Dataset Information

A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.

ABSTRACT: Urinary albumin-to-creatinine ratio (ACR) is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR, but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR. The association between ACR and microvascular function (responses to acetylcholine [ACH] and sodium nitroprusside) was tested in the SUMMIT study. Two-sample Mendelian randomization (MR) was used to infer the causal effects of 11 metabolic risk factors, including glycemic, lipid, and adiposity traits, on ACR. MR was performed in up to 440,000 UK Biobank and 54,451 CKDGen participants. ACR was robustly associated with microvascular function measures in SUMMIT. Using MR, we inferred that higher triglyceride (TG) and LDL cholesterol (LDL-C) levels caused elevated ACR. A 1 SD higher TG and LDL-C level caused a 0.062 (95% CI 0.040, 0.083) and a 0.026 (95% CI 0.008, 0.044) SD higher ACR, respectively. There was evidence that higher body fat and visceral body fat distribution caused elevated ACR, while a metabolically "favorable adiposity" phenotype lowered ACR. ACR is a valid marker for microvascular function. MR suggested that seven traits have causal effects on ACR, highlighting the role of adiposity-related traits in causing lower microvascular function.

SUBMITTER: Casanova F

PROVIDER: S-EPMC7611011 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.

Casanova Francesco F Wood Andrew R AR Yaghootkar Hanieh H Beaumont Robert N RN Jones Samuel E SE Gooding Kim M KM Aizawa Kunihiko K Strain W David WD Hattersley Andrew T AT Khan Faisel F Shore Angela C AC Frayling Timothy M TM Tyrrell Jessica J

Diabetes 20200108 5

Urinary albumin-to-creatinine ratio (ACR) is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR, but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR. The association between ACR and microvascular function (responses to acetylcholine [ACH] and sodium nitroprusside) was tested in the SUMMIT study. Two-samp ...[more]

PMID: 31915152

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Project description:BackgroundUrine albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR) are important markers of kidney damage and are used for prognosis in persons with chronic kidney disease (CKD). Despite how commonly these measurements are done in clinical practice, relatively few studies have directly compared the performance of these 2 measures with regard to associations with clinical outcomes, which may inform clinicians about which measure of urinary protein excretion is best. We studied the association of ACR and PCR with common complications of CKD.Study designCross-sectional study.Setting & participants3,481 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorsACR and PCR.OutcomesWe examined the association between ACR and PCR with measures of common CKD complications: serum hemoglobin, bicarbonate, parathyroid hormone, phosphorus, potassium, and albumin.MeasurementsRestricted cubic spline analyses adjusted for estimated glomerular filtration rate (eGFR; calculated by the MDRD [Modification of Diet in Renal Disease] Study equation) were performed to study the continuous association with our predictors with each outcome.ResultsMean eGFR was 43±13 (SD)mL/min/1.73 m2 and median values for PCR and ACR were 140 and 46 mg/g, respectively. In continuous analyses adjusted for eGFR, higher ACRs and PCRs were similar and both were associated with lower serum hemoglobin, bicarbonate, and albumin levels and higher parathyroid hormone, phosphorus, and potassium levels. Across all outcomes, the associations of ACR and PCR were similar, with only small absolute differences in the outcome measure. Similar associations were seen in patients with diabetes mellitus.LimitationsParticipants largely had moderate CKD with low values for ACR and PCR, so results may not be generalizable to all CKD populations.ConclusionsIn persons with CKD, ACR and PCR are relatively similar in their associations with common complications of CKD. Thus, routine measurement of PCR may provide similar information as ACR in managing immediate complications of CKD.

Project description:Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable. Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006-2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations. Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101). Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed.

Dataset Information

A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.

Publications

A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.

Similar Datasets

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