Altered HDL Proteome Predicts Incident CVD in Chronic Kidney Disease Patients.
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ABSTRACT:
SUBMITTER: Shao B
PROVIDER: S-EPMC8566900 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein-SFTPB (pulmonary surfactant protein B)-predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker-and perhaps mediator-of CVD risk in patients with T1DM.
| S-EPMC9010748 | biostudies-literature
Project description:Low HDL-cholesterol (HDL-C) concentrations are a typical trait of the dyslipidemia associated with chronic kidney disease (CKD). In this condition, plasma HDLs are characterized by alterations in structure and function, and these particles can lose their atheroprotective functions, e.g., the ability to promote cholesterol efflux from peripheral cells, anti-oxidant and anti-inflammatory proprieties and they can even become dysfunctional, i.e., exactly damaging. The reduction in plasma HDL-C levels appears to be the only lipid alteration clearly linked to the progression of renal disease in CKD patients. The association between the HDL system and CKD development and progression is also supported by the presence of genetic kidney alterations linked to HDL metabolism, including mutations in the APOA1, APOE, APOL and LCAT genes. Among these, renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients, being present also in acquired LCAT deficiency. This review summarizes the major alterations in HDL structure and function in CKD and how genetic alterations in HDL metabolism can be linked to kidney dysfunction. Finally, the possibility of targeting the HDL system as possible strategy to slow CKD progression is reviewed.
| S-EPMC10182177 | biostudies-literature
Project description:Background and objectivesThe matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.Design setting participants and measurementsA community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.ResultsThere was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman ρ = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).ConclusionsHigher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.
| S-EPMC5511996 | biostudies-literature
Project description:CVD remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD profoundly affects HDL composition and functionality, but whether abnormal HDL independently contributes to cardiovascular events in CKD patients remains elusive. In the present study, we assessed whether compositional and functional properties of HDL predict cardiovascular outcome among 526 nondialysis CKD patients who participate in the CARE FOR HOMe study. We measured HDL cholesterol, the content of HDL-associated proinflammatory serum amyloid A (SAA), and activities of the HDL enzymes paraoxonase and lipoprotein-associated phospholipase A2 (Lp-PLA2). In addition, we assessed the antioxidative activity of apoB-depleted serum. During a mean follow-up of 5.1 ± 2.1 years, 153 patients reached the predefined primary endpoint, a composite of atherosclerotic cardiovascular events including cardiovascular mortality and death of any cause. In univariate Cox regression analyses, lower HDL-cholesterol levels, higher HDL-associated SAA content, and lower paraoxonase activity predicted cardiovascular outcome, while Lp-PLA2 activity and antioxidative capacity did not. HDL-cholesterol and HDL-paraoxonase activity lost their association with cardiovascular outcome after adjustment for traditional cardiovascular and renal risk factors, while SAA lost its association after further adjustment for C-reactive protein. In conclusion, our data suggest that neither HDL quantity nor HDL composition or function independently predict cardiovascular outcome among nondialysis CKD patients.
| S-EPMC6027904 | biostudies-literature
Project description:BackgroundAcute kidney disease (AKD) is defined as impaired kidney function present for <90 days with or without an acute kidney injury (AKI) event. Adults with AKD have an increased risk for progression to chronic kidney disease (CKD) and mortality. There are no data on the epidemiology of AKD in children after transplant. The aim of this study was to evaluate the incidence and risk factors for AKI, AKD, and CKD in children after transplantation.MethodsThis is a retrospective cohort study of all children undergoing non-kidney solid organ transplant between 2011 and 2019 at UPMC Children's Hospital of Pittsburgh. AKI and AKD were defined using the Kidney Disease Improving Global Outcomes criteria. Patients with a new estimated glomerular filtration rate <60 ml/min/1.73m2 persisting for >3 months met criteria for new CKD. Variables associated with AKI, AKD, and CKD were analyzed.ResultsAmong 338 patients, 37.9% met criteria for severe AKI, 13% for AKD, and 8% for a new diagnosis of CKD. Stage 3 AKI was independently associated with AKD (OR: 5.35; 95% CI: 2.23-12.86). Severe AKI was not associated with new-onset CKD, whereas AKD was associated with new-onset CKD (OR: 29.74; CI: 11.22-78.82).ConclusionAKD may be superior to AKI in predicting risk of CKD in children after non-kidney solid organ transplantation.
| S-EPMC9018890 | biostudies-literature
Project description:BACKGROUND:Urinary miRNAs may potentially serve as noninvasive biomarkers in various kidney diseases to reflect disease activity, severity and progression, especially those correlated with the pathogenesis of kidney diseases. This study demonstrates that urinary miR-196a, a kidney-enriched miRNA, can predict progression of chronic kidney disease (CKD). METHODS:Focal segmental glomerulosclerosis (FSGS) cohorts were used as the representative example of CKD. First, correlation of miR-196a with disease activity was analyzed using paired urine and plasma samples from FSGS patients with nephrotic-range proteinuria (FSGS-A), complete remission (FSGS-CR) and normal controls (NCs). Then, the value of urinary miR-196a in predicting disease progression was validated using another cohort of 231 FSGS patients who were followed-up until over 36 months or reaching end-stage renal disease (ESRD). MiR-196a levels were analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS:The results showed that urinary miR-196a significantly increased in FSGS-A compared with FSGS-CR and NCs, clearly distinguishing FSGS-A from FSGS-CR and NCs, whereas plasma miR-196a showed no difference among these groups. Moreover, urinary miR-196a, which was associated with proteinuria, estimated glomerular filtration rate (eGFR), interstitial fibrosis and tubular atrophy, significantly increased in patients progressed to ESRD compared to those not. Furthermore, patients with higher urinary miR-196a displayed poorer renal survival than those with lower urinary miR-196a. Multivariate Cox analysis confirmed urinary miR-196a as an independent risk factor for FSGS progression after adjusting for age, sex, proteinuria and eGFR. Prediction accuracy of ESRD was significantly improved by combining urinary miR-196a with other indicators including eGFR and proteinuria. CONCLUSION:Urinary miR-196a may serve as a biomarker for predicting CKD progression.
| S-EPMC5894160 | biostudies-literature
Project description:Chronic kidney disease (CKD) is associated with incident cardiovascular morbidity and mortality. Whether subclinical cardiovascular disease and target organ damage is associated with incident CKD is unknown. We investigated the relations of echocardiographic left ventricular mass (LVM) with incident CKD. We evaluated 2258 Framingham Offspring cohort participants (mean age, 57 years; 56% women) who underwent echocardiography at a routine examination and had an estimated glomerular filtration rate ≥60 mL/min per 1.73 m2. We used Cox proportional hazards regression with discrete time intervals to relate sex-standardized LVM (independent variable) to the incidence of CKD, defined as estimated glomerular filtration rate <60 L/min per 1.73 m2, on follow-up. During a median follow-up of 14.6 years, 373 (16.5%) participants developed incident CKD. Higher LVM was associated with higher risk of CKD after adjusting for prevalent cardiovascular disease, body mass index, systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, antihypertensive medication, smoking, and diabetes mellitus (hazard ratio, 1.15 [95% CI, 1.03-1.29]; P=0.017) per 1-SD increase in LVM g/m2. Further adjustment for baseline estimated glomerular filtration rate (adjusted hazard ratio, 1.16 [95% CI, 1.04-1.31]; P=0.010) and baseline urine albumin/creatinine ratio (adjusted hazard ratio, 1.18 [95% CI, 1.04-1.33]; P=0.009) slightly attenuated the association. In our community-based sample, LVM was associated with incident CKD prospectively, which suggests that the relations between CKD and subclinical cardiovascular disease may be bidirectional. Further studies are needed to confirm our findings.
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Project description:BACKGROUND:The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD. METHODS:SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment. RESULTS:We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (p < 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (p = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (p = 0.02) in the training set, an observation which was confirmed in the validation set. -Conclusion: This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD.
| S-EPMC6280192 | biostudies-literature
Project description:BACKGROUND:Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community. METHODS:Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR <60 mL · min(-1) · (1.73 m(2)) (-1), n = 276], microalbuminuria (urinary albumin to creatinine ratio ?25 mg/g in women and 17 mg/g in men, n = 191), and rapid decline in renal function [decline in eGFR ?3 mL · min(-1) · (1.73 m(2)) (-1) per year, n = 237], were evaluated using multivariable logistic regression; P < 0.006 was considered statistically significant in primary analyses. RESULTS:Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U increase in log-GDF-15, 95% CI 1.6-2.3, P < 0.0001] and rapid decline in renal function (OR, 1.6; 95% CI, 1.3-1.8; P < 0.0001). GDF-15, sST2, and hsTnI had suggestive associations with incident microalbuminuria but did not meet the prespecified P-value threshold after multivariable adjustment. Adding plasma GDF-15 to clinical covariates improved risk prediction of incident CKD: the c-statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net reclassification was 6.3% (95% CI, 2.7-9.9%). CONCLUSIONS:Higher circulating GDF-15 is associated with incident renal outcomes and improves risk prediction of incident CKD. These findings may provide insights into the mechanisms of renal injury.
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Project description:Atrial fibrillation (AF) is more prevalent in individuals with chronic kidney disease (CKD) compared to the general population. While a potential inverse correlation between lipid levels and AF has been proposed, it remains unclear if this relationship applies to CKD patients. This study examined the connection between the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) and the likelihood of AF in CKD patients. Data was gathered from 21,091 consecutive CKD patients between 2006 and December 31, 2015. We examined the link between the LDL-C/HDL-C ratio and AF in CKD patients through binary logistic regression, as well as various sensitivity and subgroup analyses. The dataset that backs up these analyses is available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230189 . Of the 21,091 CKD patients, 211 (1.00%) were diagnosed with AF. The cohort, predominantly male (79.93%), had a mean age of 60.89 ± 10.05 years. The mean LDL-C/HDL-C ratio was 1.39 ± 0.35. After adjusting for covariates, a significant inverse association was observed between the LDL-C/HDL-C ratio and the incidence of AF in CKD patients (OR = 0.422, 95% CI 0.273-0.652, P = 0.00010). The robustness of these findings was confirmed through sensitivity analysis. Subgroup analysis revealed a strong correlation between the LDL-C/HDL-C ratio and incident AF in patients without hypertension (HR = 0.26, 95% CI 0.15-0.45). Conversely, this association was absent in hypertensive patients (HR = 1.09, 95% CI 0.54-2.17). Our research shows an independent inverse correlation between the LDL-C/HDL-C ratio and the risk of AF in CKD patients. It is advised to refrain from excessively aggressive reduction of LDL levels in CKD patients, as this could elevate the risk of developing AF.
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