Kidney stones are notorious for being one of the most painful ailments, but a researcher at the University of Houston's Cullen College of Engineering has received another grant to continue his group's research into using the compound hydroxycitrate (HCA) to slow their growth.
Jeffrey Rimer, Abraham E. Dukler Professor in the William A. Brookshire Department of Chemical and Biomolecular Engineering Department, is well-known and recognized for his groundbreaking research into crystal engineering. His work in this area spans the rational design of catalytic materials to the prevention of crystals in human diseases. For nearly 17 years he has been examining new therapies for kidney stones, which are hard deposits of minerals and salts that form inside the body, and are typically passed through the urinary tract.
In 2016, Rimer was the lead author for a study published in Nature demonstrating that HCA is an effective inhibitor of calcium oxalate monohydrate crystal growth. Now, as this research proceeds to human trials and animal studies, he is a subcontractor on a grant awarded to the University of Texas Southwestern Medical School. Rimer's portion of the funding is $572,000 over five years. The total award of $2.36 million is being funded by the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) with a project start date of Aug. 5, 2023.
“This NIH grant is our first major effort to expand this research to in vivo studies, which is critical for assessing the efficacy of HCA,” he said. “This project will expand beyond studies of calcium oxalate to test the effects of HCA on calcium phosphate kidney stones.”
Rimer cautions that while they think HCA has potential for alleviating symptoms and preventing kidney stone growth better than citrate – the common treatment right now – it is not a magical cure.
“When we first published the effects of HCA in 2016, there were news articles that were being published with headlines like, 'Is this the end of kidney stones?' While this is far from the truth, a more accurate question is whether new therapeutics are capable of reducing incidence rates below levels achieved with citrate?”
Rimer noted that in past work, they saw small sections of crystal dissolving, but citrate and HCA cannot dissolve large scale crystals. However, this molecule is a highly effective inhibitor of crystal growth that has the potential to significantly delay the formation of kidney stones.
“We are targeting people with chronic cases of stone disease, with the intent to prevent or at least lessen their number of stones,” he said. “Molecules that function as inhibitors work by interacting with crystal surfaces, blocking sites for calcium and oxalate incorporation, an ultimately inhibiting crystallization. We have demonstrated in the laboratory that HCA binds to surfaces of calcium oxalate crystals and dramatically reduces their rate of growth.”
Another potential benefit of HCA that will be tested is its ability to reduce undesirable side effects that are common to citrate.
“A side effect of citrate is that your urine pH becomes more basic,” he said. “This actually promotes another type of kidney stone. Thus, the beneficial effects of citrate are partially offset by its impact on urine alkalinity.”
Rimer said that HCA has the potential to effectively reduce the rate of calcium phosphate crystal growth without raising urine pH, which would be an added benefit over citrate, particularly if this project demonstrates that HCA is a more effective crystal growth inhibitor in vivo. He called it a “dual therapeutic effect.”
The principal investigator of this project is Dr. Naim Maalouf, who is leading a team of co-investigators at UT Southwestern Medical Center that includes Drs. Khashayar Sakhaee and Orson Moe. At the University of Houston, Rimer will be working with two of his graduate students, Dipayan Chakraborty and Vraj Chauhan, and postdoctoral fellow Si Li.