Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration ra

Author: Cynda Ann Johnson, Garabed Eknoyan
Date: Sept 15, 2004

In February 2002, the Kidney Disease Outcome Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) published clinical practice guidelines for chronic kidney disease (1,2) that were based on a systematic literature review. A uniform format for summarizing strength of evidence was developed based on an evaluation of study size, applicability, results, and methodologic quality. Guideline statements were prepared from the analysis of the review, with each rationale statement graded according to the supporting level of evidence (Table 1). (1) The evidence grading system differs from the system used in American Family Physician (AFP): only AFP's evidence level C (consensus/expert opinion) compares with the NKF grade O (opinion).

Part I (3) of this two-part article reviewed the guidelines on definition and stages of chronic kidney disease, evaluation and treatment, and risk factor identification. Chronic kidney disease is defined by kidney damage (often manifested by proteinuria) or a decreased glomerular filtration rate (GFR) for three or more months. The degree of decrease in the GFR provides the basis for straightforward classification of chronic kidney disease by stages (see Table 3 in part 1 (3)). Treatment should focus on slowing disease progression and preventing complications, especially the development of cardiovascular disease. To identify chronic kidney disease and intervene early in its course, physicians should test for proteinuria and estimate GFR in at-risk patients. Part II summarizes guidelines for using tests to evaluate patients with suspected or known chronic kidney disease.

[TABLE 3 OMITTED]

Guideline 4: Estimation of GFR

The GFR is the best overall indicator of the level of kidney function. (NKF grades S, C, and R). (1) The GFR should be estimated using a prediction equation that takes into account the serum creatinine level and some or all of these variables: age, sex, race, and body size. The Modification of Diet in Renal Disease (MDRD) study equation and the Cockcroft-Gault equation provide useful estimates of the GFR in adult patients (Table 2). (4-6) The NKF guideline (1,2) notes that the serum creatinine concentration alone is not optimal for assessing the level of kidney function.

In addition to reporting the serum creatinine measurement, clinical laboratories should report the estimated GFR as determined by a prediction equation. The NKF guidelines (1,2) also recommend that autoanalyzer manufacturers and clinical laboratories calibrate serum creatinine assays using an international standard.

In most cases, measurement of creatinine clearance using a timed (e.g., 24-hour) urine collection for assessment of the GFR is not more reliable than estimation using a prediction equation. (1,2) However, a 24-hour urine sample provides information that is useful for estimating GFR in patients with exceptional dietary intake (vegetarian diet, creatine supplementation) or muscle mass (amputation, malnutrition, muscle wasting), assessing diet and nutritional status, and determining the need to start dialysis.

In clinical practice, GFR usually is estimated from the creatinine clearance or the serum creatinine concentration. Measurement of creatinine clearance requires the collection of a timed urine sample, which is inconvenient for the patient as well as frequently inaccurate. The serum creatinine concentration is affected by factors other than the GFR, including creatinine secretion, generation, and extrarenal excretion. (7,8) Thus, there is a relatively wide range for serum creatinine levels in normal persons, and the GFR must decline to about one half of the normal level before the serum creatinine concentration rises above the upper limit of normal. This situation regarding a declining GFR with "normal" creatinine is especially important in elderly patients, in whom the age-related decline in GFR is not reflected by an increase in the serum creatinine level because of a concomitant age-related decline in creatinine production.

Table 3 (1) shows the range of serum creatinine values corresponding with an estimated GFR of 60 mL per minute per 1.73 m2, depending on age, sex, and race. Note that the NKF definition of chronic kidney disease includes a GFR level below 60 mL per minute per 1.73 [m.sup.2] for three months or more (see Table 2 in part I (3)). The data in Table 3 demonstrate that minor elevations of the serum creatinine concentration may represent a substantial reduction in the GFR. Thus, with use of only the serum creatinine as the measure of kidney function, it is difficult to estimate the level of kidney function and detect earlier stages of chronic kidney disease.

The estimate of GFR from the serum creatinine concentration can be improved by using a prediction equation that also takes into account the patient's age, sex, race, and body size (e.g., the equations shown in Table 2 (4-6)). In patients with a GFR below about 90 mL per minute per 1.73 [m.sup.2], the abbreviated MDRD study equation appears to be more accurate and precise than the Cockcroft-Gault equation, but is more complicated to compute.

GFR calculators for use of the abbreviated MDRD study equation and the Cockcroft-Gault equation are available on the NKF Web site (http://www.kidney.org/kls/professionals/ gfr_calculator.cfm). These equations can be programmed or imported into laboratory systems, personal computers, and hand-held calculators. As part of the implementation of the NKF guidelines (1,2) and in cooperation with the National Institutes of Health (NIH), efforts are underway to have clinical laboratories report GFR in conjunction with the serum creatinine measurement.

Guideline 4 provides useful information for family physicians. Evidence is convincing that 24-hour urine collections for creatinine are not superior to prediction equations that are based on the serum creatinine level and other patient characteristics. Thus, it is possible to perform a straightforward serum collection, rather than subject a patient to the inconvenience of a 24-hour urine collection that then must be returned to the laboratory. Furthermore, a urine collection performed over 24 hours may be incomplete, even if the volume appears to be reasonable, leading to incorrect values for calculated creatinine clearance and possibly to inappropriate decisions about patient care. On the other hand, if the volume of urine collected over 24 hours obviously is smaller than reasonable, the laboratory value will be dismissed, resulting in wasted time and effort.

It is unlikely that the GFR will become the standard measure used by physicians

until clinical laboratories begin reporting estimated GFR values. If GFR values are to be computed and reported, the laboratory request will require patient information that not always is reported (e.g., weight, race); however, if these additional data become an expected part of the laboratory request, physicians will not have to calculate GFRs. Patients can be given their GFR "number" more dependably, and the GFR value will become a permanent part of the laboratory record.

Cooperation with the local clinical laboratory is important in another way. Differences among clinical laboratories in the calibration of serum creatinine assays can result in an error rate as high as 20 percent in GFR estimates. Consideration of differences in the calibration of creatinine assays is especially important in patients with nearly normal serum creatinine concentrations. Estimation of GFR using a prediction equation should take into account differences in creatinine calibration between the local laboratory and the laboratory where the prediction equation was developed. The National Kidney Disease Education Program, operating under the NIH, is working with clinical laboratories and autoanalyzer manufacturers to calibrate serum creatinine assays using an international standard and to build GFR reporting into the systems.

The practical implication of having the GFR readily available goes beyond the issue of classification of chronic disease: it allows adjustment of drug doses to the level of kidney function.

Guideline 5: Assessment of Proteinuria

Urine normally contains small amounts of protein. However, a persistent increase in protein excretion usually is a sign of kidney damage. The type of protein, such as low-molecular-weight globulins or albumin, depends on the type of kidney disease. Increased excretion of low-molecular-weight globulins is a sensitive marker of some types of tubulointerstitial disease. Increased excretion of albumin is a sensitive marker of chronic kidney disease resulting from diabetes mellitus, glomerular disease, or hypertension.

This article exemplifies the AAFP Annual Clinical Focus on caring for America's aging population.

TABLE 2Equations for Predicting GFR in AdultsBased on Serum Creatinine Concentration *Abbreviated MDRD study equation:GFR (mL per minute per 1.73 [m.sup.2]) = 186 x[([S.sub.Cr]).sup.-1.154] x [(Age).sup.-0.203]x (0.742 if female) x (1.210 if black)Cockcroft-Gault equation:[C.sub.Cr] (mL per minute) = (140 - age) x weight/72x [S.sub.Cr] x (0.85, if female)GFR = glomerular filtration rate; MDRD = Modification of Diet inRenal Disease; [S.sub.Cr] = serum creatinine concentration;[C.sub.Cr] = creatinine clearance.*--For each equation, [S.sub.Cr] is in milligrams per deciliter,age is in years, and weight is in kilograms.Information from references 4, 5, and 6.Strength of RecommendationKey clinical recommendations Label ReferencesGFR should be estimated using prediction C 1,2equations that take into account theserum creatinine concentration and someor all of these variables: age, sex,race, and body size.In most circumstances, untimed (spot) C 1,2urine samples, rather than 24-hoururine collections, should be used todetect and monitor proteinuria.If a urine dipstick test is positive C 1,2(1+ or greater), proteinuria should beconfirmed by a quantitative measurement(protein-to-creatinine ratio oralbumin-to-creatinine ratio) withinthree months.GFR =glomerular filtration rate.

REFERENCES

(1.) National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1-266.

(2.) National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Accessed online May 19, 2004, at: http://www.kidney.org/professionals/kdoqi/ guidelines_ckd/toc.htm.

(3.) Johnson CA, Levey AS, Coresh J, Levin A, Lau J, Eknoyan G. Clinical practice guidelines for chronic kidney disease in adults: Part I. Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician 2004;70:000-00.

(4.) 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.

(5.) Levey AS, Greene T, Kusek JW, Beck GJ. A simplified equation to predict glomerular filtration rate from serum creatinine [Abstract]. J Am Soc Nephrol 2000;11:A0828.

(6.) Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.

(7.) Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985;28:830-8.

(8.) 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.

CYNDA ANN JOHNSON, M.D., M.B.A., Brody School of Medicine at East Carolina University, Greenville, North Carolina

ANDREW S. LEVEY, M.D., Tufts University School of Medicine, Boston, Massachusetts

JOSEF CORESH, M.D., PH.D., Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

ADEERA LEVIN, M.D., University of British Columbia Faculty of Medicine, Vancouver, British Columbia

JOSEPH LAU, M.D., Tufts-New England Medical Center, Boston, Massachusetts

GARABED EKNOYAN, M.D., Baylor College of Medicine, Houston, Texas

The authors indicate that they do not have any conflicts of interest. Sources of funding: AstraZeneca Pharmaceuticals LP is the primary sponsor of the NKF K/ DOQI guidelines, Merck & Co., Inc. is the implementation sponsor, and Amgen Inc. is the founding and principal sponsor of K/DOQI.

The authors acknowledge the contributions of other members of the NKF K/DOQI Work Group and Evidence Review Team, the K/DOQI Support Group and Advisory Board, and the National Kidney Foundation.

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