Renal function tests

Renal Function Tests
Dr Malini

 Regulation of body fluid volume and osmolality
 Regulation of electrolyte balance
 Regulation of acid-base balance
 Excretion of waste products (urea, creatinine , ammonia, drugs,
toxins)
 Retention of substances vital to body – glucose, amino acids
 Regulation of blood pressure
 Production and secretion of hormones – renin, erythropoietin
 Production of vitamin D3 ( active form of vitamin D )

•Glomerular filtration excreted
•Renal tubular secretion
•Renal tubular reabsorption --- retained
Filter
Processor
Input
Arterial
Output
Venous
Output
Urine

1. Decreased urine
production
2. Clinical symptoms
3. Tests
Filter
Processor
Input
Arterial
Output
Venous
Output
Urine

 Pre-renal- Decreased
renal blood flow as in
dehydration, congestive
cardiac failure and shock
 Renal (intrarenal)
 Post-renal
(obstruction)
Filter
Processor
Input
Arterial
Output
Venous
Output
Urine
Factors affecting the renal function

 To identify renal dysfunction early.
 To diagnose renal disease.
 To monitor disease progress.
 To monitor response to treatment.
 To adjust dosage of certain drugs according to
renal function – chemotherapy
 To plan renal replacement therapy in advanced
diseases

 Older age
 Family history of Chronic Kidney disease (CKD)
 Decreased renal mass
 Low birth weight
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity

Tests to evaluate glomerular function
Tests to measure renal plasma flow
Tests to evaluate tubular function
Urine analysis
Miscellaneous tests
1. Clearance tests -
(a)creatinine
(b) urea
(c) inulin
(d) radioisotopes – 125I-
iothalamate clearance , 51Cr-
EDTA clearance
2. Calculation of creatinine clearance
from prediction equations
3. Blood biochemistry- serum
creatinine, Blood urea nitrogen (
BUN ), BUN/serum creatinine ratio
4. Microalbuminuria and proteinuria
1. Para amino hippurate test
2. Filtration fraction
1. Tubular poteinuria
2. Generalised aminoaciduria
3. Glycosuria
4. Fractional sodium excretion
5. Sp gr and osmolality of urine
6. concentration and dilution tests
7. Acid load test

 Initial step in urine formation
 Plasma that traverses the glomerular capillaries is
filtered by the highly permeable ‘ glomerular
membrane ‘
 Resultant fluid – ‘glomerular filtrate ‘ – passed into
the bowman’s capsule
 Ultrafiltrate of plasma

 GFR ---- volume of the glomerular filtrate formed each minute
by all the nephrons in both the kidneys
 Normal – 120 - 130ml/min per 1.73 m2 ( 170 – 180 L / day )
 GFR is the best test to assess excretory renal function
 GFR decreases with age , after 40 yrs, steady and progressive
fall in the GFR at a rate of 1 ml/min/year due to reduction in
number of glomeruli due to arteriosclerosis
 GFR < 60 ml/min per 1.73 m2 indicates loss of > 50% of kidney
function.
 Fall of GFR leads to accumulation of waste products of
metabolism in blood.
 GFR < 15 ml/min 1.73 m2 is associated with uremia

1. Detect suspected incipient kidney diseases.
2. Monitor course of established kidney
disease.
3. Plan replacement therapy in advanced renal
diseases.
4. Adjust dosage of certain drugs which are
nephrotoxic.

Mechanism of GFR
• hydrostatic pressure gradient
across the capillary wall
• Colloidal osmotic
pressure gradient across
the capillary wall
•Fluid pressure created by
fluid in bowman’s capsule
• permeability of
capillaries

 Based on GFR, chronic kidney diseases is divided into
following stages
1. Stage 1 – kidney damage with normal or increased GFR (
GFR > 90 ml/min/1.73m2 )
2. Stage 2 – kidney damage with mildly reduced GFR ( GFR
60-89 ml/min/1.73m2 )
3. Stage 3 – moderately reduced GFR ( GFR 30-59
ml/min/1.73m2 )
4. Stage 4 – severely reduced GFR ( GFR 15-29
ml/min/1.73m2 )
5. Stage 5 – kidney failure ( GFR < 15 ml/min/1.73m2 )

1. Clearance tests -
◦ creatinine
◦ urea
◦ inulin
◦ radioisotopes
2. Calculation of creatinine clearance from prediction
equations
3. Blood biochemistry
4. Microalbuminuria and proteinuria
16

 The ability of the glomeruli to filter a substance from
the blood is assessed by clearance studies.
 If a substance is not bound to protien or plasma, is
completely filtered by the glomeruli, neither secreted
nor reabsorbed by the tubules, then its clearance rate is
equal to the glomerular filteration rate.
 Clearance is a measure of the volume of plasma
completely freed of a given substance per minute by
the kidneys

 It is calculated by the formula –
clearance= UV
P
 U- concentration of a substance in urine in
mg/dl.
 V- volume of urine excreted in ml/min
 P- concentration of the substance in plasma
in mg/dl.
 Clearance value is expressed as ml/min

•Inulin
•radio iodine labelled hypaque
endogenous
exogenous
•Creatinine and urea ,
•Cystatin C ,
•B2 microglobulin
 The agent used for the test should be
1. Physiologically inert and preferably endogenous
2. Freely filtered by glomeruli and should be
neither reabsorbed nor secreted by renal tubules
3. It should not bind to plasma proteins and should
not be metabolized by the kidneys
4. Excreted only by kidneys

Creatinine clearance
Creatine & creatine phosphate Creatinine
non enzymatic
muscle dehydration process
 Endogenous substance not bound to plasma proteins
freely filtered by glomerulus ,not reabsorbed / minimal
secretion by tubules.
 A 24 hour urine sample preffered to overcome diurnal
variation of creatinine excretion and reduce inaccuracy
in urine collection

 After getting up in the morning , the first
voided urine is discarded.
 Subsequently all the urine passed is
colleceted in container provideded
 After getting up the next morning, the 1st
voided urine is also collected.
 A blood sample is obtained at midpoint of
urine collection - for estimation of urine
collection.

 Creatinine clearance is calculated by
 Because of secretion of creatinine by renal
tubules, this overestimates GFR by 10%
Where
U = concentration of creatinine in urine in mg/ml
V= volume of urine excreted in ml/min ( this is
calculated by the formula : volume of urine collected
/collection time in minutes. Eg. Vol of urine
collected in 24 hours ÷ 1440.)
P= concentration of creatinine in plasma in mg/dl

 Tubular secretion of creatinine results in falsely
elevated values in creatinine clearance, ----- renal
insufficiency,
 Inhibition of tubular secretion with cimetidine
substantially improves the creatinine clearance
estimate of GFR in patients with mild to moderate
renal impairment

 A small amount of creatinine is secreted by renal
tubules that increase even further in advanced renal
failure.
 Collection of urine is incomplete
 Creatinine level affected by intake of meat and muscle
mass
 Creatinine level affected by certain drugs like
cimetidine, probenecid and trimethoprim ( block
tubular secretion of creatinine)

UREA CLEARANCE
= amount of urea excreted in urine in 1 min
plasma concentration of urea
U . V
normal value - 75 ml/ min
P
U – urine concentration of urea
V --- urine flow per minute
P --- plasma concentration of urea

Measurement of plasma creatinine provides a more
accurate assessment than urea
40% - normally reabsorbed by tubules
factors can affect the urea level like:
Mild dehydration,
high protein diet,
increased protein catabolism, muscle wasting as in
starvation, liver disease
treatment with cortisol or its synthetic analogous
slightly higher in males than females.

Interpretation
Urea clearance - 70% or more ------- normal
40 – 70 % ------- mild impairment
20 – 40 % ------- moderate impairment
below 20 % -------- severe impairment•
•
low
•ll
ARF
• Falls progressively
Chronic
nephritis
•Normal
Nephrotic
syndrome
•normal
Benign
hypertension
low

 Fructose polymer ( filtered by glomeruli, neither
reabsorbed, nor secreted by tubules )
 gold standard for measuring glomerular filtration rate
 Inulin clearance in healthy young adults has mean
values of
◦ 125 mL/min/1.73 m2 in men and
◦ 110 mL/min/1.73 m2 in women.

 A bolus dose of inulin ( 25 ml of 10% solution IV ) is
administered followed by continous intravenous
infusion ( 500 ml of 1.5% solution at the rate of
4ml/min)
 Timed urine samples are collected and blood samples
are obtained at the midpoint of timed urine collection.
 Drawback –
◦ Time consuming
◦ Expensive
◦ Constant IV infusion of inulin

 Radio – isotopes in measurement of GFR
 Cr51 – EDTA
 Tc 99m – DTPA
 I125 - iothalamate
 Cystatin – c clearance
 Cysteine protease inhibitor
 Produced at a constant rate by all nucleated cells
 Superior marker of GFR than creatinine clearance
 Its not affected by sex , diet or muscle mass
 Measured by immunoassay

TESTS BASED ON GLOMERULAR FILTRATION
 Clearance tests -
◦ creatinine
◦ urea
◦ inulin
◦ radioisotopes
 Calculation of creatinine clearance from prediction equations
 Blood biochemistry
 Microalbuminuria and proteinuria
31

1. Cockcroft & Gault Formula
•Advantage –
•reduces the variability of serum creatinine estimates of GFR caused
by differences in creatinine production due to differences in muscle
mass based on sex and age.
•Diasadvantage –
•It systematically overestimates GFR in individuals who have
relatively low muscle mass in relation to their body weight such as
obese, edematous, or chronicallydebilitated individuals.
•it does not take into account variations caused by extrarenal
elimination and tubular secretion.

2. MDRD formula (mL/min/1.73 m3)
 Based on four variables --- serum creatinine,
age,race and sex.
3. For children
1. Schwartz Formula
2. Counahan Barrett Formula

 Creatinine clearance values estimated from the
formulas are more accurate than those from direct
measurements ( clearance methods ), mainly because
of
◦ inaccurate urine collections and
◦ ketones , glucose or heavy proteinuria present interfere
with the creatinine determination
◦ variations in plasma creatinine concentration

 Clearance tests -
◦ creatinine
◦ urea
◦ inulin
◦ radioisotopes
 Calculation of creatinine clearance from prediction equations
 Blood biochemistry
 Microalbuminuria and proteinuria
35

BLOOD BIOCHEMISTRY
1. Blood urea nitrogen
Amino acids
Synthesis of
tissue
proteins
Energy Ammonia
urea
Urea cycle
Excretion
in urine
 Concentration of blood urea is expressed as BUN
 Molecular weight of urea is 60 and 28 grams of nitrogen
are present in 1 mole of urea
 The real concentration of urea is BUN X (60/28).
 Utility is limited as BUN is affected by a number of non
renal factors.
 Azotemia – increase in blood level of urea
 Uremia – is a clinical syndrome resulting from this increase
 Adults – 7-18 mg / dl
 > 60 yrs - 8- 21 mg / dl

METHODS OF ESTIMATION
1. Diacetyl monoxime urea method
acid
Urea + Diacetyl monoxime yellow diazine
oxidising agent derivative
spectrophotometer
2. Urease – Berthelot reaction
urease
Urea ammonia
alkaline hypochlorite + phenol ---- stable
color
( indophenol )
spectrophotometer
Pre renal
•CCF
•shock
•Salt and
water
depletion
renal
•Impaired
renal
function
Post renal
•Obstruction
to urinary
tract
BUN INCREASED IN

2. SERUM CREATININE ( 0.7- 1.3 mg/dl ) – m
( 0.6 – 1.1 mg/dl) – f
 Is more specific and sensitive than BUN
◦ Produced from muscles at a constant rate and its level in blood not
affected by diet, protein catabolism or other exogenous factors.
◦ Not reabsorbed, very little secreted by tubules.
 With muscle mass remaining constant, increased s. creatinine
level reflects decreased GFR.
 Increased s.cr level in blood does not occur until 50% kidney
function is lost, because of significant kidney reserve.
 Thus, it is Not a sensitive indicator of early renal impairment .
 Cant diagnose early stages of CKD
 If renal function is absent, s.cr rises by 1- 1.5 mg/dl/day.
Increased Decreased
Pre – renal , renal and
post renal azotemia
Pregnancy
Large amounts of dietary
meat
Elderly – reduced muscle
mass
Acromegaly , gigantism

GFR
[pCreat]
140 mL/min
(100%)
0 mL/min
(0%)
Change within an individual
patient is usually more
important than the absolute
value

1. Jaffe’s reaction ( alkaline picrate reaction):
Creatinine + picrate yellow red colour
 False positive reaction – non creatinine chromogens (glucose,
protein, fructose, ascorbic acid, acetoacetate, acetone,
cephalosporins)
 Thus true creatinine is less by 0.2-0.4mg/dl when estimated
by this method.
 Falsely low values- bilirubin and hemoglobin
2. Hare ‘s method :
 Isolating creatinine by absorption into Lloyd’s reagent
Alkaline
solution
Spectrophotometer at 485 nm

3. Enzymatic measurement
1. Cr ---------------------------- ammonia + N- methyl hydantion
Cr iminohydrolase
 Ammonia + NADH + 2-oxoglutarate------------- NAD + Glutamate
Glutamate dehydrogenase
 Consumption measured as a decrease in absorbance at 340 nm is
used to measure the concentration of creatinine.
2. Creatinine -------------------------------creatine
Cr amidohydrolase
 Creatine ----------------hydrogen peroxide
hydrolysis by imidinohydrolase
and sarcosine oxidase
 2,4 dichlorophenol sulfonate -----------
colorless
polymer which
is measured at
510 nm

 Advantage of enzymatic method-
 Interference by glucose and other Jaffe chromogens in
creatinine measurement does not occur with
enzymatic methods.
4. The ultimate reference standard for
creatinine measurement is isotope dilution–
mass spectrometry (IDMS)

BUN / S . CREATININE RATIO
•To discriminate pre renal and post renal azotemia from renal
azotemia
•Normal ratio is 12:1 - 20 : 1
Increased bun – normal
serum creatinine
Disproportionate increase in
bun with increased s.
Creatinine
Renal hypoperfusion Obstruction to urine outflow
(post renal azotemia)
High protein diet
Increased protein catabolism
Diffusion of urinary urea back
into the blood from tubules
due to backpressure
Gastro intestinal
hemorrhage
Decreased BUN / creatinine ratio ( <10:1 )
Acute tubular necrosis
Starvation , low protein diet
Severe liver disease

44
Clearance tests - creatinine
urea
inulin
radioisotopes
Calculation of creatinine clearance from prediction
equations
Blood biochemistry
Microalbuminuria and albuminuria

 Defined as urinary excretion of 30-300mg/24 hrs of
albumin in urine
 Significance
◦ Earliest sign of renal damage in diabetes mellitus (diabetic
nephropathy).
◦ Independent risk factor for cardiovascular disease in diabetes
mellitus.

 Cannot be detected by routine tests for proteinuria.
Methods are
1. Measurement of albumin-creatinine ratio in a random
urine sample.
2. Measurement of albumin in an early morning or random
urine sample
3. Measurement of albumin in 24 hr sample.
4. Test strips
5. Exact quantitation by radioimmunoassay or enzyme linked
immunosorbent assay

Proteinuria
• High molecular weight proteins are retained in the circulation by
the glomerular filter (Albumin, Immunoglobulins)
• Low molecular weight proteins are filtered then reabsorbed by
renal tubular cells
• Proteinuria can be
1. Glomerular:
◦ Mostly albumin, because of its high concentration and therefore high
filtered load
2. Tubular:
◦ Low molecular weight proteins not reabsorbed by tubular cells (e.g.
alpha-1 microglobulin)
3. Overflow:
◦ Excessive filtration of one protein exceeds reabsorbtive capacity (Bence-
Jones, myoglobin

 >300mg/24 hours is termed clinical or overt and
indicates overt clinical damage.
 Detected by –
 Heat and acetic acid test
 Sulphosalicylic acid test
 Dipsticks

small peptide (molecular weight 11.8 kDa),
 present on the surface of most cells and in low concentrations
in the plasma.
 completely filtered by the glomeruli and is reabsorbed and
catabolized by proximal tubular cells.
The plasma concentration of β2-microglobulin is a good index
of GFR in normal people, being unaffected by diet or muscle
mass.
 increased in multiple myeloma and lymphoma

TESTS TO MEASURE RENAL PLASMA FLOW
1. Para amino hippurate test
2. Filtration fraction

 Not filtered at the glomerulus
 All secreted into the proximal tubules
 Thus PAH clearance is a measure of renal
plasma flow – which is the total quantity of
plasma perfusing the glomerular capillaries

Filtration fraction
Is the fraction of plasma passing through the kidneys which is
filtered at the glomerulus = GFR
RPF
Inulin clearance ---- GFR
PAH --------------------RPF FF = CIN/CPAH
where CIN is inulin clearance, and CPAH PAH clearance

Interpretation
•Normal
•increases
Early
hypertension
•increases
Malignant
hypertension
•decreases
glomerulonephri
tis

Proximal tubule - 65 % of filtered Na+ Cl-, Ca2+, PO4,
HCO3
-. 75-90% of H20. Glucose, carbohydrates, amino
acids, and small proteins
Loop of Henle - 25% of filtered Na+.
Distal tubule - 8% of filtered Na+,HCO3-.
Collecting duct - remaining 2% of Na+ only if the
hormone aldosterone is present. H20 depending on
hormone ADH.
REABSORPTION

SECRETION
Proximal tubule – uric
acid, bile salts,
metabolites, some drugs,
creatinine
Distal tubule – Most
active secretion takes
place here . organic acids,
K+, H+, drugs, Tamm-
Horsfall protein (main
component of hyaline
casts).

57
 TESTS BASED ON TUBULAR FUNCTION
1. Specific gravity and osmolality of urine
3. Acid load test
6. Glycosuria

 Normal specific gravity is 1.003 to 1.030.
 Depends on the state of hydration and fluid
intake.
 Measured by-urinometer
-refractometer
-dipsticks

 Take 2/3 of urinometer container with
urine
 Allow the urinometer to float into the urine
 Read the graduation at the lowest level of
urinary meniscus
 Correction of temperature & albumin is a
must.
 Urinometer is calibrated at 15or 200c
 So for every 3oc increase/decrease
add/subtract 0.001
 For 1gm/dl of albumin add0.001

 Causes of increased specific gravity –
◦ Reduced perfusion ( with preservation of concentrating ability
of tubules)
◦ Proteinuria
◦ Glycosuria
◦ Glomerulonephritis
◦ Urinary tract obstruction
 Causes of reduced specific gravity
◦ Diabetes insipidus
◦ Chronic renal failure
◦ Impaired concentrating ability due to diseases of tubules.

 As a test of renal function, it gives information about the
ability of the renal tubules to concentrate the glomerular
filterate.
 This concentrating ability is lost in diseases due to renal
tubules.
 Fixed specific gravity of 1.010 – cannot be lowered or
increased by increasing or decreasing the fluid intake
respectively
An indication of chronic renal failure
 As specific gravity is approximate only , measurement of
osmolarity preferred when concentrating ability being
assessed

 The most commonly employed test to evaluate tubular
function
 Most sensitive method to determine the ability of
concentration
osmolality Specific gravity
Osmolality measures the number of
dissolved particles in a solution.
Ratio of mass of a solution to the mass of
water i.e. measures total mass of solute.
Exact number of solute particles in a
solution
Depends both number and nature of
dissolved particles
Does not get affected Measurement get affected by presence of
solutes of large molecular weight like
proteins and glucose
Thus , osmolality is preferred

 By an instrument called osmometer
 Principle- When solutes are dissolved in a solvent, certain
changes takes place like
 lowering of freezing point
 increase in boiling point
 decrease in vapor pressure
 increase of osmotic pressure of solvent
 Largely due to ADH (anti-diuretic hormone)
 Can reach maximum of 1200 mOsm/L
 Normal range:300-900mOsm/L, plasma 285+10
These properties
are used in
osmometer

 Used to distinguish from
 If urine and plasma osmolality are almost similar- there
is defective tubular reabsorption of water
pre renal azotemia acute renal failure due to acute
tubular necrosis
Ratio is higher Ratio is lower

65
2. Concentration and dilution tests
3. Acid load test
4. Tubular proteinuria
6. Glycosuria

URINE CONCENTRATION TEST ( water Deprivation
test )
PRINCIPLE
Restricted fluid intake ---- normal kidneys conserve water ---
concentrated urine with increased specific gravity.
Dehydration
ADH
Water selectively reabsorbed
Urine – high solute concentration
Normally urine osmolality (>800
mosm/kg of water)&
sp.gravity(>1.025) should rise after
water deprivation –concentrating
ability of tubules is normal.
If it not then Desmopressin
administered to differentiate
between central & nephrogenic
diabetes insipidus.

• Normal meal
• Instructed not to take any water or other
liquids after dinner , during night
• Discard urine passed during night
• Next morning – no fluids , breakfast delayed
• Urine specimens collected at – 8 , 9 and 10 AM
• Specific gravity and urine osmolality measured.

RESULTS
Specific gravity of atleast one sample > 1.025 and urine
osmolality > 800mosm/kg ---  normal
Specific gravity doesn’t even reach upto 1.025--- patient is
unable to concentrate
the urine
Desmopressin is administered
Urinary concentrating
capacity is corrected-
central diabetes
insipidus
Not corrected –
nephrogenic diabetes
insipidus

 Contra indicated
1. Elderly
2. Those with heart disease
3. Incipient renal failure
4. High fever
5. Already dehydrated
patients
 Unreliable
1. Water and electrolyte
disturbances
2. Pregnancy
3. Edema
4. Low salt / low protein diet
5. Abnormal solutes n urine
add to specific gravity
Normal result doesn’t rule out renal disease !

 Procedure
• No water after midnight
• Empty the bladder in the morning at 7 am and discard
the urine
• 1000 – 1200 ml water provided during the next 30
minutes
• Urine sp gravity, volume and osmolality measured every
hour for the next 4 hours.
• Plasma levels of ADH and serum osmolality also
measured hourly.

 Normal –
◦ >90% of water should be excreted,
◦ sp gravity <1.003
◦ osmolality <100 mosm/kg.
◦ Plasma level of ADH should be appropriate for serum osmolality
 Renal tubular disease
 Solute concentration of urine remains constant despite excess water
◦ Specific gravity does not fall to 1.003
◦ < 80% water voided in 4 hours
Contraindicated
◦ Elderly
◦ Those with heart disease
◦ Incipient renal failure
Test also impaired in
Adrenocortical insufficiency
Malabsorption
Obesity
Ascitis
CCF
Cirrhosis
dehydration

 Fluid with-held overnight -- 12 hours
 Sp gr of 1st and 2nd urine sample measured in the morning
 Sp gr > 1.025 ----- hydrate the patient with 1000 – 1200 ml
water provided during the next 30 minutes
 Urine sp gravity measured every hour for the next 4 hours
 If sp gr of morning sample – not reached 1.022 --- wait till the
third specimen is collected
 still the same------ do not wait further, proceed with dilution
test

Results -----
are interpreted in the same way as that of
concentration and dilution test done seperately

 Volume of water excreted in excess , than necessary to keep
the urine isotonic to plasma
 Total amount of solutes in the urine is measured form urine
osmolality and urine volume
 And then the amount of water required to hold that quantity
of solute at the same osmolality of plasma = osmotic
clearance
 Free water clearance = urine volume - osmotic clearance
CH2O = V - (Uosm × V/Posm)

 Negative free water clearance = amount of water that
would have to be added to make the urine isotonic to
plasma
 Negative free water clearance (TcH2O) = Cosm - V
 In the presence of normal renal function, the kidneys
usually concentrate the urine, and therefore Uosm is greater
than Posm, resulting in a negative value for CH2O.

76
3. Acid load test
4. Tubular proteinuria
6. Glycosuria

 Also known as tubular acidosis test, ammonium
chloride loading test, urine acidification test
 Gold standard for diagnosis of distal or type 1 renal
tubular acidosis.
 Procedure –
◦ Urine pH and plasma osmolality are measured after
overnight fasting.
◦ If pH < 5.4 – acidifying ability of renal tubules is normal
◦ If pH > 5.4 and plasma bicarbonate are low – renal tubular
acidosis

 If neither of the two results obtained- further testing done
 Patient is given ammonium chloride orally (0.1mg/kg) over 1
hr after overnight fast and urine samples collected hourly for
next 6-8 hours.
 Ammonium ions dissociate into H+ and NH3.
 Ammonium chloride makes the blood acidic
 If pH < 5.4 in any of the samples, acidifying ability of distal
tubules is normal

79
3. Acid load test
6. Glycosuria

 Proteinuria may be due to:
1. An abnormality of the glomerular basement membrane.
2. Decreased tubular reabsorption of normal amounts of
filtered proteins.
3. Increased plasma concentrations of free filtered proteins.
4. Decreased reabsorption and entry of protein into the
tubules consequent to tubular epithelial cell damage.
 Measurement of β2 and alpha1 microglobulin excretion
provides a sensitive method of assessing tubular integrity -
proximal tubular damage

 Accounts for 5% of glycosuria
 Renal threshold
◦ The highest glucose level in blood at which glucose appears in
urine and which is detectable by routine laboratory test.
◦ The normal renal threshold for glucose is 180mg/dl.
◦ Threshold substances need a carrier protein to transport them
from tubular lumen to the blood.
◦ When the carrier is saturated, the threshold is reached and
the substance is excreted.

 Renal Glycosuria- a benign condition in which renal threshold
is set below 180 mg/dl but glucose tolerance is normal.
 Transmitted as autosomal dominant.
 The number of glucose transporters in the tubules is
decreased or the affinity of the transporters for glucose is
decreased.
 Other conditions where glycosuria occurs with blood glucose
<180mg/dl –
 Renal tubular diseases like fanconi syndrome and toxic
renal tubular damage

83
3. Acid load test
6. Glycosuria

 This refers to percentage of filtered sodium that has been absorbed
and percentage that has been excreted.
 This is better indicator of tubular absorption of sodium than
quantification of urine sodium alone.
 FE = (Ux/Px) × (Pcreat/Ucreat) X 100
 When the substance excreted in the urine has a clearance less than
creatinine clearance, fractional excretion is less than 1.
 FE of sodium is often used to distinguish between acute tubular
necrosis and prerenal azotemia.
 FE of sodium of less than 1% – prerenal azotemia.
 Value greater than 1% --- acute tubular necrosis ( sodium
reabsorption due to tubular injury)

Renal Failure Index (RFI)
Renal failure index is another formula that is used for the
differential diagnosis of acute renal failure. It is expressed as
UNa+
(Ucreat/Pcreat).
FENa+ × 1.4 = Renal failure index
Fractional reabsorption is the quantity of a substance
reabsorbed expressed as a fraction of the filtered load.
FR = 1 - FE

syndromes causes Lab features Microscopic
examination
Pre-renal azotemia Dehydration
CHF
sepsis
BUN/creatinine > 30 : 1
Urine Fe Na <<1%
Free water clearance
strongly negative
Sp gr & osmolality near
max conc
Urine protein < 1 gm/
day
Hyaline casts often
present
Nephrotic syndrome Membranous
nephropathy
Minimal change disease
SLE
Focal sclerosis
AIDS
Diabetes
Amyloidosis
Inc lipoproteins,alpha- 2
macroglobulin,
T.G , ADH
BUN/ creat may be high
as above
Urine protein > 3.5 gm /
day
Oval fat bodies
Nephritic syndrome Postinfectious GN
Goodpasture syndrome
Wegner”s granulomatosis
Other forms of vasculitis
SLE
Hematuria
Proteinuria
RBC casts

syndromes causes Lab features Microscopic
examination
Tubular syndrome Ischemia
- most common cause
damages loop of henle
toxins
Usu damage PCT
BUN / creat < 20
Fe Na . 1%
zero
Muddy brown gr.
casts
interstital nephritis Hypersensitivity reaction
Follow uti
Antibiotic eg . Penicillin ,
sulfonamides , NSAIDS
BUN / creat. < 20
Fe Na > 1%
zero
Eosinophils
Tubular proteinuria
Obstructive
uropathy
Malignancy
Older men
Neurological disease
Acute-
BUN / creat. > 20
Fe Na < 1%
negative
Chronic-
BUN / creat. < 20
Fe Na > 1%
May be WBC ,
bacteria ,nitrite

TYPE Uosm Una
(milieq/L)
FeNa BUN/Cr
PRE-RENAL >500 <10 <1% >20
RENAL <350 >20 >2% <15
POST-RENAL <350 >40 >4% >15

Renal function tests

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