Doctor David Goldfarb is a recognized authority on medical prevention of kidney stones, and has played a very important international role as an expert and brilliantly informed advocate for high quality care of the millions of patients with this disease.

The American College of Medicine, through its organ – The Annals of Internal Medicine – is known for publishing excellent guidelines that primary care physicians can use in their practices to achieve a reliable quality of outcomes.

Here we have come upon a true conflict between experts like Dr. Goldfarb and the College of Medicine. He was chosen, by right of his expertise, as a peer reviewer of the defective guidelines the College promulgated last fall, improper and misleading guidelines for stone prevention by changes of diet and use of medications. He rejected the work as technically flawed and exhibiting the defects that arise when ignorance is coupled to public authority. The work was published despite his rejection, an odd and unusual response of a fine journal.

More: David had worked on guidelines promulgated by a far more important and better informed source, the American Urological Association, which speaks with genuine authority and experience for the very physicians who care for stone patients and are trained as part of the certification to conduct such treatment – the real experts in fact. These AUA guidelines are outstanding in that within the limitations of the science available they offer physicians a realistic way of managing care for patients that appears sound and unlikely to do harm.

That his negative review held no sway is unfortunate, and a surprise.

Dr. Goldfarb has chosen to respond to the College in a way that seems to me just, proper, and responsible, and he offered his letter for publication here, on this site which reaches the kidney stone research community, expert physicians in the field, and many of the patients and their families who must view with considerable consternation such confusions and disregard among experts concerning their care.

Here is his personal introduction to the matter, followed by his letter.

Introduction to the ACP Guidelines Problem

In 2012, the Agency for Heathcare Research and Quality (AHRQ), part of the U.S. Department of Health and Human Services, issued a report entitled “Recurrent Nephrolithiasis in Adults: Comparative Effectiveness of Preventive Medical Strategies. The report documented the relative paucity of clinical trials that constitute the body of evidence regarding appropriate strategies for kidney stone prevention. Based on that evidence, two groups endeavored to turn the AHRQ report into clinical guidelines. Each took very different approaches to their projects.  In November 2014, the Annals of Internal Medicine published “Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians.” The publication followed shortly after the Journal of Urology’s publication of “Medical management of kidney stones: AUA guideline.” As a participant in, and vice-chair of the AUA guidelines committee, chaired by Dr. Peggy Pearle, I was pleased with our result and disappointed with that of the American College of Physicians, an organization of which I have long been a proud member. Their clinical guidelines are approved by the ACP’s Clinical Guidelines Committee, and then by the ACP’s Board of Regents. In the following letter to the ACP and the Annals, I address some of the shortcomings of the ACP guidelines.

Letter to the American College of Physicians

 

May 9, 2015

Wayne J. Riley, MD, MPH, MBA, MACP, President, Board of Regents: wayne.riley@vanderbilt.edu

Tanveer P. Mir, MD, MACP, Chair, Board of Regents: Tanveer.Mir@nyumc.org

Andrew Dunn, MD, FACP, Chair, Board of Governors c/o mbieter@acponline.org

Steven E. Weinberger, MD, FACP, Executive Vice President/Chief Executive Officer:

sweinberger@acponline.org

Mary Ann Forciea, MD, FACP, Chair, Clinical Guidelines Committee, c/o aqaseem@acponline.org

Thomas D. Denberg, MD, PhD, FACP, Immediate Past Chair, Clinical Guidelines Committee

c/o aqaseem@acponline.org

Christine Laine, MD, MPH, FACP, Editor in Chief, Annals of Internal Medicine, claine@acponline.org

Re: ACP and Kidney Stones

Dear ACP Colleagues,

I would like to express my distress regarding the ACP’s recent issuance of guidelines regarding the medical management of kidney stones.(1) This document does not serve ACP well, nor does it do anything positive for the care of the neglected population of people afflicted by kidney stones.

I recognize that “expert opinion” is currently in disrepute in this era of evidence-based medicine. However, I have a previous history with respect to kidney stones and ACP that is relevant background to this letter. Since 2003, I have been the author of the section of PIER, and then Smart Medicine, entitled Nephrolithiasis. I also authored “In the Clinic: Nephrolithiasis” for Annals.(2)

I then served as a reviewer for Annals for the AHRQ review on kidney stones.(3) I thought that was a valuable work that summarized the evidence regarding kidney stone evaluation and management. I was then invited to write the ACP Journal Club entry on the AHRQ review.(4)

Following that publication, ACP endeavored to develop a set of guidelines regarding prevention of kidney stones. I was asked to review the kidney stones guidelines for Annals. I recommended rejection of the manuscript for many good reasons, and at first it appeared that Annals also rejected it. It was therefore surprising that the paper was eventually published in Annals, without much revision to my eye, and without being sent back to me or (as far as I know) other reviewers. This publication was not of any practical use to practitioners caring for patients with kidney stones.

I understand that these ACP guidelines concentrate exclusively on the results of randomized controlled trials. In the absence of adequate RCT data, an appropriate response might be to not write guidelines at all. Or one could choose instead to acknowledge that in the absence of RCT data, writing guidelines based on “expert opinion” is preferable to nothing, given the clinical need. That is what the American Urological Association’s committee on Medical Management of Kidney Stones decided.(5) I served as vice-chair of that committee and as a representative of the American Society of Nephrology.

It is rather frustrating to read these ACP guidelines in the context of what my goals as a kidney stone doctor are. I try to advance the idea that kidney stones cause significant pain, misery and cost and that they are preventable. The ACP guidelines offer no practical advice that advances this goal. The guidelines do not achieve any utility with respect to diagnosis, evaluation or therapy. As a result they have no pedagogical value: I would not distribute the paper to a resident or a fellow if instruction in the care of patients were the goal.

The ACP guidelines express skepticism about whether kidney stone composition is important; whether 24 hour urine chemistry is worthwhile; and even express uncertainty about whether increasing fluid intake is important. It is true that RCTs have not proven that these tests or therapies are useful. But I disagree that “guidelines” need to be promulgated, leaving practitioners ignorant about what reasonable course should be taken when seeing a patient with stones, when RCTs are lacking. The guidelines suggest that thiazides, allopurinol and citrate may be useful for kidney stone prevention but offer no guidance about how those drugs would be deployed in the absence of kidney stone composition and 24 hour urine chemistry results. Should I give allopurinol to patients with cystinuria? And how would I detect cystinuria if determination of kidney stone composition is of questionable utility? Are thiazides appropriate for uric acid stones? Should potassium citrate be given to some or all stone-formers?

Some of these questions are not ever going to be addressed by RCTs. For instance, I would consider an RCT of citrate therapy for uric acid stones to be highly unethical, given the ease and near 100% efficacy of urinary alkalinization for prevention of these stones. The ACP guidelines fail to make this critical distinction and leave internists dangerously unprepared to take care of this increasingly prevalent and easily prevented stone type.

The painful correspondence from my colleagues around the world after publication of these guidelines included queries about how this publication was possible, and how ACP could publish “garbage” or “a total waste”. At the March 2015 “Consensus Conference for the Metabolic Diagnosis and Medical Prevention of Calcium Nephrolithiasis and its Systemic Manifestations”, held in Rome, discussion about authoring an international dissent regarding the ACP guidelines was a popular topic, demonstrating the worldwide interest in the topic.

Several other points about the ACP document are worth making. None of the authors of the paper have a single other co-authorship in PubMed relevant to kidney stones, other than the AHRQ review. I believe that none of the authors are nephrologists or urologists, none have a kidney stone clinic, none appear at, or present research at, kidney stone meetings, none have any experience regarding management of kidney stones as far as we know. This author list clearly expresses disdain regarding “expert opinion” or perhaps for sub-specialty care. (At least the AHRQ review included one urologist among its authors).

While perhaps ACP regards my participation on the AUA committee as a conflict of interest in voicing these criticisms, I have two other complaints. First, the ACP guidelines failed to cite the AUA guidelines, although the temporal sequence would certainly have allowed that. The ACP document could have said to practitioners, “rather than express ignorance when patients with kidney stones ask you for advice, check out the 36 “expert-opinion-based” recommendations made by AUA; we don’t endorse them but you may find them useful in your practice”. (The ACP guidelines could have also referred internists to Smart Medicine). Second, I was frankly astounded that our letter to Annals (co-authored by the chair and me, vice-chair, of the AUA committee) was not selected for publication (though it remains as a comment on the website. This may be taking ACP’s apparent bias against specialists, or experts, a bit too far.

(And for the record, allopurinol should not be regarded as useful therapy for uric acid stones in the absence of urinary alkalinization, as Qaseem et al suggest in their reply to the letter of Krambeck and Lieske(6): “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.”(7) The authors would discourage that practice, as I do, if they were more familiar with the non-RCT kidney stone literature).(8)

I have been proud of my tenure as author of the PIER/Smart Medicine section on stones and assumed that ACP has valued it. Grading recommendations based on the strength of evidence is a strength of that body of work. If it is time to delete most of the opinion-based recommendations I make there, I will sadly have to recognize that times have changed.

The bottom line here is that I consider the ACP guidelines destructive of good medical care of patients with kidney stones. I believe that patient care will be adversely affected. It is possible that third party payers will cease paying for kidney stone composition and 24 hour urine analysis. Urologists and emergency medicine physicians do not routinely practice kidney stone prevention, though they are the practitioners most likely to first see the patients. There is a real potential role for internists then to appropriately manage patients with kidney stones, as they manage patients with diabetes, hypertension and coronary artery disease. Recently, kidney stones have been linked to all three of these co-morbidities through observational and physiological investigations, implying a pathophysiology that may have great import for internists seeing stone formers.(9) Instead, in my experience, internists regard nephrolithiasis as an abstruse field that somehow exceeds their generalist capabilities or as a disorder that produces only a transient, if painful, phenomenon of no consequence.

I cannot argue about the product of the AHRQ review and the relative deficiencies of the RCT-based evidence in lithology; I consider the AHRQ manuscript a useful prod to highlight the need for additional work (and funding). But the ACP’s censoring of expert opinion, and the Annals publishing outside a serious peer-review process, cannot be countenanced as “good practices”. These practices have led to a set of guidelines that I feel are not worthy of ACP, Annals and the internal medicine community.

The opinions offered here are mine alone, and not representative of any other committee or organization.

Yours truly,

David S. Goldfarb, M.D., FACP, FASN

Clinical Chief, Nephrology Division,

NYU Medical Center

Professor of Medicine and Physiology,

NYU School of Medicine

President, ROCK Society 2015-2016

(Research on Calculus Kinetics)

References

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. Goldfarb DS. In the clinic. Nephrolithiasis. Annals of internal medicine. 2009;151(3):ITC2.
3. 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(7):535-43.
4. Goldfarb DS. ACP Journal Club. Review: Thiazide, citrate, or allopurinol reduces recurrence after >/= 2 kidney stone episodes. Ann Intern Med. 2013;159(2):JC12.
5. 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.
6. Krambeck AE, Lieske JC. Prevention of recurrent nephrolithiasis in adults. Ann Intern Med. 2015;162(7):528-9.
7. Qaseem A, Fink HA, Denberg TD. Prevention of recurrent nephrolithiasis in adults. Ann Intern Med. 2015;162(7):529.
8. Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens. 2004;13(2):181-9.
9. Sakhaee K, Maalouf NM, Sinnott B. Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management. Journal of Clinical Endocrinology and Metabolism. 2012;97(6):1847-60.