Amir Qaseem, MD, PhD; Paul Dallas, MD; Mary Ann Forciea, MD; Melissa Starkey, PhD; Thomas D. Denberg, MD, PhD; for the Clinical Guidelines Committee of the American College of Physicians *
Note: Clinical practice guidelines are “guides” only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians’ judgment. All ACP clinical practice guidelines are considered automatically withdrawn or invalid 5 years after publication, or once an update has been issued.
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations.
Financial Support: Financial support for the development of this guideline comes exclusively from the ACP operating budget.
Disclosures: Authors followed the policy regarding conflicts of interest described at www.annals.org/article.aspx?articleid=745942. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=M13-2908. Any financial and nonfinancial conflicts of interest of the group members were declared, discussed, and resolved. A record of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/clinical_information/guidelines/guidelines/conflicts_cgc.htm.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190. N. Independence Mall West, Philadelphia, PA 19106; e-mail, email@example.com.
Current Author Addresses:Drs. Qaseem and Starkey: 190 N. Independence Mall West, Philadelphia, PA 19106.Dr. Dallas: Virginia Tech Carilion School of Medicine, 1906 Bellview Avenue, Roanoke, VA 24014.
Dr. Forciea: University of Pennsylvania Health System, 3615 Chestnut Street, Philadelphia, PA 19104.
Dr. Denberg: Carilion Clinic, PO Box 13727, Roanoke, VA 24036.
Author Contributions:Conception and design: A. Qaseem, M.A. Forciea, T. Denberg.
Analysis and interpretation of the data: A. Qaseem, P. Dallas, M.A. Forciea, M. Starkey, T. Denberg.
Drafting of the article: A. Qaseem, P. Dallas, M.A. Forciea, M. Starkey, T. Denberg.
Critical revision of the article for important intellectual content: A. Qaseem, P. Dallas, M.A. Forciea, M. Starkey, T. Denberg.
Final approval of the article: A. Qaseem, P. Dallas.
Statistical expertise: A. Qaseem.
Administrative, technical, or logistic support: A. Qaseem, M. Starkey.
Collection and assembly of data: A. Qaseem, M. Starkey.
The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of preventive dietary and pharmacologic management of recurrent nephrolithiasis in adults.
This guideline is based on published literature on this topic that was identified using MEDLINE, the Cochrane Database of Systematic Reviews (through March 2014), Google Scholar, ClinicalTrials.gov, and Web of Science. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline include symptomatic stone recurrence, pain, urinary tract obstruction with acute renal impairment, infection, procedure-related illness, emergency department visits, hospitalizations, quality of life, and end-stage renal disease. This guideline grades the quality of evidence and strength of recommendations using ACP's clinical practice guidelines grading system. The target audience for this guideline is all clinicians, and the target patient population is all adults with recurrent nephrolithiasis (≥1 prior kidney stone episode).
ACP recommends management with increased fluid intake spread throughout the day to achieve at least 2 L of urine per day to prevent recurrent nephrolithiasis. (Grade: weak recommendation, low-quality evidence)
ACP recommends pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol to prevent recurrent nephrolithiasis in patients with active disease in which increased fluid intake fails to reduce the formation of stones. (Grade: weak recommendation, moderate-quality evidence)
Do results of baseline stone composition and blood and urine chemistries predict the effectiveness of diet and/or pharmacologic treatment on final health outcomes and intermediate stone outcomes, as well as reduce adverse effects?
Do results of follow-up blood and urine biochemistry measurements predict final health outcomes and intermediate stone outcomes in adults being treated to prevent recurrence?
What is the effectiveness and comparative effectiveness of different dietary therapies on final health outcomes and intermediate stone outcomes?
What is the evidence that dietary therapies to reduce risk for recurrent stone episodes are associated with adverse effects?
What is the effectiveness and comparative effectiveness of different pharmacologic therapies on final health outcomes and intermediate stone outcomes?
What is the evidence that pharmacologic therapies to reduce risk for recurrent stone episodes are associated with adverse effects?
Table 1. The American College of Physicians’ Guideline Grading System
Table 2. Evidence for Prevention of Stone Recurrence With Dietary and Pharmacologic Interventions
Summary of the American College of Physicians guideline on dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults.
ESRD = end-stage renal disease.
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David S. H. Bell, MD
November 20, 2014
Pharmacologic Management of Nephrolithiasis Qaseem et al in their clinical guideline from the American College of Physicians did not indicate under what circumstances citrates, thiazides or allopurinol should be utilized to avoid a recurrence of nephrolithiasis.1 Obviously if hypercalciuria is present thiazide diuretics should be utilized. However, utilization of thiazides in the presence of uricosuria may be counterproductive. With uricosuria, allopurinol should be utilized but allopurinol and citrates may also be successfully utilized in the absence of either hypercalciuria or uricosuria. In the obese, insulin resistant or type 2 diabetic patients there is a high frequency of an acidic urine due to hyperinsulinemia inducing both a decreased production of ammonia in the proximal tubule and decreasing clearance of sodium. The resulting lower urine PH can result in uric acid "coming out" of solution and crystallizing.2 While in the obese, insulin resistant or diabetic subjects the majority of calculi are composed of calcium oxylate the proportion of uric acid stones is higher than in controls (35.8% versus 11.3%).3 Normal excretion of uric acid is less than 800 mg/day but in the presence of an acid urine uric acid can crystallize at levels of as low as 200 mg/day. In this situation the most effective therapies to prevent the formation of stones are allopurinol to reduce uricosuria and citrates to neutralize the acid urine. In the absence of an analysis of a previous stone or hypercalciuria the presence of a low urine PH should suggest that therapy with allopurinol and/or a citrate will result in a decreased formation of calculi.4References:1) Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the american college of physicians. Ann Intern Med(2014)161(9):659-67.2) Sakhaee K1, Adams-Huet B, Moe OW, Pak CY. Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int(2002)62(3):971-9.3) Daudon M1, Traxer O, Conort P, Lacour B, Jungers P. Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol(2006)17(7):2026-33.4) Bell DS. Beware the low urine pH--the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes. Diabetes Obes Metab(2012)14(4):299-303.
Amy E. Krambeck, John C. Lieske
December 2, 2014
We read with interest the recent Clinical Practice guidelines from the American College of Physicians (ACP) for the Prevention of Kidney Stones in Adults. The recommendations for drinking at least 2 L of fluid per day and the use of thiazide diuretics, citrate, or allopurinol when fluids alone are insufficient mirror recent guidelines released by the American urological Association (AUA). However, several features of the ACP recommendations are in disagreement with those of the AUA. For example, baseline stone composition is not recommended by ACP, nor is 24-hour urine analysis for stone risk factors. Kidney stone analysis by infrared spectroscopy is relatively inexpensive and very precise and, in our opinion, essential to properly diagnose the form of kidney stone disease. For example, a thiazide diuretic would not be helpful for patient with uric acid kidney stones or someone with cystinuria, both of which can be determined by stone analysis alone. Furthermore, a 24-hour urine analysis can help to guide logical therapeutic choices and specific dietary advice for an individual patient. For example, pharmacotherapy may not be helpful for individuals where a very low urine volume is the only major risk factor, and individuals with enteric hyperoxaluria need very specific therapy geared towards dietary measures to reduce oxalate loads. In these cases allopurinol or thiazide would probably not have any benefit. Although rare, certain genetic conditions associated with stone disease such as primary hyperoxaluria can be diagnosed by extreme abnormalities noted on 24 hour urine studies. Early intervention in such diseases can slow disease progression. These are just a few situations in which urine studies would be diagnostic and extremely helpful for management of patients, and demonstrate potential flaws in the minimalistic approach recommended by the ACP. Like many disorders, kidney stone disease is complicated with a variable phenotype. The ACP guidelines do little to acknowledge or highlight these issues. Current studies indicate that less than 10% of individuals with kidney stone disease undergo a full metabolic workup to prevent further stone formation (1). The approach implied by the ACP guidelines will do little to increase the rate of appropriate metabolic evaluations or help to abate the rising stone disease incidence in the United States (2). In contrast, the AUA guidelines appear to be more balanced and, in general, contain much more useful advice for a physician faced with a patient suffering from recurrent kidney stones. Amy E. Krambeck, MDAssociate Professor of UrologyJohn C. Lieske, MDProfessor of MedicineFellow American College of PhysiciansMayo Clinic O’Brien Urology Research CenterRochester, MNReferences1. Milose JC, Kaufman SR, Hollenbeck BK, Wolf JS, Jr., Hollingsworth JM. Prevalence of 24-hour urine collection in high risk stone formers. The Journal of urology. 2014;191(2):376-80.2. Scales CD, Jr., Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. European urology. 2012;62(1):160-5.
Margaret S. Pearle, David S. Goldfarb
University of Texas Southwestern, Dallas, TX, NYU School of Medicine, New York, NY
December 22, 2014
Writing guidelines when there is a paucity of medical evidence
To the Editor,
We were disappointed by the recent Clinical Practice guidelines from the American College of Physicians (ACP) about prevention of recurrent nephrolithiasis.(1) The guidelines were based exclusively on randomized controlled trial-generated evidence, which had been summarized in a recent review sponsored by the Agency for Healthcare Research and Quality.(2) That valuable review documented that there was a relative paucity of high quality evidence regarding kidney stone prevention. The members of the American Urological Association’s guideline panel on Medical Management of Kidney Stones therefore recognized that, if the trial data were limited, useful guidelines require access to a broader set of data than could be derived solely from randomized controlled trials.(3) The resulting AUA guidelines, in contrast to the ACP guidelines, relied not only on the AHRQ review but also in part on extensive studies of urine and crystal chemistry, renal physiology, pharmacology, and nutrition. They also rely, of course, on the extensive experience of a diverse group of experts, whose “expert opinion” we understand is considered a flawed body of lore. Nonetheless we believe the AUA guidelines provide a more practical basis for practitioners and patients to prevent recurrent kidney stones, a practice which needs to be advanced in an era of increasing stone prevalence.(4)
Margaret S. Pearle MD
Professor of Urology,
University of Texas Southwestern,
Chair, AUA Guidelines Panel, Medical Management of Kidney Stones
David S. Goldfarb MD, FACP
Professor of Medicine and Physiology
NYU School of Medicine,
New York, NY
Vice-Chair, AUA Guidelines Panel, Medical Management of Kidney Stones
1. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the american college of physicians. Ann Intern Med. 2014;161(9):659-67.
2. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Recurrent Nephrolithiasis in Adults: Comparative Effectiveness of Preventive Medical Strategies. Rockville MD; 2012.
3. Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-Ciocca CJ, Matlaga BR, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316-24.
4. Scales CD, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-5.
Amir Qaseem, MD,PhD, Howard A. Fink, MD, MPH, Thomas D. Denberg, MD, PhD
American College of Physicians
January 30, 2015
IN RESPONSE: Dr. Bell raised an important issue and suggests that ACP should offer guidance on what drugs to use under specific circumstances. We acknowledge in the guideline that biochemistry suggests a linkage between the mode of action of the various drugs and stone type. However, results were mixed about whether baseline biochemistry measures predicted treatment effectiveness for reducing stone recurrence risk or efficacy of dietary or pharmacologic treatments compared with control for recurrent stone outcomes. In addition, no RCTs compared risk for stone recurrence between treatments according to follow-up biochemistry measures or changes from pretreatment biochemistry values. A post hoc analysis of one RCT, described in the evidence review on which this guideline was based (1), suggested that the benefit of allopurinol treatment was limited to patients with baseline hyperuricemia or hyperuricosuria. However, this was the only available evidence from an RCT linking stone biochemistry to recurrent stone outcomes, it was only for 1 drug, and the analysis was post hoc. As we point out in the guideline, we are aware that many physicians do select medications based on stone type, for example, allopurinol for uric acid stones, and we do not discourage that practice. Drs. Krambeck and Lieske also suggest that ACP should have recommended biochemical testing to determine stone type, and suggest that such testing is inexpensive and is recommended by other organizations. However, as stated above, ACP cannot make an evidence-based recommendation in light of what is currently shown in the studies. Further, just because a test or intervention is inexpensive, it does not mean we should do it without evidence, as costs do add up. References1. Fink HA, Wilt TJ, Eidman KE, Garimella PS, MacDonald R, Rutks IR, et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med. 2013; 158:535-43. Amir Qaseem, MD, PhD, MHAAmerican College of Physicians, Philadelphia, PennsylvaniaHoward A. Fink, MD, MPHMinneapolis Veterans Affairs Medical Cente, Minneapolis, MNThomas D. Denberg, MD, PhDCarilion Clinic, Roanoke, Virginia
Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2014;161:659–667. doi: 10.7326/M13-2908
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Published: Ann Intern Med. 2014;161(9):659-667.
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