National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification

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. Table 1. Guidelines, Recommendations, Ratings, and Key References 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). Table 2. National Kidney Foundation Kidney Disease Outcomes Quality Initiative Rating of the Strength of Recommendations 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. black dark gray light gray white GFR Table 3. Risk Factors for Chronic Kidney Disease and Its Outcomes 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 albumincreatinine 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,