533-P: Association of Serum Branched-Chain Amino Acids with Kidney Function Decline in Type 2 Diabetes: The Hong Kong Diabetes Register

Background: There are recent claims that high dietary BCAA may improve insulin resistance although this conflicts with the recommendation that low protein/BCAA diet may confer renoprotection in patients with chronic kidney disease (CKD) stages 3-5. Type 2 diabetes (T2D) has dysregulated energy metabolism where excessive BCAA intake can be harmful. We examined the risk association of BCAA and rate of estimated glomerular filtration rate (eGFR) decline in a prospective T2D cohort.

Method: We measured serum BCAA in 2340 adults with CKD stages 1-2 at baseline with available stored sera. By using linear regression analysis, we examined the association of serum BCAA with annual change in eGFR, which was estimated from a linear mixed model using at least three eGFR measurements from baseline until the onset of CKD or data censored on June 2017.

Results: In this study cohort with mean±SD follow-up of 10.0±5.3 years (age 55.2±11.2 years, BMI 25.4±4.3 kg/m², HbA_1c 7.6±1.7%, annual change in eGFR -1.37±1.28 ml/min/1.73m²), patients with incident CKD had higher serum BCAA (median [IQR]: 622.7 [540.3-730] vs. 595.8 [518.3-680.3] µM; P<0.001) and usage of blood pressure (BP)-lowering drugs (56.2% vs. 33.7%; P<0.001) at baseline than those without CKD. Every doubling of serum BCAA was associated with faster eGFR decline (β -0.24 [95% CI -0.34, -0.14]; P<0.001) that remained significant after adjusting for age, sex and diabetes duration (β -0.27 [-0.37, -0.18]; P<0.001). The effect was attenuated by further adjustment of HbA_1c, BMI, lipids, BP and related drug usage (β -0.16 [-0.27, -0.05]; P=0.003), as well as by retinopathy, albuminuria and eGFR at baseline (β -0.13 [-0.23, -0.02]; P=0.016). There was no significant BCAA-sex interaction.

Conclusions: In Chinese T2D patients with CKD stages 1-2, high serum BCAA was independently associated with a modest decline in eGFR, suggesting the renoprotective effect of a low BCAA diet may be extended to early CKD with careful monitoring.