Dietary Metabolite Linked to CKD Development and Progression

Higher levels of the gut bacterial byproduct trimethylamine N-oxide (TMAO)—associated with consumption of red meat, eggs, and dairy products—are linked to the development of and mortality from chronic kidney disease (CKD), reports a study in Circulation Research.

The researchers examined the prognostic value of TMAO levels in patients with CKD and the potential role of TMAO in the development and progression of kidney disease. A gut microbiota–dependent metabolite formed during the digestion of choline and carnitine, TMAO is cleared by the kidneys. Previous studies have shown that TMAO is associated with heart disease and have identified it as a strong predictor of major adverse cardiovascular events.

In 521 patients with CKD in stable condition, the median fasting plasma TMAO level was 7.9 µmol/L—significantly higher than in control individuals without CKD. For CKD patients in the fourth versus first quartile of TMAO, the unadjusted hazard ratio (HR) for all-cause mortality at 5 years was 2.76. The association was smaller but still significant (HR 1.93) after adjustment for traditional risk factors, high-sensitivity C-reactive protein, and estimated GFR.

Measurement of TMAO provided additional prognostic value in CKD patients, with net reclassification index of 17.26 percent and differences in the area under the receiver operator characteristic curve of 63.26 versus 65.95 percent. Among control individuals without CKD, higher TMAO levels were associated with increased mortality in those with normal or elevated cystatin C levels. In animal models, higher dietary choline or TMAO levels were directly linked to progressive renal tubulointerstial fibrosis and decreased kidney function.

The results suggest that dietary-induced, microbiota-dependent differences in levels of TMAO may contribute to CKD development, progression, and mortality. Further studies of these associations are needed, including the possible effects of a diet designed to limit TMAO precursors (low in red meat, egg yolk, and high-fat dairy products) on the rate of CKD progression [Tang WHW, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res 2015; 116:448–455].