6. INDICATIONS
• Early identification of renal impairment in patients at risk.
• Diagnosis of renal disease.
• Assess response to treatment.
• Adjust dosage of certain drugs.
• Plan renal replacement therapy in advanced renal diseases.
7. CLASSIFICATION
GLOMERULUS PROXIMAL
TUBULES
DISTAL
TUBULES
Clearance tests Glycosuria Specific gravity
S. Creatinine Aminoaciduria Osmolality
BUN Tubular proteinuria Water deprivation
test
BUN/S.Creatinine Urinary excretion of
sodium
Water loading test
Proteinuria Fractional sodium
excretion
Ammonium
chloride loading test
9. GFR - RATIONALE
• Varies according to age, sex, BSA.
• Normal GFR is 120 – 130 ml/min/1.73m2.
• Declines with age.
• Fall in GFR leads to accumulation of waste products.
• GFR < 60ml/min/1.73m2
- >50% loss of renal function.
10. CHRONIC KIDNEY DISEASES
STAGE DISEASE GFR VALUE
(ml/min/1.73m2
)
Stage I Kidney disease
with
Normal GFR >90
Stage II Kidney disease
with
Mildly reduced
GFR
60-89
Stage III Kidney disease
with
Moderately
reduced GFR
30-59
Stage IV Kidney disease
with
Severely reduced
GFR
12-29
Stage V Kidney failure <15
11. METHODS TO MEASURE GFR
• Direct assessment - Clearance tests
• Indirect assessment from S. Creatinine
12. CLEARANCE TESTS
• Volume of plasma that is completely cleared of that substance
per minute.
• 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)
13. AGENT FOR CLEARANCE
STUDIES
• Not bind to plasma proteins.
• Freely filtered across glomeruli.
• Not reabsorbed
• Not secreted.
• Not metabolized by kidney.
• Excreted only through the kidney.
15. INULIN CLEARANCE TEST
• Gold standard for measurement of GFR.
Method:
• Bolus dose – 25 ml of 10 % solution.
• 500 ml of 1.5 % solution – 4 ml/ min.
• Timed urine and blood samples are collected.
16. INULIN CLEARANCE TEST
Disadvantage:
• Time consuming
• Expensive
• Need to maintain steady plasma levels
Normal values:
• Males – 125 ml/min/1.73 m2
• Females – 110 ml/min/1.73 m2
18. CREATININE CLEARANCE
TEST
Method:
• 24 hour urine sample.
• A blood sample is obtained at midpoint of urine collection.
• Final calculation is by the formula UV/P.
• Cimetidine can be used to prevent overestimation.
19.
20. CREATININE CLEARANCE
TEST
Disadvantages:
• Small amounts of creatinine secreted by renal tubules can
increase even further in advanced renal failure.
• Collection of urine is often incomplete.
• Creatinine levels are affected by -
- meat and muscle mass.
- certain drugs (cimetidine, trimethoprim)
21. CYSTATIN-C CLEARANCE TEST
Rationale:
• Protease inhibitor produced by all nucleated cells.
Advantages over creatinine:
• More sensitive and specific.
• Not affected by sex, diet and muscle mass.
22. INDIRECT ASSESSMENT OF
GFR
Convenient but insensitive.
Creatinine clearance
(140 – age in years) x Body weight in kg
( 72 x serum creatinine in mg/dl)
=
25. DISADVANTAGES - BUN
• Less sensitive.
• Completely filtered by glomeruli and 30-40 % is
reabsorbed.
• Affected by -
- Protein diet
- Upper G.I haemorrhage
- Liver function
• Considerable destruction of renal parenchyma - blood urea
elevation.
26. METHODS
1. Diacetyl monoxamine method
+ DAM
Yellow diazine derivative
High temp, strong acid, oxidizing
agent
Intensity of color is measured
Urea
27. METHODS
2. Urease Berthelot reaction
Iodophenol
Intensity of color
is measured
Urea
370 C
Urease
Ammonia
Alkaline hypochlorite
Phenol
28. CAUSES OF INCREASED BUN
PRE RENAL RENAL POST RENAL
• Shock
• CHF
• Dehydration
• High protein diet
• Trauma
• Burns
• GI haemorrhage
• Impairment of
renal function
• Obstruction of
urinary tract
29. SERUM CREATININE
Rationale:
• Creatinine is produced in muscles at a constant rate.
• Production is proportional to muscle mass and body weight.
Normal range: 0.7 to 1.3 mg/dl
34. BUN/SERUM CREATININE
RATIO
RATIO >20:1 RATIO <10:1
↑BUN WITH NORMAL
CREATININE
↑CREATININE WITH NORMAL
BUN
High protein diet
Increased protein catabolism
GI haemorrhage
Dehydration
Starvation
Low protein diet
Severe liver disease
↑BUN & CREATININE, BUT ↑IN
BUN IS MORE
↑BUN & CREATININE, BUT ↑ IN
CREATININE IS MORE
Post renal obstruction Acute tubular necrosis
35. PROTEINURIA
Rationale:
• A very small amount of albumin is excreted in urine.
• Microalbuminuria (30 to 300 mg/24 hrs)
• Clinical or overt albuminuria ( >300mg/24 hr)
44. URINE OSMOLALITY
Rationale:
• Most sensitive and most commonly employed method.
• Depends on number of dissolved particles.
• Normal value: 500 - 800 mOsm/kg of water.
46. WATER DEPRIVATION TEST
Rationale:
• Measures concentrating ability of kidney with fluid restriction.
• Differentiate between central DI and nephrogenic DI.
47. WATER DEPRIVATION TEST
Method:
Rise in specific gravity and
urine osmolality
Urinary concentrating ability
maintained
No rise in specific gravity and
osmolality
Administer desmopressin
Rise No rise
Nephrogenic DI
Central DI
Restriction of water intake
48. WATER LOADING – ADH
SUPPRESSION TEST
Rationale:
• Measures ability of kidney to dilute urine after water loading.
49. Method:
Over night fast
Drink 20 ml/kg of water in 15-20 min
• <80% excreted
• >1.003
• >100 mOsm/kg
• ADH fails to decrease
• >90% excreted
• Specific gravity <1.003
• Urine osmolality <100 mOsm/kg
• Decreased plasma osmolality and
ADH levels
Normal diluting ability
of kidney
Renal function
impairment
Collect urine for next 4 hours
65. GLOMERULUS: NO / MINIMAL
HYPERCELLULARITY
DISEASE LM IF EM
MCD Normal glomeruli,
lipid vacuolation in
tubules
Negative Loss of foot
processes, no
deposits
FSGS Focal and segmental
sclerosis and
hyalinosis
IgM, C3 Loss of foot
processes, electron
dense deposits
MGN Diffuse thickening
of capillary wall
Granular
IgG, C3
Subepithelial
deposits (spikes)
71. GLOMERULUS: WITH
HYPERCELLULARITY
DISEASE LM IF EM
MPGN Double
contour of
GBM
I – IgG, C3
II – C3,
properdin
III – C3, IgG,
Ig M
I - Sub endothelial deposits
II – Dense intra membranous
deposits
III – Sub endothelial and sub
epithelial deposits.
Acute GN Diffuse
proliferation,
leukocytic
infiltration
Irregular IgG, C3 Subepithelial deposits (humps)
Crescentic
GN
Proliferation,
crescents
I- Linear Ig G, C3
II- Granular Ig G,
C3
III - Negative
I - Linear deposits along GBM
II - Sub epithelial deposits
III - No deposits
85. RECENT ADVANCES
• Genomics and proteomics.
• Laser-capture micro dissection - selection of glomeruli or a
specific tubular segment for study.
• ISH
Advantages:
• Identification of specific mRNA expression pattern and their
correlation with diagnosis, prognosis and response.
86. SUMMARY
• Renal diseases causes no symptoms until 50-75% of kidney
function is destroyed.
• Lab tests often provide the initial recognition of renal
impairment and can be used to direct further therapy.
• The simplest diagnostic test is the examination of the urine.
• Renal biopsy is performed to establish the specific diagnosis
of renal disease.
87. REFERENCES
• U.Satyanarayana, U.Chakrapani, Biochemistry, Arunabha Sen
Books Pvt. Ltd., 2010.
• Gaw A, Murphy MJ, Cowan RA, O’Reilly DSJ, Stewart MJ,
Shepherd J. Clinical Biochemistry: An illustrated colour text
(3rd Ed). Edinburgh: Churchill Livingstone, 2004.
• Stevens LA, Levey AS. Measurement of kidney function. Med
Clin N Am 2005;89:457-73.
• Pathological basis of disease : Robbins and Cotran, 9th edition.
