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Renal Function

Clinical Pathology Department


Medicine School/Hasan Sadikin
Hospital

Topics
1.
2.
3.
4.

Renal function
Glomerular Filtration Rate (GFR)
Concept of clearance
Measurement of Glomerular
Filtration Rate
5. Indicators of Renal Disease

RENAL FUNCTION
1.
2.
3.
4.
5.
6.
7.

Excretion
Reabsorption
Acid-base homeostasis
Water and Sodium metabolism
Vascular tone
Erythropoiesis
Calcium homeostasis

To produce urine, nephrons and


collecting ducts perform 3 basic
processes:
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion

Glomerular Filtration Rate


The amount of filtrate
formed in all renal
corpuscles of both
kidneys each minute.
In adult male GFR =
125 ml/min;
female = 105 ml/min.

CONCEPT OF CLEARANCE
Renal clearance:
volume of plasma that would
theoritically have to be cleared of
the substance in order to account
for the amount of the substance
excreted in the urine during a
given period.
Relates the rate of urinary
excretion of material to the plasma
concentration of that material.

CONCEPT OF CLEARANCE

Parameters need to calculate renal


clearance of certain substance:
- the amount of substance excreted in
the
urine calculate from:
- concentration of substance in urine
(Ux)
- volume of urine (V)
- plasma concentration of the substance
(Px)

CONCEPT OF CLEARANCE

Example:
Creatinine
Creatinine is toxic substance
produced by muscle and ingested
meat.
If a person excreted creatinine
1500g/day, and normal plasma
concentration of creatinine is 1
mg/dl (10 mg/L) he needs 150 L
of plasma to cleared creatinine
creatinine clearance = 150 L/day.
Ccreat = (Ucreat X Vu)/Pcreat

CONCEPT OF CLEARANCE

Creatinine clearance formula:


Measured
Estimated
Creatinine clearance decreased with
age

CONCEPT OF CLEARANCE

Creatinine clearance formula:


Ucr (mg/dl) X V (mL/min)
Measured Ccr = ---------------------------------Pcr (mg/dl)
Ucr = concentration of creatinine in urine
Pcr = concentration of creatinine in
plasma
V = volume of 24-hour urine collection

CONCEPT OF CLEARANCE

Creatinine clearance formula:


Estimated:
(140-age) X weight (kg)
Ccr (adult male) = ------------------------------ X 72
Pcr
Ccr (adult female) = Ccr (adult male formula)
X 0.85

CONCEPT OF CLEARANCE

Creatinine clearance:
Usefull in:
Detecting renal dysfunction
Calculating dose intervals for
nephrotoxic drugs
Evaluating the effectiveness of
therapy of progressive renal disease

CONCEPT OF CLEARANCE

Increased Ccr:
1. Normal pregnancy:
Range 115-185 ml/min depent on
time of gestation, highest at the end
of the first 3 semester.
Increase in plasma volume
increase GFR increase Ccr

2. Early diabetic glomerulopathy:


arteriosclerosis constriction of
efferent arteriole GFR

damages the glomerulus


(hyperfiltration injury)

CONCEPT OF CLEARANCE

Decreased Ccr:
1. Elderly people:
GFR normally decreases with age
Ccr

2. Acute and chronic renal disease:


AKI :
-

Acute Tubular Necrosis (ATN)


Rapidly Progressive Glomerulonephritis
(RPGN)

CRF :
-

Diabetic glomerulopathy
Hypertension

MEASUREMENT OF GLOMERULAR
FILTRATION RATE
1. With exogenous substances:
Inulin (gold standard)

2. With endogenous substances:


Creatinine
Urea Nitrogen
Cystatin C

MEASUREMENT OF GFR

Creatinine:

Source:
Muscle: creatine/creatine phosphat
Ingested meat

Widely used as GFR marker:


Endogenous substance of fairly
constant production.
Not bound to plasma protein
filtered freely by the glomerulus.
Not reabsorbed by the renal tubulus
Only a small amount is secreted by
the tubulus

MEASUREMENT OF GFR

Creatinine:

Disadvantages of Cr as GFR
marker:
Depend on muscle mass
Also derived from dietary meat

Creatinine measurement:
Interfering substances: ketones,
glucose, fructose, protein, urea and
ascorbic acid.

MEASUREMENT OF GFR

Increase serum creatinine:


1. Decreased cardiac output:
Congestive heart failure, hemorrhagic shock, volume
depletion
COP GFR cr

2. Increased muscle mass (body


builder)
3. Increased tissue necrosis
third-degree burns (cr degradation cr )

4. Acute glomerulonephritis (GFR


cr )

MEASUREMENT OF GFR

Increase serum creatinine:


5. Acute or chronic renal failure
(GFR )
6. Post renal disease (GFR )
7. Creatine supplements
(Cr
5. )
degradation )
8. Drug/chemical interference
(cephalosporin, diabetes
ketoacidosis)

MEASUREMENT OF GFR

Decrease serum creatinine:


1. Increased plasma volume:
Normal pregnancy plasma vol
GFR cr .
2. Emaciated patient:
Cr muscle cr
3. Chemical interference:
hyperbilirubinemia

MEASUREMENT OF GFR

Urea

Main waste product of Nitrogencontaining chemicals in the body


Urea Nitrogen.
Its value as a measure of GFR is
not very good:
Depend largely to protein intake
(diet)
Reabsorbed in the proximal tubule
and inner medullary collecting duct

MEASUREMENT OF GFR

Increased Blood Urea


Nitrogen (BUN):
1.
2.
3.
4.
5.
6.

Decreased cardiac output


Increased protein intake
Increased tissue catabolism
Acute glomerulonephritis
Acute or chronic renal failure
Postrenal disease

MEASUREMENT OF GFR

Decreased Blood Urea


Nitrogen (BUN):
1. Increased plasma volume
2. Decreased urea synthesis
3. Decreased protein intake

MEASUREMENT OF GFR

Cystatin C

Not affected by muscle mass, sex,


race
Because small size and positive
net charge freely filtered at the
glomerulus, and completely
reabsorbed in the tubulus.
Not widely used measurement
is expensive

INDICATORS OF RENAL
DISEASE
1. Increased of serum creatinine and
BUN
2. Decreased creatinine clearance
3. Loss of urine concentration and
dilution
4. Proteinuria
5. Hematuria
6. Leucocyturia
7. Presence of renal tubular casts

Reference books
1. Henrys Clinical Diagnosis and
Management by Laboratory
Methods. Richard A.McPherson,
Matthew R.Pincus. 21st ed, 2007.
2. Laboratory Testing in Clinical
Medicine. Edward F.Goljan, Karlis
I.Sloka. 2008

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