Distinct proteomic signatures of urinary extracellular vesicles link to albuminuria and treatment responses in diabetic kidney disease
Abstract
Introduction: Urinary extracellular vesicles (uEVs) offer a noninvasive approach to gain pathophysiological insight into kidney disease and treatment effects. Our study aimed to investigate the impact of albuminuria and antialbuminuric therapies on the uEV proteome in diabetic kidney disease.
Methods: uEVs were isolated from urine samples of 20 patients with diabetes and albuminuria (age 64 years, estimated glomerular filtration rate 85 ml/min per 1.73 m2, urinary albumin creatinine ratio 130 mg/g) who participated in a crossover trial. Participants received telmisartan, empagliflozin, linagliptin, and baricitinib in random order across four 4-week treatment periods. Quantitative proteomics was performed using liquid chromatography-tandem mass spectrometry. Results were compared with two datasets (one single-nucleus, one single-cell) analyzing the effects of proteinuria and sodium-glucose cotransporter 2 inhibition (SGLT2i) on the kidney transcriptome.
Results: A total of 2,441 proteins were identified in uEVs, of which 355 were significantly associated with albuminuria. Treatment with telmisartan, empagliflozin, linagliptin, and baricitinib resulted in, respectively, 86, 313, 80, and 47 differentially abundant uEV proteins with minimal overlap between treatments. Of the albuminuria-associated uEV proteins, 100 were significantly altered by at least one treatment. The overall proteomic signature was characterized by enrichment of podocyte-associated proteins, complement…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 20 participants or records.
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