Molecular profiling of urinary extracellular vesicles in chronic kidney disease and renal fibrosis

Abstract

Chronic kidney disease (CKD) is a long-term kidney damage caused by gradual loss of essential kidney functions. A global health issue, CKD affects up to 16% of the population worldwide. Symptoms are often not apparent in the early stages, and if left untreated, CKD can progress to end-stage kidney disease (ESKD), also known as kidney failure, when the only possible treatments are dialysis and kidney transplantation. The end point of nearly all forms of CKD is kidney fibrosis, a process of unsuccessful wound-healing of kidney tissue. Detection of kidney fibrosis, therefore, often means detection of CKD. Renal biopsy remains the best test for renal scarring, despite being intrinsically limited by its invasiveness and sampling bias. Urine is a desirable source of fibrosis biomarkers as it can be easily obtained in a non-invasive way and in large volumes. Besides, urine contains biomolecules filtered through the glomeruli, mirroring the pathological state. There is, however, a problem of highly abundant urinary proteins that can mask rare disease biomarkers. Urinary extracellular vesicles (uEVs), which originate from renal cells and carry proteins, nucleic acids, and lipids, are an attractive source of potential rare CKD biomarkers. Their cargo consists of low-abundant proteins but highly concentrated in a nanosize-volume, as well as molecules too large to be filtered from plasma. Combining molecular profiling data (protein and miRNAs) of uEVs, isolated from patients affected by various forms of CKD, this review considers the possible diagnostic and prognostic value of uEVs biomarkers and their potential application in the translation of new experimental antifibrotic therapeutics.

Proteomics of urinary small extracellular vesicles in early diagnosis of kidney diseases in children‐expectations and limitations

“…Urinary EVs inform about cellular-level processes in the kidneys themselves, and are also a vehicle for transmitting regulatory information at various levels of the organ [34]. The advantage of uEV markers is that they reflect early renal changes at the subclinical level, even preceding proteinuria [35]. An important issue here is the application of a standardized diagnostic pipeline to prepare the material for specialized downstream analyses.…”

Urinary podocyte markers in diabetic kidney disease

“…Since the amount of mRNA and miRNA in urine is small, there is no reliable method to determine the gene expression library in urine [ 92 , 93 ], and identifying suitable targets is often a fishing exercise. Moreover, a urine sample contains separate compartments (i.e., conventional sediment, microvesicles, and truly cell-free supernatant), and podocyte-associated molecules (proteins, mRNA, and miRNA) are present in them at different concentrations [ 94 , 95 ]. Since the compartment to be tested determines the centrifugation protocol [ 50 , 96 ], it is a necessary but arduous task to define the suitable molecular target in each specific urinary compartment for clinical use.…”

Identification of Key Transcription Factors Associated with Chronic Kidney Disease for Early Clinical Diagnosis

“…Renal brosis is the most important pathological feature of ESKD, which is characterized by glomerulosclerosis, interstitial brosis, and immune cell in ltration in the kidney [5][6][7] . The renal brosis is accompanied by pathological accumulation of extracellular matrix (ECM) proteins, including collagens and bronectin 8 .…”