Urine proteome analysis by C18 plate–matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows noninvasive differential diagnosis and prediction of diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is one of the most common complications in diabetic patients. New noninvasive markers are still needed for the early detection of DN before identifiable alternations in kidney function or urine albumin excretion occurs. A C18 plate and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to compare the urinary protein profiles of 238 subjects from the following 4 groups: patients with type 2 diabetic (T2D) with microalbuminuria, patients with DM without micro- or macroalbuminuria, patients with micro- or macroalbuminuria due to nondiabetic disease, and healthy controls. β2-microglobulin (B2M) and Clara-cell protein (CC16) were found to be highly released in the urine of patients with proteinuria due to nondiabetic or diabetic diseases. In differentiating nephropathy from healthy subject, the B2M and CC16 markers have a combined sensitivity and specificity of 77.3% and 91.8%, respectively. In distinguishing T2D with microalbuminuria from T2D patients, the combined markers have sensitivity and specificity of 66% and 73%, respectively. The predictive ability of B2M and CC16 for early renal functional decline (ERFD) was validated in 125 T2D patients with a follow-up times. The odds ratio (OR) of combined B2M and CC16 markers for developing ERFD was 7.59 (95% CI: 1.97–29.24). The detection of B2M and CC16 with the C18 plate—MALDI-TOF MS approach could be an attractive and practical assay for rapid diagnosis of nephropathy in nondiabetic/diabetic patients and as a predictor of ERFD among T2D patients who had not manifested significant kidney disease at baseline.

Evaluation of urinary biomarkers for prediction of diabetic kidney disease: a propensity score matching analysis

“…45 Moreover, previous studies have demonstrated that it was strongly negatively correlated with eGFR, and might be used as a marker for predicting renal function decline or end-stage renal disease. [46][47][48] It is possible that β2MG is more sensitive to renal function decline than albuminuria.…”

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

“…The use of omics, specifically lipidomics and MALDI-TOF mass spectrometry, has allowed the characterization of lipid abnormalities in the study of complex metabolic disorders, such as diabetes and its complications [173,174]. Searching for novel associations between serum lipidomics and DN has been quite fruitful, as shown in Table 1.…”

BoxCar increases the depth and reproducibility of diabetic urinary proteome analysis

“…The results showed that the peptides number and sequence coverage of these proteins were both higher in BoxCar (Figure 3D, 3E). Then we chose seven potential biomarkers of diabetic nephropathy reported before to evaluate single protein identification [4,[35][36][37][38][39][40][41] (Figure 3F, 3G). The figures showed that BoxCar could both significantly increase peptides number and sequence coverage of Alpha-1acid glycoprotein (ORM1/ORM2), Alpha-2-macroglobulin (A2M) and Beta-2-microglobulin (B2M) (P < 0.05) (Table S2).…”