The Asymptomatic Kidney Stone: To Treat or Not to Treat

Many patients show up to urology clinic with kidney stones that are not causing problems at the moment.  It is well known that obstructing kidney stones can cause excruciating pain and discomfort, so the question often follows, "Should I have this stone treated before it causes problems?"  The following is a discussion of the facts surrounding Asymptomatic Kidney Stones.

It is estimated that 5% of women and 10% of men in the US have nephrolithiasis (or kidney stones).[1,2]  Most people do not know they have kidney stones until they obstruct one of the ureters, connecting the kidney to the bladder.  These symptoms may include flank pain, nausea and vomiting, hematuria (blood in the urine) or high fever.  Many patients have kidney stones and have no symptoms.  In fact, studies of patients without symptoms of nephrolithiasis who underwent imaging for other reasons demonstrate asymptomatic nephrolithiasis in 7.8-9.7% of patients, often with these patients having more than one stone and stones of a size that are likely to eventually obstruct and cause symptoms.[3,4]

Brian Matlaga, MD, MPH, Director of Stone Disease and Ambulatory

Brian Matlaga, MD, MPH

Urology at the Brady Urological Institute at Johns Hopkins recently told Practice Updates: Urology, "In general, our indications for surgery for stone patients are pain, obstruction, or infection. In most cases, patients with incidentally found stones will not meet any of these three criteria—which usually, then, results in the conservative, expectant approach."  A recent analysis by Goldsmith and Lipkin in Nature Reviews Urology reports that 50% of patients with asymptomatic stones will develop symptoms at five years.  Of these patients, half will pass spontaneously and half will require surgery.[5]  Dr. Matlaga summarizes, "I quote patients a 10% risk per year of their stone becoming symptomatic, and counsel them as to how a stone event might present and what they should do at that time." 

There are a number of characteristics that may influence the need to treat an asymptomatic stone including stone size, location and patient characteristics.  Stones >4mm have a 26% greater chance of being symptomatic than stones <4mm, and 15mm stones have a 100% chance of causing an issue.  Stones in the renal pelvis are more likely to migrate into the ureter and cause symptoms than stones in the lower pole calyx.[6]  Patient characteristics that may push a urologist to treat a stone include those patients in whom an obstructing kidney stone could have serious consequences.  These include patients with solitary kidney or baseline kidney disease, other medical comorbidities that could make a kidney infection or unplanned surgery more risky (including immunosuppresion or diabetes), patients who have surgically reconstructed urinary systems or some patients in unique professions with serious consequences of an obstructing stone (like airline pilots).  

In general, it is recommended to follow patients expectantly until an asymptomatic stones becomes symptomatic.  Patients with large stones (especially in the renal pelvis), a solitary kidney or those with a serious risk of adverse consequences due to an obstructing stone should consider earlier elective treatment of the stone.

1. Johnson, C. M., Wilson, D. M., O'Fallon, W. M., Malek, R. S. & Kurland, L. T. Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int. 16, 624–631 (1979).

2. Hiatt, R. A., Dales, L. G., Friedman, G. D. & Hunkeler, E. M. Frequency of urolithiasis in a prepaid medical care program. Am. J. Epidemiol. 115, 255–265 (1982).

3. Boyce, C. J., Pickhardt, P. J., Lawrence, E. M., Kim, D. H. & Bruce, R. J. Prevalence of urolithiasis in asymptomatic adults: objective determination using low dose noncontrast computerized tomography. J. Urol. 183, 1017–1021 (2010).

4. Lorenz, E. C. et al. Clinical characteristics of potential kidney donors with asymptomatic kidney stones. Nephrol. Dial. Transplant. 26, 2695–2700 (2011).

5. Goldsmith ZG, Lipkin ME.  When (and how) to surgically treat asymptomatic renal stones. Nat Rev Urol. 2012 Mar 27;9(6):315-20. doi: 10.1038/nrurol.2012.43.

6. Burgher, A., Beman, M., Holtzman, J. L. & Monga, M. Progression of nephrolithiasis: long-term outcomes with observation of asymptomatic calculi. J. Endourol. 18, 534–539 (2004).

Does Diet Soda Cause Kidney Cancer? Bladder Cancer?

The short answer is, "No."  

Aspartame is the low-calorie, synthetic sweetener used in most diet sodas in this country and around the world.  Aspartame was approved by the US Food and Drug Administration (FDA) in 1984 and, since then, been approved in over 100 countries and world-health organizations.  The average daily intake in the US is estimated to be about 1/10th of the Acceptable Daily Intake (ADI) that would cause a toxicity.  Said differently, a normal-person would have to drink a 12-pack of cans or 4 liters of diet soda every day to exceed the ADI as set by the FDA.[1]

However, in the 1970's a number of scientific studies raised concerns of aspartame and its byproducts causing cancer in rodents.  Since then, the role of aspartame (and other synthetic saccharins) has been highly debated in the scientific and lay-literature.  A number of epidemiologic studies since 1990 have investigated the association between artificial sweeteners and malignancies, mostly in the form of large case-control and cohort studies.  Among the best-designed and executed studies, data from two longitudinal health surveys: the Nurses’ Health Study (started in 1976, and includes121,701 female registered nurses) and the Health Professionals Follow-up Study (started 1986, including 51,529 male health professionals), found a statistically significant increase in the risk of non-Hodgkin’s lymphoma and multiple myeloma (if > 1 serving of diet soda per day).[2]  The National Institute of Health—American Association of Retired Persons diet surveillance study included 473,984 individuals found no significant increase in risk of hematopoietic neoplasms or gliomas.[3]  No study has demonstrate an increased risk of urological malignancies including kidney and prostate.[4]

Interestingly, the carcinogenic effect of synthetic saccharins is species- and organ-specific.  For instance, experimental studies on rats found an increased rate of lymphomas and leukemia in females, but not in males; and hepatocellular carcinomas and alveolar/bronchiolar carcinomas in males only.[5,6]  In addition, male rats (and not females) given high doses of sodium saccharin form precipitates in the urine and has led to a literature regarding the role of aspartame and saccharins in bladder cancer.[7]  Importantly, no epidemiological study in humans has verified an association between sweeteners and bladder cancer. [8-12]

So, while a number of studies in animals demonstrate an increased risk of urological malignancies in animals, no study demonstrates an increased risk of prostate, kidney or bladder cancer in humans.  

In summary,

Aspartame is the synthetic sweetener found in most diet soft drinks around the world; it has been approved by the FDA and numerous regulatory agencies around the world.

A number of animal studies demonstrate an increased risk of cancer with long-term exposure to aspartame and other sweeteners; the risk of malignancy varies by sex and species of animal.

Human studies demonstrate an increased risk of hematogenous malignancies (lymphoma, leukemia); but no increased risk of prostate, kidney or urothelial cancers.

Your diet soda is safe.

This entry was in response to actual patients' questions and concerns raised while in our Urology Clinic.  We will routinely respond to these inquiries.  If you have a question or issue you would like addressed, do not hesitate to reach out.



[1] Marinovich M, Galli CL, Bosetti C, Gallus S, La Vecchia C.  Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues.  Food Chem Toxicol. 2013 Oct;60:109-15. doi: 10.1016/j.fct.2013.07.040. Epub 2013 Jul 23.
[2] Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WW, Feskanich D. 2012. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr 96:1419–1428.
[3] Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, Campbell D, Hollenbeck AR, Schatzkin A. 2006. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev 15:1654–1659.
[4] S. Gallus, L. Scotti, E. Negri, R. Talamini, S. Franceschi, M. Montella, A. Giacosa, L. Dal Maso, C. La Vecchia.  Artificial sweeteners and cancer risk in a network of case-control studies.  Ann. Oncol., 18 (2007), pp. 40–44
[5] M. Soffritti, F. Belpoggi, D. Degli Esposti, L. Lambertini, E. Tibaldi, A. Rigano.  First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.  Environ. Health Perspect., 114 (2006), pp. 379–385
[6] M. Soffritti, F. Belpoggi, M. Manservigi, E. Tibaldi, M. Lauriola, L. Falcioni, L. Bua.  Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.  Am. J. Ind. Med., 53 (2010), pp. 1197–1206
[7] Capen, C.C., Dybing, E., Rice, J.M., Wilbourn, J.D., 1999. Species differences in thyroid, kidney and urinary bladder carcinogenesis. IARC Scientific Publ. No. 147. Lyon, France: International Agency for Research on Cancer.
[8] Wynder EL, Stellman SD. Artificial sweetener use and bladder cancer: a case-control study. Science1980; 207: 1214–1216. 
[9] Morrison AS, Buring JE. Artificial sweeteners and cancer of the lower urinary tract. N Engl J Med1980; 302: 537–541. 
[10] Piper JM, Matanoski GM, Tonascia J. Bladder cancer in young women. Am J Epidemiol1986; 123: 1033–1042. 
[11] Cartwright RA, Adib R, Glashan R, Gray BK. The epidemiology of bladder cancer in West Yorkshire. A preliminary report on non-occupational aetiologies. Carcinogenesis1981; 2: 343–347.
[12] Sturgeon SR, Hartge P, Silverman DT et al. Associations between bladder cancer risk factors and tumor stage and grade at diagnosis. Epidemiology1994; 5: 218–225.

Classic Manuscripts in Urology: Jewett, 1946

Hugh Judge Jewett III

Hugh J. Jewett III (1903-1990) finished the Brady Residency at Johns Hopkins Hospital under Hugh Hampton Young in 1936, became a Professor in the School of Medicine, reaching emeritus in 1969.  His work on the prognostication and evaluation of urological malignancies earned him the Barringer Medal by the American Association of Genitourinary Surgeons and the Ramon Guiteras Award by the American Urological Association.  The theme of that body of work is epitomized in this 1946 manuscript.

Hugh J. Jewett and George H. Strong. Infiltrating Carcinoma of the Bladder: Relation of Depth of Penetration of the Bladder Wall to Incidence of Local Extension and Metastases.  The Journal of Urology, 1946: 55, 366-372.

Pubmed.

In this paper, Dr. Jewett reviewed the autopsies of 127 patients with infiltrating bladder cancer from 1919-1944.  The depth of penetration of tumor into the bladder wall was documented in 107 cases and related to the incidence of 1) metastases, 2) lymphatic capillary invasion and 3) perivesical fixation.  From this data, Dr. Jewett was able to stratify patients into three groups: those with submucosal invasion, those with invasion into the detrusor muscle and those with invasion through the detrusor.  These groups served as the basis for and correspond to today's modern staging categories of non-muscle invasive (pTa, pT1), muscle invasive (pT2) and locally invasive (pT3, pT4) urothelial cancer.

Importantly, Dr. Jewett demonstrated that the number of lymph node and distant metastases, as well as the likelihood of pelvic fixation increased as the tumor grew into and through the bladder wall.  He therefore deduced that 100% of patients with submucosal invasion were potentially curable and only 26% of those with perivesical fixation were potentially curable.

In addition, this manuscript defined the lymphatic drainage of the bladder in relation to the peritoneum and abdominal wall and detailed
the principle sites of invasion of urothelial metastases (regional lymph nodes, liver, lungs and vertebral column).

This manuscript was a landmark paper, in that it described the basis for our modern-day staging of bladder cancer and developed a prognostic model that could be easily shared among physicians and patients.  It has been cited over 400 times since its original publication.

Classic Manuscripts in Urology will be posted on this blog on regular basis.  These articles are meant to highlight the achievements of our predecessors, recognize the work from which we build our careers and stimulate new conversations and discussion on a variety of urological topics.  Please feel free to comment on this manuscript, help point out its strengths and weaknesses, or suggest a new manuscript and topic. 

Stem Cells May Preserve Erectile Function after Radical Prostatectomy

Mesenchymal stem cells (MSC) are cells in the body that have the ability to differentiate or change into a variety of cell types inlcuding bone, cartilage, fat, muscle and nerves.  MSC can be found in many areas of the body - one of the best places to find MSC is in the adipose, or fat tissue of the body.  MSC have the special ability to find sites of inflammation in the body and serve an important role in the maintenance of normal tissues and the repair of damaged areas of the body.

The anti-inflammatory properties of MSC can promote regeneration of damaged tissues. [1] MSC have been used in a variety of experimental settings including the treatment of heart failure, inflammatory bowel disease, cirrhosis, diabetes, chronic obstructive pulmonary disease (COPD) and to prevent rejection after organ transplantation. [2-4] Greater than 1,000 patients around the world have received MSC to treat a variety of conditions.

MSC track to prostate cancer cells in mice. [5]

One of the biggest side effects of treatment for prostate cancer is erectile dysfunction (ED).  For some men who undergo surgery (radical prostatectomy) to treat their prostate cancer, ED can be particularly difficult to treat.  It is know that MSC will hone to areas of prostate cancer.[5]  It is believed that this natural ability of MSC may be able to be used to treat post-radical prostatectomy erectile dysfunction in men who have undergone this surgery for prostate cancer.  It is postulated that MSC can reduce post-surgery inflammation and reduce nerve damage due to the surgery.  In fact, studies in rats have demonstrated improvements in erectile function after MSC injections.[6]

Mesenchymal Stem Cells may reduce post-surgery inflammation and reduce nerve damage due to radical prostatectomy.

Trinity J. Bivalacqua, MD, PhD

Scientists and urologists at the Brady Urological Institute at Johns Hopkins have designed a clinical trial where men with prostate cancer, who are about to undergo radical prostatectomy can be treated with MSC.  "This is a very exciting opportunity to make an impact in the quality-of-life of men undergoing surgery for prostate cancer," states Trinity J. Bivalacqua, MD, PhD, one of the urologists leading this trial.  These men will receive MSC during and after surgery to prevent erectile dysfunction.  Men should consider this study if they have prostate cancer, are planning on undergoing radical prostatectomy, have not received any hormone treatment and must have excellent sexual function.  Men are not eligible if they have an active autoimmune disease, a history of blood clots or symptomatic pulmonary disease.

This is an early-stage study and only a limited number of patients will be enrolled.  If you or someone you know was recently diagnosed with prostate cancer please contact the Urology Clinic at Johns Hopkins (410-955-6100) for more information.


[1] Lotfinegad P, Shamsasenjan K, Movassaghpour A, Majidi J, Baradaran B.  Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy.  Adv Pharm Bull. 2014;4(1):5-13. Epub 2013 Dec 23.


[2] Dalal J, Gandy K, Domen J.  Role of mesenchymal stem cell therapy in Crohn's disease.Pediatr Res. 2012 Apr;71(4 Pt 2):445-51. doi: 10.1038/pr.2011.56. Epub 2012 Feb 8. Review.

[3] Roemeling-van Rhijn M, Weimar W, Hoogduijn MJ.Mesenchymal stem cells: application for solid-organ transplantation.  Curr Opin Organ Transplant. 2012 Feb;17(1):55-62. doi: 10.1097/MOT.0b013e32834ee676. Review.

[4] Takami T, Terai S, Sakaida I.  Stem cell therapy in chronic liver disease.  Curr Opin Gastroenterol. 2012 May;28(3):203-8. doi: 10.1097/MOG.0b013e3283521d6a. Review.

[5] Brennen WN, Chen S, Denmeade SR, Isaacs JT.Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer.  Oncotarget. 2013 Jan;4(1):106-17.


[6] Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK, Murthy SN, Champion HC, Hellstrom WJ, Kadowitz PJ.  Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction.  Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1278-90. Epub 2006 Oct 27.

Prostate Cancer Multidisciplinary Clinic

Multidisciplinary clinics are a relatively new trend in medicine.  The clinics offer patients the opportunity to meet, on the same day, experts from a number of fields within medicine and surgery.  For patients with cancer, this often is an opportunity to have records reviewed by expert pathologists and radiologists and to meet with a surgeon, radiation oncologist and medical oncologist in the same setting.  It prevents the patient from having to schedule multiple appointments with multiple experts in the field, creates a forum for conversation between experts in a variety of fields (rather than relying on interdepartmental consultations and discussions) and, in doing so, can streamline care.  For prostate cancer, multidisciplinary clinics from around the country demonstrate improved compliance with national guidelines, excellent oncologic outcomes and high patient satisfaction. [1,2]

Edward M. Schaeffer, MD, PhD

The Prostate Cancer Multidisciplinary Consultation (PCMDC) at Johns Hopkins has been offering this service since 2008.  Over the past 5 years, over 1,000 men with prostate cancer have been seen in the PCMDC.  Nearly 60% stay at Hopkins for their treatment: approximately 25% elect surgery, 25% radiation therapy, 10% active surveillance and 5% androgen deprivation treatment for advanced cancer.  All medical records are obtained, collated and reviewed by our experts prior to the PCMDC clinic appointment.  All prostate cancer slides obtained from the biopsy are reviewed by our expert urological pathologists and any imaging is reviewed by dedicated genitourinary radiologists.  A panel including these pathologists, radiologists, urologic oncology surgeons, radiation and medical oncologists then meet to review a patient's case.

Debasish Sundi, MD

Often changes are made, diagnoses can be adjusted and management options tweaked to best fit that patient's needs.  Under the tutelage of Edward M. Schaeffer, Associate Professor of Urology, Oncology and Pathology, and Co-Director of the PCMDC; Debasish Sundi (a senior resident at the Brady) will present data at American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium demonstrating that nearly 30% of patients who present to the PCMDC will have a change in their risk category or stage.  For example, 3% of men were down classified to very -low risk prostate cancer and became eligible for active surveillance; 6% of men were upstaged to metastatic disease and had systemic therapy initiated rather than undergoing localized treatment. [3]

In addition, the PCMDC offers a unique opportunity for research.  For instance, many patients speak favorably about their experience at PCMDC, however little data exists validating these perceptions.  Over the next several months, we will be evaluating the patient-centered experience at the Johns Hopkins PCMDC by prospectively evaluating quality of life, satisfaction with care, and illness uncertainty among patients coping with a new diagnosis of prostate cancer.  The study is conducted entirely online and is administered through the NIH-funded tool for online clinical research: Assessment Center (www.assessmentventer.net). Patients complete online questionnaires before and after their clinic appointment and can access their personalized study webpage from their personal computers, tablets, or smart phones.  By focusing on patient-reported outcomes, our goal is to show a positive impact of multidisciplinary cancer care on the quality of life of men with newly diagnosed prostate cancer.  In addition, research opportunities exist to track cancer and functional outcomes following surgery and radiation treatments.  Novel therapies including gene-based vaccinations are offered to appropriate candidate patients.  Patients with advanced malignancies who have failed traditional therapies are offered the newest and latest options from Johns Hopkins experts.

If you are a patient with prostate cancer who would like a second opinion, or if you are a physician with a patient who you would like seen at PCMDC please call 410-955-6100.

1. Aizer AA, Paly JJ, Zietman AL, et al. Multidisciplinary care and pursuit of active surveillance in low-risk prostate cancer.  J Clin Oncol. 2012 Sep 1;30(25):3071-6. doi: 10.1200/JCO.2012.42.8466. Epub 2012 Jul 30.

2.  Gomella LG, 

Lin J, 

Hoffman-Censits J, 

et al. 

Enhancing prostate cancer care through the multidisciplinary clinic approach: A 15-year experience. J Oncol Pract 2010 6:e5–e10.

3. Sundi D, Cohen JE, Cole AP, Neuman BP, Cooper J, Faisal FA, Raben MG, Song DY, Drake CG, Netto GJ, Macura KJ, DeWeese TL, Partin AW, Bivalacqua TJ, Ross AE, Schaeffer EM. Multidisciplinary clinic evaluation changes prostate cancer stage and risk stratification.  To be presented at GU-ASCO, January 30-February 1, 2014; San Francisco, California.

A New & Exciting Frontier

Greetings and welcome to the Johns Hopkins Brady Urological Institute Blog! 

The James Buchanan Brady Urological Institute and Department of Urology at Johns Hopkins Hospital is the premiere urological institution in the nation - we have been named the #1 in Urology in the US News & World Report Hospital Rankings 22 of the last 23 years.

Ninety-nine years ago to the day, January 21, 1915, the Brady Urological Institute at Johns Hopkins Hospital was opened to patients.  The Brady has a long tradition of delivering excellent urological care, dating back to our founding directer, Hugh Hampton Young.  In that tradition, we plan on delivering and disseminating our urologic knowledge to the newest generation of patients and physicians through social media.

We will post regularly on Twitter (@brady_urology), Facebook (Brady Urology) and this Blog.  We will address timely urological issues and share with you some of our history and achievements as we continue to deliver exceptional urological care and further the field through ground-breaking research.

We cannot address specific patient questions through these media, however if there is a topic or general urological question that you have, please do not hesitate to reach out.

Phillip M. Pierorazio, MD
Assistant Professor of Urology and Oncology
Director of Social Media
The James Buchanan Brady Urological Institute
Johns Hopkins Medicine