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HE WORK GROUP expanded on selected clinical topics that were not included in the scope of the review of evidence, but which nonetheless are relevant to the implementation of a clinical action plan for patients with chronic kidney disease. The clinical approach outlined below is based on guidelines contained within this report; the reader is cautioned that many of the recommendations in this section have not been adequately studied and therefore represent the opinion of members of the Work Group.

DETECTION OF CHRONIC KIDNEY DISEASE

Assessment of Risk All individuals should be evaluated during health encounters to determine whether they are at increased risk of having or of developing chronic kidney disease. Guideline 3 lists risk factors for susceptibility to and initiation of chronic kidney disease (CKD risk factors). Ascertainment of risk factors through assessment of sociodemographic characteristics, review of past medical history and family history, and measurement of blood pressure would enable the clinician to determine whether a patient is at increased risk. Patients who are found to be at increased risk should be evaluated further. Clinical Evaluation of Patients at Increased Risk Clinical evaluation of patients at increased risk of chronic kidney disease includes assessment of markers of kidney damage, estimated GFR, and blood pressure (Table 138). Unfortunately, these markers do not detect all types of chronic kidney damage. Thus, it may be difcult to detect the onset of some types of chronic kidney disease until GFR is decreased, for example, hypertensive nephrosclerosis and noninammatory tubulointerstitial diseases.

Testing for Proteinuria The algorithms recommended by NKF PARADE distinguish between individuals at increased for chronic kidney disease versus asymptomatic, healthy individuals. These algorithms have been modied by the Work Group with input from members of the PARADE Work Group (Fig 57). The algorithm for adults and children at increased risk (right side) begins with testing of a random spot urine sample with an albuminspecic dipstick. Alternatively, testing could begin with a spot urine sample for albumin-tocreatine ratio. The algorithm for asymptomatic healthy individuals (left side) does not require testing specically for albumin. This algorithim is useful for children without diabetes, in whom universal screening is recommended. Universal screening is not currently recommended for adults.
DIFFERENTIAL DIAGNOSIS OF CHRONIC KIDNEY DISEASE

Clinical Presentation Table 139 shows the relationship between stages of chronic kidney disease and clinical presentations. During the stage At Increased Risk and Stage 1 (Kidney Damage), specic

2002 by the National Kidney Foundation, Inc. 0272-6386/02/3902-0110$35.00/0 doi:10.1053/ajkd.2002.30948

American Journal of Kidney Diseases, Vol 39, No 2, Suppl 1 (February), 2002: pp S215-S222

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Fig 57. Evaluation of proteinuria in patients not known to have kidney disease. Modied from NKF PARADE. NKF PARADE does not use gender-specic denitions for abnormal albuminto-creatinine ratio. Modied with permission.6

diseases are associated with specic risk factors and are manifested by specic clinical presentations, although markers for each diagnosis have not been discovered. During Stages 2 through 4 (Decreased GFR) and Stage 5 (Kidney Failure), different diseases may have similar clinical presentations, although markers of kidney damage may persist and provide clues to diagnosis.

Simplied Classication of Chronic Kidney Disease Diseases of the kidney are classied according to etiology and pathology. A simplied classication is given in Table 140. Denitive diagnosis often requires a biopsy of the kidney, which is associated with a risk, albeit usually small, of serious complications. There-

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fore, kidney biopsy is usually reserved for selected patients in whom a denitive diagnosis can be made only by biopsy and in whom a denitive diagnosis would result in a change in either treatment or prognosis. In most patients, diagnosis is assigned based on recognition of well-dened clinical presentations and causal factors based on clinical evaluation. Clinical Evaluation Chronic kidney disease is usually silent. Therefore, clinical assessment relies heavily on laboratory evaluation and diagnostic imaging. Nonetheless, a careful history will often reveal clues to the correct diagnosis (Table 141). Blood pressure measurement is essential, but other elements of the physical examination are usually not helpful, except to assess comorbid conditions and compli-

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cations of decreased GFR. A number of drugs can be associated with chronic kidney damage, so a thorough review of the medication list (including prescribed medications, over-thecounter medications, nontraditional medications, vitamins and supplements, herbs, and drugs of abuse) is vital. Moreover, medications will require adjustment in dosage or discontinuation based on the level of GFR. Laboratory Evaluation Laboratory evaluation in all patients with chronic kidney disease should be performed (Table 142). Guideline 6 provides a guide to interpretation of proteinuria and urine sediment abnormalities and ndings on imaging studies as markers of kidney damage and a denition of clinical presentations. Based on these measurements, the clinician can usually dene the clinical presentation, thereby narrowing the differential diagnosis and guiding further diagnostic evaluation, decisions about kidney biopsy, and, often, decisions about treatment and prognosis with no need for kidney biopsy. Relationships Among Type and Stage of Kidney Disease and Clinical Presentations Tables 143, 144, and 145 show the relationships between stage of kidney disease and clinical features for diabetic kidney disease, nondiabetic kidney diseases, and diseases in the kidney transplant. Utility of Proteinuria in Diagnosis, Prognosis, and Treatment Proteinuria is a key nding in the differential diagnosis of chronic kidney disease. Proteinuria is a marker of damage in diabetic kidney disease

(Table 143), in glomerular diseases occurring in the native kidney (Table 144), and in transplant glomerular disease and recurrent glomerular disease in the transplant (Table 145). In these diseases, the magnitude of proteinuria is usually 1,000 mg/g (except in early diabetic kidney disease), and may approach nephrotic range (spot urine protein-to-creatinine ratio 3,000 mg/g). On the other hand, proteinuria is usually mild or absent in vascular diseases, tubulointerstitial diseases, and cystic diseases in the native kidney and in rejection and drug toxicity due to cyclosporine or tacrolimus in the transplant. Proteinuria is also a key prognostic nding. It is well-known that nephrotic range proteinuria is associated with a wide range of complications, including hypoalbuminemia, edema, hyperlipidemia, and hypercoagulable state; faster progression of kidney disease; and premature cardiovascular disease. However, it is now known that elevated urine protein excretion below the nephrotic range is also associated with faster progression of kidney disease and development of cardiovascular disease. Furthermore, the reduction in proteinuria is correlated with a subsequent slower loss of kidney function. Finally, proteinuria is also a guide to therapy. The benet of antihypertensive therapy, especially with angiotensin-converting enzyme inhibitors, to slow the progression of kidney disease is greater in patients with higher levels of protein-

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uria compared to patients with lower levels of proteinuria. In summary, proteinuria is not only a marker of kidney damage, it is also a guide to the differential diagnosis, prognosis, and therapy of chronic kidney disease.
ESTIMATING AND SLOWING PROGRESSION OF CHRONIC KIDNEY DISEASE IN ADULTS

Treatments to slow the progression of chronic kidney disease in adults in are shown in Table 146.
CARDIOVASCULAR DISEASE RISK ASSESSMENT AND REDUCTION

Guideline 13 reviews estimating decline in GFR and treatments to slow the GFR decline in adults. In general, GFR should be estimated from serum creatinine at least yearly in patients with chronic kidney disease and more often in patients with: GFR 60 mL/min/1.73 m2 Fast GFR decline in the past ( 4 mL/min per year) Risk factors for faster progression Ongoing treatment to slow progression Exposure to risk factors for acute GFR decline.

Guideline 15 concludes that patients with chronic kidney disease have a high risk of adverse outcomes of cardiovascular disease and should be considered in the highest-risk group for cardiovascular disease risk reduction. However, few patients with chronic kidney disease have been included in population-based epidemiologic studies of cardiovascular disease or long-term randomized clinical trials. The NKF Task Force on Cardiovascular Disease in Chronic Renal Disease recommended risk factor reduction for traditional risk factors based largely on extrapolation from the general population and evidence of safety and efcacy of interventions on risk factor levels in chronic kidney disease. It was the opinion of the CVD Task Force and the CKD Work Group that extrapolation from the

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general population to patients with chronic kidney disease is most appropriate for patients with higher levels of GFR (Stages 1 through 4) and less (but possibly still) appropriate for patients with kidney failure (Stage 5). A partial list of traditional cardiovascular disease risk factors and risk factor reduction strategies that are potentially safe and effective for patients with chronic kidney disease is shown in Table 147.
CLINICAL EVALUATION OF ADULTS WITH GFR <60 mL/min/1.73 m2 (CKD STAGES 35)

of chronic kidney disease in adults. Many complications begin to occur at GFR 60 mL/min/ 1.73 m2. Table 148 lists additional clinical evaluations (in addition to the ones listed in Tables 105 and 142) that should be performed in adults with GFR 60 mL/min/ 1.73 m2.
DECREASED GFR AND CHRONIC KIDNEY DISEASE IN THE ELDERLY

Guidelines 7 through 12 show the associations between level of GFR and complications

Guideline 1 denes a decrease in GFR of 60 to 89 mL/min/1.73 m2 as chronic kidney disease only if accompanied by a marker of kidney damage. GFR declines with age in normal individuals; therefore, it can be difcult to distinguish age-related decrease in GFR from chronic kidney disease in the elderly. Other causes of chronically decreased GFR in normal individuals without chronic kidney disease include a habitually low protein intake and unilateral nephrectomy. Data from NHANES III suggest that almost 75% of individuals 70 years old may have GFR 90 mL/min/1.73 m2, and almost 25% may have GFR 60 mL/min/1.73 m2. The fraction of elderly individuals with decreased GFR who truly have chronic kidney disease has not been systematically studied. Moreover, the health outcomes of decreased GFR in the elderly, with or without chronic kidney disease, are also not known. Clinical evaluation of elderly individuals with GFR of 60 to 89 mL/min/1.73 m2 should include an assessment for chronic kidney disease (Table 149). Additional items for clinical evaluation of

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individuals with GFR 60 mL/min/1.73 m2 are listed in Table 148. It is the opinion of the members of the Work Group that clinical interventions for the elderly with chronic kidney disease should be based on diagnosis (as described above), severity of kidney function impairment, and stratication of risk for progression of kidney disease and cardiovascular disease. There is a spectrum of risk for adverse outcomes. Patients with mild decreased GFR, low risk for progressive decline in GFR, and low risk for

cardiovascular disease have a good prognosis and may require only adjustment of the dosage of drugs that are excreted by the kidney, monitoring of blood pressure, avoidance of drugs and procedures with risk for acute kidney failure, and life-style modications to reduce the risk of cardiovascular disease. Consultation with a nephrologist may be necessary to establish the diagnosis and treatment of the type of kidney disease. Kidney function should be monitored at least yearly. Patients with moderately or severely decreased GFR or risk factors for faster decline in GFR or cardiovascular disease have a worse prognosis. In addition to the interventions mentioned above, they require assessment for complications of decreased GFR and dietary and pharmacologic therapy directed at slowing the progression of kidney disease and ameliorating cardiovascular risk factor levels. Consultation and/or co-management with a kidney disease

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care team is advisable during Stage 3, and referral to a nephrologist in Stage 4 is recommended. Kidney function may need to be monitored four

times per year or more. A multidisciplinary team approach may be necessary to implement and coordinate care.