Urine TCA cycle metabolites predict progressive CKD in T2D patients
Key tricarboxylic acid (TCA) cycle metabolites, in particular fumarate, are predictors of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D), independent of traditional cardio-renal risk factors, suggests a recent study.
Participants with a progressive CKD (n=116) had a lower level of urine citrate but significantly higher levels of lactate, fumarate and malate levels at baseline as compared with those with stable renal function (n=271).
Both fumarate and malate were risk factors for progressive CKD independent of traditional cardio-renal predictors, including estimated glomerular filtration rate (eGFR) and albuminuria. Fumarate was associated with sex (p=0.03 for interaction) and an independent predictor of progressive CKD in male but not female participants.
Such findings were reproducible in a validation study (case: n=96; control: n=402). In exploratory analysis, fumarate appeared to partially mediate the effect of oxidative stress on CKD progression.
One discovery and one validation nested case-control studies in two independent T2D cohorts examined whether baseline urine key TCA cycle metabolites (lactate, pyruvate, citrate, α-ketoglutaric acid, succinate, fumarate and malate) independently predicted the risk of CKD progression (fast eGFR decline) in individuals with T2D.
The authors recruited and followed patients with T2D in a regional hospital and at a primary care facility. Linear regression was used to estimate eGFR trajectory (slope). Progressive CKD was defined as eGFR decline of ≥5 mL/min/1.73 m2 per year.
“Metabolites in the TCA cycle are not only involved in energy metabolism but also play important roles in nonenergy production activities,” the authors said.