Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury

Abstract

Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoalbuminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor and inter-alpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.

Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case–control study

“…It is highly expressed in liver development and low levels have been found in hepatocellular and ovarian cancer [33, 34]. ITIH4 is elevated in urine of patients with T2DM and microalbuminuria and could possibly serve as a biomarker for diabetic kidney disease [35]. ITIH4 was also found to be downregulated after a very low caloric diet in patients with T2DM, possibly representing a biomarker of metabolic improvement [36].…”

Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders

“…Similarly, we chose not to further investigate inter-a-trypsin inhibitor heavy chain H4 as it is also elevated in patients with decreased renal function. 19 Urine haptoglobin has been reported to be elevated in multiple conditions, including lupus nephritis, 20 diabetic nephropathy, 21 and urothelial cancer. 22 Given the presence of haptoglobin in multiple other conditions, it likely would not be a specific marker in UTI and therefore was not chosen as a protein of interest.…”

Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease

“…Using matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis of urine from diabetic subjects with or without kidney disease, Fu and colleagues identified several ions associated with CKD in this cohort. [48] Some of the peptides could be identified as derived from vitronectin, isoform 1 of fibrinogen alpha, prothrombin, and inter-alpha-trypsin inhibitor heavy chain H4. Surprisingly, no collagen fragments were detected, possibly due to the lower resolution of MALDI-TOF in comparison to LC-or CE-ESI-MS. [49]…”