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Principles of RenalMeasurement 1

Measuring Renal Clearanceand Transport

Dr Derek [email protected]
mailto:[email protected]:[email protected]


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Introduction to RenalMeasurement

There are 2 main categories of tests forassessing renal function.

Some of these are used clinically, butsome can only be used experimentally in

the lab.

1. Modern imaging techniques macroscopic views of renal blood flow,

filtration and excretory function.2. Measurements of renal clearance of

various substances to evaluate the abilityof the kidneys to handle solutes and

water.


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Clearance Measurements

Clearance compares the rate at which theglomeruli filter a substance (H2O) orsolute) with the rate that the kidneysexcrete it into the urine.

If we measure difference in amount ofsubstance filtered and excreted, we canestimate the net amount reabsorbed orsecreted by renal tubules.

Gives us information about the 3 basicfunctions of the kidneys: Glomerular filtration Tubular reabsorption Tubular secretion


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Drawbacks of ClearanceMethods

Measuring clearance means you measureOVERALL nephron function i.e. all ~2million nephrons in both kidneys.

This gives the SUM of ALL transportprocesses occurring along nephrons.

So, no information about precise sites andmechanisms of transport.

Must therefore use studies on individualnephrons, tubule cells or cell membranesto obtain this data.


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Clearance

The clearance of a solute is the virtual volumeof blood that would be totally cleared of a solutein a given time.

Solutes come from blood perfusing kidneys.

Rate at which kidneys excrete solute into urine =rate at which solute disappears from bloodplasma.

For solute X:

Cx = Ux x V

Px

Volume of urineformed in giventime

Conc. of X insystemic blood

plasma

Clearance

Conc. of X in urine


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p-aminohippurate (PAH)

There are certain special cases where the kidneyscompletely clear X from plasma during a SINGLEPASSAGE through them.

In this case, renal clearance of X = arterial renalplasma flow.

p-aminohippurate (PAH) is such a special solute. Thus, PAH clearance is a good estimate of renalplasma flow.

However, for most substances, they are NOTcleared completely on 1st pass some X goes out

in venous blood. Thus, the virtual volume cleared of X in giventime is less than total renal plasma flow.

For most solutes then, clearance describes avirtual volume of blood totally cleared of a solute,

whereas in reality, a much larger volume of bloodis PARTIALLY CLEARED of the solute.


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Renal handling of PAH

PAH is an organic acidthat is not usuallypresent in the body,so must give by IVinfusion.

Note that there isnone left in the renalvein - all cleared infirst pass.

Drawback is thatmustnt give too muchPAH, otherwise weoverwhelm the PAHsecretory system and

the data can bemisleading.


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Measurement of GFR

GFR also assessed using principles ofclearance.

GFR = vol. of fluid filtered into Bowmanscapsule per unit time.

Same equation, GFR is Cx if X has certainrequired properties (i.e. Cinulin).

GFR = Ux x V

Px

Volume of urineformed in giventime

Conc. of X insystemic blood

plasma

Glomerularfiltration rate

Conc. of X in urine


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Solutes used to measure GFR

Required properties are:1. Solute is freely-filtered (conc. in Bowmans

space = that in blood plasma).

2. Tubules do not absorb, secrete or metabolizeX.

Thus, amount of X in urine per unit time= that which glomerulus filters per unittime.

WHAT GOES IN = WHAT COMES OUT!

INULIN is such a substance that satisfiesall of these criteria and is commonly used

to measure GFR.


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Drawbacks of Inulin

Most reliable method of measuring GFR, notuseful clinically.

Inulin must be administered by IV to getrelatively constant plasma levels.

Chemical analysis of inulin in plasma and urine istechnically demanding. Use radiolabelled compounds instead like

radioactive Vitamin B or EDTA. However, these may also bind to proteins and

distort results slightly. Problems of IV infusion of GFR marker avoided byusing an endogenous substance with inulin-likeproperties CREATININE.


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Creatinine Creatinine itself is secreted by tubules, so might

overestimate GFR by 20% in humans. However, colorimetry methods used to measure creatinineoverestimate creatinine concentrations.

Luckily, these 2 errors cancel each other out, andcalculated creatinine clearance inulin clearance.

Cheap, easy, reliable, used in clinic.

Avoids IV infusion, just requires venous blood and urinesamples.

Creatinine usually produced by creatinine phosphatemetabolism in muscle.

Must remember to take into account if person has muscledisease/damage, or has had large quantities of meat to eat.

Usually measure over 24 hr period to get reliable resultsand take samples before breakfast.

CCr = UCr x V

PCr


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Urinary Excretion of Solutes Sometimes tricky to calculate. Things like univalent electrolytes, glucose,

aas are freely filterable. However, if solute binds to protein, for

example, then its not (e.g. Ca2+, PO42-,

Mg2+, PAH). For these, you must measure plasma

binding and correct for the non-filterable

fraction of solute. Solute must also not be synthesized ordegraded.

Ammonium is synthesised, andglutamate/glutamine is degraded, as areother organic acids.

There are also complex combinations of

reabsorption and secretion with K+, uricacid and urea. Must be careful, otherwise you will get

inaccurate measurements.

UrinaryExcretionof Solute

Filtered

Load

Reabsorption

by Tubules

Secretion by

Tubules= - +


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Microscopic techniques for measuringsingle nephron rates of filtration,

absorption and secretion

Free-flowmicropuncture

Stopped-flowmicroperfusion

Continuous

microperfusion Isolated

perfused tubule


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Why use microscopictechniques?

As previously mentioned, whole clearancemethods do not reveal much about whatareas of the nephron are involved in whichtransport processes.

Impossible to determine which nephronsare responsible for overall urinaryexcretion.

Thus, physiologists have developed a

series of invasive techniques that are usedto study the function of renal cells in theresearch laboratory (not used in clinicalsetting!).


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Free-flow micropuncture


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What does this tell us?

Apply clearance concept at level of singlenephron (gives us identical equation!).

Measures [solute] in tubule fluid at site

(TFx), volume flow at site (i.e. collectionrate) and plasma conc. (Px).

Computes amount of fluid that singlenephron can filter, as well as amounts of

fluid and solutes that a single segment ofthe nephron handles.

Cx = TFx x Volume collection rate

Px


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Single nephron glomerularfiltration rate (SNGFR)

Usesmicropuncturetechniques tomonitor singlenephron.

Uses inulin as onlarge scale tomeasure GFR.

Uses sameequation tomeasure SNGFR.


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Stopped-flow microperfusion

Good for looking at how a fluid you introduce may be modified by thetubule, but does not completely reproduce continuously flowing stream of

tubular fluid. Does allow us to understand how fluid is changed by varioustransport processes can alter fluid composition.


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Continuous microperfusion

Good technique as it continuously samples the tubular fluid, andthe capillary blood, but you have to provide the fluid that comesdown the tubule. However, also allows us to makeelectrophysiological measurements.


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Isolated perfused tubule

Allows us to precisely control what goes into the tubule,but is it really representative of a true physiologicalsystem?


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Summary

There are a range of techniques for measuringrenal function, some of which are technicallychallenging.

Some useful clinically, other more suited for lab

work with animals or isolated tissue samples. These techniques concentrate more on how the

kidneys process fluid, and how efficient they areat modifying it.

In the next lecture, we will consider the imagingtechniques that are commonly used to identifyrenal problems, and some commonly-measuredparameters that may provide evidence thatsomething has gone wrong with the physiology of

these relatively inaccessible organs.

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