Assessment of kidney function TOPIC OUTLINESUMMARY & RECOMMENDATIONSINTRODUCTIONOVERVIEW OF KIDNEY FUNCTIONGLOMERULAR FILTRATION RATENormal GFR- Change in GFR with agingSignificance of a declining GFRASSESSMENT OF GFRHow to evaluate GFR: Measurement versus estimationMeasurement of GFREstimation of GFR- Using creatinine to estimate GFRNormal valuesRequirement for stable kidney functionLimitations of using creatinine- Variation in creatinine production- Variations in creatinine secretion- Extrarenal creatinine excretion- Measurement issues- Creatinine clearanceLimitations of using creatinine clearance- Estimation equationsCockcroft-Gault equationMDRD study equationsEvaluation of the MDRD and Cockcroft-Gault equations in specific populationsCKD-EPI equation- CKD-EPI is superior when GFR is normal or mildly reduced- CKD-EPI results in lower prevalence of CKD and better risk predictionChoice of equationLimitations of estimation equationsDrug dosing- BUN and GFR- Serum cystatin C- Creatinine and cystatin C in combinationSUMMARY AND RECOMMENDATIONSREFERENCESGRAPHICS View AllFIGURESSerum creatinine and GFRDistribution of serum creatinine among US males and femalesCKD-EPI and MDRD Study equations in estimating measured GFRDifferences in cystatin C according to demographic factorsCALCULATORSCalculator: Creatinine clearance (measured)Calculator: Body Surface Area (Mosteller, square root method)Calculator: Creatinine clearance estimate by Cockcroft-Gault equationCalculator: Glomerular filtration rate estimate by abbreviated MDRD study equationRELATED TOPICSAntihypertensive therapy and progression of nondiabetic chronic kidney disease in adultsCalculation of the creatinine clearanceChapter 1A: Introduction to renal functionDefinition and staging of chronic kidney diseaseDiagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney diseaseDrugs that elevate the serum creatinine concentrationEtiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure)Indications for and complications of renal biopsyPatient information: Collection of a 24-hour urine specimen (Beyond the Basics)Radiologic assessment of renal diseaseReciprocal serum creatinine concentration and chronic kidney diseaseSecondary factors and progression of chronic kidney diseaseUrinalysis in the diagnosis of kidney diseaseAssessment of kidney functionAuthors Lesley A Inker, MD, MS Ronald D Perrone, MD Section Editor Richard H Sterns, MD Deputy Editor John P Forman, MD, MSc DisclosuresAll topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Oct 2013. | This topic last updated: Jan 8, 2013.INTRODUCTION — Patients with kidney disease may have a variety of different clinical presentations. Some have symptoms that are directly referable to the kidney (gross hematuria, flank pain) or to extrarenal symptoms (edema, hypertension, signs of uremia). Many patients, however, are asymptomatic and are noted on routine examination to have an elevated serum creatinine concentration or an abnormal urinalysis.Once kidney disease is discovered, the presence or degree of kidney dysfunction and rapidity of progression are assessed, and the underlying disorder is diagnosed. Although the history and physical examination can be helpful, the most useful information is initially obtained from estimation of the glomerular filtration rate (GFR) and examination of the urinary sediment.Estimation of the GFR is used clinically to assess the degree of kidney impairment and to follow the course of the disease. However, the GFR provides no information on the cause of the kidney disease. This is achieved by the urinalysis, measurement of urinary protein excretion, and, if necessary, radiologic studies and/or kidney biopsy.This topic will provide an overview of the issues concerning assessment of the GFR in the patient with chronic kidney disease. The utility of the urinalysis, radiologic studies, and kidney biopsy are discussed separately, as is the general approach to the patient with kidney disease. (See "Urinalysis in the diagnosis of kidney disease" and "Radiologic assessment of renal disease" and "Indications for and complications of renal biopsy" and "Diagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney disease" .)OVERVIEW OF KIDNEY FUNCTION — Prior to discussing the evaluation of kidney function, it is helpful to first briefly review normal kidney physiology. (See "Chapter 1A: Introduction to renal function" .) The kidney performs a number of essential processes:It participates in the maintenance of the constant extracellular environment that is required for adequate functioning of the cells. This is achieved by excretion of some of the waste products of metabolism (such as urea, creatinine, and uric acid) and by specifically adjusting the urinary excretion of water and electrolytes to match net intake and endogenous production. The kidney is able to regulate individually the excretion of water and solutes such as sodium, potassium, and hydrogen, largely by changes in tubular reabsorption or secretion.It secretes hormones that participate in the regulation of systemic and renal hemodynamics (renin, prostaglandins, and bradykinin), red blood cell production (erythropoietin), and calcium, phosphorus, and bone metabolism (1,25-dihydroxyvitamin D3 or calcitriol).In the patient with kidney disease, some or all of these functions may be diminished or entirely absent. As an example, patients with nephrogenic diabetes insipidus have a decreased urinary concentrating ability, but other functions are entirely normal. By comparison, all kidney functions may be significantly impaired in the patient with end-stage renal disease, thereby resulting in the retention of uremic toxins, marked abnormalities in fluid and electrolyte balance, and anemia and bone disease.
GLOMERULAR FILTRATION RATE
Normal GFR — The glomerular filtration rate (GFR) is equal to the sum of the filtration rates in all of the functioning nephrons; thus, the GFR gives a rough measure of the number of functioning nephrons. The filtering units of the kidney, the glomeruli, filter approximately 180 liters per day (125 mL/min) of plasma. The normal value for GFR depends on age, sex, and body size, and is approximately 130 and 120 mL/min/1.73 m 2 for men and women, respectively, with considerable variation even among normal individuals [ 1 ].
Change in GFR with aging — An association between age and decreasing GFR has been suggested by several studies [ 2-4 ]:
In the Baltimore Longitudinal study, 254 normal individuals (without renal disease or hypertension and not taking diuretics) were followed between the years 1958 and 1981 with serial creatinine clearances as a means to estimate GFR [ 4 ]. The mean rate of decline in creatinine clearance was found to be 0.75 mL/min per year, and was greater in patients with hypertension. A fall in GFR was not observed in approximately one-third of individuals. (See 'Creatinine clearance' below.)
Using GFR estimated by the modified Modification of Diet in Renal Disease (MDRD) Study equation among participants in the NHANES III study, 38 percent of individuals age 70 or older without hypertension or diabetes had estimated GFRs of less than 60 mL/min per 1.73 m 2 [ 2 ]. By comparison, such low values were seen in only 0.7 percent of such participants between the ages of 20 to 39 years. (See 'MDRD study equations' below.)
One study from Japan calculated the creatinine clearance using the Cockcroft-Gault method among nearly 100,000 subjects older than 20 years of age who participated in a mass screening [ 5 ]. Over 80 percent of those older than 70 years of age had a calculated clearance of less than 60 mL/min. However, this remarkably high prevalence in the very old may be an artifact of how strongly age influences the Cockcroft-Gault equation. (See 'Cockcroft-Gault equation' below.)
Significance of a declining GFR — In patients with kidney disease, a reduction in GFR implies either progression of the underlying disease or the development of a superimposed and often reversible problem, such as decreased renal perfusion due to volume depletion. In addition, the level of GFR has prognostic implications in patients with chronic kidney disease, and such patients are staged, in part, according to GFR. These issues are discussed in detail separately. (See "Diagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney disease" and "Definition and staging of chronic kidney disease" .)
However, there is not an exact correlation between the loss of kidney mass (ie, nephron loss) and the loss of GFR. The kidney adapts to the loss of some nephrons by compensatory hyperfiltration and/or increasing solute and water reabsorption in the remaining, normal nephrons [ 6-8 ]. Thus, an individual who has lost one-half of total kidney mass will not necessarily have one-half the normal amount of GFR. (See 'Using creatinine to estimate GFR' below.)
These concepts have important consequences:
A stable GFR does not necessarily imply stable disease. Signs of disease progression other than a change in GFR must be investigated, including increased activity of the urine sediment, a rise in protein excretion, or an elevation in blood pressure.
Similarly, an increase in GFR may indicate improvement in the kidney disease or may imply a counterproductive increase in filtration (hyperfiltration) due to hemodynamic factors. (See "Secondary factors and progression of chronic kidney disease" .)
Some patients who have true underlying renal disease may go unrecognized because they have a normal GFR.
ASSESSMENT OF GFR
How to evaluate GFR: Measurement versus estimation — Measurement of glomer
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