renal protein loss due to inflammation

8/13/2019 Renal Protein Loss Due to Inflammation

http://slidepdf.com/reader/full/renal-protein-loss-due-to-inflammation 1/8

RENAL PROTEIN LOSS DUE TO

INFLAMMATION)

Most of the time when kidney disease is discussed, “renal insufficiency” or “chronic

kidney failure” is the subject. In renal failure, the kidney loses its ability to conserve the body’s water as it removes the body’s daily toxin build up. xcessive water consumption

is seen as an early si!n of trouble as lar!e amounts of water are re"uired to make enou!hurine. ventually toxins build up despite increased water consumption. #ei!ht loss

ensues. $he classical metabolic chan!es that result are collectively called “uremia” or

“uremic poisonin!.”

%lomerular disease is different. %lomerular disease represents more of a filtration

problem rather than a failure to excrete harmful toxins& in fact, !lomerular disease is all

about losin! protein inappropriately throu!h the kidneys. #hile it is certainly possible to

have uremia without !lomerular disease and !lomerular disease without uremia, in many

cases !lomerular disease seems to represent a situation that can pro!ress to uremia.

#'($ I) ( %*+M-*-) (/#(/0

$his illustration shows the “nephron” which is the functional unit of the kidney. $he

kidneys have thousands upon thousands of these and they serve to filter the blood, add intoxins to !et rid of, and balance the blood’s electrolytes and p' by addin! and subtractin!



salts. $he round tuft1like structure at the head of the nephron is the “!lomerulus,” where

blood is filtered.

$he delicate membranes of the !lomerulus, allow salts and very small molecules to passthrou!h while cells and lar!e molecules 2like proteins3 stay in the blood. *ater areas in

the nephron balance the salts and small molecules to make sure we keep and dump themin appropriate amounts but the !lomerulus is the filter that allows our body’s blood

proteins to be conserved. *et’s take a closer look4

$he !lomerulus is the microscopic kidney area that separates urine from blood. 5lood

comes in the afferent arteriole, is filtered in a tuft of capillaries, and then exits throu!h the

efferent arteriole. $he fluid that has been separated out is channeled into the tubules ofthe nephron for further treatment. *et us emphasi6e that the filteration membranes are

very delicate.

#hen !lomerular disease exists, holes are punched out in this filtration system allowin!

lar!e molecules 2like the proteins that one’s body needs to keep3 to enter the urine flowand be urinated away into oblivion.

'+# 7+) $' %*+M-*-) %$ *(8/0



)ources of chronic inflammation are believed to be the ultimate cause of the problem.

$he chronic inflammatory state leads to the circulation of anti!en4antibody complexes in

the blood and these complexes stick in delicate !lomerular membranes like flies in fly paper. +nce stuck there, they call in other inflammatory cells and soon a hole is eaten

into the membrane by the ensuin! reaction. $he holes in the filtration membranes are bi!

enou!h for proteins to traverse.

$here are many are many possible sources of chronic inflammation which could be!eneratin! anti!en4antibody complexes. 9hronic ear or skin infections could be the cause.

*on!1standin! dental disease could do it. ( latent more internal infection mi!ht be the

cause 2such as heartworm, :eline Infectious ;eritonitis, prostate infection, orhrlichiosis3. ven a tumor mi!ht !enerate enou!h of the immune system’s attention to

lead to this sort of reaction.

Kidney failure is one thin !ut "hen it is #o$%ounded !y lo$erular %rotein loss&

sur'i'al is su!stantially redu#ed and %ronosis is $u#h "orse(

'+# I) $' 7I(%+)I) M(70

$here are several common scenarios that mi!ht lead to the dia!nosis of !lomerular

disease.

Protein found in a routine urinalysis

( urinalysis examines a urine sample for some of its chemical contents and properties. ;rotein content is one of the parameters that is checked and semi1

"uantified in a “small, medium or lar!e” amount. +n a urinalysis report this will

be desi!nated as “<,” “<<,” or “<<<.”

$his seems like it would be easy enou!h to interpret but unfortunately there ismore to the story. ( small amount of protein in a well1concentrated sample may

be very normal while the same amount of protein a dilute sample would be hi!hly

si!nificant. 'ow dilute or concentrated the urine is depends on the patient’s waterconsumption and we need a method to examine urine protein that is independent

of the patient’s water consumption.

$o complicate matters more, protein in urine may be a reflection of inflammation

or infection in the urinary bladder 2or even blood contamination of the sample3

http://www.marvistavet.com/html/body_heartworm.html

http://www.marvistavet.com/html/fip.html

http://www.marvistavet.com/html/body_heartworm.html

http://www.marvistavet.com/html/fip.html



and not be related to the kidney at all. $o determine what is !oin! on, there are

two tests that your veterinarian may discuss4

• Urine #ulture

•

Urine Protein*reatinine ratio

$he culture of the urine should find any latent infections 2infection and its

associated inflammation easily increases protein in the bladder3. $he urine

protein4creatinine ratio "uantifies the amount of protein loss in a way that is notdependent on the patient’s water consumption. It is helpful to do the culture first

as a bladder infection will elevate the urine protein4creatinine ratio well into the

abnormal ran!e and lead to the wron! dia!nosis if infection is not ruled out.

If the urine sediment is “active” meanin! there are inflammatory cells in thesample then the patient most likely has infection and culture should be pursued. If

the urine is dilute from the patient’s excess water consumption, it may be prudentto culture the urine to rule out a more latent infection. (lternatively, if thesediment is not “active” 2and especially if the sample is not also dilute3, a recheck

urine sample in a couple of weeks to see if the urine protein is persistin! mi!ht

also be a fair idea. If there is still protein in the urine =1> weeks later, further testsare definitely in order.

S#reenin for Protein Loss After Dianosin Kidney Failure

(fter kidney failure has been discovered, if urine testin! has not yet been done,

performin! a urine tests can lead to important additional information. (!ain we

come to the same two tests4

• Urine #ulture

• Urine %rotein#reatinine ratio

In the kidney failure patient, urine is !enerally very dilute because failure includesinability to concentrate urine?conserve water. $his means that urinalysis clues that

infection is present 2visible bacteria, white blood cells etc.3 will be diluted out.

$he only way to find a latent infection is to culture the sample. If infection and

kidney failure are present to!ether, there is a !ood chance that the infection is

inside the kidney. $his means the antibiotic course must be much lon!er 2>1@weeks3 than it would be for a simple bladder infection. It also means there may be

potential for the kidney to heal with time and for function to be re!ained.;ro!nosis thus improves with documented infection.

+n the other hand, !lomerular disease accompanyin! kidney failure is very bad

news. $he kidney insufficiency is likely to pro!ress much faster when the urine

protein4creatinine ratio is abnormal.



Lo" +lood Al!u$in Le'el found on a !lood %anel

(lbumin is one of those proteins that the body really wants to conserve. $here are

plenty of substances the body needs to circulate that simply are not water solublewhich means they will not simply dissolve in the bloodstream and be pumped

around by the heart. )ubstances that will not dissolve in water, bind to albuminand the albumin carries them around like passen!ers on a subway train. (lbumin

also is important in keepin! water in the bloodstream. 2$his sounds odd but bloodis basically a li"uid and without enou!h water it slud!es and clots abnormally.

:urther, if water is not held in the vasculature, it leaks into other body cavities

such as the chest and abdomen, fillin! these cavities with li"uid.

$here are very few ways that albumin can be depleted.

• #hen an inflammatory process occurs and !lobulin levels rise due to antibody

production, albumin levels will drop in compensation so that the overall blood

protein level does not !et too hi!h. $his is normal compensation and should notlead to a dan!erously low albumin level.

• (lbumin can be lost from the intestinal tract in diseases called protein1losin!

enteropathies. $hese conditions tend to lose albumin as well as other blood proteins throu!h %I tract leaka!e.

• (lbumin is a product of the liver. If the liver fails, there may not be ade"uate

albumin produced.

• (lbumin can be lost throu!h the holes in the kidney membranes caused by

!lomerular disease. :airly advanced !lomerular disease is re"uired to produce anactual drop in blood albumin. +ne would need to beware of “nephrotic syndrome”

2see below3 and treatment would be needed.

• -rine protein4creatinine ratio of AB.C in a stable animal with normal kidney

function

tests 2normal blood creatinine3 can simply be periodically monitored.

• ( urine protein4creatinine ratio of B1= warrants investi!ation into a possible

underlyin! cause.

• ( urine protein4creatinine ratio D= warrants not only investi!ation but also

intervention.

$he International enal Interest )ociety classifies the urine protein4creatinine ratio a

little



differently for animals that are a6otemic 2have an elevated blood creatinine level34

• atios AC.= are considered normal

•

atios of C.=1C.E in do!s and C.=1C.> in cats are considered “borderline proteinuric” and warrant a test = months to see if the condition is pro!ressin!.

• atios DC.E in do!s and DC.> in cats are considered proteinuric and re"uire

intervention.

( biopsy of the kidney is needed to absolutely confirm the dia!nosis of

!lomerulonephritis and classify the !lomerular inflammation further. $his is an invasiveand potentially risky procedure and recently the usefulness of the information !leaned

from biopsy has been "uestioned.

It is much more practical to monitor the urine protein4creatinine ratio thou!h this is not aseasy as it sounds, either. +ne needs to !et an idea of the “baseline” urine

protein4creatinine ratio which means that at least a couple of samples should be checked.

2$he International enal Interest )ociety recommends runnin! the ratio on F samplesover a two week period.3 (fter this, how often the ratio should be rechecked depends on

how the patient is doin! and how the serum creatinine level is doin!.

The urine %rotein#reatinine ratio 'aries !y u% to ,-. a!o'e or !elo"/!aseline0 as a $atter of #ourse( A sinifi#ant #hane in the ratio #aused !y

disease %roression 1u%) or res%onse to thera%y 1do"n) $ust !e reater than ,-.(

I: I$G$I+ I) 9+MM77 #'($ 7+) $'($ M(0

$here are several aspects to treatment and some or all of them may be instituted

dependin! on the needs of the patient.

Lo" %rotein& Lo" sodiu$ diet

Most commercial renal diets would fit in this cate!ory. It seems paradoxical that adisease that causes body protein to be lost would be treated with a protein1

restricted diet but, in fact, supplementin! protein causes albumin to drop faster.

A*E inhi!itor

$hese medications have been shown to reduce renal protein loss. $ypicallyenalapril is recommended for do!s and bena6april is recommended for cats. $hese



medications inherently reduce blood flow to the kidneys so care must be taken in

patients with elevated creatinine ratios to be sure the uremia does not worsen.

*ower doses are used and monitorin! becomes more important.

As%irin

(spirin in very low doses can be used to reduce the tendency for blood to clot 2by

inactivatin! blood platelets3. (!ain, it is important to use low doses so as not to

disturb the kidney’s circulation by disruptin! the prosta!landin balance 2whichcould happen with anti1inflammatory doses of aspirin typically used for pain3.

;atients where nephrotic syndrome is a concern 2see below3 would definitely need

to be concerned about increased blood clottin! tendency.

O$ea , Fatty A#id Su%%le$entation

Most commercial renal diets are fortified with ome!a F fatty acids. $hese anti1

inflammatory fats have been shown to improve survival of do!s with renaldisease. It is still unclear how helpful they are for cats but studies are on!oin!.

;'+$I9 )/7+M

In severe cases of !lomerular disease, a complication called “ephrotic )yndrome” canresult due to the extreme urinary protein loss. ;atients with nephrotic syndrome develop4

• 'i!h blood pressure

• $endency to form abnormal blood clots

• dema 2swellin!3 especially of the le!s and potentially fluid accumulation in a

body cavity.

ephrotic syndrome is defined as the combination of B3 si!nificant protein loss in urine=3 low serum albumin F3 edema or other abnormal fluid accumulation >3 elevated blood

cholesterol level.3 $his is a severe complication and su!!ests a poor pro!nosis especially

if creatinine levels are elevated in the blood. 7iuretics may be needed to supplement theother treatments listed above.

:-$' )+-9)

+ther web pa!es on this subject that mi!ht be helpful4

http4??courses.vetmed.wsu.edu?vmEE=?uro!enital?!n.htm

( bit technical as it is meant as veterinary student education but still has excellent detail.

(* (M/*+I7+)I)4 $' +$' %*+M-*( 7I)()

http://www.marvistavet.com/html/body_glomerulonephritis.html

http://www.marvistavet.com/html/body_glomerulonephritis.html



$here is an additional !lomerular disease that bears mentionin! and this is renal

amyloidosis. 'ere instead of anti!en4antibody complexes dama!in! the tender !lomerular

membranes, an abnormal protein called “amyloid” is deposited in the kidney. $hiscondition is far less treatable and more rapidly pro!ressive. #e hope to have a

supplemental section on this special situation in the near future.

renal protein loss due to inflammation

Documents