Stone Disease: Medical Management and Basic Research

In this session of 39 posters, there was some very exciting basic research as well as several lines of important clinical work. On the research front, a murine model for type I cystinuria was described by Knoll and colleagues from Mannheim and Martinsried, Germany. The stones that developed in this model were 100% cystine and the mice had cystine crystalluria. This discovery opens the door for the development of more effective pharmaceutical and potential gene therapy trials (Abstract 1122). Also on the basic research front were several studies presented from major urolithiasis laboratories at the Univ. of Florida, Gainesville, Duke University, and the Vattikuti Institute of Urology, indicating that administration of free radical scavengers, such as citrate and Vitamin E, could protect both proximal tubular as well as urothelial cells from shock wave lithotripsy induced damage both in vitro and in a rat model of calcium oxalate stone disease (Abstract 1120, 1121, and 1129). With regard to shock wave lithotripsy, two abstracts were particularly provocative and likely will have significant clinical application. Willis, Lingeman, Evan and colleagues from Indianapolis (Abst. 1114) showed that pretreatment of the pig kidney with as few as 100 low energy shock waves (i.e. 12 kV) protected the kidney from damage during higher energy shock wave lithotripsy (i.e. 24 kV). The protective effect appears to be due to early vasoconstriction, as the benefit was negated when the animals were given dopamine prior to lithotripsy. Of equal importance is a companion abstract by the research group from Duke (Preminger, Zhong, Zhou et al.) (Abstract 1115) showing that progressive increase in shockwave energy produced better stone fragmentation; in this study the authors progressed from 18 to 20 to 22 kV in 500 shockwave intervals. Combining these two regimens in clinical practice could potentially lead to safer, more effective shock wave lithotripsy.

From a clinical standpoint, Maloney, Preminger, and colleagues at Duke, clearly showed that after percutaneous nephrostolithotomy, patients with residual stones as well as patients who are rendered stone free, benefit from a metabolic evaluation and initiation of directed medial therapy. Over a 2.5-3 yr. period, the stone free and residual fragment patients on medical therapy enjoyed a 70% and 73% remission from new stone formation, whereas their counterparts, who received no medical therapy, had a 3 fold less remission rate, only 25% and 23% (Abstract 1146). Lastly, there were two papers showing a favorable impact of tamsulosin (0.4 mg/day) on the passage of distal ureteral calculi. In the randomized study by Dellabella et al. (Abstract 1151), the tamsulosin group of 70 patients, which also received, like the other two groups of 70 patients each, a steroid and an antibiotic, had a 97% stone expulsion rate. The tamsulosin group also required less pain medications and returned to work sooner than in the other two arms of the study, one of which included a calcium channel blocker. In a similar (Abstract 1152), albeit not randomized study, the administration of another alpha blocker (terazosin 5 mg/day) for up to 4 weeks, resulted in an increased stone passage rate of 95% vs. 56% in the controls, when stone size was < 8mm; the corresponding figures when the stones were > 8 mm, was 56% and 29%. Of interest, among patients < 50 y.o. and with a stone > 8mm, the stone passage rate on terazosin was surprisingly good: 85% vs. 46% in controls. The authors noted a 20% decrease in stone expulsion in the terazosin group when patients were > 50 years of age. Interestingly, age had no impact on stone passage in the control group. With these data, one wonders whether the use of a steroid or antibiotic can be avoided and the patients given just the alpha blocker. Certainly this would be a safer and less expensive approach. What is needed, is a randomized study with just an alpha blocker alone among patients with a distal ureteral stone

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