Transcript Document

Chronic Kidney Disease (CKD)
Clinical and Laboratory
Management of a Killer
David Schaffner Ph.D., MT(ASCP)
Scientific Affairs Manager
Beckman Coulter, Inc.
[email protected]
Learning Objectives
•
•
•
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Analyze the incidence and epidemiology of
chronic kidney disease
Explain renal Function and physiology
Discuss the clinical management of CKD
including current guidelines for monitoring and
treatment
Identify the role of the Clinical Laboratory in the
management of CKD including creatinine
standardization and eGFR Reporting
A Worldwide Health Issue:
ESRD Rates Continue to Rise in the US
Kidney Failure Deaths Compared to Cancer
Deaths in the U.S. in 2000 (in Thousands)
160
100
57
41
30
Lung Cancer
Kidney
Failure
Colorectal
Cancer
Breast
Cancer
Prostate
Cancer
Prevalence of Renal
Insufficiency in U.S.
GFR
(mL/min/1.73 m2)
59-30
29-15
Number of People
7.7 Million
360,000
Thus, about 8 million Americans have a GFR less than
60 mL/min/1.73 m2. Plus 11 million more have a GFR
over 60 but have persistent microalbuminuria.
Incident Counts & Adjusted Rates,
By Primary Diagnosis
USRDS, 2004
Incidence of Kidney Failure
(per million population, 1990, from HSA)
USRDS, 2000
Incidence of Kidney Failure
(per million population, 2000, by HSA)
USRDS, 2000
Costs of Kidney Failure are High
(in $billions for 2002)
Kidney
Failure
Care
Total NIH
Budget
25.2
Kidney Failure
Accounts for 6% of
Medicare Payments
Lost Income for
Patients is $2-4
Billion/Yr
23.2
A Worldwide Health Issue
• Worldwide, 1.1 to 1.8 Million people have
ESRD today, and is increasing 7% per year
• China, Australia, and other countries report
similar CKD prevalence as the US at 11%
• Diabetes, a major cause of CKD, is
increasing worldwide
Review of Renal Function and Physiology
• Four (4) Major Functions:
– Excretion of protein metabolism end-products
– Regulation of fluid, electrolyte and acid-base
balance
– Hormonal Functions
– Formation of Urine
Review of Renal Function and Physiology
Review of Renal Function and Physiology
• 25% of cardiac output goes to the kidneys
• The glomerulus filters up to 130mL/minute = 180L/Day
– This glomerular filtration rate (GFR) is a key indicator of
kidney function
• Tubules conserve important metabolites and reduce the
filtration volume to ~ 1.5 L urine /day
• Normal glomeruli do not pass proteins. The more
extensive the kidney damage, more protein and larger
proteins will pass through.
CKD: Definition and Staging
per National Kidney Foundation (NKF)
Kidney Disease Outcome Quality Initiative (K/DOQI)
• Definition of Chronic Kidney Disease is:
– Kidney Damage lasting >3 months, as defined by
structural or functional abnormalities of the kidney,
with or without decreased GFR, and manifested by
either:
• Pathological Abnormalities, or
• Markers of kidney damage, including abnormalities in the
composition of blood or urine, or abnormalities in imaging
tests
OR
– GFR <60 mL/min/1.73 m2 for >3 months, with or
without kidney damage
CKD: Definition and Staging
per National Kidney Disease Education Program
(NKDEP)
• Definition of Chronic Kidney Disease is:
– The persistent and usually progressive
reduction in glomerular filtration rate
(GFR less than 60 mL/min/ 1/73 m2)
And/Or
– Albuminuria (more than 30 mg of urinary
albumin per gram of urine creatinine)
CKD: Definition and Staging
per National Kidney Foundation (NKF)
Kidney Disease Outcome Quality Initiative (K/DOQI)
• Stages of CKD are:
Stage
Description
GFR
2
(mL/min/1.73m )
At increased risk
90
(with CKD risk
factors)
Kidney damage
1.
with normal
or GFR
90
2.
Kidney damage
with mild GFR
60-89
3.
Moderate
30-59
4.
Severe
5.
Kidney Failure
GFR
GFR
15-29
<15
(or dialysis)
Risk Factors Contributing to CKD
(per K/DOQI)
• Susceptibility Factors
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Age
Race
Socioeconomic Factors
Genetic Factors / Family History
• Initiation Factors
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Diabetes
Hypertension
Autoimmune Diseases
Urinary infections and stones
The Risk of Kidney Failure
is Not Uniform
Relative risks compared to Whites:
African Americans
3.8 X
Native Americans
2.0 X
Asians/Pacific Islander 1.3 X
The relative risk of Hispanics compared to
non-Hispanics is about 1.5 X
USRDS, 2004
Complications of CKD
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Cardiovascular Disease (CVD)
Anemia of Renal Failure
Bone Disease
Others
CKD and CVD
• CKD Patients are in the highest risk group for
cardiovascular disease
• Cardiovascular events are the major cause of
morbidity and mortality in CKD patients
• Early intervention and aggressive treatment is
essential
– Manage traditional CVD risk factors
• hypertension, cholesterol, smoking, exercise, weight, etc.
– Manage specific CKD risk factors
• prothrombotic factors, chronic inflammation, , oxidative stress, etc.
CKD Predicts CVD
40
Age-Standardized Rate of
Cardiovascular Events (per 100 personyr)
36.6
35
30
25
21.8
20
15
11.29
10
5
3.65
2.11
0
≥ 60
45-59
30-44
15-29
Estimated GFR (mL/min/1.73 m2)
< 15
Go, et al., 2004
NACB Draft LMPG on Emerging Biomarkers
of Cardiovascular Disease and Stroke:
• Recommendation #1 on Markers of Renal
Impairment and CVD Risk:
– CKD Testing, including microalbuminuria and serum
creatinine for GFR estimation, should be performed
for all individuals with hypertension, diabetes,
family history of CKD, and those with CVD or at
increased risk of CVD. In addition, measurement of
serum creatinine for GFR estimation should be
performed for all individuals >65 years old. Individual
decision making is recommended for individuals with
other CKD risk factors.
Anemia of Renal Failure
CKD and Bone Disease
• Significant imbalances in mineral and bone
metabolism occur in CKD
• Long-term effects of bone disease may lead
to impaired pulmonary function, cardiac
hypertrophy, congestive heart failure
• Hyperphosphatemia and hyper-PTH
Monitoring and Treatment
(per NKDEP and NKF)
– The following information on CKD testing and
treatment is drawn directly from the US
National Kidney Disease Education Program
and from the National Kidney Foundation
CKD is Not Being Recognized or Treated
• Most practices screen fewer than 20% of
their Medicare patients with diabetes
• Patients are referred late to a nephrologist,
especially African-American men
• Less than 1/3 of people with identified CKD
get an ACE Inhibitor
Early Treatment Makes a Difference
Brenner, et al., 2001
Parallels Between Hypertension in 1972
and Kidney Disease in 2007
• Recent documentation of effective therapy
• Treatment of a silent disease to reduce risk
for a disastrous outcome
• Simple screening
• Advantages for patients care
Primary Care Providers Must be Engaged
1)
7.7 million people with GFR 30-60 mL/min/1.73 m2
2)
About 5,000 full-time nephrologists
3)
Nearly 1,500 new patients per nephrologist
Therefore, 7 new patients per day per nephrologist.
Obviously not possible.
What can Primary Care Providers do?
• Recognize who is at risk
• Provide testing and treatment
• Encourage labs to provide and report estimated GFR and
spot urine albumin/creatinine ratios
Who to Test for Chronic
Kidney Disease
Regular testing of people at risk
• Diabetes
• Hypertension
• Family History with kidney failure
• Cardiovascular disease
How to Test for Chronic
Kidney Disease*
In individuals with diabetes:
• “Spot” urine albumin to creatinine ratio
• Serum Creatinine and eGFR
In others at risk:
• “Spot” urine albumin to creatinine ratio OR standard dipstick
(Bouleware, et al., 2003)
• Estimate GFR from serum creatinine using the MDRD prediction
equation
*24 hour urine collections are NOT needed. Diabetics should be
tested once a year. Others at risk testing less frequently as long as
normal.
Who Should be Treated for
Chronic Kidney Disease
With diabetes:
• With urine albumin/creatinine ratios more than 30mg
albumin/1 gram creatinine
Without diabetes:
• With urine albumin/creatinine ratios more than 300mg
albumin/1 gram creatinine corresponding to about 1+
on standard dipstick
Or
Any patient:
• With estimated GFR less than 60 mL/min/1.73 m2
Treatment to Prevent Progression of
CKD to Kidney Failure
• Intensive glycemic control lessens progression from
microalbuminuria in type 1 diabetes
- DCCT, 1993
• Antihypertensive therapy with ACE Inhibitors lessens
proteinuria and progression
- Giatras, et al., 1997
- Psait, et al., 2000
- Jafar, et al., 2001
Meta-Analyses
• Low protein diets lessen progression
- Fouque, et al., 1992
- Pedrini, et al., 1996
- Kasiske, et al., 1998
Meta-Analyses
How to Treat for Chronic
Kidney Disease
• Maintain blood pressure less than
130/80 mmHg
• Use an Angiotensin Converting Enzyme (ACE) Inhibitor
or Angiotensin Receptor Blocker(ARB)
• More than one drug is usually required and a diuretic
should be part of the regimen
• Continue best possible glycemic control in individuals with
diabetes
How to Treat for Chronic
Kidney Disease
(continued)
• Refer to dietician for a reduced protein diet
• Consult a nephrologist early
• Team with the nephrologist for care if GFR is less than 30
mL/min/1.73 m2
• Monitor hemoglobin and phosphorous with treatment as
needed
• Monitor and treat cardiovascular risk, especially smoking
and hypercholesterolemia
Reasons for a
National Kidney Disease Education Program
(NKDEP)
• Kidney failure is a public health
problem
• Economical, effective testing and
therapy exist
• Testing and therapy are inadequately
applied
Worldwide Creatinine Standardization
Program
• The National Kidney Disease Education Program
(NKDEP) was established under the US NIH NIDDK
• NKDEP in collaboration with the International Federation
of Clinical Chemistry (IFCC) and the European
Communities Confederation of Clinical Chemistry (EC4)
has launched the Creatinine Standardization Program.
• Worldwide Program Goals
– To reduce inter-laboratory variation in creatinine assay
calibration
– To provide more accurate estimates of GFR
– To help health care providers better identify and treat
chronic kidney disease in order to prevent or delay
kidney failure and to improve patient outcomes.
NKDEP Lab Working Group –
Recommendations for Creatinine
• Creatinine methods used in reporting eGFR should be
standardized to Isotope Dilution Mass Spec (IDMS)
• Implement eGFR reporting now, using the MDRD
equation and report along with Creatinine results
• Report eGFR above 60 as >60 mL/min/1.73 m2
• Report Serum Creatinine values to 2 decimal places
for mg/dL, or to the nearest whole number for
μmol/L.
• Report eGFR to the nearest whole number.
The MDRD Equation for eGFR
• There are several equations that convert
creatinine values into an estimated GFR
(eGFR)
• NKDEP recommends the MDRD Equation
– From the Modification of Diet in Renal Disease
clinical study
– Combines Serum Creatinine results, age,
gender, race
– Should be implemented on the LIS
NKDEP Lab Working Group –
Recommendations for Creatinine and eGFR
• NKDEP states that eGFR by MDRD is
more accurate than creatinine clearance
measurements.
• NKDEP recommends that creatinine
clearance not be performed except when
basal creatinine production is expected to be
abnormal (obese, malnourished, musclewasting diseases, etc)
The MDRD Equation
• For use with conventional
Creatinine results:
eGFR (mL/min/1.73 m2) =
186 x (serum creatinine, mg/dL)-1.154
x (Age)-0.203
x 0.742 (if Female)
x 1.21 (if African-American)
The MDRD Equation
• For use with conventional IDMS-standardized
Creatinine results:
eGFR (mL/min/1.73 m2) =
186 175 x (serum creatinine, mg/dL)-1.154
x (Age)-0.203
x 0.742 (if Female)
x 1.21 (if African-American)
Versions also available in SI units (umol/L)
Sample eGFR Reports
• Sample report for a 63-year-old woman
Creatinine = 1.82 mg/dL (161 μmol/L)
eGFR if African American = 36 mL/min/1.73 m2
eGFR if non-African American = 30 mL/min/1.73 m2
• Sample report for a 63-year-old woman identified as
African American
Creatinine = 1.82 mg/dL (161 μmol/L)
eGFR = 36 mL/min/1.73 m2
• Sample report for a 62-year-old man
Creatinine = 1.35 mg/dL (119 μmol/L)
eGFR if African American = >60 mL/min/1.73 m2
eGFR if non-African American = 57 mL/min/1.73 m2
• Sample report for a 55-year-old man
Creatinine = 1.07 mg/dL (95 μmol/L)
eGFR if African American = >60 mL/min/1.73 m2
eGFR if non-African American = >60 mL/min/1.73 m2
MDRD Limitations
• NKDEP notes that the MDRD equation was
NOT validated for:
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Children <18 years
Seniors >75 years
“Normals” or GFR >90 ml/min/1.73 m2
Pregnancy
Serious comorbid conditions
Extremes of body size, muscle mass, nutritional
status
PT/EQA Implications
• PT/EQA providers are making changes in
participant grading to account for bimodal
distributions of results.
• NKDEP is communicating with PT/EQA
providers and IVD manufacturers to ensure
appropriate grading during this transition.
NKDEP Lab Working Group
Recommendations for Communications
• Communicate with clinical staff before
transitioning creatinine results
• Communicate with Pharmacy before
transitioning creatinine results
– Pharmacy may be estimating GFR by other
equations: Cockroft-Gault, Schwartz, or
Counahan-Barratt
– Transitioning to IDMS Creatinine may affect
their results. And their dosing.
Summary and Conclusions
• Chronic Kidney Disease is a worldwide
killer that is under-diagnosed and undertreated.
• Clinical Laboratorians have a critical and
central role in addressing CKD: its causes,
its complications, and its treatment
• Beckman Coulter can help you make a
difference in people’s lives.
For More Information
• www.nkdep.nih.gov
– www.nkdep.nih.gov/resources
– www.nkdep.nih.gov/labprofessionals
• www.kidney.org
• www.kdoqi.org
• www.beckmancoulter.com/customersupport
/trainingeducation/elearning/course.asp
• Clinical Chemistry 52:1; 5-18 (Jan 2006)
Thank you
David Schaffner Ph.D., MT(ASCP)
Scientific Affairs Manager
Beckman Coulter, Inc.
[email protected]