scholarly journals Liver Stiffness, Albuminuria and Chronic Kidney Disease in Patients with NAFLD: A Systematic Review and Meta-Analysis

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 105
Author(s):  
Stefano Ciardullo ◽  
Cinzia Ballabeni ◽  
Roberto Trevisan ◽  
Gianluca Perseghin

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2907 ◽  
Author(s):  
Weifeng Shang ◽  
Lixi Li ◽  
Yali Ren ◽  
Qiangqiang Ge ◽  
Ming Ku ◽  
...  

Background Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. Methods PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Results Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23–1.76])], with significant heterogeneity among these studies (I2 = 93.6%, P < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. Conclusion A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures.


2021 ◽  
Vol 12 ◽  
Author(s):  
QiFeng Liu ◽  
LiXia Yu ◽  
XiaoYa Yin ◽  
JianMing Ye ◽  
ShaSha Li

Background: The correlation between soluble Klotho (sKlotho) level and vascular calcification (VC) in patients with chronic kidney disease (CKD) remains controversial. Using meta-analysis, we aimed to address this controversy and assess the feasibility of applying sKlotho as a biomarker for VC.Methods: Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients (r), odds ratios (ORs), hazard ratio (HR) or β-values, and 95% confidence intervals (CIs) were extracted and combined according to study design or effector calculation method. Pooled effectors were generated using both random-effects models and fixed-effects models according to I2-value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis.Results: Ten studies with 1,204 participants from a total of 1,199 publications were eligible and included in this meta-analysis. The combined correlation coefficient (r) was [−0.33 (−0.62, −0.04)] with significant heterogeneity (I2 = 89%, p &lt; 0.001) based on Spearman correlation analysis, and this significant association was also demonstrated in subgroups. There was no evidence of publication bias. The combined OR was [3.27 (1.70, 6.30)] with no evidence of heterogeneity (I2 = 0%, p = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity (I2 = 63%, p = 0.10) when sKlotho was treated as a continuous variable based on multivariate logistic regression. No significant association was observed and the pooled OR was [0.29 (0.01, 11.15)] with high heterogeneity (I2 = 96%, p &lt; 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient (r) was [−0.20 (−0.40, −0.01)] with significant heterogeneity (I2 = 86%, p &lt; 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels.Conclusion: There exists a significant association between decreased sKlotho level and increased risk of VC in CKD patients. This raises the possibility of applying sKlotho as a biomarker for VC in CKD populations. Large, prospective, well-designed studies or interventional clinical trials are required to validate our findings.


Author(s):  
Ditte Marie Kirkegaard-Klitbo ◽  
Flemming Bendtsen ◽  
Jens Lundgren ◽  
Robert J de Knegt ◽  
Klaus Fuglsang Kofoed ◽  
...  

Abstract Background Liver fibrosis is associated with poor liver related outcomes and mortality. People living with HIV (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls. Methods Cross-sectional cohort study. We compared 342 PWH with 2,190 population controls aged 50-70 years. Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were computed by logistic regression. Results The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%), p&lt;0.01). HIV infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR:1.84 (1.17;2.88), p&lt;0.01); higher age (per decade, aOR:3.34 (1.81;6.18), p&lt;0.01); ALT (per 10 IU/L, aOR:1.25 (1.05;1.49), p&lt;0.01); BMI (per 1 kg/m 2, aOR:1.17 (1.05;1.29), p&lt;0.01) and previous exposure to didanosine (per year aOR:2.26 (1,01;5.06), p=0.05). Conclusions The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine and a positive HIV status was independently associated with higher odds of elevated LSM.


2021 ◽  
Vol 10 (13) ◽  
pp. 2907
Author(s):  
Alba Martínez-Escudé ◽  
Guillem Pera ◽  
Anna Costa-Garrido ◽  
Lluís Rodríguez ◽  
Ingrid Arteaga ◽  
...  

Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18–75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 ± 12 years; 61% female). Subjects with TSH ≥ 2.5 μIU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH ≥ 2.5 (μIU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of ≥ 8.0 kPa and ≥ 9.2 kPa, respectively, in subjects with TSH ≥ 2.5 μIU/mL compared with TSH < 2.5 μIU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values ≥ 10 μIU/mL.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Bakhtawar K Mahmoodi ◽  
Ron T Gansevoort ◽  
Inger Anne Naess ◽  
Pamela L Lutsey ◽  
Sigrid K Braekkan ◽  
...  

Background: Recent findings suggest that mild chronic kidney disease (CKD) might be associated with increased risk of venous thromboembolism (VTE). However, results were partially inconsistent, which may be due to lack of power. We therefore performed a meta-analysis to investigate the association between mild CKD and VTE incidence. Methods: A literature search was performed to retrieve community-based cohorts with information on the association of estimated glomerular filtration rate (eGFR) and albuminuria with VTE. Five cohorts were identified that were pooled on individual level. To obtain pooled hazard ratios (HRs) for VTE, linear spline models were fitted using Cox regression with shared-frailty. Models were adjusted for age, sex, hypertension, total cholesterol, smoking, diabetes, history of cardiovascular disease and body-mass index. Random-effect meta-analysis was used to obtain adjusted pooled HRs of VTE with CKD versus no CKD. Results: The analysis included 95,154 participants with 1,178 VTE cases and 599,453 person-years of follow-up. Risk of VTE increased continuously with lower eGFR and higher ACR (Figure). Compared with eGFR 100 mL/min/1.73m², pooled adjusted HRs for VTE were 1.3 (1.0–1.7) for eGFR 60, 1.8 (1.3–2.6) for 45 and 1.9 (1.2–2.9) for 30 mL/min/1.73m². Compared with albumin-creatinine ratio (ACR) 5 mg/g, pooled adjusted HRs for VTE were 1.3 (1.04–1.7) for ACR 30, 1.6 (1.1–2.4) for 300 and 1.9 (1.2–3.1) for 1000 mg/g. There was no evidence for interaction between eGFR and ACR (P=0.22). The pooled adjusted HR for CKD (eGFR <60 ml/min/1.73m² or albuminuria ≥30 mg/g) vs. no CKD was 1.5 (95%CI, 1.2–2.1). Results were similar for idiopathic and provoked VTE. Conclusion: Both reduced eGFR and elevated albuminuria are novel independent predictors of VTE in the general population.


2021 ◽  
Vol 12 ◽  
pp. 204062232110486
Author(s):  
Ying Cao ◽  
You Deng ◽  
Jingjing Wang ◽  
Hong Zhao ◽  
Jingyu Zhang ◽  
...  

Objective: The aim of this study was to evaluate the association between nonalcoholic fatty liver disease (NAFLD) and NAFLD with different comorbidities and risk of chronic kidney disease (CKD) and abnormal albuminuria. Materials and Methods: A total of 3872 Chinese individuals excluding those with hepatitis B or C infection and absence of alcohol abuse were included in the study. NAFLD was diagnosed by abdominal ultrasonography. The liver fibrosis was assessed by NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or abnormal albuminuria (urinary albumin-to-creatinine ratio ⩾ 3 mg/mmol). The logistic regression analysis was performed to examine the association between NAFLD and NAFLD with different comorbidities and risk of CKD. Results: The prevalence of CKD and abnormal albuminuria was higher in individuals with NAFLD than in those without NAFLD (15.8% vs 11.9%, p < 0.001; 14.8% vs 11.0%, p < 0.001). Logistic regression analysis demonstrated that NAFLD was risk factor of CKD. Notably, after adjustment for sex, age, and DM, NAFLD was associated with 1.31-fold higher risk of prevalent CKD ⩾ 1 ( p < 0.05). NAFLD individuals with elder age, DM, obesity, hypertension, MetS, and advanced liver fibrosis had higher risks of both prevalent CKD and abnormal albuminuria than those without comorbidities. Conclusions: NAFLD and NAFLD with traditional comorbidities are strongly associated with risk of prevalence of CKD and abnormal albuminuria. Patients with NAFLD especially those with coexisting comorbidities were recommended to carefully access the development of CKD.


2021 ◽  
Author(s):  
Kevin C. Maki ◽  
Meredith L. Wilcox ◽  
Mary R. Dicklin ◽  
Rahul Kakkar ◽  
Michael H. Davidson

Abstract Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥ 12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 38 trials with duration ≥ 12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 8 of other types of interventions. All-cause mortality was reported in 116/2385 (4.86%) subjects in intervention groups and 161/2404 (6.70%) subjects in control groups. The pooled RR estimate of the 24 trials ≥ 12 months with ≥ 1 event in ≥ 1 group was 0.72 (95% CI 0.57 to 0.91, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥ 6 months (31 trials), ≥ 9 months (26 trials), and > 12 months (9 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.66, 95% CI 0.38 to 1.15. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Esther D Kim ◽  
Ning Ding ◽  
Junichi Ishigami ◽  
Xuejuan Ning ◽  
Yijing Feng ◽  
...  

Background: Chronic kidney disease (CKD) strongly predicts sudden cardiac death and may elevate the risk of certain cardiac arrhythmias like atrial fibrillation; however, the relationships between CKD and various types of arrhythmia are not well-characterized. Methods: We performed a systematic review and meta-analysis by searching Embase and PubMed for prospective, cross-sectional, and case-control studies examining the associations of two key CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with arrhythmias in adults that were published until July 2018. We performed qualitative assessment of studies using the Newcastle Ottawa Quality Assessment Scale. We pooled the results using random-effects models. Results: Among 16,245 articles, we identified 34 prospective (n=24,213,233), 21 cross-sectional (n=253,328), and 4 case-control (n=1,694) studies that included diverse study populations from 19 countries and were mostly high quality. Most prospective studies examined the relationship between eGFR and atrial fibrillation (AF), and demonstrated that lower eGFR was associated with a higher risk of AF (pooled hazard ratio [HR] 1.72 [95% CI: 1.30, 2.27] comparing reduced vs. referent eGFR groups)[ Figure ]. A few studies examined albuminuria and demonstrated its associations with AF (pooled HR 2.16 [95% CI: 1.74, 2.67] comparing high vs. low albuminuria). Results were similar for cross-sectional studies. Four prospective studies reported a higher incidence of ventricular tachycardia resulting in ICD shock according to reduced eGFR (pooled HR 2.32 [95% CI: 1.74, 3.09] comparing reduced vs. referent eGFR groups). Limited number of studies examined other types of arrhythmia. Conclusion: We identified robust data on the relationship between CKD (eGFR and albuminuria) and AF. Reduced eGFR was associated with life-threatening ventricular arrhythmias. Our review highlights the need of future studies for non-AF arrhythmias, especially in the context of albuminuria.


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