Urinary proteome may hold key to stone prevention

A recent study provides the first comprehensive catalog of urinary calcium oxalate monohydrate binding proteins.

Analyses of urine samples collected from children and adults provide the first comprehensive catalog of urinary calcium oxalate monohydrate (COM) binding proteins and reveals significant differences in the level and make-up of these proteins between the two populations, urologists from Washington University School of Medicine, St. Louis, reported at the AUA annual meeting in San Diego.

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The study, which included subjects with no history of urinary stone disease (USD), is part of a larger ongoing project aiming to characterize the urinary proteome in children and adults for insights on USD pathogenesis as well as age-related clinical differences, and eventually to guide development of better prognostic approaches and therapeutic strategies.

“In previous work, we demonstrated there are populations of proteins within human urine that have very high affinity for COM. In addition, we showed that some of these proteins inhibit crystal adhesion and crystal growth and aggregation in solution,” said first author Joel Koenig, MD.

“So far, in this phase of our research, we have found there are age-related differences in the urinary proteome and specifically with regard to COM-binding proteins. Moving ahead, we are conducting additional analyses to better characterize the differences,” added Dr. Koenig, who worked on the study with Paul Austin, MD, and colleagues.

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Findings from basic chemistry studies done to measure the concentration of various proteins in the urine samples along with affinity chromatography performed using control and COM crystal-loaded columns showed that in both the pediatric and adult subjects, proteins with a high selective affinity for COM comprised a minor proportion of the total protein content of the urine. Consistent with some previous research, the proportion of proteins with a high selective affinity for COM accounted for only about 10% to 20% of total protein in the urine, Dr. Koenig reported.

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However, the total concentration of COM-binding proteins was significantly higher in the adults than in the children, and the proportion of high affinity COM-binding proteins was 39% greater in adults.

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Currently, the investigators are performing HPLC-mass spectrometry for high throughput identification of the urinary proteins and immunoblotting and ELISA for protein-specific analyses.

In terms of clinical application of their research, they hypothesize that urinary proteins found to have a strong effect for preventing COM crystal adherence and/or aggregation could be used as biomarkers to predict risk of stone recurrence and also provide therapeutic targets.

“Hopefully, with the identification of such proteins, a quick spot test of a urine specimen could reduce the need for a cumbersome 24-hour collection,” Dr. Koenig explained.

“And our ultimate goal is to use the findings from our studies to design a therapeutic intervention that might increase the secretion of the protective proteins as an approach for preventing kidney stone formation.”

As next steps, they will expand their research by comparing the urinary proteome of populations of patients with and without a history of USD and also study patients with a history of recurrent USD.

“The finding of differences in these initial groups of children and adults with no history of stone formation encourages us to keep our project going,” Dr. Koenig told Urology Times.