Urinary proteomics in youths with and without type 1 diabetes

ABSTRACT: Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Our understanding of the early kidney response to chronic hyperglycemia remains incomplete. In this study, we aimed to uncover the early, dysregulated pathways in the diabetic kidney before the onset of microalbuminuria by analysing the urinary proteomes of otherwise healthy youths with and without type 1 diabetes. Our study population included two cohorts for the discovery (N = 30) and validation (N = 30) of differentially excreted proteins. Of the 2451 proteins identified, 576 were quantified in all samples from the discovery cohort, and 34 comprised the urinary signature for early type 1 diabetes after Benjamini-Hochberg adjustment (Q < 0.05). The top pathways associated with this signature included lysosome, glycosaminoglycan degradation, and innate immune system (Q < 0.01). Notably, all enzymes involved in keratan sulfate degradation were significantly elevated in urines from youths with type 1 diabetes (fold change > 1.6). Increased urinary excretion of monocyte differentiation antigen CD14, hexosaminidase A, and lumican was also observed in the validation cohort (P < 0.05). Our findings draw attention to novel pathways such as keratan sulfate degradation in the early kidney response to hyperglycemia.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Julie Anh Dung Van  

LAB HEAD: Ana Konvalinka

PROVIDER: PXD017213 | Pride | 2020-06-01

REPOSITORIES: Pride