Plasma Symmetric Dimethylarginine and Mortality in Kidney Transplant Recipients: A Cohort Study

In this large cohort of kidney transplant recipients, plasma symmetric dimethylarginine concentrations were independently associated with a higher mortality risk Symmetric dimethylarginine may not merely be an inert uremic solute and may be involved as a uremic toxin in ongoing pathological processes.

Long-term outcome after kidney transplantation remains limited because of high risks of cardiovascular, infectious, and malignant premature death. Uremic solutes, such as urea and symmetric dimethylarginine (SDMA), are suggested to contribute to higher oxidative stress, chronic low-grade inflammation, and excess mortality. Therefore, we evaluated the associations of urea and SDMA with all-cause and cause-specific mortality in kidney transplant recipients.

Baseline plasma SDMA was measured using liquid chromatography-mass spectrometry in kidney transplant recipients enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study (Groningen, The Netherlands). We assessed prospective associations of SDMA with all-cause and cause-specific mortality using Cox regression.

We included 628 adult kidney transplant recipients (56% male, age, 53±13 years; eGFR, 52±20 ml/min per 1.73 m 2 ) at 5.4 [interquartile range, 1.8-12.0] years after transplantation. Median plasma urea was 9.6 [7.3-13.4] mmol/L, and plasma SDMA was 20 [15-25] µ g/dl. In Cox regression analyses, both plasma urea (hazard ratio per doubling, 2.21; 95% confidence interval, 2.22 to 2.85) and plasma SDMA (hazard ratio per doubling, 2.69; 95% confidence interval, 1.95 to 3.70) were strongly associated with a higher risk of all-cause mortality. These associations remained for SDMA but not urea in a fully adjusted model, and the observed associations were generally similar for all causes of death.

Plasma urea and SDMA are both associated with a higher mortality risk in outpatient kidney transplant recipients. In a model including both urea and SDMA, only the association of SDMA with mortality remained.

NCT02811835 .