Trajectories of Short-Chain Fatty Acids and Risk of Adverse Kidney Outcomes in Type 2 Diabetes: A Prospective Cohort Study

The impact of short-chain fatty acids (SCFAs) on kidney outcomes in individuals with Type 2 diabetes (T2D) is not clearly understood. This study aimed to investigate the relationship between serum SCFA levels and adverse kidney outcomes in T2D patients. 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. The mean age of the 480 T2D participants was 62.0 years. The individuals in tertile 3 of serum propionate, butyrate, and formate levels showed an 86%, 79%, and 75% reduction, respectively, in the adjusted risk of experiencing a doubling of serum creatinine or progression to ESKD, compared to those in tertiles 1 and 2 of serum propionate, butyrate and formate levels. Adjusted logistical analysis showed that the individuals in tertile 3 of serum propionate, butyrate, formate and valerate levels had a reduced risk of rapid eGFR decline by 62%, 59%, 54%, and 58%, respectively. In conclusion, T2D patients who have higher circulating levels of SCFAs, particularly propionate, butyrate, and formate, are at a reduced risk of unfavorable kidney outcomes. These SCFAs may serve as indicative biomarkers for kidney function deterioration in T2D individuals.