Probably the most important item in the checklist of a
clinician, an epidemiologist or a researcher is the “definition of disease”. What
are the criteria that make this individual labeled with disease A, and this individual
isn’t? These criteria are grouped into “the definition”.
There has been a considerable variation in definitions of
various diseases across the history of medicine. Some of these variations are
attributed to the reason for defining the disease (patient care or research
purposes). Variations also existed because of the use of early detection biomarkers
or advanced imaging modalities. The more progress we, the epidemiology researchers,
achieve in providing clinicians ways for early disease detection, the more “cases”
are expected to be detected early, potentially saved, and easily treated. This means expanding the “definition
of the disease” to encompass more people who potentially have the disease, or
have the disease in very early stages. From an epidemiologic standpoint, this
will lead to an increase in the disease prevalence.
Although clinicians, epidemiologists and researchers are
expected to view this as a privilege, many have criticized that expanding the definitions
leads to overdiagnosis. This is discussed in a recent article published in the British Medical Journal
on expanding the definition of chronic kidney disease (CKD). Ray Moynihan, the lead
author on this article, and his colleagues overviewed the story of CKD definition,
the rationale behind the 2002 NKF KDOQI ClinicalPractice Guidelines, and then discussed in details the issue of CKD overdiagnosis.
To begin with, these guidelines set the CKD definition to be
either estimated glomerular filtration rate of 60 ml/min/1.73 m2 for ≥3 months (presence
of impaired kidney function), or albuminuria ≥3 months (presence of kidney
damage). About 14% of the US adults and about 17% of the Australian adults were
labeled as CKD patients, as a result of this new definition.
The authors of the BMJ article present the evidence of
overdiagnosis. Of the evidence they presented, they conclude that without
adjusting to age and gender, about half of the individuals over 70 years old
will be labeled with CKD. Schaeffner
and colleagues from Germany published a paper in the Annals of Internal Medicine
last year presenting two novel equations to estimate kidney function in persons
aged 70 years and older, and calibrating their equation with Iohexol plasma
clearance measurement as gold standard. They found that with the measured
GFR, 47.9% of their sample has GFR less than 60 mL/min per 1.73 m2.
Using the NKF KDOQI definition, these individuals have CKD.
However, scientists against the use of eGFR threshold of
<60 ml/min/1.73 m2 as a cutoff for CKD definition question whether such CKD
definition will have any real implications on risk assessment and clinical care
of patients with cardiovascular disease. Additionally, the authors cited evidence that
suggests that because of the variability of the eGFR, diminished kidney
function as eGFR <60 ml/min/1.73 m2, needs to persist for at least 12 months
to diagnose CKD. As a consequence, this could reduce the prevalence of CKD
stage 3 by 37%.
Just last year, the US Preventive Services Task Force (USPSTF) published
a statement on the Screening for chronic kidney disease. Despite finding no evidence on the presence of
direct harms of screening for CKD, it suggested that there is “potential harms of screening include adverse
effects from venopuncture and psychological effects of labeling a person with
CKD as a result of a false-positive test”. As a result of overdiagnosis,
increased referral to nephrologists has been also observed.
The case is still open and the authors state that “it needs
further professional scrutiny and public awareness”. Patient care should be
individualized when the treating physicians receives the eGFR result below 60
ml/min/1.73 m2 or albuminuria, taking into account the patient’s age, gender, and
existing comorbidities. Needless to say, the test should be repeated after 3
months.
The authors conclude:
“Clinicians should be careful not to apply disease labels to the many older people whose eGFR falls within the definition of chronic kidney disease but who are at very low risk of developing clinical problems… It is in everyone’s interest to find the best way to maximise prevention of kidney disease and its consequences while minimising the risks and cost of overdiagnosis.”
