Urine Choline Oxidation Metabolites Predict Chronic Kidney Disease Progression in Patients With Type 2 Diabetes.

CONTEXT: Choline is metabolized in kidney tubules but the relationship between choline metabolism and kidney disease has not been systematically characterized.

OBJECTIVE

To study whether urine metabolites in the choline oxidation pathway may predict the risk of chronic kidney disease (CKD) progression in individuals with type 2 diabetes.

METHODS

Outpatients (n = 1894) with type 2 diabetes were recruited from a secondary hospital and a primary care facility. Urine choline, betaine, dimethylglycine, and sarcosine were measured by liquid chromatography-mass spectrometry. CKD progression was defined as a composite of incident end-stage kidney disease (sustained eGFR <15 mL/min/1.73m2, maintenance dialysis, renal death) and doubling of serum creatinine.

RESULTS

CKD progression occurred in 263 participants during a median follow-up of 9.2 years. High levels of urine choline and dimethylglycine were associated with an increased risk of CKD progression after adjustment for clinical risk factors (adjusted HR [95% CI], 1.32 [1.16-1.51] and 1.30 [1.14-1.47], respectively, per 1 SD). Urine choline and dimethylglycine were positively correlated with tubulopathy biomarkers, especially dickkopf-related protein 3 (dkk3, Spearman rho 0.55 and 0.53). The association between dkk3 and CKD progression was diminished but the association between choline, dimethylglycine, and CKD progression remained significant after mutual adjustments. Choline and dimethylglycine were also independently associated with risk of all-cause death (adjusted HR 1.20 [1.06-1.37] and 1.17 [1.04-1.33], respectively).

CONCLUSION

Urine choline and dimethylglycine independently predict the risk of CKD progression in individuals with type 2 diabetes. Dysregulation of intrarenal choline metabolism may be involved in tubulopathy leading to progressive loss of kidney function.