Glomerular filtration rate: Difference between revisions

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'''Glomerular filtration rate''' ('''GFR''') is the volume of fluid filtered from the renal glomerular capillaries into the [[Bowman's capsule]] per unit time.<ref>{{GeorgiaPhysiology|7/7ch04/7ch04p11}} - "Glomerular Filtration Rate"</ref>  Clinically, this is often measured to determine [[renal function]].  
'''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."<ref name="MeSH-GFR">{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2008/MB_cgi?term=Glomerular+Filtration+Rate |title=Glomerular filtration rate |accessdate=2008-01-08 |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Library of Medicine |pages= |language= |archiveurl= |archivedate= |quote=}}</ref>  Clinically, this is often measured to determine [[renal function]].  


==Measurement==
==Measurement==
Line 5: Line 5:


===Measurement using inulin===
===Measurement using inulin===
The GFR can be 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.
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===
====Modification of Diet in Renal Disease 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:<ref name="pmid11904577">{{cite journal |author= |title=K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification |journal=Am. J. Kidney Dis. |volume=39 |issue=2 Suppl 1 |pages=S1–266 |year=2002 |pmid=11904577 |doi=|url=http://www.kidney.org/professionals/kdoqi/guidelines_ckd/p5_lab_g4.htm}}</ref>
:<math>\mbox{eGFR} = \mbox{186}\ \times \ \mbox{Serum Creatinine}^{-1.154} \ \times \ \mbox{Age}^{-0.203} \ \times \ \mbox{1.21 if Black} \ \times \ \mbox{0.742 if Female}</math>
 
====Modification of Diet in Renal Disease original 6-variable formula====
The original MDRD correlates slightly better with the GFR than the revised 4-variable formula.<ref name="pmid16908915">{{cite journal |author=Levey AS, Coresh J, Greene T, ''et al'' |title=Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate |journal=Ann. Intern. Med. |volume=145 |issue=4 |pages=247–54 |year=2006 |pmid=16908915 |doi=}}</ref> The additional variables are the [[blood urea nitrogen]] and [[albumin]] levels:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
:<math>\mbox{eGFR} = \mbox{170}\ \times \ \mbox{Serum Creatinine}^{-0.999} \ \times \ \mbox{Age}^{-0.176}\ \times \ \mbox{BUN}^{-0.170}  \times \ \mbox{Albumin}^{+0.3189} \
  \ \times \ \mbox{1.18 if Black} \ \times \ \mbox{0.762 if Female}</math>
 
The 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.<ref name="pmid15611490">{{cite journal |author=Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG |title=Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease |journal=Ann. Intern. Med. |volume=141 |issue=12 |pages=929–37 |year=2004 |pmid=15611490 |doi=|url=http://www.annals.org/cgi/content/full/141/12/929}}</ref><ref name="pmid16908915">{{cite journal |author=Levey AS, Coresh J, Greene T, ''et al'' |title=Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate |journal=Ann. Intern. Med. |volume=145 |issue=4 |pages=247–54 |year=2006 |pmid=16908915 |doi=}}</ref> The equations have not been validated in acute renal failure.


===Estimation using creatinine clearance===
===Estimation using creatinine clearance===
In clinical practice, however, creatinine clearance is used to measure GFR. Creatinine is an endogenous molecule, synthesized in the body, which is freely filtered by the glomerulus (but also secreted by the renal tubules in very small amounts). [[Creatinine clearance]] is therefore a close approximation of the GFR. However, the approximation of the GFR calculation is best measured by the evaluation and visualization of the frequency and duration of urination.   The GFR is typically recorded in units of ''volume per time'', e.g. milliliters per minute (ml/min). 
====Using a direct measurement of the creatinine clearance====
By measuring the amount of creatinine excreted in the urine over one day, the creatinine clearance may be calculated. Creatinine is an endogenous molecule, synthesized in the body, which is freely filtered by the glomerulus (but also secreted by the renal tubules in very small amounts). [[Creatinine clearance]] is therefore a close approximation of the GFR. The formula for the creatinine clearance is:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
 
:<math>\mbox{Creatinine clearance }= \frac{\frac{\mbox{ Amount of creatinine in urine (mg)}}{\mbox{Duration of the urine collection (minutes)}}}{\mbox{Plasma creatinine concentration (mg}/\mbox{ml)}}</math>


Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour he excretes 75 mg of creatinine in the urine. The GFR is calculated as M/P (where M is the mass of creatinine excreted per unit time and P is the plasma concentration of creatinine).  
Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour he excretes 75 mg of creatinine in the urine. The GFR is calculated as M/P (where M is the mass of creatinine excreted per unit time and P is the plasma concentration of creatinine).  


:<math>\mbox{GFR }= \frac{\frac{75\mbox{ mg}}{60\mbox{ mins}}}{0.01\mbox{ mg}/\mbox{ml}} = 125 \mbox{ ml}/\mbox{min}</math>
:<math>\mbox{Creatinine clearance }= \frac{\frac{75\mbox{ mg}}{60\mbox{ mins}}}{0.01\mbox{ mg}/\mbox{ml}} = 125 \mbox{ ml}/\mbox{min}</math>
 
The creatinine clearance systematically overestimates the GFR due to excretion creatinine by the renal tubules. The correction factor is below:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
:<math>\mbox{Glomerlular filtration rate} = \mbox{0.81}\ \times \ \mbox{Creatinine clearance}</math>


===Estimation using Cockcroft-Gault formula===
====Using an Cockcroft-Gault estimation the creatinine clearance====
The Cockcroft-Gault formula may be used to calculate an Estimated Creatinine Clearance.<ref>[http://www.cato.at/webservice/servlet/location?goto=SERVICE_CALC&lang=EN&URL=%22calc/cato_GFR_CG.htm%22 GFR Calculator at cato.at - Cockcroft-Gault] - GFR calculation (Cockcroft-Gault formula)</ref>
The Cockcroft-Gault formula may be used to estimate the creatinine clearance without having to collect urine over a period of time.<ref>[http://www.cato.at/webservice/servlet/location?goto=SERVICE_CALC&lang=EN&URL=%22calc/cato_GFR_CG.htm%22 GFR Calculator at cato.at - Cockcroft-Gault] - GFR calculation (Cockcroft-Gault formula)</ref> However, it does not correlate as strongly with the GFR as do the MRDR formula.<ref name="pmid16908915">{{cite journal |author=Levey AS, Coresh J, Greene T, ''et al'' |title=Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate |journal=Ann. Intern. Med. |volume=145 |issue=4 |pages=247–54 |year=2006 |pmid=16908915 |doi=}}</ref>


:<math>\mbox{Creatinine clearance} = \frac { \mbox{(140 - Age)} \times \mbox{Mass (in kilograms)}} {\mbox{72} \times \mbox{Plasma Creatinine (in mg/dl)}} \times \mbox{0.85 if female}</math>
:<math>\mbox{Creatinine clearance} = \frac { \mbox{(140 - Age)} \times \mbox{Mass (in kilograms)}} {\mbox{72} \times \mbox{Plasma Creatinine (in mg/dl)}} \times \mbox{0.85 if female}</math>
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The Estimated Creatinine Clearance then estimates GFR:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
The Estimated Creatinine Clearance then estimates GFR:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
:<math>\mbox{Glomerlular filtration rate} = \mbox{0.84}\ \times \ \mbox{Cockcroft-Gault formula}</math>
:<math>\mbox{Glomerlular filtration rate} = \mbox{0.84}\ \times \ \mbox{Cockcroft-Gault formula}</math>
===Modification of Diet in Renal Disease (MDRD) formula===
The most commonly used formula is the "4-variable MDRD" which estimates GFR using four variables - serum creatinine, age, race, and gender:<ref name="pmid11904577">{{cite journal |author= |title=K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification |journal=Am. J. Kidney Dis. |volume=39 |issue=2 Suppl 1 |pages=S1–266 |year=2002 |pmid=11904577 |doi=|url=http://www.kidney.org/professionals/kdoqi/guidelines_ckd/p5_lab_g4.htm}}</ref>
:<math>\mbox{eGFR} = \mbox{186}\ \times \ \mbox{Serum Creatinine}^{-1.154} \ \times \ \mbox{Age}^{-0.203} \ \times \ \mbox{1.21 if Black} \ \times \ \mbox{0.742 if Female}</math>
The original MDRD used six variables with the additional variables being the [[blood urea nitrogen]] and [[albumin]] levels:<ref name="pmid10075613">{{cite journal |author=Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D |title=A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group |journal=Ann. Intern. Med. |volume=130 |issue=6 |pages=461–70 |year=1999 |pmid=10075613 |doi=|url=http://www.annals.org/cgi/content/full/130/6/461}}</ref>
:<math>\mbox{eGFR} = \mbox{170}\ \times \ \mbox{Serum Creatinine}^{-0.999} \ \times \ \mbox{Age}^{-0.176}\ \times \ \mbox{BUN}^{-0.170}  \times \ \mbox{Albumin}^{+0.3189} \
  \ \times \ \mbox{1.18 if Black} \ \times \ \mbox{0.762 if Female}</math>
The 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.<ref name="pmid15611490">{{cite journal |author=Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG |title=Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease |journal=Ann. Intern. Med. |volume=141 |issue=12 |pages=929–37 |year=2004 |pmid=15611490 |doi=|url=http://www.annals.org/cgi/content/full/141/12/929}}</ref><ref name="pmid16908915">{{cite journal |author=Levey AS, Coresh J, Greene T, ''et al'' |title=Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate |journal=Ann. Intern. Med. |volume=145 |issue=4 |pages=247–54 |year=2006 |pmid=16908915 |doi=}}</ref> The equations have not been validated in acute renal failure.


===Calculation using Starling equation===
===Calculation using Starling equation===
It is also theoretically possible to calculate GFR using the [[Starling equation]].<ref>{{GeorgiaPhysiology|7/7ch04/7ch04p12}} - "Forces Driving the Glomerular Filtration Rate":</ref>
It is also theoretically possible to calculate GFR using the [[Starling equation]].<ref name="isbn0-07-144040-2">{{cite book |author=Ganong, William F. |title=Review of medical physiology |publisher=McGraw-Hill Medical |location= |year=2005 |pages= |isbn=0-07-144040-2 |oclc= |doi=}}</ref>


:<math>J_v = K_f ( [P_c - P_i] - \sigma[\pi_c - \pi_i] )</math>
:<math>J_v = K_f ( [P_c - P_i] - \sigma[\pi_c - \pi_i] )</math>
Line 39: Line 49:
The equation is used both in a general sense for all capillary flow, and in a specific sense for the glomerulus:
The equation is used both in a general sense for all capillary flow, and in a specific sense for the glomerulus:


{| class="wikitable"
{| class="wikitable" align="center"
| '''General usage''' || '''Glomerular usage''' || '''Meaning of variable''' || '''Relationship to GFR''' || '''Description'''
| '''General usage''' || '''Glomerular usage''' || '''Meaning of variable''' || '''Relationship to GFR''' || '''Description'''
  |-  
  |-  
Line 60: Line 70:


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.
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 ranges==
The normal ranges of GFR, adjusted for body surface area, are:<ref name="NKDEP-FAQ">{{cite web |url=http://www.nkdep.nih.gov/professionals/gfr_calculators/gfr_faq.htm |title=GFR Frequently Asked Questions - NKDEP |accessdate=2008-01-08 |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Kidney Disease Education Program |pages= |language= |archiveurl= |archivedate= |quote=}}</ref>
{| class="wikitable" align="right"
 
|+ Normal values for eGFRs
 
{| class="wikitable"
|+ Reference Table for Population Mean eGFRs
! Age  (Years) !! Mean eGFR<ref name="NKDEP-FAQ"/>
! Age  (Years) !! Mean eGFR<ref name="NKDEP-FAQ"/>
|-
|-
Line 80: Line 89:
|-
|-
| 70+ || 75 mL/min/1.73 m<sup>2</sup>
| 70+ || 75 mL/min/1.73 m<sup>2</sup>
|- colsp="2"|Note: values are about 10% lower for females.<ref name="isbn0-07-144040-2">{{cite book |author=Ganong, William F. |title=Review of Medical Physiology |publisher=McGraw-Hill Medical |location= |year=2005 |pages= |isbn=0-07-144040-2 |oclc= |doi=}}</ref>
|}
|}
The normal ranges of GFR, adjusted for body surface area, are:<ref name="NKDEP-FAQ">{{cite web |url=http://www.nkdep.nih.gov/professionals/gfr_calculators/gfr_faq.htm |title=GFR Frequently Asked Questions - NKDEP |accessdate=2008-01-08 |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Kidney Disease Education Program |pages= |language= |archiveurl= |archivedate= |quote=}}</ref>
Values are about 10% less for females.<ref name="isbn0-07-144040-2">{{cite book |author=Ganong, William F. |title=Review of medical physiology |publisher=McGraw-Hill Medical |location= |year=2005 |pages= |isbn=0-07-144040-2 |oclc= |doi=}}</ref>






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]].
 
 
 
 
 
 
 
==References==
<references/>


==See also==
==See also==
*[[Acute kidney injury]]
*[[Chronic kidney disease]]
*[[Chronic kidney disease]]
*[[Acute kidney injury]]


==References==
<references/>


==External links==
==External links==
*[http://www.nkdep.nih.gov/professionals/ National Kidney Disease Education Program website.] Includes professional references and GFR calculators
*[http://www.nkdep.nih.gov/professionals/ National Kidney Disease Education Program website.] Includes GFR calculators


[[Category:CZ Live]] [[Category:Health Sciences Workgroup]]
[[Category:CZ Live]] [[Category:Health Sciences Workgroup]]

Revision as of 23:23, 8 January 2008

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] Clinically, this is often measured to determine renal function.

Measurement

There are several different techniques used to calculate or estimate 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

Modification of Diet in Renal Disease 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:[2]

Modification of Diet in Renal Disease original 6-variable formula

The original MDRD correlates slightly better with the GFR than the revised 4-variable formula.[3] The additional variables are the blood urea nitrogen and albumin levels:[4]

The 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.[5][3] The equations have not been validated in acute renal failure.

Estimation using creatinine clearance

Using a direct measurement of the creatinine clearance

By measuring the amount of creatinine excreted in the urine over one day, the creatinine clearance may be calculated. Creatinine is an endogenous molecule, synthesized in the body, which is freely filtered by the glomerulus (but also secreted by the renal tubules in very small amounts). Creatinine clearance is therefore a close approximation of the GFR. The formula for the creatinine clearance is:[4]

Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour he excretes 75 mg of creatinine in the urine. The GFR is calculated as M/P (where M is the mass of creatinine excreted per unit time and P is the plasma concentration of creatinine).

The creatinine clearance systematically overestimates the GFR due to excretion creatinine by the renal tubules. The correction factor is below:[4]

Using an Cockcroft-Gault estimation the creatinine clearance

The Cockcroft-Gault formula may be used to estimate the creatinine clearance without having to collect urine over a period of time.[6] However, it does not correlate as strongly with the GFR as do the MRDR formula.[3]

The Estimated Creatinine Clearance then estimates GFR:[4]

Calculation using Starling equation

It is also theoretically possible to calculate GFR using the Starling equation.[7]

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[8]
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:[8]

Values are about 10% less for females.[7]






References

  1. Anonymous. Glomerular filtration rate. National Library of Medicine. Retrieved on 2008-01-08.
  2. (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]
  3. 3.0 3.1 3.2 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. 4.0 4.1 4.2 4.3 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]
  5. 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]
  6. GFR Calculator at cato.at - Cockcroft-Gault - GFR calculation (Cockcroft-Gault formula)
  7. 7.0 7.1 7.2 Ganong, William F. (2005). Review of medical physiology. McGraw-Hill Medical. ISBN 0-07-144040-2.  Cite error: Invalid <ref> tag; name "isbn0-07-144040-2" defined multiple times with different content Cite error: Invalid <ref> tag; name "isbn0-07-144040-2" defined multiple times with different content
  8. 8.0 8.1 Anonymous. GFR Frequently Asked Questions - NKDEP. National Kidney Disease Education Program. Retrieved on 2008-01-08.

See also


External links