Beruflich Dokumente
Kultur Dokumente
hronic kidney disease (CKD) is a growing gram in 1996 increased 12.5% over the previous year,
Table 1. Staging System and Action Plan for Chronic Kidney Disease
Adapted from National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K/DOQI) Advisory Board. K/DOQI clinical practice
guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis
2002;39(2 Suppl 2):S65. With permission from Elsevier Science.
‡Kidney damage as manifested by abnormalities noted on renal pathology, blood, urine, or imaging tests.
the term chronic kidney disease was chosen by the CKD GFR was subsequently developed by the CKD Work
Work Group. Group (Table 1).
The first order of business for the work group was to Defining CKD using this staging system provides a
define and classify CKD. The glomerular filtration rate common language for communication between the
(GFR) is the best overall measure of kidney function. various health care providers. The system will allow
Factors that influence GFR include both structural (or more reliable estimates of the prevalence of earlier
functional) kidney disease as well as patient age. In gen- stages and of populations at increased risk for CKD. In
eral, the annual decline of GFR with age is approxi- addition, evaluation of factors associated with a high
mately 1 mL/min per 1.73 m2 of body surface area, risk of progression can be recognized. Treatments can
beginning after the patient reaches approximately be more effectively examined and the development of
20 to 30 years of age.11 Although a chronic decline in adverse outcomes in this population can be more easily
GFR (a level of less than 60 mL/min per 1.73 m2 for determined. Finally, a classification and staging system
≥ 3 months) is evidence of CKD, substantial kidney also facilitates the application of clinical practice guide-
damage can exist without a decrease in GFR. In this lines, clinical performance measures and quality im-
circumstance, kidney damage is defined as a structural provement programs.
or functional abnormality of the kidney that can lead
to impaired kidney function that persists for 3 months ESTIMATION OF GFR AS AN INDEX OF KIDNEY
or more with or without a decreased GFR. Manifest- FUNCTION
ations of kidney damage can include pathologic abnor- Serum creatinine is the most commonly used bio-
malities noted on renal biopsy specimens or abnormali- chemical parameter for estimating GFR and as such has
ties revealed by blood, imaging, or urine tests. Utilizing been employed as an index of renal function. However,
this definition, CKD is present if the GFR is less than it is not an accurate measure of GFR, and it is especially
60 mL/min per 1.73 m2. In addition, CKD is present if inaccurate as an estimate of GFR when the serum creati-
the GFR is greater than or equal to 60 mL/min per nine level is between 1 and 2 mg/dL. This is because
1.73 m2 if other evidence of kidney damage also exists. creatinine, unlike inulin, is secreted by the renal tubules.
A classification and staging system based on the level of As renal function declines, the amount of creatinine
secreted by the tubules increases and raises the amount The Cockcroft-Gault equation ([140 – age in years] ×
of creatinine in the urine (not filtered by the glomeru- weight in kg/[72 × serum creatinine], with the result for
lus). The ability of the renal tubule to secrete creatinine females multiplied by 0.85) was originally developed to
is maximal at a serum creatinine concentration of ap- estimate creatinine clearance.12 Although it provides an
proximately 2 mg/dL. This effect acts to falsely increase adequate estimate of GFR, the MDRD equations are
the creatinine clearance, resulting in an overestimation more accurate.13 MDRD equation 7 is the preferred for-
of GFR. The serum creatinine concentration is also mula, but it requires measurement of blood urea nitro-
affected by body mass, muscle mass, diet, drugs, and lab- gen (BUN) and serum albumin. The formula is (170 ×
oratory analytical methods. “Normal” ranges of serum [serum creatinine (mg/dL)]– 0.999 × [age (years)]– 0.176 ×
creatinine quoted by laboratories are particularly mis- [0.762 if female] × [1.18 if African American] × [BUN
leading because they do not take into account the age, (mg/dL)]–0.170 × [albumin (g/dL)]+0.318). An abbreviated
race, sex, or body size of the individual. As an example, form of the MDRD equation that does not require
consider the following patients, both of whom have BUN or albumin measurement was also developed and
a serum creatinine level of 1.3 mg/dL. “Patient A” is a is: (186 × [serum creatinine (mg/dL)]– 1.154 × [age
20-year-old, 80-kg man. “Patient B” is an 80-year-old, (years)]– 0.203 × [0.742 if female] × [1.21 if African
60-kg woman. Using the Cockcroft-Gault equation, pa- American]) and maintains reasonably good accuracy.
tient A’s GFR is estimated at 102 mL/min per 1.73 m2, Links to calculators for these equations can be found at
which is within the normal range, whereas patient B’s http://www.kidney.org/professionals/doqi/index.cfm.
GFR is estimated at 32 mL/min per 1.73 m2. Patient B’s The MDRD equation was tested in a large sample of
GFR is clearly reduced and suggests the presence of sig- patients (N = 558) with a range of kidney diseases
nificant CKD. Unfortunately, patients such as patient B and ethnicities (European Americans and African
are often thought of as having relatively normal kidney Americans).13 GFR values were validated in the sample
function and will receive medications that are not prop- group using urinary clearance of 125I-iothalamate as the
erly dosed for their levels of kidney function. In addi- gold standard. It is important to recognize that certain
tion, prophylaxis for exposure to nephrotoxins such as patient groups were not well represented in the MDRD
radiocontrast media may be overlooked because the study sample. Groups not evaluated include patients at
renal function is assumed to be normal. extremes of age and body size; the severely malnour-
Nephrologists have known for decades that inulin ished or obese; patients with skeletal muscle diseases,
clearance is the gold standard test for measuring GFR. paraplegia, or quadriplegia; vegetarians; those with
Unfortunately, this test is cumbersome and relatively rapidly changing kidney function; and patients prior to
expensive, and it is not widely available for clinical use. dosing drugs with significant toxicity that are excreted
Iothalamate (125I-iothalamate) clearance is used at some by the kidneys. Therefore, clearance measurements are
centers to estimate GFR and is a reasonably accurate still required in groups who were underrepresented in
substitute for the inulin clearance method. This method the MDRD sample to fully validate the formula for all
is also expensive and somewhat cumbersome to per- patients.
form as a routine clinical test. A 24-hour urine collec-
tion for creatinine clearance is the accepted alternative PREVALENCE OF CKD STAGES
measure of GFR because it is widely available and is a The next goal of the CKD Work Group was to obtain
test that is familiar to most clinicians. However, this test is prevalence estimates for each stage of CKD. Prevalence
often difficult for patients to carry out and perform cor- estimates were obtained by utilizing a reference group
rectly, and it is less accurate than either inulin or iothala- comprised of patients evaluated in the Third National
mate clearance. Health and Nutrition Examination Survey (NHANES
To simplify estimation of renal function in patients, III).8 Between 1988 and 1994, NHANES III enrolled
GFR estimates from prediction equations are utilized. 33,994 Americans aged 2 months and older. In this sam-
These formulas take into account serum creatinine level, ple of patients, the MDRD equation was used to estimate
age, gender, race, and body size, and they are better esti- GFR. In addition to abnormal GFR levels, the presence
mates of GFR than serum creatinine concentration of micro- or macroalbuminuria on spot urine specimens
alone. The formulas used are sufficiently accurate and, as was considered sufficient evidence of kidney damage.
a result, are recommended by most nephrologists. The The prevalence of each GFR category was subsequently
two most widely used are the Cockcroft-Gault and the determined (Table 2). The level of albuminuria was
Modification of Diet in Renal Disease Study (MDRD) used to estimate the prevalence of the first 2 stages. (The
equations. ratio of albumin [and protein] to creatinine in spot
urine samples has been documented to reliably corre- Table 2. US Prevalence of Chronic Kidney Disease by
late with 24-hour urine measurements for albumin and Stage
protein.14)
Stage 1 and 2 estimates are based on a single mea- Prevalence*
GFR (mL/min
surement of albuminuria. As one might suspect, over- Stage Description per 1.73 m2) N (1000s) %
estimation of prevalence for these stages may result
1 Kidney damage† ≥ 90 5900 3.3
from this approach—microalbuminuria was persistent
with normal
in only 61% of a subset of 1241 patients that were re- or increased
tested.8 However, this overestimation may be balanced GFR
by the exclusion of other patients with kidney disease
2 Mild decrease 60–89 5300 3.0
not manifested by albuminuria. For example, kidney in GFR
damage may also manifest as hematuria, pyuria, or ab-
3 Moderate 30–59 7600 4.3
normal imaging tests. These important kidney param-
decrease in
eters were not evaluated in the NHANES III popula- GFR
tion.
4 Severe decrease 15–29 400 0.2
A staging system based on severity of disease is justi-
in GFR
fied from several perspectives. Adverse outcomes of
CKD are directly related to the prevailing level of kid- 5 Kidney failure < 15 or dialysis 300 0.1
ney function. Furthermore, CKD tends to worsen over Adapted from National Kidney Foundation (NKF) Kidney Disease
time, and the risk for adverse outcomes increases over Outcome Quality Initiative (K/DOQI) Advisory Board. K/DOQI clin-
time with disease severity. In addition, it is well docu- ical practice guidelines for chronic kidney disease: evaluation, classifi-
mented that as GFR declines, the prevalence of hyper- cation, and stratification. Kidney Disease Outcome Quality Initiative.
Am J Kidney Dis 2002;39(2 Suppl 2):S50. With permission from
tension, anemia, elevated parathyroid hormone level,
Elsevier Science.
hyperphosphatemia, hypocalcemia, and hypoalbumine-
mia increases.15,16 GFR = glomerular filtration rate.
In the past decade, several treatments have been into stages according to estimated GFR and the pres-
shown to slow the progression of CKD. In diabetic ence or absence of kidney damage and proposes a stage-
patients these include tight glucose control and nor- based clinical action plan. The complete K/DOQI
malization of blood pressure.5,6 Strict blood pressure Clinical Practice Guidelines for Chronic Kidney Disease:
control (< 125/75 mm Hg) in diabetic patients and in Evaluation, Classification, and Stratification can be
nondiabetic patients with proteinuria is associated with found at the Web site address http://www.kidney.org/
a slower rate of decline of GFR.16 – 18 ACE inhibitors and professionals/doqi/kdoqi/toc.htm. In addition, a CKD
angiotensin-receptor blockers may slow progression by Web site for primary care practitioners was developed by
mechanisms other than blood pressure lowering.19,20 the Yale University Nephrology Section and can be
Other potentially important therapies include dietary found at http://kidney.med.yale.edu.ckd.
protein restriction, lipid control with statins, smoking The next article in this series will review available
cessation, and correction of anemia. These aspects will interventions for slowing the progression of CKD. Future
be discussed more fully in a future article addressing articles will address anemia and mineral metabolism dis-
the therapies employed to reduce progression of CKD. turbances associated with CKD, cardiovascular disease in
In patients with moderate impairment (GFR of patients with CKD, and the preparation of patients for
30–60 mL/min per 1.73 m2), a search for uremic com- renal replacement therapy. HP
plications (eg, anemia, abnormalities in mineral met-
abolism) should be undertaken. In addition, treatment REFERENCES
of these processes should be initiated. In contrast, the 1. Obrador GT, Ruthazer R, Arora P, et al. Prevalence of
focus of care for patients with severe impairment (GFR and factors associated with suboptimal care before initia-
of 15–30 mL/min per 1.73 m2) should be on appropri- tion of dialysis in the United States. J Am Soc Nephrol
ate preparation for renal replacement therapy. Elec- 1999;10:1793–800.
2. Kausz AT, Khan SS, Abichandani R, et al. Management of
trolyte and acid-base disturbances such as hyperkalemia
patients with chronic renal insufficiency in the North-
and metabolic acidosis need to be monitored and treat- eastern United States. J Am Soc Nephrol 2001;12:1501–7.
ed aggressively. Nutritional state should be assessed and 3. Duncan L, Heathcote J, Djurdjev O, Levin A. Screening
dietary counseling undertaken to optimize protein for renal disease using serum creatinine: who are we
intake without inducing hyperphosphatemia, hyper- missing? Nephrol Dial Transplant 2001;16:1042–6.
kalemia, or metabolic acidosis. Also, correction of ane- 4. Nissenson AR, Collins AJ, Hurley J, et al. Opportunities
mia and mineral metabolism disturbances should con- for improving the care of patients with chronic renal in-
tinue during this late stage. sufficiency: current practice patterns. J Am Soc Nephrol
In addition to those patients who already have CKD, 2001;12:1713–20.
there is an even larger group of patients who are at risk 5. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect
for the development of CKD. This group includes pa- of angiotensin-converting-enzyme inhibition on diabet-
ic nephropathy. The Collaborative Study Group [pub-
tients with diabetes mellitus, hypertension, and systemic
lished erratum appears in N Engl J Med 1993;330:152].
lupus erythematosus, as well as chronic analgesic drug N Engl J Med 1993;329:1456–62.
users. In addition, African Americans appear to be at 6. The effect of intensive treatment of diabetes on the devel-
higher risk for kidney damage than other racial groups. opment and progression of long-term complications in
As part of the initial evaluation of high-risk patients, the insulin-dependent diabetes mellitus. The Diabetes
CKD Work Group advised measurement of blood pres- Control and Complications Trial Research Group. N Engl
sure, serum creatinine level (to estimate GFR), and J Med 1993;329:977–86.
protein- or albumin-to-creatinine ratio in a spot urine 7. Giatras I, Lau J, Levey AS. Effect of angiotensin-converting
specimen to assess for kidney damage. Other selected enzyme inhibitors on the progression of nondiabetic renal
tests, such as renal ultrasonography, computed tomog- disease: a meta-analysis of randomized trials. Angiotensin-
raphy or magnetic resonance imaging of the kidneys, Converting-Enzyme Inhibition and Progressive Renal
Disease Study Group. Ann Intern Med 1997;127:337–45.
serum electrolyte levels, and urinalysis may be indicated
8. National Kidney Foundation (NKF) Kidney Disease
in specific clinical situations. Outcome Quality Initiative (K/DOQI) Advisory Board.
K/DOQI clinical practice guidelines for chronic kidney
CONCLUSION
disease: evaluation, classification, and stratification.
The rising incidence and prevalence of CKD in the Kidney Disease Outcome Quality Initiative. Am J Kidney
United States has mandated a unified approach to its Dis 2002;39(2 Suppl 2):S1–246.
evaluation and classification. The approach put forth by 9. US Renal Data System. USRDS 2001 annual data report.
the NKF’s CKD Work Group stratifies patients with CKD Bethesda (MD): National Institutes of Health, National
Copyright 2003 by Turner White Communications Inc., Wayne, PA. All rights reserved.