Key result
Mendelian randomization analyses demonstrated a causal association between urinary albumin and type 2 diabetes (OR 1.33 per SD change in albumin), as well as causal associations of UNa/UK and albumin with systolic blood pressure.
Why the study?
Urinary biomarkers are associated with hypertension and CVD, but the nature of these associations is incompletely understood.
Do urinary sodium-potassium ratio and albumin-creatinine ratio causally affect cardiovascular outcomes and risk factors in adults without baseline CVD or CKD?
Observational (n=478,311)
Yes
Do urinary sodium-potassium ratio and albumin-creatinine ratio causally affect cardiovascular outcomes and risk factors in adults without baseline CVD or CKD?
Higher urinary sodium-to-potassium ratio is causally associated with higher blood pressure, and urinary albumin has a bidirectional causal association with blood pressure and type 2 diabetes.
Answers are grounded in this paper and cite their sources.
Does not support immediate clinical changes; leaves open whether targeting albumin or urinary electrolytes improves diabetes or blood pressure outcomes.
Background Urinary biomarkers are associated with hypertension and cardiovascular disease (CVD), but the nature of these associations is incompletely understood. Methods We performed multivariable-adjusted regression models to assess associations of urinary sodium-potassium ratio (UNa/UK), and urinary albumin adjusted for creatinine (UAlb/UCr) with cardiovascular risk factors, CVD and type 2 diabetes (T2D) in 478,311 participants of the UK Biobank. Further, we studied above associations separately in men and women, and assessed the causal relationships of these kidney biomarkers with cardiovascular outcomes using the two-sample Mendelian randomization (MR) approach. Results In observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation (AF), coronary artery disease (CAD), ischemic stroke, lipid-lowering medication and T2D. In contrast, UAlb/UCr showed significant positive associations with AF, CAD, heart failure, hemorrhagic stroke, lipid-lowering medication and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. Generally, we detected consistent directionality in sex-stratified analyses, with some evidence for sex differences in the associations of urinary biomarkers with T2D and obesity. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with systolic BP (beta SBP ≥2.63; beta DBP ≥0.85 SD increase in systolic BP per SD change UNa/UK and UAlb/UCr; P ≤0.038), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P =0.023). Conclusion Our Mendelian randomization analyses mirror and extend findings from randomized interventional trials which have established sodium intake as a risk factor for hypertension. In addition, we detect a feed-back causal loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.
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Zanetti et al. (2018) conducted an observational in Cardiovascular disease and Type 2 Diabetes (n=478,311). Urinary sodium-potassium ratio (UNa/UK) and urinary albumin-creatinine ratio (UAlb/UCr) vs. Lower levels of urinary biomarkers was evaluated on Type 2 Diabetes (Mendelian randomization analysis) (OR 1.33, p=0.023). Mendelian randomization analyses demonstrated a causal association between urinary albumin and type 2 diabetes (OR 1.33 per SD change in albumin), as well as causal associations of UNa/UK and albumin with systolic blood pressure.
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