Five-Protein Panel Promising as Biomarker for Ureteropelvic Junction Obstruction

By Anne Harding

July 07, 2020

NEW YORK (Reuters Health) - A panel of five proteins offers promise as a biomarker for kidney damage in ureteropelvic junction obstruction (UPJO), new research shows.

"We're starting hopefully to find a way that they could noninvasively assess the patient's kidney damage in response to this specific type of injury, because right now there's really not a good way to do it," study author Dr. Linda H. Shapiro of the University of Connecticut Health Center (UCHC) in Farmington told Reuters Health in a video call.

While ultrasounds can help identify patients with UPJO, in some cases before birth, kidney enlargement does not always indicate obstruction, Dr. Shapiro noted. Patients typically undergo a nuclear-medicine study known as MAG3 to clarify the diagnosis, she added, but the test is invasive and results are frequently equivocal, so patients may need repeat MAG3 tests.

The new pilot study, published in the Journal of Pediatric Urology, used bladder urine samples from 21 boys under age 2 with UPJO and 22 age- and sex-matched controls.

Dr. Shapiro and her team used mass spectrometry-based proteomics analysis to identify proteins that were present in the UPJO patients but not in controls. They found 171 proteins that were absent from 72.7% of the control samples. Fifty of these proteins appeared in at least 52.4% of the UPJO patients.

The authors then ranked these proteins by odds ratios and validated the top 10 by ELISA. Five proteins were found at median protein concentrations 2.9- 9.4-fold higher in the UPJO samples compared to the control samples: prostaglandin-reductase-1, ficolin-2, nicotinate-nucleotide pyrophosphorylase (carboxylating), immunoglobulin superfamily-containing leucine-rich-repeat-protein and vascular cell adhesion molecule-1.

"Most of the patients had at least three of the five proteins, and none of the controls had more than one," Dr. Shapiro said. "We don't have a huge sampling, but it worked pretty well."

She noted that she and her colleagues have since validated the panel in 40 more patients.

"What it's telling me as a clinician is, if this combination of proteins is elevated, this kidney is currently obstructed and it's not draining well and these are the signals that the kidney's giving us to say 'I'm obstructed, I'm undergoing inflammation, injury, damage,'" co-author Dr. Fernando A. Ferrer of Icahn School of Medicine at Mount Sinai, in New York City, told Reuters Health in a video call.

Because the test was done in bladder urine, he added, samples could be collected non-invasively. Using artificial intelligence and modeling, he added, other physiologic markers could be incorporated such as hypertension.

"It could potentially eliminate the need to do the MAG3 test," Dr. Ferrer said. "It would be very significant in the way that you would create a totally noninvasive way to diagnose and follow these patients. The cost savings obviously would be enormous too."

The authors are now planning to test the biomarker panel in 400 patients.

The study was funded by the National Heart, Lung, and Blood Institute.

SOURCE: Journal of Pediatric Urology, online June 10, 2020.