Trimethylamine-N-oxide (TMAO) and predicted risk of cardiovascular events after partial nephrectomy

Abstract

Emerging evidence suggests that uremic toxins, in particular trimethylamine-N-oxide(TMAO), indoxyl-sulfate(IS), and p-cresyl-sulfate(PCS), may associate with increased risk of cardiovascular events(CVe). However, whether uremic toxins increase after partial nephrectomy(PN) and their correlation with risk for CVe remains unknown. 100 patients managed with PN were retrospectively reviewed. TMAO/IS/PCS levels were examined by liquid chromatography-mass-spectrometry. Renal-parenchymal-volume-preservation(RPVP) was estimated from CT scans. Predicted risks for CVe were obtained using the Framingham score. Linear regression assessed association between uremic toxins, GFR and risk of CVe. Logistic regression evaluated factors associated with post-PN TMAO. TMAO, IS and PCS increased from 1.7, 3.7 and 3.5μmol/L before PN to 3.6, 5.4 and 7.4μmol/L at latest follow-up, respectively, while GFR declined from 102 to 93ml/min/1.73m2 (all p<0.001). TMAO, IS and PCS levels all negatively correlated with GFR(all p<0.001). Predicted 10-year risk of CVe increased from 1.1% pre-PN to 1.7% post-PN(p<0.001), primarily due to increased age(p<0.001), blood pressure(p=0.002) and total cholesterol(p=0.003). TMAO(β=0.038) and GFR (β=-0.02) were independent predictors for predicted 10-year CVe risk on multivariable-analysis. Increased TMAO was an early and sustained finding maintained through 5 years, unlike IS, PCS and eGFR. On multivariable analysis, increased pre-PN TMAO(OR=2.79) and decreased RPVP(OR=3.23) were identified as independent risk factors for higher post-PN TMAO, while ischemia type/duration failed to correlate. Uremic toxin levels increased after PN correlating with reduced GFR. Higher TMAO independently associated with greater predicted 10-year CVe risk. Parenchymal mass preserved rather than ischemia time or type associated with increased TMAO.