Laboratory tests of renal function

Laboratory tests of renal function

Junfu HuangJunfu Huang

Southwestern HospitalSouthwestern Hospital

TMMUTMMU

Anatomy of KidneyAnatomy of Kidney

Functions of the kidneyFunctions of the kidney

Excretion ofExcretion of Metabolite Waste: Metabolite Waste: urea, uric acid,cretinineurea, uric acid,cretinine

Urine Production,regulation of Urine Production,regulation of homeostasis, water, acid base homeostasis, water, acid base balancebalance

Endocrine Function: renin, Endocrine Function: renin, erythropoietin, erythropoietin, 1,25 -1,25 -dihydroxycholecalciferoldihydroxycholecalciferol

Renal function testsRenal function tests

Detect renal damageDetect renal damage Monitor functional damageMonitor functional damage Distinguish between Distinguish between

impairment and failureimpairment and failure

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?

NO Urine!NO Urine!

Clinical Clinical symptomssymptoms

TestsTests

Filter

Processor

InputArterial

OutputVenous

OutputUrine

Where can it break?Where can it break?

Pre-renalPre-renal

RenalRenal

Post-renalPost-renal

Filter

Processor

InputArterial

OutputVenous

OutputUrine

Laboratory tests of renal functionLaboratory tests of renal function

Glomerular Function TestsGlomerular Function Tests Renal Tubular Function TestsRenal Tubular Function Tests

Section 1 Investigation of Glomerular FunctionSection 1 Investigation of Glomerular Function

Renal Blood Flow: 1200-1400ml/minRenal Blood Flow: 1200-1400ml/min Renal Plasma : 600-800ml/minRenal Plasma : 600-800ml/min 20% of plasma: glomerular filtration20% of plasma: glomerular filtration

GFR:Glomerular Filtrtion RateGFR:Glomerular Filtrtion Rate

ConceptConcept

Renal CleranceRenal Clerance

ConceptConcept Virtual volume of plasma from which Virtual volume of plasma from which

the substance in question has been the substance in question has been completely removed during a given time completely removed during a given time interval.interval.

C=UV/PC=UV/P U:urine concentrtion P:plasma con.U:urine concentrtion P:plasma con. V:urine flow rateV:urine flow rate

Usefulness of Renal CleranceUsefulness of Renal Clerance

Freely filtrated, neither secrected,nor Freely filtrated, neither secrected,nor reabsorbed: Inulin:GFR Determinationreabsorbed: Inulin:GFR Determination

Freely Filtrated , small amounts Freely Filtrated , small amounts secreted ,whithout reabsoption:Cretinine:GFRsecreted ,whithout reabsoption:Cretinine:GFR

Free filtrated,completelyeabsorption:GlucoseFree filtrated,completelyeabsorption:Glucose

Tubular Maxima Reabsorption RateTubular Maxima Reabsorption Rate

Inulin CleranceInulin Clerance

Polymer of fructosePolymer of fructose MW:5500MW:5500 Free filtration,without secretion and Free filtration,without secretion and

reabsorptionreabsorption GFRGFR Method Method Reference Interval:2.0-2.3ml/minReference Interval:2.0-2.3ml/min

Endogenous Creatinine ClearanceEndogenous Creatinine Clearance

100g,98% stored in musle,MW:113100g,98% stored in musle,MW:113 Cretine psosphate---cretine—cretinineCretine psosphate---cretine—cretinine Freely filtration, small mounts:secretionFreely filtration, small mounts:secretion Exogenous and Endogenous CreatinineExogenous and Endogenous Creatinine Grossly Investigate the GFRGrossly Investigate the GFR

MethodMethod

24h urine collection method24h urine collection method

modified 4h urine collection methodmodified 4h urine collection method

Clerance CorrectionClerance Correction ：： Ccr x SBSA/IBSACcr x SBSA/IBSA

Plasma ureaPlasma urea

Serected and reabsorbed by Serected and reabsorbed by tubules,freely filrtatedtubules,freely filrtated

quick, simple measurementquick, simple measurement wide reference range 3 - 8 mmol/Lwide reference range 3 - 8 mmol/L sensitive but non-specific index of sensitive but non-specific index of

illnessillness

Factors influencing plasma urea concentration

GIT protein

Kidney filtration

Liver amino acids

Plasma urea

reabsorption excretion

Tissue protein

Distribution volume

Urea excretionUrea excretion

filtered at glomerulusfiltered at glomerulus about 40% filtered urea is reabsorbed about 40% filtered urea is reabsorbed

by renal tubules in healthby renal tubules in health more urea is reabsorbed if rate of more urea is reabsorbed if rate of

tubular flow is slowtubular flow is slow tubular flow rate is slow when there is tubular flow rate is slow when there is

renal hypoperfusionrenal hypoperfusion

Increased plasma ureaIncreased plasma urea

GI bleedGI bleed traumatrauma renal hypoperfusionrenal hypoperfusion

decreased RBFdecreased RBFdecreased ECFVdecreased ECFV

acute renal acute renal impairmentimpairment

chronic renal chronic renal diseasedisease

post-renal post-renal obstructionobstructioncalculuscalculustumourtumour

UreaUrea

Useful test but must be Useful test but must be interpreted with great careinterpreted with great care

Always consider input, output Always consider input, output and patient’s fluid volumeand patient’s fluid volume

Plasma creatininePlasma creatinine

50 - 140 umol/L50 - 140 umol/L increases in concentration as GFR increases in concentration as GFR

decreasesdecreases analytical interferences analytical interferences

(acetoacetate - DKA)(acetoacetate - DKA) NOTNOT proportional to renal damage proportional to renal damage

Plasma CreatininePlasma Creatinine

GFRGFR

[pCreat][pCreat]

140 mL/min140 mL/min0 mL/min0 mL/min

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

Plasma creatinine in chronic renal disease Plasma creatinine in chronic renal disease

May increase to 1000 umol/LMay increase to 1000 umol/L Plot of recipricol of plasma creatinine Plot of recipricol of plasma creatinine

concentration predicts when concentration predicts when intervention is required in end stage intervention is required in end stage renal failurerenal failure

TimeTime

1/ [pCreat]1/ [pCreat]

Plasma Uric AcidPlasma Uric Acid

20%:foods;80%:purine metabolism20%:foods;80%:purine metabolism Small amounts: conjugated with Small amounts: conjugated with

albuminalbumin Free Filtrated,98%-100%:reabsorbedFree Filtrated,98%-100%:reabsorbed Plasma UA concentration: depend on Plasma UA concentration: depend on

glomerular filtration and tubular glomerular filtration and tubular reabsorptionreabsorption

Progression of chronic renal diseaseProgression of chronic renal disease

1

Creatinine clearancemL/min

Plasma change

60 - 120 none

30 - 60 increased creatinine,increased urea

20 - 30 increased potassium,decreased bicarbonate

10 -20 increased phosphate,increased uric acid

Plasma Cystatin CPlasma Cystatin C

Cysteine proteinase inhibitorCysteine proteinase inhibitor Produced by nucleated cellsProduced by nucleated cells MW:13000, free filtration,reabsorbed MW:13000, free filtration,reabsorbed

and metabolized by tubulesand metabolized by tubules Plasma CysC concentrtion: depend on Plasma CysC concentrtion: depend on

glomerular filtrationglomerular filtration

Carbamylated hemoglobinCarbamylated hemoglobin

Urea—blood—cyanate—Hb Urea—blood—cyanate—Hb carbamylated—CarHbcarbamylated—CarHb

ARFARF ：： no changes(1 weeks)no changes(1 weeks) CRF: increaseCRF: increase

Laboratory tests of renal functionLaboratory tests of renal function

glomerular filtration rate glomerular filtration rate impracticalimpractical creatinine clearance creatinine clearance unreliableunreliable plasma creatinine plasma creatinine specific but insensitivespecific but insensitive plasma urea plasma urea subject to problemssubject to problems urine volume urine volume often forgotten!often forgotten!

Section 2 Investigation of Tubular FunctionSection 2 Investigation of Tubular Function

Distal nephron Function testsDistal nephron Function tests

1. Mosenthal test1. Mosenthal test

Concentration dilution testConcentration dilution test

8 AM :Voiding and Discarded8 AM :Voiding and Discarded

10,12,14,16,18,20:00 and 8:00 next day:10,12,14,16,18,20:00 and 8:00 next day:

collecting urine samplescollecting urine samples

Determing the urine volume and gravityDeterming the urine volume and gravity

2.Urine Osmolarity2.Urine Osmolarity 3.Acute Oliguria3.Acute Oliguria

Prenal?Prenal?

Renal?Renal?

Proximal tubular Function testsProximal tubular Function tests

1.Low MW proteins in urine1.Low MW proteins in urine

2.Tubular maximal glucose reabsorption2.Tubular maximal glucose reabsorption

3.Tubular maximal PAH secretion3.Tubular maximal PAH secretion

4.Amino acide in urine4.Amino acide in urine

Fanconi SyndromeFanconi Syndrome

Section 3 Effective Renal Blood FlowSection 3 Effective Renal Blood Flow

Isotope Method:Isotope Method:131131I-OIHI-OIH PAH Clearance:PAH Clearance:

20%:filtrated,80%:secreted by tubules20%:filtrated,80%:secreted by tubules

Section 4 Investigation of renal tubular acidosisSection 4 Investigation of renal tubular acidosis

Tubular Acidosis:I,II,III.IVTubular Acidosis:I,II,III.IV I:distal formI:distal form II:proximal formII:proximal form

NH4Cl Loading TestNH4Cl Loading Test

Oral administration of NH4ClOral administration of NH4Cl Artificial Metabolic AcidosisArtificial Metabolic Acidosis Urine Sample CollectionUrine Sample Collection pH determinationpH determination

Fraction of HCO3- excretionFraction of HCO3- excretion

HCOHCO33--:85-90%: reabsorbed by proximal :85-90%: reabsorbed by proximal

tubules; 10-15%: reabsorbed by distal tubulestubules; 10-15%: reabsorbed by distal tubules Oral Administration of NaHCOOral Administration of NaHCO33

Urine CollectionUrine Collection Determination of PDetermination of PCrCr,U,UCrCr,P,PHCO3HCO3,U,UHCO3HCO3

Caculation:Caculation:

FEFEHCO3HCO3=U=UHCO3HCO3.P.PCrCr/U/UCrCr.P.PHCO3HCO3