Renal function- basic datafor students and residentsRenal function- basic datafor students and residents

Department of PaediatricsDepartment of Paediatrics

Section for Pediatric Nephrology Section for Pediatric Nephrology

University Hospital Motol, Prague University Hospital Motol, Prague

Functions of the kidneyFunctions of the kidney

regulation e.g. homeostasis,regulation e.g. homeostasis,

water, acid/basewater, acid/base

excretion e.g. urea, creatinineexcretion e.g. urea, creatinine

endocrine endocrine e.g.e.g. renin, renin,

erythropoietin, erythropoietin,

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

Renal function testsRenal function tests

detect renal detect renal damagedamage

monitor functional monitor functional damagedamage

help determine help determine etiologyetiology

Laboratory tests of renal functionLaboratory tests of renal function

glomerular filtration glomerular filtration raterate (GFR) (GFR)

plasma creatinineplasma creatinine plasma ureaplasma urea urine volumeurine volume urine ureaurine urea minerals in urineminerals in urine

urine proteinurine protein urine glucoseurine glucose hematuriahematuria osmolalityosmolality

Kidney FunctionKidney Function

A plumbers viewA plumbers view

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OutputVenous

OutputUrine

Kidney – basic dataKidney – basic data

UUrine excreted dailyrine excreted daily in adults: in adults: ccacca 1.5L 1.5L KKidney only idney only ca ca 1% of total body weight1% of total body weight, despite it, despite it The renal bThe renal blood flowlood flow== 20% of 20% of cardiac outputcardiac output Plasma renal flow= PRF ca 600 mL/Plasma renal flow= PRF ca 600 mL/MMin./1.73 Min./1.73 M2 2

Reflects two processes Reflects two processes UltrafiltrationUltrafiltration (GFR) (GFR): 180: 180 L/dayL/day Reabsorption: >99%Reabsorption: >99% of the amount filtered of the amount filtered

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

Decreased urine Decreased urine productionproduction

Clinical Clinical symptomssymptoms

TestsTests

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Where can it break?Where can it break?

Pre-renalPre-renal

RenalRenal (intrarenal)(intrarenal)

Post-renalPost-renal (obstruction)(obstruction)

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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

Tests of renal functionTests of renal function

glomerular filtration glomerular filtration raterate=GFR=GFR

plasma creatinineplasma creatinine= P= Pcrcr

plasma ureaplasma urea-P-Pureaurea

urine volumeurine volume= V= V urine urea-urine urea- U Uureaurea

cystatin C in plasma?cystatin C in plasma?

urine proteinurine protein urine glucoseurine glucose hematuriahematuria osmolalityosmolality

Renal Function Tests- Urine volumes

Renal Function Tests- Urine volumes

AAddults: ults: 1.5 L/24 h1.5 L/24 h

typical in healthtypical in health, , oliguria < 400 mLoliguria < 400 mL, , anuria < 100 mLanuria < 100 mL, , polyuria > 3000 mLpolyuria > 3000 mL Children: ca 1.5 ml/Kg Children: ca 1.5 ml/Kg

of b.w./1 hour! of b.w./1 hour!

Principle of of ClearancePrinciple of of Clearance

Some substances when filtered enter the tubules Some substances when filtered enter the tubules are are not reabsorbed and so not reabsorbed and so 100% excreted100% excreted= = GFR (inulin= gold standard for GFR, GFR (inulin= gold standard for GFR, creatinine (but this one partially reabsorbed, creatinine (but this one partially reabsorbed, particularly in uremia, then cparticularly in uremia, then clearancelearance <GFR<GFR

Some substances are filtered, enter tubules, and Some substances are filtered, enter tubules, and more of the substance more of the substance is secreted is secreted enters the enters the tubules by excretion. Clearance>GFRtubules by excretion. Clearance>GFR

Some substances are filtered, enter tubules,Some substances are filtered, enter tubules, but but are completely reabsorbed, so they did not are completely reabsorbed, so they did not reach the final urine (e.g. cystatin C) reach the final urine (e.g. cystatin C)

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 inulin, creatinine, EDTA and clearence of inulin, creatinine, EDTA and

DTPA (DTPA (==both derivates of acetic acid), cystatin both derivates of acetic acid), cystatin C C

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

Also service of nuclear medicine dptm.Also service of nuclear medicine dptm. Follow up the inulin clearence, EDTA or Follow up the inulin clearence, EDTA or

DTPA clearence labelling the substances DTPA clearence labelling the substances with chromium or Tcwith chromium or Tcm99 m99

Where will you catch the activity with Where will you catch the activity with detectors? detectors?

Never in the kidney or bladder area!!Never in the kidney or bladder area!!

Glomerular filtration rateGlomerular filtration rate

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

Schwartz equationSchwartz equation : : GFR= GFR= v v xx 0.808 0.808

PPcrcr

(umol/L) (umol/L)

How to assess easy if plasma creatinine is OK?How to assess easy if plasma creatinine is OK?

PPcrcr max= V max= Vcmcm x 0.61 (v= body height in cm x 0.61 (v= body height in cm

Creatinine and Urea Plasma Concentration- hyperbolic correlation

Creatinine and Urea Plasma Concentration- hyperbolic correlation

GFRGFR 50% 50%

pCr,pCr,pUreapUrea

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

00 mL/minmL/min(0%)(0%)

Tendency in individual patients Tendency in individual patients is is more important than the more important than the one value, one value, ever test if the hydration is OK. In ever test if the hydration is OK. In patients with CRI always note also patients with CRI always note also the BSA! the BSA! Lower limit today not 80 ml/Min. Lower limit today not 80 ml/Min. /1.73 m/1.73 m2 2 but 90 ml/Min./1.73 mbut 90 ml/Min./1.73 m22

NormalNormal rangerange->->

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

Urea cycleUrea cycle

CO2CO2NH3NH3

aspartateaspartate

UreaUrea

3 ATP3 ATP

UreaUreaCycleCycle

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

UreaseUreasesolutionsolution

Urea + 3H2OUrea + 3H2O

HCO3¯ + 2NH4 + OH¯HCO3¯ + 2NH4 + OH¯

ureaseurease

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

Urea EF may be useful in pts. on diureticsUrea EF may be useful in pts. on diuretics

Plasma creatinine and renal functionsPlasma creatinine and renal functions

CreatineCreatine: main storage compound of hi: main storage compound of high gh energy phosphate needed for muscle metabolism energy phosphate needed for muscle metabolism..

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

CreatineCreatine CreatinineCreatinine

((Waste product)Waste product)H2OH2O

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

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))

Analytical methods (Cr) Analytical methods (Cr)

Normal rNormal rangeange P Pcrcr

Male 0.6-1Male 0.6-1..2 mg/dL2 mg/dL,,

Female 0.5-1.0 mg/dLFemale 0.5-1.0 mg/dL

Be careful in children!!Be careful in children!!

Remember theRemember the max. max. plasma creatinine plasma creatinine value!! value!!

BUN: creatinine ratio BUN: creatinine ratio

Pre-renalPre-renal disorders disorders BUN:Cr ratio >20BUN:Cr ratio >20

RenalRenal disorders disorders BUN:BUN: Cr nl but both Cr nl but both

elevatedelevated Post-renalPost-renal

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OutputUrine

Osmolality of urineOsmolality of urine

Measures urine concentrating abilityMeasures urine concentrating ability Depends on # of particles, not size or chargeDepends on # of particles, not size or charge Largely due to ADH (Largely due to ADH (aanti-nti-ddiuretic iuretic hhormone)ormone) Can reach maximum of 1200 mOsm/LCan reach maximum of 1200 mOsm/L Normal range:Normal range: 300-900mOsm/L300-900mOsm/L, plasma 285, plasma 285++1010 prior to collection, fluid intake restricted, first prior to collection, fluid intake restricted, first

void submitted for evaluationvoid submitted for evaluation MeasurMeasuring using the fact of ing using the fact of freezing point freezing point

depressiondepression

Standardized renal concentration capacity test

Standardized renal concentration capacity test

11. Voiding completely at 9 p.m. (WC). Voiding completely at 9 p.m. (WC) 22. Desmopressin administration (since 2006 as . Desmopressin administration (since 2006 as

nasal spray). nasal spray). DDAVP is a Czech invention !!DDAVP is a Czech invention !! 33. Collection of urine (9 p.m. – 7 a.m.). Collection of urine (9 p.m. – 7 a.m.) 4. 4. TTesting of urine osmolality in this sample (not esting of urine osmolality in this sample (not

tthe morning urine onlyhe morning urine only!)!) 5. 5. The lower limit of normal value= 950 The lower limit of normal value= 950

mOsm/kg of urinemOsm/kg of urine 6. Short testing- Desmopressin, collection for 4 6. Short testing- Desmopressin, collection for 4

hours only= at least 900 mOsm/kg of urine hours only= at least 900 mOsm/kg of urine

Urine dipsticksUrine dipsticks

Strip impregnated with reagents for the substances in Strip impregnated with reagents for the substances in question within a urine samplequestion within a urine sample

Substance level can be altered in the setting of pathology Substance level can be altered in the setting of pathology within the urinary tractwithin the urinary tract

Measured substances:Measured substances: Modern dipsticks with multiplied zones:Modern dipsticks with multiplied zones:

Protein, hemoglobin, glucose, Protein, hemoglobin, glucose, urobilinogen, urobilinogen, nitrite, nitrite, leukocytes,leukocytes, specific gravity, and pH specific gravity, and pH

Should be a tool everywhere on the level of primary Should be a tool everywhere on the level of primary carecare!!!!!!