Evidenced-based guidelines are still subjective. That statement summarizes the rather frightening conclusion I made after my first involvement in a large-scale effort to engage in literature review, synthesis, and preparation of evidenced-based guidelines as part of the Kidney Disease Outcome Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF).
I expect that my conclusion about the subjectivity of evidence-based guidelines seems heretical, but I was not altogether surprised. In the 30 years since I began my medical education, I have observed that medical opinions “based on the literature” change. I will never forget my third year of medical school at the University of California, Los Angeles, when a young (now older and famous) infectious disease specialist, talking to our small group of on-service students, avowed, “You can’t say anything without an article, but the evidence keeps changing!” That was a conversation stopper—for me, anyway.
I know that quoting an article is not the same as referring to a conclusion that comes from a rigorous evidence-based review, and that the strength of evidence from a single article is weak, but I was struck by how, even when an initial literature search yields thousands of articles, there will be few articles that can be compared easily. It is even difficult to narrow down a topic in a manner that allows reasonable comparisons.
Do not think that I am being negative—I actually was fascinated. I was surrounded by experts in the field of chronic kidney disease. These professionals were friendly, inclusive, and hardworking, but the evidence-extraction process was painful for all of us. At all steps along the way, subjective decisions had to be made. For example, the data summary form that a member of the team prepared for our use dictated what data would be extracted for later use and, to some extent, how it would be interpreted. From this beginning, we sorted and combined information, and then began debating what the evidence really was saying to us. Throughout the process, more subjective interpretation was required than I would have expected. Individual biases could not be removed totally from the equation—nor, in my opinion, should they have been.
Finally, we began to write the guidelines. I could feel the near desperation of some Work Group members who believed deeply that certain guidelines were crucial to the appropriate management of the patient with chronic kidney disease, although the evidence in favor of these guidelines did not seem to be compelling. For my part, I was keenly aware of my role of representing practicing family physicians who would be responsible for carrying out the guidelines within the largest segment of the population. Were the guidelines practical? Were they affordable? Would the care of our patients be improved by adherence to these guidelines? Would funding or oversight agencies use nonadherence to the guidelines against us? How could we become attuned to a set of guidelines on a topic that is much less familiar to us than hypertension or high cholesterol levels?
Eventual consensus resulted in the NKF K/DOQI guidelines that were published in 20021,2 and now are being summarized in a two-part article in American Family Physician.3,4 I am pleased with the guidelines. I supported their use by family physicians and immediately began incorporating them into my practice.
During the process of developing the clinical practice guidelines, I greatly increased my understanding of chronic kidney disease. For me, the most important lessons were as follows:
Chronic kidney disease is greatly under-diagnosed and undertreated, resulting in lost opportunities for prevention.
Chronic kidney disease is defined by the presence of proteinuria and a decreased glomerular filtration rate (GFR).
Standard urine dipsticks are acceptable screening tools for proteinuria.
Proteinuria can be diagnosed by a ratio of greater than 30 mg of albumin to 1 g of creatinine in an untimed (spot) urine sample. A 24-hour urine collection, which frequently is incomplete, does not yield a more accurate result.
The GFR is superior to the serum creatinine concentration as the best overall index of kidney function and should be used for staging the disease.
The GFR can be estimated using standard prediction equations. A 24-hour urine collection is not required for estimating the GFR.
In summary, the K/DOQI guidelines recommend testing for proteinuria and estimating the GFR in patients who are at risk for chronic kidney disease.
The process of applying clinical evidence to practical recommendations is evolving. It already had evolved by the time that I participated in an NKF Work Group on hypertension in chronic kidney disease. As this process continues to improve, I am reassured that the principles involved in evidence-based medicine remain sound. I urge family physicians to participate in the formulation of clinical practice guidelines if they are given the opportunity to do so.