Download Chronic kidney disease (CKD) has become a public health issue

Shannon Mikrut
Capstone Screening Project:
Screening for Chronic Kidney Disease using the Glomerular Filtration Rate (GFR) and Urine Analysis in
high-risk populations in Florida
Shannon Mikrut
MPH 510
April 26, 2013
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Chronic kidney disease (CKD) has become a public health issue affecting people of all ages all
over the world. CKD is the ninth leading cause of death in the United States (Centers for Disease Control
and Prevention (CDC), 2013). Twenty six million American adults have some level of CKD (Wetmore,
Palsson, Belmont, Sigurdsson, Franzson, & Indridason, 2010).The prevalence CKD has reached
proportions with 10–13% of the populations in Taiwan, Iran, Japan, China, Canada, India and the United
States (Stenvinkel, 2010). In general terms, CKD is defined as the loss of kidney functioning over time and
has been broken down into a five stage progressive classification system that is used internationally
(Stenvinkel, 2010). When the kidneys are not functioning properly the nephrons, the functioning unit of the
kidneys which are responsible for filtration, reabsorption and secretion are damaged and unable to properly
filter and keep chemicals within the body balanced (Silverthorn, Ober, Garrison, Silverthorn, & Johnson,
2010). There is no way to gain back nephron functioning once it has been lost. CKD is associated with fluid
overload, sodium and potassium imbalances, mineral and bone disorders, and anemia (CDC, 2013). When
advanced, the disease can lead to complete kidney failure, also referred to as end stage renal disease
(ESRD), and eventually death. CKD is largely under diagnosed around the world due to being
asymptomatic in its early stages (1-3) (Stenvinkel, 2010). Most people are not diagnosed with CKD until it
has progressed to the severe stages and are in need of serious medical attention (Vassalotti, GraczWeinstein, Gannon, & Brown, 2006). Currently, there are no cures for CKD. Transplantation and dialysis
are the only options for progressive CKD patients. Because rates of CKD are increasing in the United
States and is commonly undiagnosed, screening for the disease has grown in importance.
Key risk factors for CKD include diabetes, high blood pressure, heart disease, age, and family
history of CKD (National Institute of Health (NIH), 2013). “Due to an increased amount of people being
diagnosed with diabetes and hypertension and the estimation that the percentage of the population above 60
years of age will double from 11% in 2007 to 22% in 2050, an increase in the prevalence of CKD can be
expected in years to come” (Stenvinkel, 2010). Other risk factors that can contribute to CKD include age,
obesity, elevated cholesterol, repeated acute kidney injuries (such as kidney stones, drug use, and
infections), race and ethnicity (CDC, 2013). CKD is more widespread among people of African American,
Hispanic, and Native American descent due to higher rates of diabetes and hypertension in these
populations (NIH, 2012). African Americans were nearly four times more likely to progress to ESRD than
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white people in 2007 (CDC, 2013). Indigenous peoples also have higher rates of CKD among both children
and adults (White, Wong, Sureshkumur, & Singh, 2010). CKD can affect people of any age but prevalence
is increasing in ageing adults (Ng & Anpalahan, 2011). According the NIH (2012), the prevalence of CKD
in people ages 60 and older in the United States jumped from 18.8 to 24.5 percent.
According to the United States Census Bureau (2013), Florida has a high population of Hispanics
and elderly people (Florida Bureau of Vital Statistics, 2010). CKD is found to be more prevalent in peoples
of Hispanic decent. Additionally, heart disease, diabetes and CKD are among the ten leading causes of
death in Hispanic populations (CDC, 2012). Screening for CKD in this state could be beneficial to aid in
early diagnosis. In 2010, more than 4.2 million Hispanics resided in Florida; the third largest Hispanic
population in the U.S. (U.S. Census Bureau, 2013). Florida is also a popular state for retirees who
permanently relocate due to the warm climate. Florida is also popular for “snowbirds”, older people who
are often retired that temporarily reside in Florida or other warm states during the winter months. The
Florida Bureau of Vital Statistics (2010) states that Florida has a relatively higher population of adults over
the age of 50 than the rest of the United States.
There are three commonly used screening tests used in today’s health community. First, a serum
creatinine test, most commonly referred to as the Glomerular Filtration Rate (GFR), is a measurement used
to test how well the kidneys are functioning by testing how much serum creatinine is present in the blood.
Creatinine is produced by the muscles in the body and builds up in the blood when the kidneys are not
functioning at normal levels. Taking the creatinine levels found in the serum creatinine test a formula is
used to provide the estimated GFR (eGFR). The GFR estimates how much blood passes through the
glomeruli, tiny filters in the kidneys, each minute (NIH, 2012). GFR naturally decreases with age, so
gender, age, weight, height, and race are also considered in the GFR formula. Rates of 90-120 mL/min/1.73
m2 are considered normal, rates of <60 mL/min/1.73 m2 signify chronic kidney disease, while rates of <15
mL/min/1.73 m2 signify kidney failure and require immediate medical attention (NIH, 2012). The GFR is
the measurement used to classify what stage a CKD patient is at. The GFR is considered the best method to
test kidney functioning (National Kidney Foundation, 2013). One major limitation with the GFR is that
most people’s GFRs are not affected in the early stages of CKD. Therefore, early diagnosis can be hindered
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if only using this measurement method. There are several different GFR formulas used to determine the
eGFR.
The second screening method is a urine analysis, which measures levels of protein and other
components in the urine. Protein, red, and white blood cells are not commonly found in urine and their
presence can indicate that the kidneys are compromised (NIH, 2012). Two different urine tests are
commonly used to test the presence of protein in the urine. The albumin to creatinine ratio urine analysis
tests for albumin, a blood protein. A value of less than 30 mg/gm per day is normal, while a value of 30
mg/gm per day or higher means there is an unusual amount of albumin in the urine and may be a sign of
kidney disease (National Kidney Foundation, 2013). CKD is confirmed when two out of three albumin
urine analysis test are 30 mg/gm per a day or higher. White blood cells, red blood cells, and other
components in the urine may also be tested for to determine if the kidneys are not filtering properly
(National Kidney Foundation, 2013). The urine albumin analysis is particularly crucial in detecting stages 1
and 2 of CKD (Vassalotti et al., 2006). The second urine test that can be used is a protein to creatinine ratio.
This urine test is the most accurate way to measure protein in the urine (National Kidney Foundation,
2013). A value of 200 mg/gm or less per day is normal and a value higher than 200 mg/gm is too high. The
benefit of these urine analyses is that they do not require a 24-hour urine sample, which often can be hard
to collect.
Checking blood pressure is the third common method used to indicate that the kidneys are not
functioning at normal strength. A blood pressure of 140/90 is considered high blood pressure (National
Kidney Foundation, 2013). Elevation of both systolic and diastolic blood pressure is a predictor of ESRD in
patients with etiologies of CKD (Vassalotti et al., 2006). CKD can cause high blood pressure, as well as
high blood pressure can cause CKD (Levey, Atkins, Coresh, Cohen, Collins, Eckardt, Nahas, Jaber, Jadoul,
Levin, Powe, Rossert, Wheeler, Lameire, & Eknoyan, 2007). Blood pressure testing alone is not considered
an indication of CKD; many screenings combine all three methods together to form a diagnosis. Additional
testing beyond the three commonly used CKD screening methods includes a kidney biopsy and/or kidney
imaging performed by a physician (NIH, 2012).
The GFR is used as a marker for CKD, but the albumin test is most often used to detect the earliest
signs of CKD (Vassalotti et al., 2006). Dual testing of CKD using GFR and creatinine to albumin testing is
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most commonly used when screening for CKD (Vassalotti et al., 2006). Estimated GFR testing is better to
test kidney functioning than creatinine serum testing only. However, GFR is difficult to interpret in many
populations such as people who are pregnant, obese, malnourished, certain ethnic groups, people under the
age of 18, people who are inpatient in the hospital, people who are in the early stages of the disease, and
people with acute kidney injury (Vassalotti et al., 2006). A person’s GFR is relatively normal in the early
stages of CKD and often this test is ineffective in detecting stages 1 and 2 of CKD (Vassalotti et al., 2006).
The GFR is more accurate in the later stages of the disease. Gaps that are common in CKD include late
diagnosis, inadequate screening in high risk groups, poor management of the disease, and late referrals to
nephrologists (Vassalotti et al., 2006). According to Vassalotti et al. (2006), most disease treatment
programs throughout the world have focused on addressing ESRD rather than early diagnosis and
prevention. A screening program focused on early diagnosis could really benefit CKD patients.
In more technical terms CKD is defined as, “kidney damage or glomerular filtration rate (GFR)
<60 mL/min/1.73 m2 for 3 months or more, irrespective of cause” (Levey, Eckhardt, Tsukamoto, Levin,
Coresch, Rossert, DeZeeuw, Hostetter, Lamiere, & Eknoyan, 2005, p. 2089). Accurate estimation of the
GFR is crucial as it is an important component in determining the proper care for a patient. The GFR is
important for detecting and staging CKD, determining medications and dosages, and stratifying risk (Early,
Miskulin, Lamb, Levey, & Uhlig, 2012). In a cross sectional study by Early et al. (2012) two different
GFR formulas were compared to see which is more accurate. The Modification of Diet in Renal Disease
(MDRD) equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) measurements
were used. The MDRD is most commonly used, but is known to be less accurate at higher GFR levels in
ethnic groups outside of the North America, Australia, and Europe. The researchers studied twelve different
studies that met their criteria, comprising of 12,898 patients. The study found that the CKD-EPI equation
was more accurate, precise, and less biased than the MDRD. Accuracy ranged from 59% to 95% and bias
ranged from 14-22mL/min per 1.73 m2.
In a study completed by Madder, Hickman, Crimmins, Puri, Marinescu, McCullogh, & Safian
(2011), serum creatinine (SCr) and I-iothalamate GFR (I-GFR) were measured in 50 patients with renal
artery stenosis (RAS). GFR estimates were calculated using the equations MDRD, CKD-EPI, and
Cockroft-Gault (CG). Between 1998 and 2007, 541 I-GFR measurements were performed in 254
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consecutive patients with RAS. MDRD, CKD-EPI, and CG GFR estimates demonstrated sensitivity (86%
to 95%), t specificity (67% to 71%), and AUC (0.86 to 0.94) for identifying I-GFR <60 mL/min per 1.73
m(2). GFR estimates had good specificity (87% to 95%), poor sensitivity (0% to 45%), and poor reliability
(AUC, 0.61 to 0.65) for detecting 20% changes in I-GFR over follow-up (Madder, Hickman, Crimmins,
Puri, Marinescu, McCullogh, & Safian, 2011).
Urine analysis testing is a major diagnostic test for CKD (Vassalotti et al., 2006). A study was
completed by Methven, MacGregor, Traynor, O’Reilly, & Deighan (2010) to evaluate the effectiveness of
the protein to creatinine ratio (TPCR) and albumin to creatinine ratio (ACR). Throughout the study, 6,842
were analyzed; 3,484 were analyzed prior to 2006 and 3,358 were analyzed after 2006. Data assay changed
for ACR testing in 2006. The lower limit of detection for ACR changed during the study; ACR was
reported as <3 or <10 mg/mmol. These values were analyzed as 3 or 10 mg/mmol, respectively to ensure
that this change did not affect the findings. The data was re-analyzed excluding any pair of results that
included ACR <10 mg/mmol. Accounting for the change in assay, the study found that ACR was more
specific but less sensitive, while the TPCR was more sensitive and less specific. When using the TPCR test
the sensitivity was 91.3% versus 78.2% for ACR. The specificity for TPCR was 87.5% versus 94.6% for
ACR. The study found a positive predictive value (PPV) for TPCR of 82.5% to 90.0% for ACR. TCPR
had a negative predictive value (NPV) of 94.0% while ACR had a NPV of 87.5%. A likelihood positive
ratio (LR+) of 7.3 versus 14.5 was found and a likelihood negative ratio (LR-) of 0.1 versus .23. These
study results indicate that TPCR outperforms ACR at predicting 0.5 g/day, area under the curve 0.967 vs
0.951, P < 0.001 (Methven et al., 2010).
The results of the sensitivity, specificity, and PPV indicate that there is no absolute conclusion that
only on screening test will be most effective in diagnosing CKD. In order to improve sensitivity and
specificity of the screening tests continued research into GFR equations could explore measures that would
better sense early stages of CKD. The GFR is the best measure for CKD diagnoses, yet early detection in
this disease is crucial.
In the United States a program called KEEP (Kidney Early Evaluation Program) was founded by
The National Kidney Foundation in August of 2000. KEEP provides free screenings to individuals ages 18
or older who are at risk of CKD, have high blood pressure, diabetes, or a family history of CKD. KEEP
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travels around the U.S. in hopes to raise awareness, provide free screening, and educate individuals about
CKD. KEEP uses a blood, urine, and blood pressure test to screen for CKD. This initiative has also spread
to Japan. According to Vassalotti et al. (2006), the program has helped increase awareness and early
diagnosis for CKD. The KEEP program has found through their screening questionnaire that only 2% its
participants were aware of CKD, while 29% actually meet the diagnostic criteria for CKD (Vassalotti et al.,
2006). Gaps that are common in CKD include late diagnosis, inadequate screening in high risk groups, poor
management of the disease, and late referrals to a nephrologists (Vassalotti et al., 2006). According to
Vassalotti et al. (2006), most disease treatment programs throughout the world have focused on addressing
ESRD rather than early diagnosis and prevention. A screening program focused on early diagnosis could
really benefit CKD patients.
As a public health professional and epidemiologist, there are a few ethical considerations for CKD
screening. First, there is an ethical guideline that minimizes risk and protects welfare of individuals in a
screening research study. Going through the screening process can invoke psychological distress for the
individual. Individuals may also experience discomfort and scarring from medical professionals obtaining a
blood sample for analysis.
Secondly, because CKD is a wide-spread disease, affecting millions of people worldwide, public
trust must be maintained and is of utmost importance when conducting CKD screening. By using proper
screening equipment, knowledgeable medical staff, and protecting the confidentiality of participant’s, this
aids in protecting the integrity of the general population. In addition, utilizing community representatives
for advocacy of CKD screening also can maintain and encourage the public’s trust.
Given all the information, data, and ethical considerations stated above, I would recommend a
community mobile unit that offers a free voluntary CKD screening to individuals who are at risk for CKD
each year in the state of Florida. Despite the eGFR being considered the gold standard, I would recommend
also obtaining a urine analysis to better diagnose CKD, due to the GFR’s limitation to detect early signs of
CKD. Early diagnosis creates opportunity for early intervention.
According to Moyer (2012), there is not enough evidence for or against administering CKD
screening for healthy individuals. Therefore, CKD screening would be provided to individuals ages 18 and
older who have high blood pressure, diabetes, heart disease, and/or a family history of CKD. Due to CKD
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becoming increasingly prominent in individuals ages 60 and older, anyone over the age of sixty would also
be encouraged to participate in the free screening regardless of any health conditions. The mobile unit
would travel throughout the state in the winter months (mid October-March) to perform the screenings.
Due to Florida’s has high population Hispanics and adults over the age of 50, the winter months will
provide an increased opportunity of targeting people at risk, raising awareness, and promoting early
diagnosis in residents both that live and do not permanently live in the state.
The screenings would be done primarily by trained nurses and a few specialty physicians
following similar techniques as the KEEP program. I would make sure that there are public service
announcements that indicate what the mobile screening unit does, who does the screening, and where the
unit will be on which day. By informing the public about the service prior to the mobile unit arriving at a
particular location it will increase the likelihood of people participating in the screening.
When performing the screening, I would have the initial screening start with medical staff
obtaining the individual’s self reported medical history, weight, height, waist measurement, blood pressure
test and blood sample to calculate the eGFR. In addition, a urine sample would be obtained to test for
protein in the urine. Due to the albumin test’s increased ability to detect early signs of CKD, this test would
be beneficial to perform. The urine analysis takes less than 24-hours and is relatively cost efficient. The
results to the screening will be administered the same day and any lab work done would be mailed directly
to the individual. Participants are encouraged to follow-up with their doctors to further evaluate the results
of the tests, receive additional testing if necessary, and discuss treatment plans. Clinician and specialist
referrals will also be available if the individual does not have a doctor. While following the screening
process, medical staff can take the opportunity to provide educational materials, answer any questions, and
provide follow-up questions the participant can ask their primary care physician. If the medical staff finds
that an individual has an eGFR below 60, additional testing would be completed for calcium, phosphorus
and PTH levels. Problems with these three levels are common in kidney failure (UK National Kidney
Federation, 2011).
As indicated, I would increase the participation of the screening by using the public service
announcements that explain what the screening is, where the mobile unit will be, and when the unit will be
at the set location. The public health community would help increase participation by lobbying with
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government representatives about why this screening is important. Through lobbying, the hope would be
that the representatives would advocate in their communities and provide funding endorsements. Adding
on, I would “campaign” to local businesses, local universities, national and/or local organizations to
increase awareness about the screening and offer the opportunity of sponsorship, which would be displayed
on the mobile unit. I would inquire if businesses, churches, or local community centers would be willing to
display brochures and educational information about CKD and the screening. Public health professionals
can work in the community to promote awareness, early screening, education, and prevention methods. The
communities I would focus on would be those with a high Hispanic and/or elderly population; who are at
an increased risk of CKD. I would also go to cities such as Jacksonville, Sarasota, Fort Myers, Orlando, and
other large cities for the screening, given the large population of people in these areas. There would be an
emphasis on traveling to all areas of the state with the hopes that stops in larger communities would draw
others from smaller surrounding towns.
Overall, there is an understanding that there needs to be more studies conducted about the
effectiveness of CKD screenings in the United States. Due to CKD’s continued growth and “silent” nature,
there is a need for early diagnosis, prevention measures, and educational services. I am hopeful that the
United States will make efforts to raise awareness, explore preventative and treatment options, and provide
CKD screenings on a larger scale throughout the country.
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