0.00001, respectively), the all-cause mortality and the incidence of adverse events (AEs) were similar to placebo (RR: 0.90 (95% CI: 0.80, 1.00), p = 0.05; RR: 1.00 (95% CI: 0.98, 1.01), p = 0.65, respectively).
CONCLUSION
The observed renal and cardiovascular benefits of finerenone were significant and did not cause unacceptable side-effects. Finerenone may represent a promising therapeutic tool for CKD associated with T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Naphthyridines; Potassium
PubMed: 36273065
DOI: 10.1007/s00228-022-03408-w -
American Journal of Kidney Diseases :... Sep 2020Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the... (Comparative Study)
Comparative Study Meta-Analysis
RATIONALE & OBJECTIVE
Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data.
STUDY DESIGN
Systematic review of randomized controlled trials and network meta-analysis.
SETTING & STUDY POPULATION
Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent.
SEARCH STRATEGY & SOURCES
MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis.
DATA EXTRACTION
Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.
ANALYTICAL APPROACH
Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture.
RESULTS
36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty.
LIMITATIONS
Lack of longer-term data; heterogeneous end point definitions.
CONCLUSIONS
Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent.
Topics: Adult; Calcimimetic Agents; Calcium; Cardiovascular Diseases; Cinacalcet; Comorbidity; Female; Fractures, Bone; Heart Failure; Humans; Hyperparathyroidism, Secondary; Male; Mortality; Naphthalenes; Nausea; Parathyroid Hormone; Peptides; Pyrrolidines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Vomiting
PubMed: 32475604
DOI: 10.1053/j.ajkd.2020.02.439 -
World Journal of Urology Jul 2023To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in... (Meta-Analysis)
Meta-Analysis
PURPOSE
To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in boys with posterior urethral valves (PUV).
METHODS
A systematic search was performed in December 2022. Descriptive and comparative studies with a defined pressure pop-off group were included. Assessed outcomes included end-stage renal disease (ESRD), kidney insufficiency (defined as chronic kidney disease [CKD] stage 3 + or SCr > 1.5 mg/dL), and kidney function. Pooled proportions and relative risks (RR) with 95% confidence intervals (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analyses were performed according to the study design and techniques. The risk of bias was assessed with the QUIPS tool and GRADE quality of evidence. The systematic review was prospectively registered on PROSPERO (CRD42022372352).
RESULTS
A total of 15 studies describing 185 patients with a median follow-up of 6.8 years were included. By the last follow-up, overall effect estimates demonstrate the prevalence of CKD and ESRD to be 15.2% and 4.1%, respectively. There was no significant difference in the risk of ESRD in patients with pop-off compared to no pop-off patients [RR 0.34, 95%CI 0.12, 1.10; p = 0.07]. There was a significantly reduced risk for kidney insufficiency in boys with pop-off [RR 0.57, 95%CI 0.34, 0.97; p = 0.04], but this protective effect was not re-demonstrated after excluding studies with inadequate reporting of CKD outcomes [RR 0.63, 95%CI 0.36, 1.10; p = 0.10]. Included study quality was low, with 6 studies having moderate risk and 9 having a high risk of bias.
CONCLUSIONS
Pop-off mechanisms may be associated with reducing the risk of kidney insufficiency, but current certainty in the evidence is low. Further research is warranted to investigate sources of heterogeneity and long-term sequelae in pressure pop-offs.
Topics: Male; Humans; Kidney Failure, Chronic; Kidney; Renal Insufficiency, Chronic; Urethral Obstruction; Disease Progression
PubMed: 37330439
DOI: 10.1007/s00345-023-04451-7 -
Oral Diseases Jan 2023Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages.
MATERIALS AND METHODS
MEDLINE, Cochrane Central Register of Trials and EMBASE, up to April 4, 2021 were searched. RCTs, prospective and retrospective cohort studies, case-control studies and cross-sectional studies were considered. JBI's Critical Appraisal Tool for risk of bias assessment was used. The risk of PD was calculated using the Mantel-Haenszel odds ratios (MH-OR); weighted mean difference for clinical attachment level (CAL) and periodontal probing depth (PPD) were also evaluated.
RESULTS
Out of 1949 titles screened, 142 full texts were evaluated and 17 studies were included. CKD was associated to higher risk of PD (MH-OR = 2.36, [95% C.I. 1.25, 4.44]; p = 0.008), higher mean CAL (WMD = 0.41 mm [95% C.I. 0.22, 0.60]; p < 0.0001) and mean PPD (WMD = 0.25 mm [95% C.I. 0.03, 0.47]; p = 0.02) compared to healthy individuals. Severe CKD (stages 4-5 vs 2-3) resulted at higher risk of PD (MH-OR = 2.21, [95% C.I. 1.07, 4.54]; p = 0.03). Heterogeneity and risk of bias were high.
CONCLUSIONS
An association between PD and CKD was found. It could be appropriate to consider PD a frequent CKD comorbidity.
Topics: Humans; Prospective Studies; Cross-Sectional Studies; Retrospective Studies; Periodontitis; Renal Insufficiency, Chronic; Chronic Periodontitis
PubMed: 34726333
DOI: 10.1111/odi.14062 -
The Lancet. Diabetes & Endocrinology Jul 2024Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.
METHODS
In this systematic review and meta-analysis, we queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. This study is registered with PROSPERO, CRD42024513836.
FINDINGS
We included 15 trials (N=100 952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0·71 [95% CI 0·67-0·77]), 28% in patients with type 2 diabetes (0·72 [0·67-0·77]), 32% in patients with chronic kidney disease (0·68 [0·61-0·77]), and 28% in patients with atherosclerotic cardiovascular disease (0·72 [0·66-0·79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0·86 [95% CI 0·79-0·93]), 15% in patients with type 2 diabetes (0·85 [0·79-0·91]), 11% in patients with chronic kidney disease (0·89 [0·82-0·96]), and 13% in patients with atherosclerotic cardiovascular disease (0·87 [0·78-0·97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death).
INTERPRETATION
SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.
FUNDING
None.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Humans; Heart Failure; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Renal Insufficiency, Chronic; Hospitalization
PubMed: 38768620
DOI: 10.1016/S2213-8587(24)00102-5 -
BMJ Open Mar 2022To summarise available chronic kidney disease (CKD) diagnostic and prognostic models in low-income and middle-income countries (LMICs).
OBJECTIVE
To summarise available chronic kidney disease (CKD) diagnostic and prognostic models in low-income and middle-income countries (LMICs).
METHOD
Systematic review (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). We searched Medline, EMBASE, Global Health (these three through OVID), Scopus and Web of Science from inception to 9 April 2021, 17 April 2021 and 18 April 2021, respectively. We first screened titles and abstracts, and then studied in detail the selected reports; both phases were conducted by two reviewers independently. We followed the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies recommendations and used the Prediction model Risk Of Bias ASsessment Tool for risk of bias assessment.
RESULTS
The search retrieved 14 845 results, 11 reports were studied in detail and 9 (n=61 134) were included in the qualitative analysis. The proportion of women in the study population varied between 24.5% and 76.6%, and the mean age ranged between 41.8 and 57.7 years. Prevalence of undiagnosed CKD ranged between 1.1% and 29.7%. Age, diabetes mellitus and sex were the most common predictors in the diagnostic and prognostic models. Outcome definition varied greatly, mostly consisting of urinary albumin-to-creatinine ratio and estimated glomerular filtration rate. The highest performance metric was the negative predictive value. All studies exhibited high risk of bias, and some had methodological limitations.
CONCLUSION
There is no strong evidence to support the use of a CKD diagnostic or prognostic model throughout LMIC. The development, validation and implementation of risk scores must be a research and public health priority in LMIC to enhance CKD screening to improve timely diagnosis.
Topics: Adult; Developing Countries; Female; Glomerular Filtration Rate; Humans; Middle Aged; Poverty; Prognosis; Renal Insufficiency, Chronic
PubMed: 35292503
DOI: 10.1136/bmjopen-2021-058921 -
International Journal of Molecular... Nov 2022Chronic kidney disease (CKD) is a widely diffuse pathological condition which deeply impacts upon an affected patient's quality of life and its worldwide rate is... (Review)
Review
Chronic kidney disease (CKD) is a widely diffuse pathological condition which deeply impacts upon an affected patient's quality of life and its worldwide rate is predicted to further rise. The main biological mechanism underlying CKD is renal fibrosis, a non-reversible process representing, for the affected system, a point of no return of tissue damage and dysfunction, deeply reducing the possible therapeutic strategies at the disposal of physicians. The best tool clinicians can use to address the extent of renal fibrosis at any level (glomeruli, tubule-interstitium, vasculature) is kidney biopsy that, despite its overall safety, remains an invasive procedure showing some shortcomings. Thus, the identification of novel non-invasive renal fibrosis biomarkers would be of fundamental importance. Here, when systematically reviewing the available evidence on serological biomarkers associated with renal fibrosis evaluated in patients suffering from CKD in the last five years, we found that despite the presence of several promising biomarkers, the level of observed evidence is still very scattered. Probably, the use of multiple measures capable of addressing different aspects involved in this condition would be the most suitable way to capture the high complexity characterizing the renal fibrotic process, having consequently a great impact on clinical practice by maximizing prevention, diagnosis, and management.
Topics: Humans; Quality of Life; Fibrosis; Biomarkers; Renal Insufficiency, Chronic; Kidney Glomerulus
PubMed: 36430625
DOI: 10.3390/ijms232214139 -
Journal of Nephrology Dec 2022As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our... (Review)
Review
BACKGROUND
As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our aim was to perform a systematic review to describe obstetric and renal outcomes in women with CKD following ART.
METHODS
The following databases were searched from 1946 to May 2021: (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) Embase and (4) MEDLINE.
RESULTS
The database search identified 3520 records, of which 32 publications were suitable. A total of 84 fertility treatment cycles were analysed in 68 women. Median age at time of pregnancy was 32.5 years (IQR 30.0, 33.9 years). There were 60 clinical pregnancies resulting in 70 live births (including 16 multifetal births). Four women developed ovarian hyperstimulation syndrome which were associated with acute kidney injury. Hypertensive disorders complicated 26 pregnancies (38.3%), 24 (35.3%) pregnancies were preterm delivery, and low birth weight was present in 42.6% of pregnancies. Rates of live birth and miscarriage were similar for women with CKD requiring ART or having natural conception. However, more women with ART developed pre-eclampsia (p < 0.05) and had multifetal deliveries (p < 0.001), furthermore the babies were lower gestational ages (p < 0.001) and had lower birth weights (p < 0.001).
CONCLUSION
This systematic review represents the most comprehensive assessment of fertility outcomes in patients with CKD following ART. However, the high reported live birth rate is likely related to reporting bias. Patient selection remains crucial in order to maximise patient safety, screen for adverse events and optimise fertility outcomes.
Topics: Infant; Pregnancy; Infant, Newborn; Humans; Female; Renal Insufficiency, Chronic; Kidney; Reproductive Techniques, Assisted; Acute Kidney Injury; Live Birth
PubMed: 36396849
DOI: 10.1007/s40620-022-01510-x -
Renal Failure Dec 2024Researchers have delved into noninvasive diagnostic methods of renal fibrosis (RF) in chronic kidney disease, including ultrasound (US), magnetic resonance imaging... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
Researchers have delved into noninvasive diagnostic methods of renal fibrosis (RF) in chronic kidney disease, including ultrasound (US), magnetic resonance imaging (MRI), and radiomics. However, the value of these diagnostic methods in the noninvasive diagnosis of RF remains contentious. Consequently, the present study aimed to systematically delineate the accuracy of the noninvasive diagnosis of RF.
MATERIALS AND METHODS
A systematic search covering PubMed, Embase, Cochrane Library, and Web of Science databases for all data available up to 28 July 2023 was conducted for eligible studies.
RESULTS
We included 21 studies covering 4885 participants. Among them, nine studies utilized US as a noninvasive diagnostic method, eight studies used MRI, and four articles employed radiomics. The sensitivity and specificity of US for detecting RF were 0.81 (95% CI: 0.76-0.86) and 0.79 (95% CI: 0.72-0.84). The sensitivity and specificity of MRI were 0.77 (95% CI: 0.70-0.83) and 0.92 (95% CI: 0.85-0.96). The sensitivity and specificity of radiomics were 0.69 (95% CI: 0.59-0.77) and 0.78 (95% CI: 0.68-0.85).
CONCLUSIONS
The current early noninvasive diagnostic methods for RF include US, MRI, and radiomics. However, this study demonstrates that US has a higher sensitivity for the detection of RF compared to MRI. Compared to US, radiomics studies based on US did not show superior advantages. Therefore, challenges still exist in the current radiomics approaches for diagnosing RF, and further exploration of optimized artificial intelligence (AI) algorithms and technologies is needed.
Topics: Humans; Renal Insufficiency, Chronic; Fibrosis; Magnetic Resonance Imaging; Ultrasonography; Sensitivity and Specificity; Kidney
PubMed: 38938187
DOI: 10.1080/0886022X.2024.2367021 -
European Urology Focus Jan 2022Reduced renal function impairs salt and water homeostasis, which can drive nocturnal or 24-h polyuria. Nocturia can arise early in chronic kidney disease (CKD).... (Review)
Review
CONTEXT
Reduced renal function impairs salt and water homeostasis, which can drive nocturnal or 24-h polyuria. Nocturia can arise early in chronic kidney disease (CKD). Evidence-based recommendations can facilitate management outside nephrology clinics.
OBJECTIVE
To conduct a systematic review (SR) of nocturia in CKD and achieve expert consensus for management in primary care and in specialist clinics outside nephrology.
EVIDENCE ACQUISITION
Four databases were searched from January 2000 to April 2020. A total of 4011 titles and abstracts were screened, and 108 studies underwent full-text screening. Seven studies met the inclusion criteria and two were identified through other sources. Consensus was achieved among an expert panel with public involvement using the nominal group technique (NGT).
EVIDENCE SYNTHESIS
Several plausible mechanisms contribute to nocturnal or 24-h polyuria in CKD, but there is little evidence on interventions to improve nocturia. NGT assessment recommendations for nocturia (at least two voids per night) in patients with CKD or at risk of CKD being assessed in a non-nephrology setting are: history (thirst, fluid intake), medication review (diuretics, lithium, calcium channel antagonists, nonsteroidal anti-inflammatory medications), examination (oedematous state, blood pressure), urinalysis (haematuria and albumin/creatinine ratio), blood tests (blood urea, serum creatinine and electrolytes, estimated glomerular filtration rate), and a bladder diary. Renal ultrasound should follow local CKD guidelines. Treatment options include optimising blood pressure control, dietary adjustment to reduce salt intake, fluid advice, and a medication review. Referral to specialist nephrology services should follow local guidelines.
CONCLUSIONS
CKD should be considered when evaluating patients with nocturia. The aim of assessment is to identify mechanisms and instigate therapy, but the latter may be more applicable to reducing wider morbidity associated with CKD than nocturia itself.
PATIENT SUMMARY
People with kidney disease can suffer severe sleep disturbance because of a need to pass urine overnight. We looked at published research and found some useful information about the underlying mechanisms. A group of experts was able to develop practical approaches for assessing and treating this condition.
Topics: Consensus; Humans; Nocturia; Polyuria; Primary Health Care; Renal Insufficiency, Chronic
PubMed: 35031353
DOI: 10.1016/j.euf.2021.12.010