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Renal Function
Tests
Notes on renal function tests By Dr. Ashish Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes
OVERVIEW
1. Indications
2. Classification
a. Tests for glomerular function
i. Clearance tests
1. Inulin clearance
2. creatinine clearance
3. cystatin c clearance
4. urea clearance
ii. Blood biochemistry
1. BUN
2. Sr. Creatinine
3. BUN/Sr. Creatinine ratio
4. Urine proteins
b. Tests for tubular function
i. Tests for proximal tubular function
1. Glycosuria, aminoaciduria, LMW proteinuria
2. Urinary concentration of Na+
3. Functional excretion of Na+
ii. Tests for distal tubular function
1. Specific gravity
2. Urine osmolality
3. Water deprivation test
4. Water loading ADH suppression test
5. Ammonium chloride loading test
3. Each test in detail
2.
3.
4.
5.
* Classification
Disease
Kidney disease with
Kidney disease with
Kidney disease with
Kidney disease with
Renal Failure
GFR
Normal GFR
Mild decreased GFR
Moderate dec GFR
Severe dec GFR
Value
(ml/min/1.73m2)
>90
60-89
30-59
15-29
<15
C = UV/P
C = clearance (ml/min), U=Concentration of substance in urine (mg/dl), V=Volume of urine
per min (ml/min), P=concentration of substance in plasma (mg/dl)
Ideal agent for clearance studies:
No ideal agent has been found, however the agent used should fulfill most of the
following criteria:
i.
Should not bind to plasma proteins
ii.
should be freely filtered across glomeruli
iii.
should not be reabsorbed
iv.
should not be metabolized by kidney
v.
should be excreted only through the kidney
Agents used:
Exogenous
i.
ii.
iii.
iv.
Inulin
radiolabelled EDTA
Radiolabelled 125I thiocynate
99
Tc-DTPA
i.
ii.
iii.
Endogenous
Creatinine
Urea
Cystatin C
Normal Values:
Inulin clearance
As we can see from the graph, as the creatinine clearance decreases, the remaining
nephrons in the kidney decrease
Also the dotted line shows that the serum creatinine begins to rise only after 50% of the
nephrons are damaged, i.e. serum creatinine though useful is a less sensitive indicator
of renal function.
Disadvantages:
1. small amounts of creatinine secreted by renal tubules can increase even further in
advanced renal failure
2. Creatinine level is affected by intake of meat and muscle mass
3. collection of urine is incomplete often
4. Creatinine levels are affected by drugs such as cimetidine, probenecid and
trimethoprim that block tubular secretion
10
Clearance tests are more helpful in this scenario of detection of early renal impairment
11
Creatinine clearance
12
*Blood Biochemisty
Amino acids
Energy
Ammonia
Urea Cycle
Urea
Excretion in urine
Rationale:
1. Completely filtered by glomeruli and 30-40 % is reabsorbed
2. State of hydration affects estimation
3. Affected by non renal factors such as
- high protein diet
- upper g.i. hemorrhage
4. Less sensitive considerable destruction of renal parenchyma has to occur
before urea is elevated
13
Methods:
1. Direct method (Di acetyl monoxamine method)
Urea
+ DAM
Alkaline hypochlorite
Ammonia
Urease
Iodophenol
Phenol
Normal levels:
Normal
1.
2.
3.
4.
Pre renal
shock
CHF
dehydration
high protein diet,
trauma, burns, g.i.
hemorrhage
Renal
Impairment of renal function
Post renal
Obstruction of urinary tract
14
The dotted line shows that the serum creatinine begins to rise only after 50% of the
nephrons are damaged, i.e. serum creatinine though useful is a less sensitive indicator of
renal function.
15
Methods:
1. Jaffes method
Creatinine
+ Picric acid
Alkaline reagent
Colored product
Spectrophotometer
Picric acid also reacts with glucose, protein and fructose, hence actual level is 0.2 to 0.4
mg /dl lower
2. Enzymetic method
Creatinine
Colored product
enzymes
spectrophotometer
Normal Range:
Serum Creatinine
Causes of:
Increased serum creatinine
1. Azotemia
2. dietary meat
3. Acromegaly, gigantism
16
12:1 to 20:1
Causes of
Ratio >20:1
INCREASED BUN WITH NORMAL CREATININE
1.
2.
3.
4.
Ratio <12:1
INCREASED CREATININE WITH NORMAL
BUN
1. Starvation
2. Low protein diet
3. severe liver disease
In these three conditions, there is
increased creatine breakdown in muscles
to synthesize proteins increased
creatinine
BUN is normal
17
(iv) Proteinuria
Rationale:
1. Normally a very small amount of albumin is excreted in urine.
2. Earlest evidence of glomerumlar damage in diabetes mellitus is occurrence of
microalbuminuria (albuminuria in range of 30 to 300 mg/24 hrs)
3. Albuminuria >300mg/24 hour is termed clinical or overt proteinuria and indicates
significant glomerular damage.
For details see notes on urine analysis Protein in urine
18
2. Generalised aminoaciduria
i. many aminoacids are excreted in urine due to proximal tubular dysfunction
3. Tubular proteinuria (Low molecular weight proteinuria)
i. substances such as beta 2 microglobulin, retinol binding protein, lysozyme and alpha
1 microglobulin are completely reabsorbed by tubules
ii. Detected by urine protein electrophoresis.
19
20
+
Hence to avoid this we can measure the exact quantity of Na+ reabsorbed as a fraction of
amount of Na+ filtered to amount excreted
As with above test, this test is used to differentiate between pre and renal azotemia
Method:
F Na+ =
Urine Na+
Plasma Creatinine
Plasma Na+
Urine Creatinine
100
Values:
1. Pre renal azotemia - <1%
2. ATN - >3%
21
1. Proteinuria
2. Glycosuria (diabetes
mellitus)
3. Nephrotic syndrome
4. urinary tract
obstruction with
preserved
concentrating ability
5. decreased renal
perfusion with
preserved
concentrating ability
1. Diabetes insipedus
2. CRF with decreased
concentrating ability
3. increased water
intake
Normal Value:
Specific gravity
1.003 to 1.030
22
Method:
0.1 M sucrose
Semipermeable
Membrane
as water enters
The tube, its level
rises
Water
Simple osmometer
23
Application: (Urine : plasma osmolality ratio is calculated, used to differentiate pre renal
and renal azotemia)
Decreased urine:plasma osmolality ratio
(either urine osmolality is decreased or
plasma osmolality is increased)
Seen in Acute tubular necrosis (decreased
concentrating ability)
24
(iii) Water deprivation test for urine osmolality and specific gravity
Rationale:
Measures concentrating ability of kidney with fluid restriction
Method:
Measurement of urine osmolality and specific gravity
Measurement of urine osmolality and specific gravity and comparison with earlier values
Administer desmopressin
Central DI
(diabetes insipedus)
No rise
Nephrogenic DI
* false positive result is obtained in case of low salt, low protein diet or major electrolyte
disturbances
25
1.
2.
3.
4.
Measure
Specific gravity
urine volume
osmolality (serum and urine)
plasma levels of ADH
Scenario 1
1. >90% of fluid load excreted in 4 hours
2. specific gravity <1.003 after 4 hours
3. Urine osmolality <100 mOsm/kg after 4 hrs
4. ADH level decreased with decreased
osmolality
Scenario 2
1. <80% excreted
2. >1.003
3. >100 mOsm/kg
4. ADH fails to decrease
26
Method:
Measure baseline urinary pH and plasma HCO3- levels
Scenario 1
1. Urine pH <5.4
2. plasma HCO3- Normal
/high
Scenario 2
1. Urine pH > 5.4
2. Plasma HCO3- low
Scenario 3
Inconclusive results
Normal renal
Acidifying ability
If pH <5.4, acidifying
Ability maintained
Notes on renal function tests By Dr. Ashish Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes