1. Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease
- Author
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Hima Sapa, Orlando M. Gutiérrez, Michael G. Shlipak, Ronit Katz, Joachim H. Ix, Mark J. Sarnak, Mary Cushman, Eugene P. Rhee, Paul L. Kimmel, Ramachandran S. Vasan, Sarah J. Schrauben, Harold I. Feldman, Jesse C. Seegmiller, Henri Brunengraber, Thomas H. Hostetter, Jeffrey R. Schelling, Joseph Massaro, Clary Clish, Michelle Denburg, Susan Furth, Bradley Warady, Joseph Bonventre, Sushrut Waikar, Gearoid McMahon, Venkata Sabbisetti, Josef Coresh, Morgan Grams, Casey Rebholz, Alison Abraham, Adriene Tin, Chirag Parikh, Jon Klein, Steven Coca, Bart S. Ferket, Girish N. Nadkarni, Daniel Gossett, Brad Rovin, Andrew S. Levey, Lesley A. Inker, Meredith Foster, Ruth Dubin, Rajat Deo, Amanda Anderson, Theodore Mifflin, Dawei Xie, Haochang Shou, Shawn Ballard, Krista Whitehead, Heather Collins, Jason Greenberg, and Peter Ganz
- Subjects
Methylamines ,Cardiovascular Diseases ,Nephrology ,Diabetes Mellitus ,Humans ,Diabetic Nephropathies ,Oxides ,Arginine ,Biomarkers - Abstract
Cardiovascular disease (CVD) is a major cause of mortality among people with diabetic kidney disease (DKD). The pathophysiology is inadequately explained by traditional CVD risk factors. The uremic solutes trimethylamine-N-oxide (TMAO) and asymmetric and symmetric dimethylarginine (ADMA, SDMA) have been linked to CVD in kidney failure with replacement therapy (KFRT), but data are limited in populations with diabetes and less severe kidney disease.Observational cohort.Random subcohort of 555 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants with diabetes and estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 mADMA, SDMA, and TMAO assayed by liquid chromatography-mass spectrometry in plasma and urine.Cardiovascular mortality (primary outcome); all-cause mortality and incident KFRT (secondary outcomes).Plasma concentrations and ratios of urine to plasma concentrations of ADMA, SDMA, and TMAO were tested for association with outcomes. Adjusted Cox regression models were fitted and hazard ratios of outcomes calculated per standard deviation and per doubling, and as interquartile comparisons.The mean baseline eGFR was 44 mL/min/1.73 mSingle cohort, restricted to patients with diabetes and eGFR 60 mL/min/1.73 mHigher plasma concentrations and lower ratios of urine to plasma concentrations of uremic solutes were independently associated with cardiovascular and all-cause mortality in DKD. Associations of ratios of urine to plasma concentrations with mortality suggest a connection between renal uremic solute clearance and CVD pathogenesis.
- Published
- 2022