S.LOW1, A.M.C.MOH1, J.WANG1, J.P.KOVALIK2, J.CHING2, H.N.WEE2, K.V.CHUA2, K.A1, Y.M.SHAO1, S.C.LIM1
Khoo Teck Puat Hospital1, Duke-NUS Graduate Medical School2
We have previously reported that sarcopenia is associated with chronic kidney disease (CKD) progression. The pathophysiological mechanism is unclear. We examined the interplay of low skeletal muscle mass, metabolites and CKD progression in Type 2 Diabetes(T2D) using metabolomics analysis.
We conducted a prospective cohort study of 1109 patients from SMART2D cohort. Skeletal muscle mass was measured with bio-impedance analysis. CKD progression was defined as deterioration across KDIGO estimated glomerular filtration rate categories with ≥25% drop from baseline. Acylcarnitines, amino acids and lipids were quantitated using mass spectrometry. Mediation analysis was done based on Baron and Kenny Framework, adjusting for demographics, clinical covariates and medication.
The participants’ mean age was 58.8±9.0 years. Over a period of up to 8.6 years, CKD progression occurred in 33.3% of patients. Principal component analysis identified the following principal components(PCs): PC1-phosphatidylethanolamines(PE): PE(34:1),PE(36:1),PE(36:4),PE(38:3), PE(38:5),PE(38:6),PE(40:6) and PE(40:7); PC-2-acylcarnitines(C2, C4-OH, C6); and PC3-amino acids(Serine and Tryptophan). Baseline skeletal muscle mass index(SMI) was inversely associated with CKD progression (Odds Ratio(OR) 0.853; 95%CI 0.741-0.982; p=0.027). PC1 was associated with baseline SMI (ß -0.499; 95%CI -0.619 to -0.379; p<0.001) and CKD progression (OR 1.113; 95%CI 1.040-1.191; p=0.002). PC1 accounted for 29.4% of association between SMI and CKD progression. There was no evidence of mediation of the association by the PCs.
Our study revealed a previously unrecognised mediating role of PE in association between low skeletal muscle mass and CKD progression. Low SMI may enhance lipotoxic effects on kidney. The finding may help clinicians in risk stratification and intervention through a targeted approach.