Back to the Top
Hello all,
Can anyone tell me what a typical glomerular filtration rate for a
large adult male rat is?
Thanks,
Alene
Back to the Top
Alene,
> Can anyone tell me what a typical glomerular filtration rate for a
> large adult male rat is?
Based on allometric theory with an allometric coefficient of 3/4 and
confirmed by extensive observations in humans the standard adult GFR
value is 121 ml/min (gfrstd) in a 70 kg (wtstd) person. Other GFR values
can be predicted from:
GFR=gfrstd*(wt/wtstd)^(3/4)
The predicted value is 1.2 ml/min for a 150 g rat which can be compared
with experimentally determined values of inulin clearance of 1.3 to 1.4
ml/min in 140-160 g male Wistar rats (Jobin & Bonjour 1985).
An empirical estimate of the allometric coefficient obtained by Rhodin
et al. was 0.632 with a corresponding gfrstd of 112 ml/min. This
predicts 2.3 ml/min for a 150 g rat. Based on this limited example it
seems that allometric theory does a better job than empiricism for
extrapolation from humans to rats.
The GFR for a 0.5 kg adult rat is expected to be 3 ml/min and for a 1 kg
adult RAT (!) it will be 5 ml/min. Sex is unimportant - only size
matters for adults (Rhodin et al. 2008).
Nick
Jobin J, Bonjour JP. Measurement of glomerular filtration rate in
conscious unrestrained rats with inulin infused by implanted osmotic
pumps. American Journal of Physiology- Renal Physiology. 1985;248(5):
734-8.
Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, et
al. Human renal function maturation -- a quantitative description using
weight and postmenstrual age. Pediatr Nephrol. 2008. In press
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.aaa.auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Back to the Top
The following message was posted to: PharmPK
Alene,
Experimental values depend on the strain of rat. While inulin clearance
measurements in healthy adult humans can easily have a difference of 50%
(i.e., 90-140 mL/min), rats can be anywhere from 1 to 6mL/min. This can
make data conclusions a bit tricky, without sufficient analysis of
concurrent elimination processes.
Hope that helps.
-Shawn
*******************
SHAWN SPENCER, PhD.
Assistant Professor of Biopharmaceutics
Dyson Bldg., Rm 227
College of Pharmacy and Pharmaceutical Sciences
Florida A&M University
Tallahassee, FL 32307
shawn.spencer.-at-.famu.edu
Back to the Top
Dear Alene,
For a 0.25 kg rat, the GFR is 1.31 mL/min (refer Davies & Morris,
Pharmaceutical Research, Vol,10 (7), 1993)
Regards
L. Chakradhar
Back to the Top
The following message was posted to: PharmPK
Alene and Nick
As a human pharmacologist I find a rat GFR of about 2ml per minute
surprisingly low and even wonder how a rat could survive on filtering
such a small volume, so I looked up renal blood flow to get a kind of
baseline. The best reference was Delp, Evans and Duan (1998) who found
that the proportion of cardiac output to kidneys was 13-14% using a
microsphere technique in male Fischer-344 rats. Cardiac output was
lower in 2 mo old juvenile rats (51 +/- 4 ml/min) than in 6 mo old
adults (106 +/- 5 ml/min) or in 24 mo old aged (119 +/- 10 ml/min) rats,
but cardiac index was not different among groups. Using the mean and
the 13% figure the mean renal blood flow was approximately 6.63, 13.78
and 15.47 ml per minute respectively.
I don't know what proportion of the blood flow goes via GFR but I
would have thought most of it does and certainly more than 50%, so
with apologies to Nick for using such a manifestly empirical method, I
would expect the estimate by inulin clearance he cited to be rather low.
Ref: Delp MD, Evans M & Duan C (1998) J Appl Physiol 85: 5, 1813-1822.
Andrew Sutton
Back to the Top
The following message was posted to: PharmPK
My aplogies to all and Nick in particular. Digging deeper I found
that the fluid resorption process in a rat is more efficient than I
thought so an adult GFR of 1.5 to 2 ml/min from a renal blood flow of
around 13 to 15 ml/min isn't as low as I had imagined.
Andrew Sutton
Back to the Top
Andrew,
> My aplogies to all and Nick in particular. Digging deeper I found
> that the fluid resorption process in a rat is more efficient than I
> thought so an adult GFR of 1.5 to 2 ml/min from a renal blood flow
of
> around 13 to 15 ml/min isn't as low as I had imagined.
Thank you -- I appreciate that you made the effort to look more closely
at the empirical data. Note that in my last email I did give some
directly measured estimates of rat GFR to compare them with the
allometric prediction from adult humans.In the case of GFR the
prediction from humans over a size range of nearly 500 fold is within
12.5% of the observed average rat GFR (N=6; between rat CV of 25%)
(Jobin & Bonjour 1985). Its alway nice to see the data and compare it
with theory :-)
Thanks also for providing some numbers that confirm rat renal physiology
is indeed like that in humans who have a GFR of around 120 ml/min and a
renal blood flow around 1100 ml/min (Davies & Shock 1950). It is
unfortunate that while many details of the subjects reported by Davies &
Shock are provided in their JCI paper it is not possibly to directly
calculate the GFR or RBF in relation to weight. They scaled using body
surface area which at that time was thought to be sensible but we now
know that there is no good scientific reason to use BSA and indeed BSA
is clearly worse than theoretically sound weight based allometric
scaling (Peters 1983, recently confirmed within the human species by
Rhodin et al. 2008).
Davies DF, Shock NW. AGE CHANGES IN GLOMERULAR FILTRATION RATE,
EFFECTIVE RENAL PLASMA FLOW, AND TUBULAR EXCRETORY CAPACITY IN ADULT
MALES. J Clin Invest. 1950;29(5):496.
Jobin J, Bonjour JP. Measurement of glomerular filtration rate in
conscious unrestrained rats with inulin infused by implanted osmotic
pumps. American Journal of Physiology- Renal Physiology. 1985;248(5):
734-8.
Peters R. The ecological implications of body size. Cambridge: Cambridge
University Press; 1983.
Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, et
al. Human renal function maturation -- a quantitative description using
weight and postmenstrual age. Pediatr Nephrol. 2008. In press.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-a-.auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Back to the Top
The following message was posted to: PharmPK
.... and many thanks to you Nick for injecting a quantitative element
into a subject that has long fascinated me: extrapolating from rat to
man.
What do you think was the error that Davies and Shock made in assuming
that body area would be a reliable parameter? On the surface (no pun
intended) it looks like a reasonable approximation to volume and since
I suspect that the same assumption is made in the use of body mass
index to calculate human doses...I'm bound to ask if we can we learn
anything useful about BMI from this? I have always been conscious of
the limitations of BMI but not known how to improve upon it. For
example, could we make a useful correction by using skinfold
thickness, waist measurements or other practical measure? As always,
and as your emails illustrate, it's quantifying the assumptions or
the advantage of using another procedure that's at the heart of the
matter.
Sincerely
Andrew
Back to the Top
Andrew,
The field of allometry has long ago discarded the BSA theory (first
proposed by the French in the 1830s). Neither subsequent theory of how
body structure and function relate to mass nor direct observation of
the relationship supports the BSA method. See Savage et al. 2004 for a
relatively recent review of allometric history and current state of
the art. The magnitude of the 'error' of using BSA instead of 3/4
allometry for clearance is discussed in Holford 1996. BSA isn't as bad
as the much more common linear "per kg" method of scaling but 3/4
allometry is numerically better, much more elegant (when was the last
time you saw what was filtered by the glomerulus appear through the
skin?) and supported by extensive observations.
Body composition (e.g. as reflected in BMI) is a related issue because
it needs to be considered when asking what is meant by 'weight'. Some
useful thinking and proposals based on weight, height and sex have
come from the clinical pharmacology group at the University of
Queensland. See Duffull et al. 2004 and Janmahasatian et al. 2005.
Rhodin et al. 2008 extended these concepts to account for differences
in body composition when trying to sort out size and maturation
influences on GFR.
Nick
Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM. A standard
weight descriptor for dose adjustment in the obese patient. Clin
Pharmacokinet. 2004;43(15):1167-78.
Holford NHG. A size standard for pharmacokinetics. Clin Pharmacokinet.
1996;30:329-32.
Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B.
Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):
1051-65.
Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, et
al. Human renal function maturation - a quantitative description using
weight and postmenstrual age. Pediatr Nephrol. 2008. In press
Savage VM, Gillooly JF, Woodruff WH, West GB, Allen AP, Enquist BJ, et
al. The predominance of quarter-power scaling in biology. Functional
Ecology. 2004;18(2):257-82.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.-a-.auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Rat GFR" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)