Trajectories of short-chain fatty acids and risk of adverse kidney outcomes in type 2 diabetes: a prospective cohort study

Abstract

Objectives: The impact of short-chain fatty acids (SCFAs) on kidney outcomes in individuals with Type 2 diabetes (T2D) is not clearly understood. This prospective study aimed to investigate the relationship between serum SCFA levels and adverse kidney outcomes in T2D patients.

Methods: T2D patients were recruited between October 2016 and June 2020 and followed until December 2021. The serum levels of nine SCFAs were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were defined as a doubling of serum creatinine levels or progression to end-stage kidney disease (ESKD). Secondary outcomes included an annual decline in estimated glomerular filtration rate (eGFR) of more than 5 ml/min/1.73 m² or a rapid 25% reduction in eGFR during the follow-up period.

Results: The mean age of the 480 T2D participants was 62.0 years. The individuals in highest tertile of serum propionate (>18.91 μM), butyrate (>8.90 μM), and formate (>163.34 μM) levels were significantly associated with lower risk of experiencing a doubling of serum creatinine or progression to ESKD compared to those in the combined lower tertiles of serum propionate, butyrate and formate levels (adjusted hazard ratio (HR)=0.13, 0.20, 0.26, respectively). Adjusted logistical analysis showed that the individuals in highest tertile of serum propionate, butyrate, formate, and valerate (>3.93 μM) levels were significantly associated with lower risk for eGFR decline > 5 ml/min/1.73 m² per year compared to those in the combined lower tertiles of serum propionate, butyrate, formate, and valerate levels (adjusted odds ratio (OR)=0.38, 0.41, 0.46, 0.42, respectively).

Conclusions: Higher circulating levels of SCFAs, particularly propionate, butyrate, and formate, are associated with a substantially lower risk of kidney outcomes in T2D population. These SCFAs may serve as indicative biomarkers for kidney function deterioration in T2D individuals.

Keywords: Type 2 diabetes; creatinine; end-stage kidney disease; estimated glomerular filtration rate; short-chain fatty acids.