Glomerular filtration rate

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Glomerular filtration rate (GFR) is "the volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance."[1] The GFR if used to measure renal function in patients with acute kidney injury or chronic kidney disease.[2]

Measurement

There are several different techniques used to calculate the glomerular filtration rate (GFR or eGFR).

Measurement using inulin

The GFR is most accurately determined by injecting inulin (not insulin) into the plasma. Since inulin is neither reabsorbed nor secreted by the kidney after glomerular filtration, its rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter.

However, due to difficulties with accurately infusing inulin, various easier methods of estimating the GFR are available.

Estimation of the GFR

In comparing the methods detailed below, the original 6 variable MDRD correlates slightly better with the GFR than the revised 4-variable formula (R2=0.890 versus R2=0.882).[3] Both MDRD equations are better than Cockcroft-Gault formulae.

The MDRD equations have been validated in patients with chronic kidney disease; however both versions underestimate the GFR in healthy patients with GFRs over 60 mL/min.[4][3] The equations have not been validated in acute renal failure.

When estimating the GFR "in very large or very small patients, multiply the reported eGFR by the estimated body-surface area (BSA) in order to obtain eGFR in units of mL/min":[5]

Modification of Diet in Renal Disease (MDRD) equations

MDRD revised 4-variable formula

The most commonly used formula is the "4-variable MDRD" which estimates GFR using four variables - serum creatinine, age, race, and gender:[6]

MDRD original 6-variable formula

The two additional variables are the blood urea nitrogen and albumin levels:[7]


Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

The CKD-EPI may be more accurate than the MDRD equations[8], especially at higher GFRs[9]

The CKD-EPI calculation uses age, race, gender, and serum creatinine (creatinine method must be traceable to isotope dilution mass spectrometry - IDMS) and is available online at http://mdrd.com/ and http://www.qxmd.com/calculate-online/nephrology/ckd-epi-egfr .

Estimation using creatinine clearance

For more information, see: Creatinine clearance.

Food and Drug Administration provides guidance on the labeling of prescription medications to guide dosing for patients with impaired renal function.[10] Although this categorization uses estimated creatinine clearance, using estimated glomerular filtration yields similar recommendations for dosing adjustments.[11]

The Estimated Creatinine Clearance is higher than the estimates GFR because of tubular secretion of creatinine:[7]

Calculation using Starling equation

It is also theoretically possible to calculate GFR using the Starling equation.[12]

The equation is used both in a general sense for all capillary flow, and in a specific sense for the glomerulus:

General usage Glomerular usage Meaning of variable Relationship to GFR Description
Pc Pgc Capillary hydrostatic pressure Direct Increased by dilation of afferent arteriole or constriction of efferent arteriole
Pi Pbs Interstitial hydrostatic pressure Inverse
πc πgc Capillary oncotic pressure Inverse Decreased by nephrotic syndrome
πi πbs Interstitial oncotic pressure Direct
Kf Kf Filtration coefficient Direct Increased by inflammation
σ σ Reflection coefficient Inverse
Jv GFR net filtration n/a

Note that is the net driving force, and therefore the net filtration is proportional to the net driving force.

In practice, it is not possible to identify the needed values for this equation, but the equation is still useful for understanding the factors which affect GFR, and providing a theoretical underpinning for the above calculations.

For example, GFR can increase due to hypoproteinemia because of the reduction in plasma oncotic pressure. GFR can also increase due to constriction of the efferent arteriole but decreases due to constriction of the afferent arteriole.

Normal ranges

Normal values for eGFRs
Age (Years) Mean eGFR[13]
20-29 116 mL/min/1.73 m2
30-39 107 mL/min/1.73 m2
40-49 99 mL/min/1.73 m2
50-59 93 mL/min/1.73 m2
60-69 85 mL/min/1.73 m2
70+ 75 mL/min/1.73 m2

The normal ranges of GFR, adjusted for body-surface area, are:[13]

Values are about 10% less for females.[12]

Reporting eGFRs

Reporting eGFRs may increase rates of referrals to nephrologists.[14]

References

  1. Anonymous. Glomerular filtration rate. National Library of Medicine. Retrieved on 2008-01-08.
  2. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med. 2006 Jun 8;354(23):2473-83. PMID 16760447
  3. 3.0 3.1 Levey AS, Coresh J, Greene T, et al (2006). "Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate". Ann. Intern. Med. 145 (4): 247–54. PMID 16908915[e]
  4. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG (2004). "Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease". Ann. Intern. Med. 141 (12): 929–37. PMID 15611490[e]
  5. The National Kidney Disease Education Program. (2009) Chronic Kidney Disease and Drug Dosing: Information for Providers National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), U.S. Department of Health & Human Services (DHHS).
  6. (2002) "K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification". Am. J. Kidney Dis. 39 (2 Suppl 1): S1–266. PMID 11904577[e]
  7. 7.0 7.1 Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999). "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. 130 (6): 461–70. PMID 10075613[e]
  8. 1. Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, et al. Comparison of Risk Prediction Using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate. JAMA. 2012 May 9;307(18):1941–51. DOI:10.1001/jama.2012.3954
  9. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. (2009). "A new equation to estimate glomerular filtration rate.". Ann Intern Med 150 (9): 604-12. PMID 19414839. PMC PMC2763564[e]
  10. Food and Drug Administration, Guidance for Industry: Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing and Labeling, US Department of Health and Human Services, Rockville, MD (1998) May.
  11. Stevens LA, Nolin TD, Richardson MM, Feldman HI, Lewis JB, Rodby R et al. (2009). "Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations.". Am J Kidney Dis 54 (1): 33-42. DOI:10.1053/j.ajkd.2009.03.008. PMID 19446939. PMC PMC2756662. Research Blogging.
  12. 12.0 12.1 12.2 Ganong, William F. (2005). Review of medical physiology. McGraw-Hill Medical. ISBN 0-07-144040-2. 
  13. 13.0 13.1 Anonymous. GFR Frequently Asked Questions - NKDEP. National Kidney Disease Education Program. Retrieved on 2008-01-08.
  14. Hemmelgarn BR, Zhang J, Manns BJ, James MT, Quinn RR, Ravani P et al. (2010). "Nephrology visits and health care resource use before and after reporting estimated glomerular filtration rate.". JAMA 303 (12): 1151-8. DOI:10.1001/jama.2010.303. PMID 20332400. Research Blogging.

See also


External links