# Significant Changes in Low-Abundance Protein Content Detected by Proteomic Analysis of Urine from Patients with Renal Stones After Extracorporeal Shock Wave Lithotripsy

## TL;DR

This study finds that ESWL treatment for kidney stones causes changes in low-abundance proteins in urine, which could help detect kidney damage.

## Contribution

The study identifies specific low-abundance urinary proteins as potential biomarkers for ESWL-induced kidney damage.

## Key findings

- Proteomic analysis revealed significant changes in low-abundance urinary proteins after ESWL treatment.
- Proteins like matrix metalloproteinase 7 and alpha1-antitrypsin may serve as biomarkers for kidney damage.
- Changes in proteins related to inflammation, fibrosis, and oxidative stress were confirmed by Western blot analysis.

## Abstract

Although extracorporeal shock wave lithotripsy (ESWL) is effectively used to remove kidney stones of <2–2.5 cm in size, it can also cause kidney damage. Since urine directly reflects renal functions, it can be used to find potential indicators of possible kidney dysfunctions. In particular, this can be achieved by analyzing the protein composition of urine. In this work, using a more advanced technology known as mass spectrometry, we examined urine collected from patients with nephrolithiasis 2 h before and 24 h after their treatment with ESWL. After concentrating urine samples to increase their protein content, our proteomic analysis showed significant changes in a number of low-abundance urinary proteins that are involved in tissue inflammation and fibrosis, as well as oxidative processes. Notably, some of them could be considered as bioindicators of kidney damage caused by ESWL, thus facilitating diagnosis and therapeutic treatments.

Extracorporeal shock wave lithotripsy (ESWL), although a highly effective method for the treatment of kidney stones, can cause significant kidney damage. Since urinary protein composition directly reflects kidney function, proteomic analysis of this fluid may be useful to identify changes in protein levels induced by patient exposure to ESWL as a sign of kidney damage. To this end, we collected urine samples from 80 patients with nephrolithiasis 2 h before and 24 h after exposure to ESWL, which were concentrated and subsequently processed with a commercially available enrichment method to extract low-abundance urinary proteins. These were then separated by 2D electrophoresis and subsequently analyzed by a proteomic approach. A large number of proteins were identified as being related to inflammatory, fibrotic, and antioxidant processes and changes in the levels of some of them were confirmed by Western blot analysis. Therefore, although further experimental confirmation is needed, our results demonstrate that ESWL significantly influences the low urinary protein profile of patients with nephrolithiasis. Notably, among the identified proteins, matrix metalloproteinase 7, alpha1-antitrypsin, and clusterin, as well as dimethyl arginine dimethyl amino hydrolase 2 and ab-hydrolase, may play an important role as putative biomarkers in the monitoring and management of ESWL-induced renal damage.