Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease.

Link: https://doi.org/S0272-6386(22)00577-7
Authors: Sapa, Hima; Gutiérrez, Orlando M; Shlipak, Michael G; Katz, Ronit; Ix, Joachim H; Sarnak, Mark J; Cushman, Mary; Rhee, Eugene P; Kimmel, Paul L; Vasan, Ramachandran S; Schrauben, Sarah J; Feldman, Harold I; Seegmiller, Jesse C; Brunengraber, Henri; Hostetter, Thomas H; Schelling, Jeffrey R; ,

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. ADMA, 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. Higher 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.