2. INDICATIONS FOR KIDNEYFUNCTION TESTS
1. Early identification of impairment of renal function
in patients with increased risk of chronic renal
disease
2. Diagnosis of renal disease
3. Follow the course of renal disease and assess
response to treatment.
4. Plan renal replacement therapy (dialysis or renal
transplantation) in advanced renal disease.
5. Adjust dosage of certain drugs (e.g.
chemotherapy) according to renal function
3. Classificationof kidney functiontests
Teststo evaluateglomerular
function
1. Clearance tests to measure
glomerular filtration rate:
Creatinine clearance, and
Urea clearance
2. Calculation of cr clearance
from prediction equation
3. Blood biochemistry: sr. cr,
BUN, BUN/sr. cr
4. Microalbuminuria and
albuminuria
Teststo evaluatetubular
function
1. Tests to assess proximal
tubular function:
• Glycosuria,
phosphaturia,
uricosuria
• Aminoaciduria
• Tubular proteinuria
• Fractional sodium excretion
2. Test to asses distal
tubular function:
• Specific gravity and
osmolality of urine
• Water deprivation test and
water loading test
• Ammonium chloride loading
4. Glomerular Filteration Rate(GFR)
• Rateatwhichfluidpassintonephronsafterfiltration
• Besttest for assessmentof excretoryrenalfunction
• Variesaccordingto age,sex,andbodyweight of an
individual.
• NormalGFR in youngadultsis120-130ml/min per1.73m2.
• Creatinineclearanceiscommonlyusedasameasureof GFR.
Equationscanbeusedto estimate GFRfrom serum
creatininevalue.
• GFR declineswith age(duetoglomerular
arteriolosclerosis)
5. Following methods are used to measure GFR:
(1) Clearance tests and
(2) Prediction equations.
• If a substance is not bound to protein in plasma, is completely
filtered by the glomeruli, and is neither secreted nor
reabsorbed by the tubules, then its clearance rate is equal to
the glomerular filtration rate (GFR).
• Clearance of asubstancerefers to the volume of plasma, whichis
completely cleared of that substanceper minute; it is calculated
from the followingformula:
• Clearance = UV/P where,
U=concentration of asubstance in urine inmg/dl;
V=volume of urine excreted in ml/min; and
P=concentration of the substancein plasma inmg/dl.
6.
7. • Theagent used for measurement of GFR
should have following properties:
(1)It should be physiologically inert andpreferably
endogenous,
(2)It should be freely filtered by glomeruli and
should be neither reabsorbed nor secretedby
renal tubules,
(3)It should not bind to plasma proteins and should
not be metabolized by kidneys,and
(4)It should be excreted only by the kidneys.
However, there is no such ideal endogenousagent
8. Theagentsusedfor measurementof GFR are
• Exogenous:Inulin, Radiolabelled ethylenediamine
tetraacetic acid(51Cr-EDTA),125I-iothalamate
• Endogenous:Creatinine,Urea,CystatinC
9. • Onemajor problem with clearance studiesis
incomplete urine collection.
• Abnormal clearance occursin:
(i) pre-renal factors: reduced blood flow dueto
shock, dehydration, and congestive cardiac
failure;
(ii) renal diseases;and
(iii) obstruction to urinaryoutflow.
10. LIMITATIONS FOR GFR
• AKI
• PREGNANCY
• AGE<18 YEARS
• LESS RELIABLE IN MALNOURISHED
• UNDER ESTIMATE NEAR NORMAL VALUES
• ELDERLY PERSONS
11. InulinClearance
• Inulin- inert plant polysaccharide (a fructose polymer)
• filtered by the glomeruli
• Method- A bolus dose of inulin (25 ml of 10% solution IV) is
administered followed by constant intravenous infusion (500
ml of 1.5% solution at the rate of 4 ml/min). Timed urine
samples are collected and blood samples are obtained at the
midpoint of timed urine collection.
• the ‘gold standard’ (or reference method) for estimation
of GFR.
• Disadvantages- time consuming, expensive, constant
intravenous infusion of inulin is needed to maintain
steady plasma level, and difficulties in laboratory
analysis.
• This test is largely limited to clinical research.
12. Clearanceof RadiolabeledAgents
• Urinary clearance of radiolabeled iothalamate
(125Iiothalamate) correlates closely with inulin
clearance.
• Drawbacks- expensive with risk of exposure to
radioactive substances.
• Other radiolabelled substances used are 51Cr-EDTA and
99Tc-DTPA.
13. CystatinClearance
• cysteine protease inhibitor of MW 13,000, which
is produced at a constant rate by all the nucleated
cells.
• It is not bound to protein, is freely filtered by
glomeruli and is not returned to circulation after
filtration.
• It is amore sensitive and specific marker of
impaired renal function than plasmacreatinine.
• Its level is not affected by sex, diet, or muscle
mass.
• It is measured byimmunoassay.
14. CreatinineClearance
• most commonly used test for measuring GFR.
• produced constantly from creatine in muscle.
• completely filtered by glomeruli and not reabsorbed by
tubules, a small amount is secreted by tubules.
• A 24-hour urine sample is preferred to overcome the
problem of diurnal variation of creatinine excretion and
to reduce the inaccuracy in urine collection.
• A blood sample for estimation of plasma creatinine is
obtained at midpoint of urine collection.
• Creatinine clearance is calculated from
(1) concentration of creatinine in urine in mg/ml (U),
(2) volume of urine excreted in ml/min (V) and
(3) concentration of creatinine in plasma in mg/dl (P).
15. UreaClearance
• filtered by the glomeruli
• 40% of the filtered amount is reabsorbed by the tubules.
• The reabsorption depends on the rate of urine flow.
• not a sensitive indicator of GFR.
• clearance tests are more helpful in early cases.
• If biochemical tests are normal and renal function
impairment is suspected, then creatinine clearance test
should be carried out.
• If biochemical tests are abnormal, then clearance tests
need not be done.
16. URINE ANALYSIS
Urine examination is an extremely valuable and most easily
performed test for the evaluation of renal functions.
It includes physical or macroscopic examination, chemical
examination and microscopic examination of the sediment.
17. MACROSCOPIC EXAMINATION
Colour
Normal- pale yellow in colour due to pigments
urochrome,urobilin
Cloudiness may be caused by excessive cellular
material or protein crystallization or precipitation of
salts upon standing at room temperature or in the
refrigerator.
If the sample contains many red blood cells, it
would be cloudy as well as red.
18. COLOR OF URINE
Normal Deep yellow---- conc. Of urochrome pigment
Red Blood, Hemoglobulinuria, myoglobinuria, beetroot ( chukandar)
orange rifampicin
yellow Concentrated urine, ( dehydration, jaundice, B complex,
sulfasalazine)
Green Methylene blue
Black Severe hemoglobinuri, methyldopa
Brown Bilirubin, phenothiazides
19. VOLUME
Normal- 800 ml -2.5 L/day
Oliguria- Urine Output < 300ml/day
Seen in
Acute glomerulonephritis
Renal Failure
Polyuria- Urine Output > 2.5 L/day
Seen in
Increased water ingestion
Diabetes mellitus and insipidus.
Anuria- Urine output < 100ml/day
Seen in renal shut down
20. SPECIFIC GRAVITY
Normal ranges 1.002 – 1.025
Varies with quantity of urine
Low SG
CRF
diabetes insipidus
Absence ofADH
Renal tubular demage
High SG
Dehydration
diabetes mellitus
Albuminuruia
Acute nephritis
21. PH:
Urine pH ranges from 4.5 to 8
Normally it is slightly acidic lying between 6 – 6.5.
After meal it becomes alkaline.
On exposure to atmosphere, urea in urine splits
causing NH4
+ release resulting in alkaline reaction.
22. CHEMICAL EXAMINATION
Glucose:
Diabetes
Impaired Renal tubular
False positive or negative – large dose of vitamin C,
tetracycline or levodopa
Ketones:
Diabetic- diabetic ketoacidosis
Starvation
Protein:
Normal protein loss from urine is less than 150mg
/24 hrs.
23. MICROSCOPIC EXAMINATION
White cell:
More than 10 or more wbc per cm- UTI
Stone, tubulointestinal nephritis, tuberculosis, papillary necrosis
Red cell:
2-5 per high power field – hematuria
Cast:
Cylindrical structure- kidney tubule-coagulation of protein
Hyaline cast: concentrated urine, fever, diuretic therapy, after
exercise
Granular cast: found in chronic glomerulonephritis, diabetic
nephropathy and malignant hypertension
White cell cast: acute pyelonephritis
Red cell cast: glomerulonephritis
Epithelial cast: acute tubular necrosis and interstitial nephritis
26. BloodBiochemistry
• Twobiochemical parameters arecommonly
used to assessrenal function:
1. blood urea nitrogen(BUN)
2. serum creatinine
• insensitive markers of glomerularfunction.
27. • Causesof increased BUN:
1.Pre-renal azotemia: shock, congestiveheart
failure, salt and waterdepletion
2. Renalazotemia: impairment of renalfunction
3.Post-renal azotemia: obstruction of urinarytract
4.Increased rate of production ofurea:
• High protein diet
• Increased protein catabolism (trauma, burns,
fever)
• Absorption of amino acids and peptides froma
large gastrointestinal hemorrhage or tissue
hematoma
28. Serumcreatinine
• Creatinine is anitrogenous waste product formed
in muscle from creatine phosphate. Endogenous
production of creatinine is proportional tomuscle
massand body weight.
• Serumcreatinine is amore specific and more
sensitive indicator of renal function ascompared
to BUNbecause:
1. It is produced from muscles at aconstant rate
and its level in blood is not affected by diet,
protein catabolism, or other exogenousfactors;
2. Itis not reabsorbed, and very little is secreted
by tubules.
29. • Causesof Increased Serum Creatinine Level
1. Pre-renal, renal, and post-renalazotemia
2. Largeamount of dietary meat
3. Active acromegaly and gigantism
• Causesof DecreasedSerumCreatinine Level
1. Pregnancy
2. Increasing age(reduction in musclemass)
30. BUN/SerumCreatinineRatio
• discriminate pre-renal and post-renal azotemia from renal
azotemia.
• Normal ratio is 12:1 to 20:1.
• Causesof Increased BUN/Creatinine Ratio (>20:1):
1.Increased BUNwith normal serumcreatinine:
• Pre-renal azotemia (reduced renal perfusion)
• High protein diet
• Increased protein catabolism
• Gastrointestinal hemorrhage
2. Increase of both BUNand serum creatinine with
disproportionately greater increase of BUN:
• Post-renal azotemia (Obstruction to the outflow of urine)
Obstruction to the urine outflow causes diffusion of urinary
urea back into the blood from tubules because of
backpressure.
32. DYMANIC TESTS FOR TUBULAR
FUNCTION
• FRACTIONAL EXCRETION- SODIUM, CALCIUM,
PHOSPHORUS
URINARY CONC X SER CREAT / SERUM CONC OF
SOLUTE X URINARY CREAT
• FBH- LOW FRACTIONAL EXCRETION OF Ca
• HYPOPHOSTAEMIC RICKETS- INCREASED FRAC EXT
OF Ph
• FENa- <1- VOLUME DEPLETION
>1- ATN
36. Intravenous Urography
• It gives excellent definition of collecting
system and ureters, and remains superior for
examining renal papillae.
• Xrays of serial intervals after administration of
intravenous bolus of iodinated contrast
Pyelography
• It Is direct injection of contrast in collection
system.
• Antegrade pyelography is insertion of needle
in to pelvicalyceal system under USG
guidance.
38. Computed Tomography
• Done in patients in particularly having mass
within the kidney
Magnetic Resonance Imaging
• It gives excellent and distinct differentiation
between different tissues.
Radionuclide studies
• These include gamma ray emitting
radiopharmaceuticals, excreted by kidney and
catched by Gamma Camera.
• Diethylenetriamine pentaacetic acid 99mTc-DTPA is
done.