Lipidomics Profiling Reveals Serum Phospholipids Associated with Albuminuria in Early Type 2 Diabetic Kidney Disease

Early screening and administration of DKD are beneficial
for renal
outcomes of type 2 diabetic patients. However, the current early diagnosis
using the albuminuria/creatine ratio (ACR) contains limitations. This
study aimed to compare serum lipidome variation between type 2 diabetes
and early DKD patients with increased albuminuria through an untargeted
lipidomics method to explore the potential lipid biomarkers for DKD
identification. 92 type 2 diabetic patients were enrolled and divided
into two groups: DM group (ACR < 3 mg/mmol, n =
49) and early DKD group (3 mg/mmol ≤ ACR < 30 mg/mmol, n = 43). Fasting serum was analyzed through an ultraperformance
liquid mass spectrometry tandem chromatography system (LC-MS). Orthogonal
partial least-squares discriminant analysis (OPLS-DA) and univariate
and multivariate analysis were performed to filter differentially
depressed lipids. Receiver operating characteristic (ROC) curves were
used to estimate the diagnostic capability of potential lipid biomarkers.
We found that serum phospholipids including phosphatidylserine (PS),
sphingomyelin (SM), and phosphatidylcholine (PC) were significantly
upregulated in the DKD group and were highly correlated with the ACR.
In addition, a panel of two phospholipids including PS(27:0)-H and
PS(30:2e)-H showed good performance to help clinical lipids in early
DKD identification, which increased the area under the curve (AUC)
from 0.568 to 0.954. The study exhibited the serum lipidome variation
in early DKD patients, and the increased phospholipids might participate
in the development of albuminuria. The panel of PS(27:0)-H and PS(30:2e)-H
could be a potential biomarker for DKD diagnosis.