Page 41 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

30 APPLIED PHYSIOLOGY

TABLE 2-1 Effects of Selected so its clearance can be used to estimate GFR in the steady
Vasoactive Mediators on state. The only requirements for determination of endog-
enous creatinine clearance are an accurately timed urine
Glomerular sample (usually 24 hours), determination of the patient’s
Hemodynamics body weight, and measurement of serum and urine creat-
inine concentrations.
Afferent Efferent
Substance Arteriole Arteriole In the dog and cat, creatinine is filtered by the
glomeruli and is neither reabsorbed nor secreted by the
tubules. 18–20,22 In most clinical pathology laboratories,
Vasodilators
Acetylcholine Relax Relax creatinine is measured by the alkaline picrate reaction.
Nitric oxide Relax Relax This reaction is not entirely specific for creatinine and
Dopamine Relax Relax measures another group of substances collectively known
Bradykinin Relax Relax as noncreatinine chromogens. These substances are
Prostacyclin Relax Relax found in plasma, where they may constitute up to 50%
Prostaglandin E 2 Relax No effect of the measured creatinine at normal serum creatinine
concentrations, but only small amounts appear in
Prostaglandin I 2 Relax Relax
Vasoconstrictors urine. 21,22 When the creatinine concentration is deter-
Norepinephrine Constrict Constrict mined using the alkaline picrate reaction, the presence
Angiotensin II Constrict Constrict of noncreatinine chromogens causes endogenous creati-
Endothelin Constrict Constrict nine clearance to underestimate GFR. This problem
Thromboxane Constrict Constrict may be avoided by using more accurate methods (e.g.,
Vasopressin No effect Constrict
peroxidase-antiperoxidase) to measure the creatinine
From Valtin H, Schafer JA. Renal function. Boston: Little, Brown, 1995: concentration. 22 Values for endogenous creatinine
107. clearance in the dog and cat are approximately 2 to 5
mL/min/kg. 5,17,22
Amount filtered ¼ amount excreted To circumvent the problem of noncreatinine
chromogens and to improve accuracy, some investigators
P x GFR ¼ U x V
have advocated determination of exogenous creatinine
clearance. In this test, which is somewhat more cumber-
where P x is the plasma concentration of x (milligrams per
some, creatinine is administered subcutaneously to the
milliliter), U x is the urine concentration of x (milligrams
animal to increase the serum creatinine concentration
per milliliter), V is the urine flow rate (milliliters per min-
and reduce the relative effect of the noncreatinine
ute), and GFR is the glomerular filtration rate (milliliters
chromogens. For example, a normal dog may have a
per minute). Dividing both sides of the equation by P x :
serum creatinine concentration of 1.0 mg/dL, of which
0.5 mg/dL represents noncreatinine chromogens. This
GFR ¼ U x V =P x
measurement represents a 50% error. If, however, the
Note that this equation is the same as the formula for dog’s serum creatinine concentration is increased to
clearance presented before. Thus, the renal clearance of 10 mg/dL by subcutaneous administration of creatinine,
a substance that is neither reabsorbed nor secreted is the noncreatinine chromogens still represent only
equal to GFR. Inulin is a polymer of fructose with a 0.5 mg/dL, and the error is reduced to 5%. Exogenous
molecular mass of 5200 da. It is not bound to plasma creatinine clearance exceeds endogenous creatinine clear-
proteins and is freely filtered by the glomeruli. It is neither ance and more closely approximates inulin clearance in
20
reabsorbed nor secreted by the tubules. It is not the dog.
metabolized by the kidneys or any other organ. It is The amount of any substance excreted by the kidneys
uncharged and not subject to the Gibbs-Donnan effect. is the algebraic sum of the amount filtered and the
In summary, inulin is an ideal substance for the measure- amount handled by the tubules:
ment of GFR, and inulin clearance is the laboratory stan-
dard for GFR determination. Normal values for GFR as U x V ¼ P x GFR þ T x
measured by inulin clearance are 3 to 5 mL/min/kg in
the dog 16,21 and 2.5 to 3.5 mL/min/kg in the cat. 16,45 where T x is the amount handled by tubules (milligrams
per minute).
Inulin clearance is not used clinically because it
The term T x is a positive number if the substance
requires intravenous infusion of inulin and an assay that
experiences net secretion and a negative number if it
is not routinely available in most clinical pathology
experiences net reabsorption. Dividing both sides of
laboratories. Creatinine is produced endogenously in
the equation by P x yields the familiar clearance formula:
the body and excreted primarily by glomerular filtration,