National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and StratificationFREE
Publication: Annals of Internal Medicine
Volume 139, Number 2
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Abstract
Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression.
Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality.
This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin–creatinine ratio in untimed (spot) urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.
Chronic kidney disease is a worldwide public health problem. In the United States, the incidence and prevalence of kidney failure are rising, the outcomes are poor, and the costs are high. The number of persons with kidney failure who are treated with dialysis and transplantation is projected to increase from 340 000 in 1999 to 651 000 in 2010 (1). The major outcomes of chronic kidney disease, regardless of cause, include progression to kidney failure, complications of decreased kidney function, and cardiovascular disease (CVD). Increasing evidence indicates that some of these adverse outcomes can be prevented or delayed by early detection and treatment (2). Unfortunately, chronic kidney disease is underdiagnosed and undertreated, resulting in lost opportunities for prevention (3-5), in part because of a lack of agreement on a definition and classification of stages in the progression of chronic kidney disease (6) and a lack of uniform application of simple tests for detection and evaluation.
In February 2002, the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) published 15 clinical practice guidelines on chronic kidney disease [7]. The goals of the guidelines are to 1) define chronic kidney disease and classify its stages, regardless of underlying cause; 2) evaluate laboratory measurements for the clinical assessment of kidney disease; 3) associate the level of kidney function with complications of chronic kidney disease; and 4) stratify the risk for loss of kidney function and development of CVD. Our goal is to disseminate the simple definition and five-stage classification system of chronic kidney disease, to summarize the major recommendations on early detection of chronic kidney disease in adults (Table 1), and to consider some of the issues associated with these recommendations. Because of the high prevalence of early stages of chronic kidney disease in the general population, this information is particularly important for general internists and specialists.
Methods
The guidelines of the K/DOQI are based on a systematic review of the literature. The approach used for the review was outlined by the Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research) (46), with modifications appropriate to the available evidence and the goals of the K/DOQI Work Group.
The Work Group considered diverse topics, which would have been too large for a comprehensive review of the literature. Instead, a selective review of published evidence was used to focus on specific questions: a summary of reviews for established concepts and a review of original articles and data for new concepts. The strength of recommendations is graded according to a new classification (Table 2) recently adopted by the K/DOQI Advisory Board (see Appendix 1).
Framework
The Work Group defined two principal outcomes of chronic kidney disease: the progressive loss of kidney function over time (Figure 1) and the development and progression of CVD. Figure 1, which defines stages of chronic kidney disease, as well as antecedent conditions, outcomes, risk factors for adverse outcomes, and actions to improve outcomes, is a model of the course of chronic kidney disease. This diagram provides a framework that has previously been lacking for the development of a public health approach to chronic kidney disease.
Figure 1. Evidence model for stages in the initiation and progression of chronic kidney disease (
CKD ) and therapeutic interventions. Shaded ellipses represent stages of chronic kidney disease; unshaded ellipses represent potential antecedents or consequences of chronic kidney disease. Thick arrows between ellipses represent risk factors associated with the initiation and progression of disease that can be affected or detected by interventions: susceptibility factors (black), initiation factors (dark gray), progression factors (light gray), and end-stage factors (white) (Table 3). Interventions for each stage are given beneath the stage. Persons who appear normal should be screened for chronic kidney disease risk factors. Persons known to be at increased risk for chronic kidney disease should be screened for chronic kidney disease. Complications refer to all complications of chronic kidney disease and its treatment, including complications of decreased glomerular filtration rate (GFR) (hypertension, anemia, malnutrition, bone disease, neuropathy, and decreased quality of life) and cardiovascular disease. Reprinted with permission from reference 7.
Risk factors for chronic kidney disease are defined as attributes associated with increased risk for adverse outcomes of chronic kidney disease (Table 3). The guidelines focus primarily on identifying susceptibility factors and initiation factors (to define persons at increased risk for developing chronic kidney disease) and progression factors (to define persons at high risk for worsening kidney damage and subsequent loss of kidney function). Because kidney disease usually begins late in life and progresses slowly, most persons in the stage of decreased glomerular filtration rate (GFR) die of CVD before they develop kidney failure. However, decreased GFR is associated with a wide range of complications, such as hypertension, anemia, malnutrition, bone disease, neuropathy, and decreased quality of life, which can be prevented or ameliorated by treatment at earlier stages. Treatment can also slow the progression to kidney failure. Thus, measures to prevent, detect, and treat chronic kidney disease in its earlier stages could reduce the adverse outcomes of chronic kidney disease.
Cardiovascular disease deserves special consideration as a complication of chronic kidney disease because 1) CVD events are more common than kidney failure in patients with chronic kidney disease, 2) chronic kidney disease seems to be a risk factor for CVD, and 3) CVD in patients with chronic kidney disease is treatable and potentially preventable (48-50). The 1998 Report of the NKF Task Force on Cardiovascular Disease in Chronic Renal Disease recommended that patients with chronic kidney disease be considered in the highest risk group for subsequent CVD events and that most interventions that are effective in the general population should also be applied to patients with chronic kidney disease (49).
Definition and Classification of Stages of Chronic Kidney Disease
Guideline 1. Definition and Stages of Chronic Kidney Disease
Adverse outcomes can often be prevented or delayed through early detection and treatment of chronic kidney disease. Earlier stages of chronic kidney disease can be detected through routine laboratory measurements.
Chronic kidney disease is defined as either kidney damage or decreased kidney function (decreased GFR) for 3 or more months (level A recommendation).
Kidney disease can be diagnosed without knowledge of its cause. Kidney damage is usually ascertained by markers rather than by kidney biopsy. According to the Work Group, persistent proteinuria is the principal marker of kidney damage (8, 9). An albumin–creatinine ratio greater than 30 mg/g in untimed (spot) urine samples is usually considered abnormal; proposed sex-specific cut points are greater than 17 mg/g in men and greater than 25 mg/g in women (10, 11). Other markers of damage include abnormalities in urine sediment, abnormalities in blood and urine chemistry measurements, and abnormal findings on imaging studies. Persons with normal GFR but with markers of kidney damage are at increased risk for adverse outcomes of chronic kidney disease.
Glomerular filtration rate is the best measure of overall kidney function in health and disease (12). The normal level of GFR varies according to age, sex, and body size. Normal GFR in young adults is approximately 120 to 130 mL/min per 1.73 m2 and declines with age (12-15). A GFR level less than 60 mL/min per 1.73 m2 represents loss of half or more of the adult level of normal kidney function. Below this level, the prevalence of complications of chronic kidney disease increases.
Although the age-related decline in GFR has been considered part of normal aging, decreased GFR in the elderly is an independent predictor of adverse outcomes, such as death and CVD (51-53). In addition, decreased GFR in the elderly requires adjustment in drug dosages, as in other patients with chronic kidney disease (54). Therefore, the definition of chronic kidney disease is the same, regardless of age. Because GFR declines with age, the prevalence of chronic kidney disease increases with age; approximately 17% of persons older than 60 years of age have an estimated GFR less than 60 mL/min per 1.73 m2 (16).
The guidelines define kidney failure as either 1) GFR less than 15 mL/min per 1.73 m2, which is accompanied in most cases by signs and symptoms of uremia, or 2) a need to start kidney replacement therapy (dialysis or transplantation). Approximately 98% of patients with kidney failure in the United States begin dialysis when their GFR is less than 15 mL/min per 1.73 m2 (17). Kidney failure is not synonymous with end-stage renal disease (ESRD). End-stage renal disease is an administrative term in the United States. It indicates that a patient is treated with dialysis or transplantation, which is the condition for payment for health care by the Medicare ESRD Program. The classification of ESRD does not include patients with kidney failure who are not treated with dialysis and transplantation. Thus, although the term ESRD provides a simple operational classification of patients according to treatment, it does not precisely define a specific level of kidney function.
The level of kidney function, regardless of diagnosis, determines the stage of chronic kidney disease according to the K/DOQI chronic kidney disease classification (level A recommendation).
Data from the Third National Health and Nutrition Examination Survey (NHANES III) show the increasing prevalence of complications of chronic kidney disease at lower levels of GFR (7). These data and other studies provide a strong basis for using GFR to classify the stage of severity of chronic kidney disease. Table 4 shows the classification of stages of chronic kidney disease and the prevalence of each stage, estimated by using data from NHANES III (16). Approximately 11% of the U.S. adult population (20 million persons from 1988 to 1994) have chronic kidney disease. The prevalence of early stages of disease (stages 1 to 4; 10.8%) is more than 100 times greater than the prevalence of kidney failure (stage 5; 0.1%). The burden of illness associated with earlier stages of chronic kidney disease has not been systematically studied (55, 56). The National Institute of Diabetes and Digestive and Kidney Disease has initiated a prospective cohort study, the Chronic Renal Insufficiency Cohort (CRIC) study, for this purpose.
Guideline 2. Evaluation and Treatment
The evaluation and treatment of patients with chronic kidney disease require understanding the separate but related concepts of diagnosis, comorbid conditions, severity of disease, complications of disease, and risks for loss of kidney function and CVD.
Each patient should have a clinical action plan based on the stage of disease, as defined by the K/DOQI classification (level B recommendation).
Starting treatment at the right point in the progression of chronic kidney disease is essential to prevent adverse outcomes. Defining the stage of chronic kidney disease is the key first step in developing the appropriate clinical action plan (Table 4).
Diagnosis of chronic kidney disease is traditionally based on pathology test results and etiology. A simplified classification emphasizes diseases in native kidneys (diabetic or nondiabetic in origin) and kidney diseases in the transplant. Diabetic kidney disease is the largest single cause of kidney failure in the United States; the earliest manifestation is microalbuminuria with a normal or elevated GFR (stage 1 according to the guidelines). Nondiabetic kidney diseases include glomerular, vascular, tubulointerstitial, and cystic kidney diseases.
The differential diagnosis of chronic kidney disease in a specific patient is based on the history, physical examination, and laboratory evaluation (Tables 5 and 6), as described in standard texts and recent reviews (57, 58). The remainder of the evaluation of chronic kidney disease is similar for most types of kidney disease. Specific treatment depends on the cause of kidney disease; a thorough search for reversible causes should be carried out in each patient. However, many aspects of treatment are not specific to the cause; these are reviewed in the NKF K/DOQI clinical practice guidelines on chronic kidney disease and other topics (available at www.kdoqi.org).
Treatment of comorbid conditions, interventions to slow progression of kidney disease, and measures to reduce the risk for CVD should begin during stage 1 and stage 2. Hypertension is both a cause and a complication of chronic kidney disease and should be carefully controlled in all patients. Evaluation and treatment of other complications of decreased GFR, such as anemia, malnutrition, bone disease, neuropathy, and decreased quality of life, should be undertaken during stage 3, as the prevalence of these complications begins to rise when GFR declines to less than 60 mL/min per 1.73 m2. Preparation for kidney replacement therapy should begin during stage 4, well before the stage of kidney failure. Initiation of dialysis and transplantation is triggered by the onset of uremic symptoms. Preparations for these treatments should begin when GFR declines to less than 15 mL/min per 1.73 m2 (stage 5). The clinical action plan for each stage should include actions begun in preceding stages.
Patients with chronic kidney disease should be referred to a specialist for consultation and comanagement if the patient's personal physician cannot adequately evaluate and treat the patient. A nephrologist should participate in the care of patients with a GFR less than 30 mL/min per 1.73 m 2 (level B recommendation).
The guidelines endorse a model in which primary physicians and specialists share responsibility for the care of persons with chronic kidney disease. Most patients with stage 1 to 3 chronic kidney disease are under the care of primary care providers, generalists, or specialists other than nephrologists. As kidney disease worsens, the need for consultation and comanagement with nephrologists increases. Recent studies show that many patients do not see a nephrologist until shortly before dialysis. Late referral is associated with increased mortality after initiation of dialysis (18-22). The Work Group identified a specific level of kidney function as a threshold for referral to a nephrologist in order to facilitate more timely preparation for kidney replacement therapy and perhaps improve outcomes.
Guideline 3. Persons at Increased Risk for Chronic Kidney Disease
Some persons who do not have kidney damage and who have normal or elevated GFR are at increased risk for development of chronic kidney disease.
All persons should be assessed as part of routine health encounters to determine whether they are at increased risk for developing chronic kidney disease on the basis of clinical and sociodemographic factors (level C recommendation).
Persons at increased risk for developing chronic kidney disease should undergo testing to identify markers of kidney damage and to estimate the GFR (level C recommendation).
Table 3 presents examples of clinical and sociodemographic factors that increase susceptibility to or initiate chronic kidney disease. The proportion of persons at increased risk for chronic kidney disease is not known. Table 7 shows the large number of patients with risk factors for chronic kidney disease. Estimates indicate that the number of persons at increased risk may exceed the number of patients with chronic kidney disease (1, 23-31).
Table 6 presents recommendations for evaluating adults at increased risk for chronic kidney disease. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (32) and the American Diabetes Association (9) recommend testing adults with high blood pressure or diabetes for chronic kidney disease. Many other persons may also be at increased risk for chronic kidney disease (Table 7). Therefore, the Work Group also recommended testing persons who have a family history of chronic kidney disease, are older than 60 years of age, or who belong to U.S. racial or ethnic minorities.
The guidelines in Table 6 are especially important for generalist physicians, who are uniquely positioned to detect chronic kidney disease in its earliest stages.
The NKF K/DOQI guidelines recommend testing more persons for chronic kidney disease than do other evidence-based guidelines. The U.S. Preventive Health Services Task Force (USPSTF) recommends testing patients with hypertension or diabetes but not other subgroups (59). However, data provided in the NKF K/DOQI guidelines suggest that the prevalence of earlier stages of chronic kidney disease is higher than previously suspected and that earlier detection and treatment can prevent or delay the loss of kidney function and development of chronic kidney disease. The Work Group calls upon the USPSTF to reevaluate its guidelines in light of the evidence cited in this report. The research community should evaluate risks and benefits of various testing schedules for specific subgroups of persons at increased risk for developing chronic kidney disease.
Evaluation of Laboratory Measurements for the Clinical Assessment of Kidney Disease
Guideline 4. Estimation of GFR
Estimates of GFR are the best overall indices of the level of kidney function.
Physicians should estimate the level of GFR from prediction equations that take into account the serum creatinine concentration and some or all of the following variables: age, sex, race, and body size. The Modification of Diet in Renal Disease (MDRD) study and CockcroftGault equations provide useful estimates of GFR in adults (level A recommendation).
Glomerular filtration rate can be estimated from serum creatinine levels by using prediction equations that also take into account age, sex, race, and body size. Two such equations are:
where C Cr is creatinine clearance, S Cr is serum creatinine concentration in mg/dL, age is in years, and weight is in kg. Appendix Table 1 shows the range of values of serum creatinine that correspond to an estimated GFR of 60 mL/min per 1.73 m2, depending on age, sex, and race. Thus, minor elevations of serum creatinine concentration may be consistent with a substantial reduction in GFR.
The MDRD study equation has many advantages. It is more accurate and precise than the Cockcroft–Gault equation for persons with a GFR less than approximately 90 mL/min per 1.73 m2 (34, 35). This equation predicts GFR as measured by using an accepted method (urinary clearance of 125I-iothalamate). It was developed on a large (n > 1000) database containing persons with various kidney diseases and was tested on a validation database containing more than 500 additional patients. It does not require height or weight and has been validated in kidney transplant recipients and African-Americans with nephrosclerosis (36). Nonetheless, questions remain about the equation's generalizability because it has not been validated in diabetic kidney disease, in patients with serious comorbid conditions, in normal persons, or in persons older than 70 years of age. Clinical conditions in which it may be necessary to measure GFR by using clearance methods include extremes of age and body size, severe malnutrition or obesity, diseases of skeletal muscle, paraplegia or quadriplegia, vegetarian diet, rapidly changing kidney function, and calculation of the dose of potentially toxic drugs that are excreted by the kidneys.
Clinicians should not use serum creatinine concentration as the sole means to assess the level of kidney function (level A recommendation).
The serum creatinine concentration is affected by factors other than GFR, such as creatinine secretion and generation and extrarenal excretion (37, 38). As a result, there is a relatively wide range for serum creatinine in normal persons. This wide range means that GFR must decline to approximately half the normal level before the serum creatinine concentration rises above the upper limit of normal (Appendix Table 1). In the elderly, the serum creatinine concentration does not reflect the age-related decline in GFR because of a concomitant age-related decline in muscle mass that reduces creatinine generation. Thus, it is difficult to use the serum creatinine concentration alone to estimate the level of kidney function, to detect earlier stages of chronic kidney disease, or to adjust drug dosages.
Clinical laboratories should report an estimate of GFR using a prediction equation in addition to reporting the serum creatinine measurement (level C recommendation).
Use of GFR (rather than serum creatinine measurement) to characterize kidney function is a critical element in the Working Group's strategy for improving care of patients with chronic kidney disease. Clinical laboratories can help to implement GFR estimates. Laboratories should calibrate their serum creatinine results to the same level as the laboratory in which the MDRD prediction equation was developed. Clinical laboratories will need to work with physicians and administrators to develop reporting systems that meet their needs. In the interim, a GFR calculator with the abbreviated MDRD study equation is available on the NKF Web site (www.kdoqi.org).
Autoanalyzer manufacturers and clinical laboratories should calibrate serum creatinine assays using an international standard (level A recommendation).
Differences among clinical laboratories in calibration of serum creatinine assays can account for errors in GFR estimates as high as 20%, which are especially important in individuals with near-normal serum creatinine concentration (39, 40). Failure to adjust for differences in calibration accounts for some of the current controversy regarding the performance of prediction equations in selected clinical populations (60) or the prevalence of reduced GFR in the general population (61-63).
Measurement of creatinine clearance by using timed (for example, 24-hour) urine collections does not provide more accurate estimates of GFR than do prediction equations (level A recommendation).
Measurement of creatinine clearance requires collection of a timed urine sample, which is inconvenient and frequently inaccurate. In the MDRD study, predicted GFR provided a more accurate estimate of GFR (as measured by urinary clearance of 125I-iothalamate) than measured creatinine clearance (34). Thus, the guidelines recommend obtaining 24-hour urine collections only for the special clinical circumstances discussed earlier.
Guideline 5. Assessment of Proteinuria
Persistently increased protein excretion is usually a marker of kidney damage.
Under most circumstances, untimed urine samples should be used to detect and monitor proteinuria (level A recommendation).
It is usually not necessary to obtain a timed urine collection (overnight or 24-hour) to measure proteinuria (level A recommendation).
Normal persons usually excrete very small amounts of protein in the urine. Increased excretion of albumin is a sensitive marker for chronic kidney disease due to diabetes, glomerular disease, and hypertension. Increased excretion of low-molecular-weight globulins is a sensitive marker for some types of tubulointerstitial disease.
In this guideline, the term proteinuria refers to increased urinary excretion of albumin or any other specific protein; albuminuria refers specifically to increased urinary excretion of albumin. Microalbuminuria refers to albumin excretion that exceeds the normal range but is below the minimum level for detection by tests for total protein.
The American Diabetes Association (9) and an earlier position paper by the NKF (8) recommend assessment of proteinuria to detect chronic kidney disease. The ratio of protein or albumin to creatinine in an untimed urine specimen has replaced protein excretion in a 24-hour collection as the preferred method for measuring proteinuria. Using a ratio corrects for variations in urinary protein concentration due to hydration and is far more convenient than timed urine collections. The ratio of protein or albumin to creatinine in an untimed urine sample is an accurate estimate of the protein or albumin excretion rate (41-45).
A proposed algorithm for testing for proteinuria distinguishes persons at increased risk for chronic kidney disease from asymptomatic, healthy persons (Figure 2). A sample of urine from the first voiding after awakening is preferred, but a random specimen is acceptable. The algorithm for adults at increased risk (Figure 2, right) begins with testing of a random untimed urine sample with an albumin-specific dipstick. Patients with a positive result on a disptick test for albuminuria (1+ or greater) should undergo confirmation of proteinuria by measuring the albumin–creatinine ratio on an untimed urine sample within 3 months. Alternatively, testing could begin with an untimed urine sample for the albumin–creatinine ratio. Patients with two or more positive results on quantitative tests temporally spaced over 3 months have persistent proteinuria and should undergo further evaluation for chronic kidney disease (as stated in Guideline 2).
Figure 2. Evaluation of proteinuria in patients not known to have kidney disease.
The Work Group recommends a cutoff value for an albumin–creatinine ratio greater than 30 mg/g in men and women. Some studies suggest sex-specific cutoff values for an albumin–creatinine ratio of greater than 17 mg/g in men or greater than 25 mg/g in women (10, 11). Reprinted with permission from reference 7.
The standard dipstick for protein and the untimed urine measurements for total proteincreatinine ratio are also useful for detecting proteinuria in adults not at increased risk for developing chronic kidney disease (Figure 2, left). However, adults at increased risk for chronic kidney disease with a negative result for protein on a standard dipstick test, especially those with diabetes, should undergo testing with either an albumin-specific dipstick or an untimed urine measurement for the albumin–creatinine ratio. It was the opinion of the Work Group that monitoring proteinuria in adults with chronic kidney disease should use the albumin–creatinine ratio or total proteincreatinine ratio if the albumin–creatinine ratio is high (>500 to 1000 mg/g). The guidelines review causes of false-positive and false-negative results in measuring urinary albumin or total protein.
Summary
Chronic kidney disease affects approximately 11% of the U.S. adult population (20 million people from 1988 to 1994). The prevalence of earlier stages of disease (10.8%) is more than 100 times greater than the prevalence of kidney failure (0.1%). Adverse outcomes of chronic kidney disease, including loss of kidney function and development of kidney failure and CVD, can often be prevented or delayed through early detection and treatment. In particular, physicians should consider using interventions to slow the progression of kidney disease in all patients with chronic kidney disease and should place patients with chronic kidney disease in the highest-risk group for CVD risk factor reduction and other treatments for CVD. Each patient with chronic kidney disease should have a clinical action plan, based on the stage of disease, as defined by the NKF K/DOQI guidelines. All patients with chronic kidney disease and persons at increased risk for chronic kidney disease should undergo measurement of proteinuria (as a marker of kidney damage) and GFR. Quantitative assessment of proteinuria is useful for detection, differential diagnosis, prognosis, and treatment of chronic kidney disease. The ratio of concentration of albumin to creatinine in untimed urine samples should be used to detect and monitor proteinuria. Glomerular filtration rate, as estimated by prediction equations based on serum creatinine concentration, age, race, sex, and body size, is useful for detecting chronic kidney disease, classifying its severity, estimating progression, managing complications, and deciding on referral to a nephrologist.
Appendix 1: Grading the Strength of Recommendations
Because of the nature of the questions addressed by the Work Group, evidence for the NKF K/DOQI guidelines on chronic kidney disease is based primarily on observational studies and is not readily graded according to the usual recommendations, such as those of the U.S. Preventive Services Task Force (USPSTF) (59).
The guidelines reference 667 articles, of which 367 are original articles tabulated and graded according to four dimensions: study size, applicability (generalizability) depending on study participants, results, and methodologic quality depending on type of study. In the original publication, strength of evidence for each link in the chain of reasoning was rated in the rationale accompanying each guideline (64). The body of evidence was classified according to whether it was based on an analysis of individual patient data from a single, large, generalizable study of high methodologic quality, such as the analyses of the NHANES III database; a compilation of original articles; a review of reviews and other selected original articles; or opinion. All statements represented the consensus of the Work Group, were reviewed by external reviewers, and were approved by the NKF K/DOQI Advisory Board.
In this paper, each guideline statement is classified according to a new classification recently adopted by the NKF K/DOQI Advisory Board (47). In this classification, each recommendation and the strength of evidence underlying each recommendation are rated separately. Ratings of recommendations are similar to that of the USPSTF (Table 2), but several key features of the rating of the strength of evidence differ from that of the USPSTF (Appendix Table 2). First, the classification of strength of evidence based on methodologic quality and applicability is explicitly identified. Second, high-level methodologic quality can be assigned to observational studies as well as to clinical trials. Third, applicability takes into account whether the outcomes measures are hard clinical outcomes or surrogates and whether the study population is the target population (in this case, patients with chronic kidney disease) or a population other than the target population. This latter distinction is particularly important in the study of CVD, in which extrapolation from studies in the general population contributes substantially to the body of evidence.
Appendix 2: Members of the K/DOQI Work Group, the Evidence Review Team, and a K/DOQI Ad Hoc Group
In addition to the authors, members of the Work Group include Kline Bolton, MD; Kathy Schiro Harvey, MS, RD, CSR; T. Alp Ikizler, MD; Cynda Ann Johnson, MD, MBA; Paul L. Kimmel, MD; John Kusek, PhD; Kenneth L. Minaker, MD; Robert Nelson, MD, PhD; Helmut Rennke, MD; Beth Witten, MSW; Susan Furth, MD, PhD; Kevin V. Lemley, MD, PhD; Ronald J. Portman, MD; and George Schwartz, MD. In addition to the authors, members of the Evidence Review Team include Tauqeer Karim, MD; Lara Rayan, MD; Inas Al-Massry, MD; Priscella Chew, MPH; Brad C. Astor, PhD, MPH; and Deirdre DeVine, MLitt.
Members of the K/DOQI Ad Hoc Group to develop the K/DOQI classification of strength of recommendations and evidence include Bertram L. Kasiske, MD; Katrin L. Uhlig, MD; Earl P. Steinberg, MD; Adeera Levin, MD; Nathan Levin, MD; Garabed Eknoyan, MD; Andrew S. Levey, MD; and Joseph Lau, MD.
References
1.
United States Renal Data System. Excerpts from the 2000 U.S. Renal Data System Annual Data Report: Atlas of End Stage Renal Disease in the United States. Am J Kidney Dis. 2000;36:S1-S279.
2.
Remuzzi G, Ruggenenti P, Perico N. Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition. Ann Intern Med. 2002;136:604-15. [PMID: 11955029]
3.
McClellan WM, Knight DF, Karp H, Brown WW. Early detection and treatment of renal disease in hospitalized diabetic and hypertensive patients: important differences between practice and published guidelines. Am J Kidney Dis. 1997;29:368-75. [PMID: 9041212]
4.
Obrador GT, Ruthazer R, Arora P, Kausz AT, Pereira BJ. Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States. J Am Soc Nephrol. 1999;10:1793-800. [PMID: 10446948]
5.
Coresh J, Wei GL, McQuillan G, Brancati FL, Levey AS, Jones C, . Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2001;161:1207-16. [PMID: 11343443]
6.
Hsu CY, Chertow GM. Chronic renal confusion: insufficiency, failure, dysfunction, or disease. Am J Kidney Dis. 2000;36:415-8. [PMID: 10922323]
7.
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002;39:S1-246. [PMID: 11904577]
8.
Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis. 1999;33:1004-10. [PMID: 10213663]
9.
Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002;25:213-29. [PMID: 11772918]
10.
Warram JH, Gearin G, Laffel L, Krolewski AS. Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. J Am Soc Nephrol. 1996;7:930-7. [PMID: 8793803]
11.
Jacobs DR Jr, Murtaugh MA, Steffes M, Yu X, Roseman J, Goetz FC. Gender- and race-specific determination of albumin excretion rate using albumin-to-creatinine ratio in single, untimed urine specimens: the Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol. 2002;155:1114-9. [PMID: 12048225]
12.
Smith HW. Comparative physiology of the kidney. In: Smith HW, eds. The Kidney: Structure and Function in Health and Disease. New York: Oxford Univ Pr; 1951:520-74.
13.
Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950;29:496-507.
14.
Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc. 1985;33:278-85. [PMID: 3989190]
15.
Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol. 1976;31:155-63. [PMID: 1249404]
16.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1-12. [PMID: 12500213]
17.
Obrador GT, Arora P, Kausz AT, Ruthazer R, Pereira BJ, Levey AS. Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. Kidney Int. 1999;56:2227-35. [PMID: 10594799]
18.
Obrador GT, Pereira BJ. Early referral to the nephrologist and timely initiation of renal replacement therapy: a paradigm shift in the management of patients with chronic renal failure. Am J Kidney Dis. 1998;31:398-417. [PMID: 9506677]
19.
Ismail N, Neyra R, Hakim R. The medical and economical advantages of early referral of chronic renal failure patients to renal specialists [Editorial]. Nephrol Dial Transplant. 1998;13:246-50. [PMID: 9509429]
20.
Kinchen KS, Sadler J, Fink N, Brookmeyer R, Klag MJ, Levey AS, . The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med. 2002;137:479-86. [PMID: 12230348]
21.
Avorn J, Bohn RL, Levy E, Levin R, Owen WF Jr, Winkelmayer WC, . Nephrologist care and mortality in patients with chronic renal insufficiency. Arch Intern Med. 2002;162:2002-6. [PMID: 12230424]
22.
Levinsky NG. Specialist evaluation in chronic kidney disease: too little, too late [Editorial]. Ann Intern Med. 2002;137:542-3. [PMID: 12230357]
23.
Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, . Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care. 1998;21:518-24. [PMID: 9571335]
24.
Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, . Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-13. [PMID: 7875754]
25.
Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, . Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778-99. [PMID: 9588729]
26.
Profiles of General Demographic Characteristics: 2000 Census of Population and Housing, United States. U.S. Census Bureau. Washington, DC: U.S. Government Printing Office; 2001.
27.
Day JC. Population Projections of the United States by Age, Sex, Race, and Hispanic Origin: 1995 to 2050. U.S. Census Bureau, Current Population Reports, P25-1130. Washington, DC: U.S. Government Printing Office; 1996.
28.
Elixhauser A, Klemstine K, Steiner C, Bierman AS. Procedures in U.S. Hospitals, 1997. HCUP Fact Book No. 2. Rockville, MD: Agency for Healthcare Research and Quality; 2001.
29.
HCUPnet. Healthcare Cost and Utilization Project. Accessed at www.ahrq.gov/data/hcup/hcupnet.htm on 19 May 2003.
30.
McGoldrick MD, Bailie GR. Nonnarcotic analgesics: prevalence and estimated economic impact of toxicities. Ann Pharmacother. 1997;31:221-7. [PMID: 9034424]
31.
Fries JE. NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal. J Rheumatol. 1991;18:6-10.
32.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, . The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 2003;289:2560-71. [PMID: 12748199]
33.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41. [PMID: 1244564]
34.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-70. [PMID: 10075613]
35.
Levey AS, Greene T, Kusek JW, Beck GJ, Group MS. A simplified equation to predict glomerular filtration rate from serum creatinine [Abstract]. J Am Soc Nephrol. 2000;11:A0828.
36.
Lewis J, Agodoa L, Cheek D, Greene T, Middleton J, O'Connor D, . Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate. Am J Kidney Dis. 2001;38:744-53. [PMID: 11576877]
37.
Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985;28:830-8. [PMID: 2418254]
38.
Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem. 1992;38:1933-53. [PMID: 1394976]
39.
Ross JW, Miller WG, Myers GL, Praestgaard J. The accuracy of laboratory measurements in clinical chemistry: a study of 11 routine chemistry analytes in the College of American Pathologists Chemistry Survey with fresh frozen serum, definitive methods, and reference methods. Arch Pathol Lab Med. 1998;122:587-608. [PMID: 9674541]
40.
Coresh J, Astor BC, McQuillan G, Kusek J, Greene T, Van Lente F, . Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis. 2002;39:920-9. [PMID: 11979335]
41.
Schwab SJ, Christensen RL, Dougherty K, Klahr S. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med. 1987;147:943-4. [PMID: 3555378]
42.
Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309:1543-6. [PMID: 6656849]
43.
Rodby RA, Rohde RD, Sharon Z, Pohl MA, Bain RP, Lewis EJ. The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. The Collaborative Study Group. Am J Kidney Dis. 1995;26:904-9. [PMID: 7503064]
44.
Zelmanovitz T, Gross JL, Oliveira JR, Paggi A, Tatsch M, Azevedo MJ. The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care. 1997;20:516-9. [PMID: 9096972]
45.
Nathan DM, Rosenbaum C, Protasowicki VD. Single-void urine samples can be used to estimate quantitative microalbuminuria. Diabetes Care. 1987;10:414-8. [PMID: 3622198]
46.
Woolf SH. Manual for Clinical Practice Guideline Development. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1991.
47.
National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis. 2003;41 Suppl 3 S1-S91.
48.
27th Bethesda Conference. Matching the Intensity of Risk Factor Management with the Hazard for Coronary Disease Events. September 14-15, 1995. J Am Coll Cardiol. 1996;27:957-1047. [PMID: 8609361]
49.
Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, . Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32:853-906. [PMID: 9820460]
50.
Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis. 2000;35:S117-31. [PMID: 10766010]
51.
Fried LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, . Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. JAMA. 1998;279:585-92. [PMID: 9486752]
52.
Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA, Tracy RP, . Cardiovascular disease risk status in elderly persons with renal insufficiency. Kidney Int. 2002;62:997-1004. [PMID: 12164883]
53.
Manjunath G, Tighiouart H, Coresh J, Macleod B, Salem DN, Griffith JL, . Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int. 2003;63:1121-1129. [PMID: 12631096]
54.
Aronoff GR, Berns JS, Brier ME, Golper TA, Morrison G, Singer I, . Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. Philadelphia: American College of Physicians; 2002.
55.
Hsu CY, Chertow GM, Curhan GC. Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency. Kidney Int. 2002;61:1567-76. [PMID: 11967006]
56.
Coladonato J, Klassen P, Owen WF Jr. Perception versus reality of the burden of chronic kidney disease in the United States [Editorial]. J Am Soc Nephrol. 2002;13:1686-8. [PMID: 12040000]
57.
Remuzzi G, Schieppati A, Ruggenenti P. Clinical practice. Nephropathy in patients with type 2 diabetes. N Engl J Med. 2002;346:1145-51. [PMID: 11948275]
58.
Levey AS. Clinical practice. Nondiabetic kidney disease. N Engl J Med. 2002;347:1505-11. [PMID: 12421894]
59.
Guide to Clinical Preventive Services, 2nd ed, 1996. Report of the U.S. Preventive Services Task Force. Alexandria, VA: International Medical Publishing; 1996. Accessed at www.ahrq.gov/clinic/cpsix.htm on 19 May 2003.
60.
Bostom AG, Kronenberg F, Ritz E. Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. J Am Soc Nephrol. 2002;13:2140-4. [PMID: 12138147]
61.
Clase CM, Garg AX, Kiberd BA. Prevalence of low glomerular filtration rate in nondiabetic Americans: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol. 2002;13:1338-49. [PMID: 11961022]
62.
Coresh J, Eknoyan G, Levey AS. Estimating the prevalence of low glomerular filtration rate requires attention to the creatinine assay calibration [Letter]. J Am Soc Nephrol. 2002; 13:2811-2; author reply 2812-6. [ 12397055]
63.
McClellan W. As to diseases, make a habit of two things to help, or at least do no harm. J Am Soc Nephrol. 2002;13:2817-9. [PMID: 12397056]
64.
Steinberg EP, Eknoyan G, Levin NW, Eschbach JW, Golper TA, Owen WF, . Methods used to evaluate the quality of evidence underlying the National Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: description, findings, and implications. Am J Kidney Dis. 2000;36:1-11. [PMID: 10873866]
Information & Authors
Information
Published In
Annals of Internal Medicine
Volume 139 • Number 2 • 15 July 2003
Pages: 137 - 147
History
Published online: 15 July 2003
Published in issue: 15 July 2003
Keywords
Copyright
© 2003 American College of Physicians.
Authors
Metrics & Citations
Metrics
Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
Download article citation data for:
National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Ann Intern Med.2003;139:137-147. [Epub 15 July 2003]. doi:10.7326/0003-4819-139-2-200307150-00013
National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Ann Intern Med.2003;139:137-147. [Epub 15 July 2003]. doi:10.7326/0003-4819-139-2-200307150-00013
View More
Login Options:
Purchase
You will be redirected to acponline.org to sign-in to Annals to complete your purchase.
Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.
Create your Free Account
You will be redirected to acponline.org to create an account that will provide access to Annals.
Comments
0 Comments