Early rather than delayed lithotripsy is better for patients with symptomatic, obstructing ureteral stones, according to a new study.
“Emergent lithotripsy, either ureteroscopic or extracorporeal, can be offered as an effective and safe treatment for patients with symptomatic ureteral stone,” Riccardo Autorino, MD, of Case Western Reserve University in Richmond Heights, Ohio, and colleagues concluded in Urolithiasis, published online ahead of print.

Dr Autorino' s group evaluated emergent vs delayed lithotripsy in separate systematic reviews and meta-analyses of ureteroscopy (URS) and extracorporeal shock wave lithotripsy (ESWL). An “emergency” procedure occurred variably within 6 to 72 hours of presentation. 

Emergent URS performed as well as delayed URS, according to a meta-analysis based on 4 studies (including 1 randomized controlled trial) of 1513 patients. The investigators reported no significant differences in stone-free rate, complication rate, and the need for auxiliary procedures. Stone-free meant the absence of a stone or fragments of 3 mm or less. Emergent ureteroscopy typically is reserved for distal stones, they noted.

Emergent ESWL was associated with more than twice the odds of achieving stone-free status and half the odds of auxiliary procedures compared with delayed ESWL. Again, no differences in rates of complications, such as hematuria or mucosal injury, were observed. “If amenable to ESWL, based on stone and patient characteristics, an emergent approach should be strongly considered,” Dr Autorino and colleagues stated. This meta-analysis involved 6 studies (including 4 randomized trials) of 711 patients. The investigators could not perform sensitivity analyses by stone size and location. 

Early treatment of stones with colic is preferable because ureteral edema can develop within 48 hours and interfere with stone clearance, the team suggested. A previous study published in the Journal of Endourology (2010;24:2059-2066) found that treatment after 48 hours is associated with longer clearance of proximal ureteral stones less than 1 cm and higher rates of retreatment and auxiliary procedures. 

Implementing emergent lithotripsy would depend on the availability of URS and ESWL. It is possible that specific machines and technologies affect results. More research is warranted.

Researchers have found evidence that a natural fruit extract is capable of dissolving calcium oxalate crystals, the most common component of human kidney stones. This finding could lead to the first advance in the treatment of calcium oxalate stones in 30 years.

Jeffrey Rimer, associate professor of chemical engineering at the University of Houston, was lead author of the study, published in the online edition of Nature. The work offers the first evidence that the compound hydroxycitrate (HCA) is an effective inhibitor of calcium oxalate crystal growth that, under certain conditions, is actually able to dissolve these crystals. Researchers also explain how it works.

The findings are the result of a combination of experimental studies, computational studies and human studies, Rimer said.

Kidney stones are small, hard mineral deposits that form inside the kidneys, affecting up to 12 percent of men and seven percent of women. High blood pressure, diabetes and obesity can increase the risk, and the reported incidence is on the rise.

Preventive treatment has not changed much over the last three decades. Doctors tell patients who are at risk of developing stones to drink lots of water and avoid foods rich in oxalate, such as rhubarb, okra, spinach and almonds. They often recommend taking citrate (CA), in the form of potassium citrate, a supplement that can slow crystal growth, but some people are unable to tolerate the side effects.

The project grew out of preliminary work done by collaborator John Asplin, a nephrologist at Litholink Corporation, who suggested HCA as a possible treatment. HCA is chemically similar to CA and is also available as a dietary supplement.
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"HCA shows promise as a potential therapy to prevent kidney stones," the researchers wrote. "HCA may be preferred as a therapy over CA (potassium citrate)."

In addition to Rimer and Asplin, authors on the paper include Giannis Mpourmpakis and his graduate student, Michael G. Taylor, of the University of Pittsburgh; Ignacio Granja of Litholink Corporation, and Jihae Chung, a UH graduate student working in Rimer's lab.

The head-to-head studies of CA and HCA determined that while both compounds inhibit the growth of calcium oxalate crystals, HCA was more potent and displayed unique qualities that are advantageous for the development of new therapies.

The team of researchers then used atomic force microscopy, or AFM, to study interactions between the crystals, CA and HCA under realistic growth conditions. According to Rimer, the technique allowed them to record crystal growth in real time with near-molecular resolution.

Chung noted that the AFM images recorded the crystal actually shrinking when exposed to specific concentrations of HCA. Rimer suspected the initial finding was an abnormality, as it is rare to see a crystal actually dissolve in highly supersaturated growth solutions. The most effective inhibitors reported in the literature simply stop the crystal from growing.

It turned out that Chung's initial finding was correct. Once they confirmed it is possible to dissolve crystals in supersaturated solutions, researchers then looked at reasons to explain why that happened.

Mpourmpakis and Taylor applied density functional theory (DFT) - a highly accurate computational method used to study the structure and properties of materials - to address how HCA and CA bind to calcium and to calcium oxalate crystals. They discovered HCA formed a stronger bond with crystal surfaces, inducing a strain that is seemingly relieved by the release of calcium and oxalate, leading to crystal dissolution.

HCA was also tested in human subjects, as seven people took the supplement for three days, allowing researchers to determine that HCA is excreted through urine, a requirement for the supplement to work as a treatment.

While Rimer said the research established the groundwork to design an effective drug, questions remain. Long-term safety, dosage and additional human trials are needed, he said.

"But our initial findings are very promising," he said. "If it works in vivo, similar to our trials in the laboratory, HCA has the potential to reduce the incidence rate of people with chronic kidney stone disease."