Renal Function Renal Function

Dr Manal AbdAllaDr Manal AbdAlla

Associate Professor Clinical Associate Professor Clinical PathologyPathology

Renal FunctionRenal Function

Renal AnatomyRenal Anatomy KidneysKidneys Bilateral uretersBilateral ureters NephronsNephrons1.1. GlomerulusGlomerulus2.2. Proximal convuluting tubulesProximal convuluting tubules3.3. Loop of HenleLoop of Henle4.4. Ascending Loop of HenleAscending Loop of Henle5.5. Distal convuluting tubulesDistal convuluting tubules6.6. Collecting ductsCollecting ducts

Functions of the kidneyFunctions of the kidney

regulationregulation e.g. homeostasis, e.g. homeostasis,

water, acid/base and electrolyteswater, acid/base and electrolytes

excretionexcretion e.g. urea, creatinine e.g. urea, creatinine and uric acidand uric acid

endocrineendocrine e.g.e.g. renin, renin,

Erythropoietin and Erythropoietin and prostaglandin prostaglandin

1,25 dihydroxycholecalciferol1,25 dihydroxycholecalciferol- - conversion only in kidney! conversion only in kidney!

The major NPN eliminated The major NPN eliminated by the renal systemby the renal system

1.1. UreaUrea

2.2. CreatinineCreatinine

3.3. Uric acid Uric acid

4.4. ammoniaammonia

Indication of Renal function tests

Indication of Renal function tests

Assessment of Assessment of renal diseasesrenal diseases

Detection of water Detection of water balance disorderbalance disorder

Evaluation of acid Evaluation of acid base state disorderbase state disorder

Renal functionRenal function

Glomural function Glomural function :: Filtration of plasmaFiltration of plasma Tubular functionTubular function:: ReabsorbtionReabsorbtion SecretionSecretion SynthsisSynthsis

FiltrateFiltrate isToxic waste isToxic waste products and products and Substance valuable Substance valuable to bodyto body

The kidney return The kidney return the valuable the valuable substance and substance and excrete the toxic wast excrete the toxic wast productsproducts

Kidney FunctionKidney Function

A plumbers viewA plumbers view

Filter

Processor

InputArterial

OutputVenous

OutputUrine

How do you know it’s broken?How do you know it’s broken?

Decreased urine Decreased urine productionproduction

Clinical Clinical symptomssymptoms

TestsTests

Filter

Processor

InputArterial

OutputVenous

OutputUrine

Where can it break?Where can it break?

Pre-renalPre-renal

RenalRenal (intrarenal)(intrarenal)

Post-renalPost-renal (obstruction)(obstruction)

Filter

Processor

InputArterial

OutputVenous

OutputUrine

Causes of kidney functional disordersCauses of kidney functional disorders

Pre-renal Pre-renal e.g. e.g. decreased decreased intravascular intravascular volumvolum

Renal Renal e.g. e.g. acute acute tubular necrosistubular necrosis

Postrenal Postrenal e.g.e.g. ureteral ureteral obstructionobstruction

Renal function tests Renal function tests

Renal function tests include :Renal function tests include :Blood urea and blood urea Blood urea and blood urea

nitrogen nitrogen Serum creatinine Serum creatinine Creatinine clearence Creatinine clearence Serum uric acidSerum uric acidUrine analysis Urine analysis

Nonprotein Nitrogen (NPN)Nonprotein Nitrogen (NPN)

Monitored through renal (kidney) Monitored through renal (kidney) functions by measuring excretion or functions by measuring excretion or absorption of by products.absorption of by products.

Consist of 15 compounds that can be Consist of 15 compounds that can be analyzed to monitor renal functionsanalyzed to monitor renal functions

Nonprotein Nitrogen (NPN)Nonprotein Nitrogen (NPN)

Monitored through renal (kidney) Monitored through renal (kidney) functions by measuring excretion or functions by measuring excretion or absorption of by products.absorption of by products.

Consist of 15 compounds that can be Consist of 15 compounds that can be analyzed to monitor renal functionsanalyzed to monitor renal functions

UreaUrea: Blood Urea Nitrogen or BUN :: Blood Urea Nitrogen or BUN :

Constitutes Constitutes ½ of the NPN substances in ½ of the NPN substances in circulating blood.circulating blood.

Synthesized in the liver from COSynthesized in the liver from CO22 and and NHNH44 arising from deamination of A.A. by arising from deamination of A.A. by the Kreb cycle.the Kreb cycle.

Transported by plasma to kidneys and Transported by plasma to kidneys and filtered by the glomerulus.filtered by the glomerulus.

Most urea is excreted in urineMost urea is excreted in urine 40% is reabsorbed by renal tubules. This 40% is reabsorbed by renal tubules. This

is good indicator of renal function.is good indicator of renal function.

Plasma urea (BUN)Plasma urea (BUN)

= BUN (= BUN (bblood lood uurea rea nnitrogen)itrogen)Urea: product of protein catabolismUrea: product of protein catabolismSynthesized by liver,Synthesized by liver, m majority ajority

excreted by kidneyexcreted by kidney, partially , partially reabsorbed in tubulireabsorbed in tubuli

Plasma concentration increases with Plasma concentration increases with decreased GFRdecreased GFR

Blood Urea Nitrogen (BUN)Blood Urea Nitrogen (BUN)

Urea is the major end product of protein and Urea is the major end product of protein and amino acid catabolism and it is generated in amino acid catabolism and it is generated in the liver through the urea cycle. Most of the the liver through the urea cycle. Most of the urea is ultimately excreted by the kidneys.urea is ultimately excreted by the kidneys.

Urea is freely filtered by the glomeruli. Urea is freely filtered by the glomeruli. depending on the state of hydration and depending on the state of hydration and therefore the rate of urine flow, 40% to 80% therefore the rate of urine flow, 40% to 80% of the filtered urea is passively reabsorbed of the filtered urea is passively reabsorbed with water, mostly in the proximal tubules. with water, mostly in the proximal tubules.

Plasma UreaPlasma Urea

Reference range Reference range 15- 40 mg / dl 15- 40 mg / dl

Causes of increased plasma urea Causes of increased plasma urea : Pre-renal: Pre-renal::

High protein diet High protein diet

DehydrationDehydration

CHFCHF

Catabolic state (fever-trauma-burn )Catabolic state (fever-trauma-burn )

GIT haemorrhageGIT haemorrhage

These conditions are accompanied by normal serum These conditions are accompanied by normal serum creatinine levelcreatinine level

Plasma UreaPlasma Urea

Renal causesRenal causes: decreased excretion : decreased excretion

Loss of functioning nephrons e.g. acute or chronic Loss of functioning nephrons e.g. acute or chronic glomuerulonephritis, and acute chronic renal failureglomuerulonephritis, and acute chronic renal failure

Both urea and creatinine are increased proportionallyBoth urea and creatinine are increased proportionally

Postrenal causes Postrenal causes ::

Obstruction of the urinary tract by :stones, enlarged Obstruction of the urinary tract by :stones, enlarged prostateprostate

Both urea and creatinine are increased but the Both urea and creatinine are increased but the increased urea is more than creatinineincreased urea is more than creatinine

Prerenal:Prerenal: related to the renal circulation. related to the renal circulation. The flow of blood to the kidney’s.The flow of blood to the kidney’s.

Ex: Urea goes through the kidneys for Ex: Urea goes through the kidneys for excretion and reabsorption. If there is a excretion and reabsorption. If there is a prerenal problem, the urea doesn’t make prerenal problem, the urea doesn’t make it to the kidney’s to be filtered, so there is it to the kidney’s to be filtered, so there is an increase or build-up of urea in the an increase or build-up of urea in the blood.blood.

Diseases:Diseases: Congested Heart Failure, Shock, Congested Heart Failure, Shock, Hemorrhage, dehydrationHemorrhage, dehydration

Azotemia: Increased in urea in the blood .Azotemia: Increased in urea in the blood .

RenalRenal: involves the kidney – there is a : involves the kidney – there is a lack of ability to function correctly- lack of ability to function correctly- decrease ability to excrete.decrease ability to excrete.

Decrease renal function see an Decrease renal function see an increase in blood urea levels.increase in blood urea levels.

Diseases:Diseases: acute/chronic renal acute/chronic renal failure, glomerulonephritis, tubular failure, glomerulonephritis, tubular necrosis, chronic nephritis, necrosis, chronic nephritis, polycystic kidney.polycystic kidney.

Renal: involves the kidney – there is a Renal: involves the kidney – there is a lack of ability to function correctly- lack of ability to function correctly- decrease ability to excrete.decrease ability to excrete.

Decrease renal function see an Decrease renal function see an increase in blood urea levels.increase in blood urea levels.

Diseases: acute/chronic renal Diseases: acute/chronic renal failure, glomerulonephritis, tubular failure, glomerulonephritis, tubular necrosis, chronic nephritis, necrosis, chronic nephritis, polycystic kidney.polycystic kidney.

Post renalPost renal: obstruction of the flow of : obstruction of the flow of the urine from the kidneys. Kidney the urine from the kidneys. Kidney function impaired- unable to excrete function impaired- unable to excrete normally.normally.

DiseasesDiseases: Kidney stone, tumor, UTI : Kidney stone, tumor, UTI or other sever infectionor other sever infection

Enzymatic conductivity rate method for measuring ureaEnzymatic conductivity rate method for measuring urea

UreaseUreasesolutionsolution

Urea + H2OUrea + H2O

2NH4 +Co22NH4 +Co2

NH4+salicylate+NaCIO NH4+salicylate+NaCIO by action of by action of nitroprusside results in nitroprusside results in IndophenolIndophenol

ureaseurease

Decreased Plasma ureaDecreased Plasma urea

causas of decreasa urea:causas of decreasa urea: Severe prolonged starvation Severe prolonged starvation Malabsorbtion (low amino acid )Malabsorbtion (low amino acid ) Severe chronic liver diseasesSevere chronic liver diseases Decreased urea find in Decreased urea find in

overdilution in cases of increased overdilution in cases of increased secretion of ADHsecretion of ADH

Excessive plasma dilution in I.V Excessive plasma dilution in I.V

Urea in patients with kidney diseases

Urea in patients with kidney diseases

Useful test but must be interpreted with great Useful test but must be interpreted with great carecare, urea plasma level is more than , urea plasma level is more than creatinine dependent on protein intake creatinine dependent on protein intake Most useful when considered along with Most useful when considered along with creatininecreatinine

High in high protein intake, low in severe liver High in high protein intake, low in severe liver dysfunction dysfunction

UreaUrea level normaly 2.5 -6.6 mmol/L level normaly 2.5 -6.6 mmol/L

Urea cycleUrea cycle

CO2CO2NH3NH3

aspartateaspartate

UreaUrea

3 ATP3 ATP

UreaUreaCycleCycle

Urea Urea

Blood urea nitrogen (BUN) = blood urea Blood urea nitrogen (BUN) = blood urea / 2.14 / 2.14

Normal blood urea nitrogen =7 – 18 Normal blood urea nitrogen =7 – 18 mg/dl (2.5 – 6.5 mmol / l )mg/dl (2.5 – 6.5 mmol / l )

Normal blood urea = 20 – 40 mg/dl Normal blood urea = 20 – 40 mg/dl Mgm /dl x o.36 = mmol/lMgm /dl x o.36 = mmol/l

creatininecreatinine

Creatine: synthesized in the liver Creatine: synthesized in the liver from arginine, glycine and from arginine, glycine and methionine. Transported to methionine. Transported to muscles to be converted to muscles to be converted to phosphocreatine- energyphosphocreatine- energy..

creatininecreatinine

Muscles creatine phosphate Muscles creatine phosphate is reservoir of phosphoryl is reservoir of phosphoryl group needed for formation group needed for formation of ATP as catalyzed by of ATP as catalyzed by creatine kinase creatine kinase enzyme(CK) enzyme(CK)

Plasma creatinine and renal functionsPlasma creatinine and renal functions

Creatine phosphate +ADP+H produce Creatine phosphate +ADP+H produce

Creatinine: anhydride of creatine!Creatinine: anhydride of creatine!

ATP + Creatine ATP + Creatine CreatinineCreatinine

((Waste product)Waste product)H2OH2O

creatininecreatinine

In most circumstances the measurement of In most circumstances the measurement of plasma plasma creatinine can provide a creatinine can provide a specific specific test test of glomerular function. Serumof glomerular function. Serum creatinine concentration is often creatinine concentration is often interpreted as a measure of glomeurlar interpreted as a measure of glomeurlar filtration rate and is used as an index filtration rate and is used as an index of renal function in clinical practice.of renal function in clinical practice.

..

creatininecreatinine The reference range is wide. . Its level The reference range is wide. . Its level

is function of muscle mass affected is function of muscle mass affected greatly by changes in greatly by changes in muscle mass. muscle mass. Plasma creatinine should not be Plasma creatinine should not be measured until 8 hours after a measured until 8 hours after a meal meal as there is some evidence that the as there is some evidence that the concentration increases after meat concentration increases after meat ingestion.ingestion. Insensitive monitor- see Insensitive monitor- see after >50% of damage has occurred.after >50% of damage has occurred.

creatininecreatinine

Everyday up to 20 % of Everyday up to 20 % of muscle creatine and its muscle creatine and its phosphate dehydrates phosphate dehydrates and cycles to form and cycles to form creatinine ( waste creatinine ( waste products )products )

CreatinineCreatinine

Creatin is waste product of Creatin is waste product of muscle metabolismmuscle metabolism

Urea is waste product of Urea is waste product of protein metabolismprotein metabolism

Creatinine Creatinine

Creatinine molecular weight is Creatinine molecular weight is 113 it is ready filtered by the 113 it is ready filtered by the glomurli and unlike urea not glomurli and unlike urea not reabsorbed by renal reabsorbed by renal tubules .However small amounts tubules .However small amounts secreted by the renal tubules at secreted by the renal tubules at high serum concentration high serum concentration

creatininecreatinine

Normal level = 55 – 120 Normal level = 55 – 120 micromole / litermicromole / liter

Or 0.7 – 1.4 mgm /dlOr 0.7 – 1.4 mgm /dl

CrCr

A better index would A better index would related creatinine to related creatinine to muscle mass or lean muscle mass or lean body weightbody weight

CrCr By virtue of its relative independence By virtue of its relative independence

from such factors as diet (protein from such factors as diet (protein intake), degree of hydration, and protein intake), degree of hydration, and protein metabolism, the plasma creatinine is a metabolism, the plasma creatinine is a significantly more reliable screening significantly more reliable screening test or index of renal function than is test or index of renal function than is the BUN.the BUN.

The plasma creatinine tends to increase The plasma creatinine tends to increase somewhat more slowly than the BUN in somewhat more slowly than the BUN in renal disease but also decreases more renal disease but also decreases more slowly with hemodialysis.slowly with hemodialysis.

Evaluate with BUN as a ratio to help Evaluate with BUN as a ratio to help differentiate between renal and differentiate between renal and prerenal disease of azotemia.prerenal disease of azotemia.

Increase ratio: prerenal (shock, Increase ratio: prerenal (shock, CHF, dehydration)CHF, dehydration)

Decrease ratio: renalDecrease ratio: renal

Analytical methods:Analytical methods:

1.1. Jaffe:Jaffe: Colormetric method: looks for a red Colormetric method: looks for a red

to orange color change.to orange color change. Utilizes picric acidUtilizes picric acid Disadvantage: nonspecific and Disadvantage: nonspecific and

subject to interference from subject to interference from pyruvate glucose, ascorbate and pyruvate glucose, ascorbate and acetone.acetone.

2.2. Fuller method:Fuller method: More accurateMore accurate Use’s fuller’s earth or Lloyd Use’s fuller’s earth or Lloyd

reagentreagent Use a protein free filter for the Use a protein free filter for the

sample- less interference.sample- less interference.

3.3. Kinetic Jaffe:Kinetic Jaffe: Various enzymatic methodsVarious enzymatic methods Utilizes reagent picirate- measures Utilizes reagent picirate- measures

rate of color change in absorbance rate of color change in absorbance @ 520nm @ 20 seconds and 80 @ 520nm @ 20 seconds and 80 seconds.seconds.

Disadvantage: substance Disadvantage: substance interferenceinterference

Advantage: inexpensive, rapid and Advantage: inexpensive, rapid and easy.easy.

Specimen: Serum, plasma Specimen: Serum, plasma or urineor urine

Avoid hemolysis, lipemic, Avoid hemolysis, lipemic, and ictericand icteric

Urine needs to refrigerated.Urine needs to refrigerated.

Jaffe´ reaction for measuring creatinine, simple, but better is enzymatic method

Jaffe´ reaction for measuring creatinine, simple, but better is enzymatic method

Creatinine + alkaline picrate solutionCreatinine + alkaline picrate solution

Bright orange/red colored complexBright orange/red colored complexabsorbs light at 485nmabsorbs light at 485nm

(many interfering substances in blood(many interfering substances in bloodCan be minimized using rate methodCan be minimized using rate method))

Decreased plasma CreatinineDecreased plasma Creatinine

In sever muscle wasting diseasesIn sever muscle wasting diseases In cases of starvationIn cases of starvation In vegetarian personIn vegetarian person Treatment with corticosteroid( protein Treatment with corticosteroid( protein

catabolic effect )catabolic effect ) Pregnancy due to dilutionPregnancy due to dilution

Plasma CreatininePlasma Creatinine

Causes of increased serum creatinine Causes of increased serum creatinine : : Pre-renal Pre-renal : e.g., impaired renal blood flow as in : e.g., impaired renal blood flow as in

decreased blood bressure , fluid depletion and decreased blood bressure , fluid depletion and renal artery stenosis renal artery stenosis

Renal causes Renal causes : Loss of the functioning nephrons : Loss of the functioning nephrons as in acute or chronic glom. Nephritits and as in acute or chronic glom. Nephritits and acute or chronic renal failure acute or chronic renal failure

Post – renal Post – renal causes : Obstructioncauses : Obstruction

Plasma creatininePlasma creatinine

Other causas of increase Other causas of increase creatininecreatinine

Large muscle massLarge muscle mass High meat intake in dietHigh meat intake in diet Vigrous muscle exerciseVigrous muscle exercise Analytical errors as in case of Analytical errors as in case of

medication such as medication such as acetoacetate ,cephalosporin,salsylacetoacetate ,cephalosporin,salsylate and cemitidineate and cemitidine

Plasma creatinine vs. GFRnot linear, hyperbolic correlation!

Plasma creatinine vs. GFRnot linear, hyperbolic correlation!

GFRGFR

[pCreat][pCreat]

140 mL/min140 mL/min(100%)(100%)

0 mL/min0 mL/min(0%)(0%)

Change within an Change within an individual patient is usually individual patient is usually more important than the more important than the absolute valueabsolute value

Creatinine ClearanceCreatinine Clearance

It is the amount of plasma which is completely cleared from It is the amount of plasma which is completely cleared from creatinine per unite time creatinine per unite time

Normal level 70 – 110 ml/minNormal level 70 – 110 ml/min

Clearance of a substance is the volume of plasma Clearance of a substance is the volume of plasma from which the substance is cleared in the urine from which the substance is cleared in the urine in a unit timein a unit time

Many substance can be used for clearance as Many substance can be used for clearance as urea , creatinine and inuline urea , creatinine and inuline

Creatinine ClearanceCreatinine Clearance

Creatinine is the best used Creatinine is the best used substance because : substance because :

It is endogenous substance It is endogenous substance synthesized at a constant rate synthesized at a constant rate

It is filtered by the glom. And not It is filtered by the glom. And not reabsorbed and is only slightly reabsorbed and is only slightly secreted by PCT secreted by PCT

It is analysed inexpensivelyIt is analysed inexpensively

Glomerular filtration rateGlomerular filtration rate

Glomerular filtrationGlomerular filtration== major physiologic major physiologic responsibility of kidneyresponsibility of kidney, , GFR used as index of GFR used as index of overall excretory functionoverall excretory function

Methods:Methods: clearence of creatinineclearence of creatinine

GFRGFR= = UUxx x V x V (V=volum of urine/ 1 (V=volum of urine/ 1 mminute or 1 second)inute or 1 second)

P P xx x= clearence of substance usedx= clearence of substance used

Glomerular filtration rateGlomerular filtration rate

GGFR in children, value always FR in children, value always adapted to the BSA!! Ideal BSA adapted to the BSA!! Ideal BSA in adults is 1.73min adults is 1.73m22

Ratio Ratio

Blood urea nitrogen /creatinine Blood urea nitrogen /creatinine ratio = 20 : 1 ratio = 20 : 1

High ratio means increased urea High ratio means increased urea this occures in pre-renal causes this occures in pre-renal causes

Increased urea but normal Increased urea but normal creatinine creatinine

RatioRatio

Normal ratio with marked increas in Normal ratio with marked increas in urea and creatinine is seen in renal and urea and creatinine is seen in renal and postrenal causes postrenal causes

Uric AcidUric Acid

Uric acid is the end product of the Uric acid is the end product of the metabolism of purinesmetabolism of purines

Uric acid is filtered at the glomeruli, Uric acid is filtered at the glomeruli, reabsorbed in the proximal convoluted reabsorbed in the proximal convoluted tubule, followed by secretion in the tubule, followed by secretion in the lower portion of the proximal tubule, and lower portion of the proximal tubule, and further reabsorption in the distal tubulefurther reabsorption in the distal tubule