# Post-ESWL urinary osteopontin level and ion-activity product of calcium oxalate are associated with stone recurrence after 5-year follow-up

## TL;DR

This study found that higher levels of urinary osteopontin and calcium oxalate supersaturation after kidney stone treatment are linked to a higher risk of stone recurrence over five years.

## Contribution

The study identifies urinary osteopontin and ion-activity product of calcium oxalate as novel post-treatment predictors of kidney stone recurrence.

## Key findings

- Urinary osteopontin and calcium oxalate supersaturation at four weeks post-ESWL were significantly associated with stone recurrence over five years.
- Most CaOx-related proteins increased after ESWL, suggesting ongoing risk despite stone removal.

## Abstract

Calcium oxalate (CaOx) is the predominant component in over 80% of kidney stones. The formation and retention of kidney stones involve multiple mechanisms, including overgrowth on Randall’s plaques—subepithelial calcium phosphate deposits in the renal papillae—and interactions between urinary crystals and renal tubular epithelial cells. Previous studies have shown that specific urinary proteins can either promote or inhibit CaOx crystal nucleation, growth, and retention. This study investigates changes in the urinary excretion of CaOx-related proteins before and after extracorporeal shock wave lithotripsy (ESWL), aiming to identify protein markers associated with stone formation and recurrence over a 5-year follow-up.

This study enrolled 54 patients with renal or ureteral stones treated with ESWL and 13 healthy controls. 24-hour urine samples were collected preoperatively and at 2 and 4 weeks post-ESWL for biochemical analysis. CaOx-related proteins were measured semi-quantitatively in urine samples before and after ESWL, including nucleolin-related protein (NRP), nuclear pore complex p62 (NPC), hyaluronic acid (HA), SLC26A6, CXCR4, osteopontin (OPN), Tamm-Horsfall protein (THP) and Matrix Metalloproteinase (MMPs). Statistical analyses, including Pearson correlation and logistic regression, were performed to identify factors related to 5-year stone recurrence. Statistical significance was set at p < 0.05.

Before ESWL, stone patients exhibited significantly higher levels of NPC, HA, and CXCR4. All examined markers, except for Tamm-Horsfall protein, increased significantly at two weeks after ESWL. At four weeks post-EWSL, OPN and SLC26A6 remained higher. Correlations were observed between CXCR4, MMPs, stone size and ion-activity product of calcium oxalate (APCaOX), a measure of urinary calcium oxalate supersaturation. Logistic regression identified urinary OPN and APCaOX at 4 weeks post-ESWL as significant factors influencing 5-year stone recurrence, with a recurrence rate of 48.4%.

The persistence of certain urinary proteins after ESWL implied the risk of stone recurrence despite stone removal. The stone recurrence at 5 years was significantly associated with higher urinary OPN and higher APCaOX levels at four weeks post-ESWL, suggesting the potential predictive value of these markers.

Approval was obtained from the ethics committee of National Taiwan University Hospital (National Taiwan University Hospital Ethics Committee approval: 200706054M).