© Springer International Publishing Switzerland 2015David A. Schulsinger (ed.)Kidney Stone Disease10.1007/978-3-319-12105-5_30
30. Update: What Is New on the Horizon?
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Stephen Y. Nakada
The treatment options for kidney stones have expanded immensely over the past 30 years, and new concepts in diagnosis and treatment continue to evolve from the research bench to the patient bedside. Advances in imaging capabilities, increased power, durability, and maneuverability of laser stone fragmentation technology, and novel tools to improve patient involvement in surgical decision-making are at the forefront of stone management. In addition, animal models, including rodent, swine, and even fruit flies, hold future promise for advancing our understanding of the progression and management of stone disease. New drug treatments with innovative mechanisms may provide tomorrow’s urologist with new strategies for both therapy and prevention. Similarly, probiotics have received increased focus as a potential approach to the breakdown of oxalate in the digestive tract, a component in nearly 80 % of kidney stones. Perhaps the most unique development is the recent application of robotic-assisted surgery for both basic and complex stone management. A multitude of exciting new therapies, techniques, and technologies are on the horizon, and the future is bright for the management of kidney stones. In closing, we review the most recent American Urological Association (AUA) guidelines for the medical management of stone disease.
Patients presenting to the emergency room with classic symptoms of kidney stones including flank pain, pain that spreads to the lower abdomen and groin, pain with urination, blood in the urine, and/or nausea and vomiting are typically diagnosed using a CT scan. This imaging test is more sensitive than x-ray, and can reveal more reliable information on the exact size and position of stones. Though these are both key factors in determining treatment, the chemical composition of a stone is also beneficial for providers to know. Different types of stones have different degrees of hardness (measured in “Hounsfield Units”), and are best treated with different medical or surgical modalities. In the past, the only way to determine stone composition was by sending an actual sample of a patient’s stone, collected via spontaneous passage or surgical means, to a laboratory. However, new dual-energy CT (DECT) is a promising new technology that may help clinicians more accurately distinguish stone type at the time of presentation and diagnosis. Though this technology is still in the early stages of development, a recent study  found DECT imaging correctly identified stone composition in 74 % of cases, as opposed to only 52 % with standard CT. Even more impressively, DECT was able to correctly differentiate non-uric acid stones from uric acid stones in 93 %, versus only 40 % using CT. Though further improvement and testing is needed, DECT may help providers better select the most effective and safe treatment for kidney stones based on size, location, and chemical composition.
Though traditionally used as an imaging (US) or fragmenting tool (SWL), ultrasound technology has advanced greatly over the last 5 years to the point where ultrasonic propulsion can be used to move stones within the urinary tract . Though minimally invasive techniques for stone fragmentation, including SWL, ureteroscopy (URS), and percutaneous nephrolithotomy (PNL), have improved considerably in the last decade, residual fragments may still cause recurrent symptoms and may require future intervention. In these cases ultrasonic propulsion may be an effective tool in the urologist’s arsenal for clearing residual stones. With this technology, stones could be repositioned at a clinic visit with the patient awake, in a procedure similar to standard ultrasound imaging. Additionally, ultrasonic propulsion could supplement medical expulsive therapy in patients presenting with small stones. Similarly, painful obstructing stones may be able to be moved back into a non-obstructing position in the renal pelvis, thereby reducing pain and avoiding an emergent procedure and narcotic analgesic medications .
Shared Decision Making (SDM)
There has been a considerable shift in healthcare over the last decade to increase focus on patient centered care . In contrast to the traditional view with the clinician making decisions on behalf of the patient, shared decision making with greater patient input has become a key emphasis for providers, legislators, and patients themselves. The shared decision making model consists of three steps: (1) introducing choice, (2) describing options, often with the use of an integrated informative handout, and (3) helping patients explore options and make decisions . The use of a shared decision-making aid is supported by extensive research, including over 80 randomized trials that demonstrate increased knowledge gain for patients, as well as improved patient confidence and involvement with decisions made .
Currently, shared decision making aids exist in multiple areas of urology, including BPH  and prostate cancer . However, until recently the use of a shared decision making aid in patients with kidney stones had not been explored. Patients with kidney stones requiring surgical treatment pose an ideal opportunity for the implementation of a shared decision making aid, as multiple reasonable treatment options exist. Depending on various patient and stone factors, surgical options may include shockwave lithotripsy, ureteroscopy, and/or percutaneous nephrolithotomy. Early development and testing of a shared decision making aid that compared shockwave lithotripsy and ureteroscopy showed that 86 % of patients found the aid helpful, and 79 % preferred the shared decision process compared to a typical office discussion . With the addition of further patient input and validation, kidney-stone-focused shared decision aids will soon become widely available to physicians and patients. As urologists continue to search for strategies to improve patient outcomes and satisfaction in stone disease, shared decision aids will play a key role in both the transfer of information and collective treatment choice.
Animal Models to Understand Stone Disease
Animal models have long been used in medicine to better understand the mechanisms of disease and potential application of new therapies. Kidney stone formation is a complex series of events that occurs through multiple pathways, ultimately causing crystal formation and growth that becomes a kidney stone. Animal models are used to simplify this complicated process into a series of distinct steps that can be individually studied and used to evaluate new therapies. In particular, rodent, swine, and even fruit fly models of stone formation are at the cutting edge of new research exploring the various types and treatments of kidney stones.
As discussed previously, the majority of kidney stones are composed primarily of calcium oxalate (CaOx), and appropriately the majority of animal models are based on formation of these stones. In both animals and humans, high concentrations of oxalate in the urine (hyperoxaluria), causes crystal formation with calcium ions to eventually form kidney stones. The initial CaOx model in rats was achieved by adding ethylene glycol (a chemical found in antifreeze) to the animal’s drinking water . Ethylene glycol is converted to oxalate by the liver then absorbed through the gastrointestinal tract, resulting in hyperoxaluria and subsequent stone formation within the kidney. However, ethylene glycol is toxic to multiple organ systems, including the kidney, making it difficult to differentiate if cellular damage is secondary to the initial ethylene glycol, or the crystallization and formation of stones . The more recent rat model of nephrolithiasis is achieved by feeding the animal high concentrations of a different oxalate precursor, hydroxyproline (a derivative of the common amino acid proline found in many Western diets) . This model more accurately models the increase in oxalate secondary to diet, and avoids the renal toxicity seen in ethylene glycol models.
One of the interesting new rat models is the formation of CaOx stones in obese rats that have undergone gastric bypass surgery . In spite of the many benefits of gastric bypass surgery for weight loss, it is now known that in humans this surgery increases risk for kidney stones secondary to hyperoxaluria . Normally, free oxalate and calcium in the gut lumen bind and are passed harmlessly out of the gastrointestinal tract via stool. However, patients with gastric bypass have an increase in fatty acids that bind calcium, leading to an increase in unbound oxalate. This increased oxalate is absorbed in the bloodstream, where it eventually makes it to the kidney causing hyperoxaluria .
Though rats have historically served as the primary animal metabolic model for stone disease, the last decade has seen the development and advancement of a hydroxyproline induced swine model [16, 17]. Swine have been extensively studied in biomedical research, and are remarkably similar to humans in both genitourinary anatomy and physiology . In addition, they have comparable nutritional needs as omnivores, and similar gastrointestinal functioning. The anatomical parallels to humans make swine an ideal surgical model, and as techniques to encourage stone formation improve, this model will be a major player in testing new minimally invasive stone treatments and medications.
Finally, one of the newer and more innovative animal models has been the emergence of Drosphila melanogaster (fruit fly) as a translational model of stone disease . Though anatomically and physiologically different than humans, drosophila fed high-oxalate diets form stones in 2–3 days, in sharp contrast to the weeks required for the previously mentioned models . This short formation period allows researchers to quickly and economically study the mechanistic cycle of stone development. Another advantage over other models is low financial cost, and the minimized constraints from ethical and institutional review boards. Additionally, another drosophila model has been constructed based on the genetic removal of gut oxalate transporters, resulting in a build-up of oxalate and resulting hyperoxaluria . Though still in the early phases of development, this research may provide the foundation for isolating human genes responsible for kidney stone disease.
New Medications and Probiotics
Most symptomatic kidney stones are treated with increased fluids, pain control, and an alpha-blocker (a medication that relaxes the ureteral smooth muscle, improving passage of stones or fragments), or surgically managed. Though there have been no major pharmacologic breakthroughs for the treatment of stone disease in the twenty-first century, two new therapies have shown promise in initial laboratory testing.