Stoller Research Program

Stoller Research Program

Contact Information:

Department of Urology
Box 0738
San Francisco, CA 94143-0738

415.476.1611  (Phone) 
415.476.8849  (Fax)

Marshall.Stoller@ucsf.edu  (Email)

Funding: WHI

CT vs US for Diagnosing Urolithiasis

Although there have been several studies that have evaluated the diagnostic accuracy of computed tomography (CT) as compared with ultrasound (US) for diagnosing urolithiasis, there have been no studies that have compared patient outcomes when each of these studies were used as the first diagnostic test among patients with suspected renal colic. Outcomes studies and comparative effectiveness studies are needed to determine which tests will lead to the greatest overall improvement in patient outcomes, at a cost we can afford. These studies must include an assessment of diagnostic accuracy, but also must assess other important outcomes that would influence choices to obtain one imaging test over another, such as quality of life, complication rates due to missed diagnoses, safety and costs.

We propose conducting a randomized controlled trial of CT versus US for the initial evaluation of patients with suspected renal colic seen in a large urban ED.  We will compare accuracy of these two tests but also compare several outcomes including quality of life measures, use of health care resources, complications related to delayed diagnosis, and total radiation exposure as they vary by randomization to each of these tests. An assessment of these outcomes will inform the development of evidenced based guidelines for evaluation of patients with suspected renal colic. Cost-effectiveness and patient-outcome studies are essential to decide how best to use advanced imaging technology, while minimizing costs associated with its use.

Stones Research

As a world’s expert in urinary stone disease, Dr. Stoller’s research has been committed to understanding the fundamental mechanisms underlying stone formation and the calcification process. This has led to identifying links between urinary stones and other diseases such as atherosclerosis and coronary artery disease, illnesses that also involve ectopic calcification. He recently published several large population-based studies in cohorts of more than 80,000 patients demonstrating a link between urinary stones and vascular disease. These studies highlighted the importance of weight control, diet (including low sodium and animal protein intake), and exercise in not only preventing heart and vascular disease, but also in preventing urinary stone formation.

To better explain why these associations exist, Dr. Stoller has led a team of researchers in developing a novel model of urinary stones and calcification in the common fruit fly. This work has led to the discovery of several mechanisms by which the calcification process may be driven that will ultimately translate to new medical therapies for the treatment of urinary stones. In addition to this basic science work, he has studied several other aspects related to urinary stone disease.

The etiology of cystine urinary stone disease is unique and differs from that seen in patients who form calcium stones. Stoller has investigated a family pedigree and identified mutations on the SLC3a1 gene. A DNA library has been developed for cystine stone formers and their families. A knock-out mouse model for this gene is being developed in the hopes of developing new prophylactic agents and to better understand Type 1 cystinuria. Stoller has found linkage of Type II cystinuria to 19q13.1 gene. He has also found codominant inheritance of two cystinuric alleles at the 19q13.1 locus that produce an extreme cystine stone-forming phenotype.

Stoller has investigated a variety of agents to optimize the radiographic visualization of urinary stones. Utilizing a variety of bisphosphonates, he has successfully demonstrated the potential to preoperatively determine stone composition with methyldiphosphonates. The urolithoscintigraph also will have the potential to more optimally visualize stones for fluoroscopically targeted ESWL-systems. A variety of bisphosphonates are being developed as delivery agents to coat stone fragments, with the hopes of inhibiting future stone growth. In vitro models have demonstrated that numerous bisphosphonates can inhibit artificial calcium oxalate monohydrate crystals and real human calculi growth. Inhibition of calculi fragment growth by metal-bisphosphonate complexes has resulted in a new assay to assess surface activity of urolithiasis inhibitors.

Patients with urolithiasis are interested in dietary modifications to help reduce their stone recurrence rates. The role of sodium has been thought to be uniformly detrimental for calcium-based calculi. Studies on the role of dietary sodium in hypocitruric calcium stone formers have shown that sodium may actually be beneficial. Increased sodium intake in hypocitruric patients significantly increases voided volumes and reduces recurrent risk factors.

Hypocitruric calcium stone-forming patients have difficulty taking multiple medications three to four times daily. Research has found that lemonade can substantially increase voided citrate levels, a known important inhibitor of urinary stone disease. The reduced cost and increased long-term compliance with such medications will hopefully reduce stone recurrence rates.

In vitro studies have found that fluoride has the potential to dissolve calcium-based stones. A variety of herbal medications and lentils are being actively investigated as alternative medications for stone prophylaxis. The role of diet remains critical in our understanding of stone prevention.

The prevention of urinary stone disease is essential in managing patients with urolithiasis. A database has been developed with more than 10,000 patients with complete 24-hour urinary chemistries and serum parameters. This has resulted in the definition of unique risk factors in the elderly and will be used for future research endeavors. He utilizes comprehensive metabolic evaluations to help reduce recurrence rates.

Physical Activity and Dietary Energy Intake are Independently Associated with Incident Kidney Stones in Women: A Report from the Women’s Health Initiative Observational Study (WHI OS).

Context: Obesity is a strong risk factor for kidney stone development, but the role of physical activity and recent dietary energy intake in potentially modulating this risk remains poorly understood. 

Objectives: To evaluate the relationship between incident kidney stone formation and physical activity, dietary energy intake, and body mass index (BMI).

Design, Settings and Participants: Longitudinal study of postmenopausal women participating in the Women’s Health Initiative Observational Study.  Overall, 84,225 women with no history of nephrolithiasis completed the WHI food frequency questionnaire.  Women reported kidney stone development annually with a median follow up of 8 years.

Main Outcome Measures: The independent association of baseline weekly physical activity (METs per week), calibrated dietary energy intake, and BMI with the development of incident kidney stones was evaluated with a priori adjustment for age, race/ethnicity, region, income, and dietary water, sodium, animal protein, and calcium intake.  Activity intensity was evaluated, stratified by weekly physical activity category.

Results: Overall, 2,392 women (2.8%) reported an incident kidney stone. Women in the lowest physical activity category had a 14% (aOR 0.86, 95% CI 0.76-0.99) decreased risk of incident stones compared to sedentary women in adjusted analyses.  As weekly activity increased, there was up to a 31% (aOR 0.69, 95% CI 0.60-0.79) decreased risk of incident stones with a dose-response effect that plateaued above 10 METs per week.  Intensity of activity was not associated with stone formation.  Greater dietary energy intake was associated with up to a 44% (aOR 1.44, 95% CI 1.03-2.00) increased risk of incident stones after adjustment. However, lower dietary energy intake did not protect against stone formation (aOR 0.99, 95% CI 0.72-1.36). Greater BMI category increased the risk of incident stones (p=0.003) in adjusted analyses.

Conclusions: These data suggest that greater physical activity may reduce the risk of incident kidney stones in postmenopausal women, primarily due to the amount of activity, rather than exercise intensity.  Higher dietary energy intake may increase the risk of incident stones while lower energy intake is not protective. These effects are independent of the risks associated with BMI and dietary water, sodium, animal protein, and calcium intake.