Endocrine Abstracts

Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease It is defined by glomerular filtration rate (GFR) impairment and/or presence of increased urinary albumin excretion (UAE). However, these parameters are nonspecific and somewhat delayed manifestations of renal damage. Thus, earlier DKD new biomarkers are strongly warranted.

Objective: To investigate the urinary peptidomics profile of type 2 diabetes mellitus (DM) patients with different stages of DKD.

Methods: Casual urine samples were collected from 66 type 2 DM patients matched by age, gender and time of diabetes duration. Urine natural occurring peptides were purified by ultrafiltration under denaturing conditions and analyzed by LC–MS/MS. UAE was assessed by immunoturbidimetry and GFR was estimated by CKD-EPI equation. Kruskall–wallis, Mann–Whitney and χ2 tests were performed when appropriate; Perseus software was used to perform hierarchical clustering of significantly up- and down-regulated proteins.

Results: Type 2 DM patients (mean age=−61.5±9.7 years; males=47.1%) were stratified by the levels of albuminuria (normal (n=27), moderately increased (MI, n=18) and severely increased (SI, n=21)). A total of 116 urinary proteins were detected by LC/-MS/MS. A distinct proteomic profile was identified in patients with SI albuminuria, represented by 11 proteins. When GFR values were analyzed, we observed that 13 urinary proteins differed significantly in the 9 patients with GFR <60 ml/min per 1.73 m² when compared to 57 patients with GFR ≥60 ml/min per 1.73 m². Among the most remarkably different urinary protein profile, alpha-1 type I collagen was around 10% less expressed in SI patients, while alpha-1 antitrypsin, plasma protease C1 inhibitor and apolipoprotein-1 were ~twofold increased in these patients.

Conclusions: LC–MS/MS analysis revealed that at least 11 urinary proteins were differentially expressed in type 2 DM patients according to DKD severity. This study confirms the previously described findings in other populations and also detected novel proteins commonly altered in patients with GFR impairment and increased albuminuria.