Lipidomic Signature of Progression of Chronic Kidney Disease in the Chronic Renal Insufficiency Cohort.
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ABSTRACT: Introduction
Human studies report conflicting results on the predictive power of serum lipids on progression of chronic kidney disease (CKD). We aimed to systematically identify the lipids that predict progression to end-stage kidney disease.Methods
From the Chronic Renal Insufficiency Cohort, 79 patients with CKD stage 2 to 3 who progressed to ESKD over 6 years of follow up were selected and frequency-matched by age, sex, race, and diabetes with 121 non-progressors with less than 25% decline in estimated glomerular filtration rate (eGFR) during the follow up. The patients were randomly divided into Training and Test sets. We applied liquid chromatography-mass spectrometry-based lipidomics on visit year 1 samples.Results
We identified 510 lipids, of which the top 10 coincided with false discovery threshold of 0.058 in the Training set. From the top 10 lipids, the abundance of diacylglycerols (DAGs) and cholesteryl esters was lower, but that of phosphatidic acid 44:4 and monoacylglycerol (MAG) 16:0 was significantly higher in progressors. Using logistic regression models a multi-marker panel consisting of DAGs, and MAG independently predicted progression. The c-statistic of the multimarker panel added to the base model consisting of eGFR and urine protein-creatinine ratio (UPCR) as compared to that of the base model was 0.92 (95% Confidence Interval [CI]: 0.88-0.97), and 0.83 (95% CI: 0.76-0.90, P<0.01), respectively; an observation which was validated in the Test subset.Conclusion
We conclude that a distinct panel of lipids may improve prediction of progression of CKD beyond eGFR and UPCR when added to the base model.
SUBMITTER: Afshinnia F
PROVIDER: S-EPMC5402253 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. METHODS:Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. RESULTS:Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. CONCLUSION:In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.
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Project description:BackgroundBeverages are a source of calories and other bioactive constituents but are an understudied aspect of the diet. Different beverages have varying effects on health outcomes.ObjectivesWe created the Healthy Beverage Score (HBS) to characterize participants' beverage patterns and examined its association with chronic kidney disease (CKD) progression, incident cardiovascular disease (CVD), and all-cause mortality among individuals with CKD.MethodsWe conducted a prospective analysis of 2283 adults aged 21-74 y with a baseline estimated glomerular filtration rate of 20-70 mL · min-1 · 1.73 m-2 from the Chronic Renal Insufficiency Cohort. Diet was assessed using a 124-item FFQ at visit 1 (2003-2008). The HBS, ranging from 7 to 28 possible points, consisted of 7 components, each scored from 1 to 4 based on rank distribution by quartile, except alcohol, which was based on sex-specific cutoffs. Participants were given more points for higher consumption of low-fat milk and of coffee/tea, for moderate alcohol, and for lower consumption of 100% fruit juice, whole-fat milk, artificially sweetened beverages, and sugar-sweetened beverages. CKD progression, incident CVD, and mortality were ascertained through January 2018. We conducted multivariable Cox proportional hazards models.ResultsThere were 815 cases of CKD progression, 285 cases of incident CVD, and 725 deaths over a maximum of 14 y of follow-up. Compared with participants in the lowest tertile of the HBS, participants in the highest tertile had a 25% lower likelihood of CKD progression (HR: 0.75; 95% CI: 0.63, 0.89; P-trend = 0.001) and a 17% lower likelihood of all-cause mortality (HR: 0.83; 95% CI: 0.69, 1.00; P-trend = 0.04) after adjusting for sociodemographic, clinical, and dietary factors. There was no significant trend for incident CVD.ConclusionsAmong individuals with CKD, a healthier beverage pattern was inversely associated with CKD progression and all-cause mortality. Beverage intake may be an important modifiable target in preventing adverse outcomes for individuals with CKD.
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Project description:Background and purposeChronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors.MethodsThe study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates.ResultsIn 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria.ConclusionsProteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.
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