It’s time to look beyond 24-hour urine collection when it comes to kidney stones, according to Marshall L. Stoller, MD, FACS, who presented the annual John K. Lattimer Lecture on Saturday.
“If you see a door with peeling paint, if you just paint over the peeling paint, it will peel again. In many ways, that’s what we’re doing with kidney stone patients. We are just dealing with the stone and it’s just a matter of time until they come back,” said Dr. Stoller, Professor and Vice Chair of Urology at the University of California, San Francisco, who titled his lecture “Biomineralization in Urology.”
Dr. Stoller said it’s also time to eliminate the arbitrary division between nephrology and urology before taking AUA2018 attendees on a visual tour through the kidney, highlighting his own team’s research into the structure of the kidney and mineral formation in the papillary.
“The nephrologists look at reabsorption and secretion,” he said. “As urologists, we should think about inside the tubule and outside of the tubule. We need to appreciate that the nephron and the papilla are part and parcel of the process of the pathophysiology of urinary stone disease.”
To better understand stone disease, Dr. Stoller said it’s necessary to reexamine papillary form and function.
“We need to look at the functional zonation of the papilla: the proximal part mainly with the glomeruli and initial filtrate, the middle area that really doesn’t have a lot of biominerals, and the distal area that has water conservation,” he said.
Dr. Stoller reminded the audience that urologists believed the prostate was a homogenous organ 30 years ago, and that the transitional zone and the posterior zone where cancer occurs were unknown at the time.
“We are at that same intersection when we think about the papilla today,” he said.
Technology has allowed urologists to look at individual nephrons within the papilla, including individual nephrons coming through different sizes of tubules and their relationship to the vascularity of the papilla. This essentially eliminates the artificial barrier between nephrology and urology, Dr. Stoller said, and moves urologists toward answering the question of how stones are formed as they view the intratubular and interstitial biomineralization processes.
“We see these as time-sequential events, and as a result new therapies can be based on some new targets,” he said.
Dr. Stoller described the progression from ions to Randall’s plaque, beginning with ions and cations at the angstrom level, which precluster to plate-like structures in the intratubular aspects of the papilla. He said they evolve into calcified nanoparticles in the papilla and then become amorphous calcium phosphate crystals, which become part of the Randall’s plaque. Randall’s plaque is thought to be the nidus for stone formation.
“There are so many different targets that we can go after rather than chasing the values of 24-hour urine collection,” Dr. Stoller said. “We believe that early intervention rather than surgical extraction is the way to go, and this is where we have to go in the future to get new medications.”
Dr. Stoller said it’s necessary to identify coupling mechanisms from the intratubular to the interstitial biominerals in the papilla, and to understand the biophysical cues that trigger biochemical expressions going from a compliant to a stiff papilla.
“We need to delineate the interfaces of papillary biominerals to the stones — the normal to the pathologic,” he said, adding that these steps will lead to new therapies for patients with kidney stones.