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Download MBBS Renal Function Test Lecture PPT

Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Renal Function Test Lecture PPT

This post was last modified on 30 November 2021




RENAL FUNCTION TEST

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DR. S. SHEKHAR

ASSOC. PROFESSOR

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DEPT. OF BIOCHEMISTRY
FUNCTIONS OF KIDNEY

1. Maintenance of homeostasis:

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The kidneys are responsible for the regulation of water,

electrolyte & acid-base balance in the body.

2. Excretion of metabolic waste products:

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The end products of protein & nucleic acid metabolism

are eliminated from the body. These include urea,
creatinine, creatine, uric acid, sulfate & phosphate

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3. Retention of substances vital to body:
The kidneys reabsorb & retain several substances of

biochemical importance in the body e.g. glucose,
amino acids etc

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4. Hormonal functions:
A. Erythropoietin:



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A peptide hormone, stimulates haemoglobin synthesis

and formation of erythrocytes.

B. 1,25-Dihydroxycholecalciferol (calcitriol):

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The active form of vitamin D is finally produced in the

kidney. It regulates calcium absorption from the gut.

C. Renin:

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A proteolytic enzyme liberated by kidney, stimulates

the formation of angiotensin II which, in turn, leads to

aldosterone production.

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Angiotensin II & aldosterone hormones involved in

the regulation of electrolyte balance.
URINE FORMATION

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? Nephron is the functional unit of kidney.
? Each kidney is composed of approximately one million

nephrons.

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? Nephron, consists of a Bowman's capsule (with blood

capillaries), proximal convoluted tubule (PCT), loop of
Henle, distal convoluted tubule (DCT) & collecting

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tubule.

? About 1200 ml of blood (650 ml plasma) passes through

the kidneys, every minute.

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? About 120-125 ml is filtered per minute by the

kidneys & this is referred to as glomerular filtration

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rate (GFR).

? With a normal GFR (120-125 ml/min), the glomerular

filtrate formed in an adult is about 175-180 litres/day,

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out of which only 1.5 litres is excreted as urine.

? More than 99% of the glomerular filtrate is

reabsorbed by the kidneys.

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? Urine formation basically involves two steps

glomerular filtration & tubular reabsorption.
Glomerular filtration

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? This is a passive process that results in the

formation of ultra filtrate of blood.

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? All the (unbound) constituents of plasma, with a

molecular weight < 68,000, are passed into the
filtrate.

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? The glomerular filtrate is almost similar in

composition to plasma except proteins and cell.


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Tubular reabsorption
? The renal tubules (PCT, DCT & collecting

tubules) retain water & most of the soluble
constituents of the glomerular filtrate by

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reabsorption.

? This may occur either by passive or active

process.

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Renal threshold

? There are certain substances in the blood whose

excretion in urine is dependent on their concentration.

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? Such substances are referred to as threshold substances.
? At the normal concentration in the blood, they are

completely reabsorbed by the kidneys.

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? But when their blood levels are elevated beyond the

normal range exceeding the tubular reabsorption capacity
the excesss is excreted in urine.

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? The renal threshold of a substance is defined as its

concentration in blood (or plasma) beyond which it is
excreted into urine.

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v



The renal threshold for

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Glucose --------180 mg/dl
Ketone bodies--- -3 mg/dl
Calcium ----------10 mg/dl
Bicarbonate ------ 30 mEq/l

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vTubular maximum (Tm):
? The maximum reabsorptive capacity of the

renal tubules to absorb a particular substance.

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? Tubular maximum for glucose is 375 mg/min
INDICATION

1. Detection of renal damage
2. Assessment of extent of renal damage

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3. Monitoring the progression of renal damage /

disease

4. Monitoring and adjusting the dose of

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potentially renal toxic drugs

5. Before giving renal excretory contrast in some

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diagnostic procedure
CLASSIFICATION

I. GLOMERULAR FILTRATION CAPACITY TEST

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I. Clearance tests
II. Serum urea
III. Serum creatinine

II. GLOMERULAR

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FILTRATION

BARRIER

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INTEGRITY TEST

A. Proteinuria
B. Hematuria
C. Urine protein electrophoresis

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III. TUBULAR FUNCTION TESTS
A. Reabsorption test
B. Renal concentration test/ water deprivation test

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C. Osmolality
D. Specific Gravity
E. Urine dilution test
F. Sodium Excretion Test
G.Ammonium Chloride loading test or urinary

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acidification test

IV. COMPLETE URINE ANALYSIS
I. GLOMERULAR FILTRATION CAPACITY TEST

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? It measures the total filtration occuring at glomerulus.
? These indicates the percentage, or fraction of the total

nephron that are functioning.

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A decrease in 50% filtration capacity


indicates that about half of the total nephrons have

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lost their function.
1. RENAL CLEARANCE TESTS

? To assess the rate of glomerular filtration & renal

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blood flow.

? "The renal clearance of a substance is defined as the

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volume of plasma from which the substance is
completely cleared by the kidneys per minute."

? This depend on
- plasma conc. of the substance & it's

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excretary rate

- GFR
- Renal plasma flow

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Renal Clearance Tests

? The GFR (Normal = 120 ml/minute )
? Usually equal to clearance of that substance and is

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calculated by the following equation

U x V
C =
P

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Where, C = Clearance of the substance (ml/mt)
U = Conc.of substance in urine (mg/L)
P = Conc.of substance in plasma (mg/L)
V = Vol.of the urine passed per minute
Renal metabolic

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Clearance Value

Example

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change



Vs GFR

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Substance only

Clearance = GFR

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Inulin

filtered

( No reabsorbtion

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No secretion)

Substance filtered

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Clearance < GFR

Urea

and reabsorbed

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Substance filtered

Clearance > GFR

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Creatinine

and secreted
A. Urea clearance test

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? Urea is the end product of protein metabolism.

? After filtered by the glomeruli, it is partially

reabsorbed by the renal tubules.

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? So, Urea clearance is less than the GFR & it is

influenced by the protein content of the diet.

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? Urea clearance is not as sensitive as creatinine

clearance.
Urea clearance test

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? Urea clearance is defined as the volume (ml) of plasma

that would be completely cleared of urea per minute.

? If the output of urine is more than 2 ml per minute.

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[ V > 2ml/min]


This is referred to as maximum urea clearance & the

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normal value is around 75 ml/min

? It is calculated by the formula:

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U X V

Cm =

P

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? Cm=Maximum urea clearance.
? U = Urea concentration in urine (mg/dl).
? V = Urine excreted per minute in ml.
? P = Urea concentration in plasma.

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Standard urea clearance

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? The urea clearance drastically changes when the

volume of urine is less than 2 ml/min.

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[ V < 2ml/min]

? This is known as standard urea clearance (C) & the

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normal value is around 54 ml/min

? Standard urea clearance is calculated by a modified

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formula

U X V

Cs =

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P

? A urea clearance value below 75 % of the normal

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indicates renal damage.


? Usually blood urea level start rising only when

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the clearance value falls below 50% of the
normal.

? Urea clearance values may not always coincide

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with blood urea level.

? Urea is reabsorbed by the renal tubule and

hence tubular function affects urea clearance.

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? Normal level of blood urea: 20-40 mg/dl
B. Creatinine clearance test

? Creatinine is an excretory product derived from

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creatine phosphate in muscle.

? The excretion of creatinine is rather constant &

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is not influenced by body metabolism or

dietary factors.

? Creatinine is filtered by the glomeruli & only

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marginally secreted by the tubules.

? Creatinine clearance may be defined as the

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volume (ml) of plasma that would be

completely cleared of creatinine per minute.
Procedure:

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? In the traditional method, creatinine content of a 24 hr

urine collection & the plasma concentration in this

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period are estimated.

? The creatinine clearance (C) can be calculated as

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follows:



U X V

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Ccr = P
U = Urine concentration of creatinine.
V = Urine output in ml/min (24 hr urine volume

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divided by 24 x 60)

P = Concentration of creatinine.


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? The normal range of creatinine clearance is

around 120-145 ml/min.

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? A decrease in creatinine clearance ( <75% of

normal ) indicate a decrease GFR reflecting
renal damage.

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? It is helpful in the early detection of functional

impairment of kidney and also for monitoring
the patients with renal insufficiency

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? In older people, the clearance is decreased.
Creatinine clearance test as a GFR marker

Advantages

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Disdvantages

1. It is not affected by diet or 1. Secreted by tubule, so

exercise

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clearance > GFR

2. Extrarenal factors will rarely

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interfere.

2. Overestimate GFR by

10-20 ml/min

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3. Conversion of creatine

phosphate to creatinine is 3. Very early stages of

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spontaneous, non-enzymatic.

decrease in GFR (50-70

4. As the production is

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ml/min) may not be

continuous, the blood level

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identified by creatinine

will not fluctuate. Blood

clearance (creatinine

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may be collected at any time.

blind area).

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Relation between GFR AND Plasma Creatinine
C. Inulin Clearance Test

? Method of choice when accurate determination

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of GFR is required.

? Inulin is polysacharide of Fructose.
? Freely filtered by glomerulus not reabsorbed not

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secreted or metabolically altered by the renal

tubule.

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? Normal value : 120 ml/mt.
? Disadvantages :need for its

IV adminstration

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technically difficulty of



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analysis

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D. Cystatin C as a filtration marker

? It is a LMW nonglycosylated protein produced at a

constant rate by all nucleated cells in the body,

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? Freely filtered by the glomeruli, and totally reabsorbed

by the renal tubules.

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? It is not secreted, by the tubules. Thus, its plasma level is

determined by GFR.

? Normal adults have circulating level of approx. 1mg/l.

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? This is better indicator of renal function as compared to

creatinine in early stages of GFR impairment as it is
independent of age,gender,body composition & muscle
mass.

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E. Estimated GFR (eGFR)

? A simpler technique of estimating creatinine

clearance and there by GFR is by using serum

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creatinine level.

? This would eliminate the need for timed urine

collections.

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? A commonly used formula is Cockcroft-Gault

equation.

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? Ccr = (140 ? age in years) ? weight in Kg (0.85 in

females)/72 ? Pcr in mg/dL

? The factor 0.85 is used in females assuming that they

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have 15% less muscle mass.
MDRD (Modification of Diet in Renal Disease) Formula

? This equation directly estimates GFR.

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? The estimated GFR (eGFR) (mL/min/1.73m2)

eGFR = 186 ? (Creatinine/88.4) -1.154 ? (Age) ?0.203 ?

0.742 (if female)

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? Estimates GFR adjusted for body surface area.
? Designed for use with laboratory creatinine test.
? Is more accurate than creatinine clearance measured from

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24-hour urine collections or estimated by the Cockcroft-
Gault formula.



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GRADING OF CHRONIC KIDNEY DISEASE
2. Serum urea

? Urea is major nitrogenous end product of protein and

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amino acid catabolism, produced by liver and distributed
throughout intracellular and extracellular fluid.

? Urea is freely filtered by the glomeruli
? 40-70% of it is passively absorbed by diffusion into

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renal tubules depending upon urine flow rate.

? The reference interval - 10-40 mg/dl
? High protein diet causes significant increases in plasma

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urea concentrations
? Many renal diseases with

various glomerular, tubular,

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interstitial or vascular damage can cause an increase

in plasma urea concentration

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? Nonrenal factors can affect the urea level

a) Mild dehydration,
b) high protein diet,
c) increased protein catabolism,

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d) muscle wasting as in starvation,
e) reabsorption of blood proteins after a GIT

haemorrhage,

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f) treatment with cortisol or its synthetic

analogous
? States associated with

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elevated levels of urea in blood are

referred to as uremia or azotemia

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? Causes of plasma urea elevations:
Prerenal: renal hypoperfusion
Renal: acute tubular necrosis
Postrenal: obstruction of urinary flow

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? Parallel determination of urea and creatinine is

performed to differentiate between pre-renal and post-
renal azotemia

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? Pre-renal azotemia leads to increased urea levels, while

creatinine values remain within the reference range.

? In post-renal azotemias both urea and creatinine levels

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rise, but creatinine in a smaller extent
BLOOD UREA NITROGEN (BUN)

? Sometimes, blood urea level is expressed as blood urea

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nitrogen (BUN)

? BUN is the nitrogen content of urea present in blood
? Molecular weight of urea is 60 in which the

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contribution of nitrogen atoms is 28

? Therefore, BUN equals blood urea multiplied by 28/60

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i.e. nearly 0.47

? The normal range of BUN is 10-20 mg/dl
? A rise in nitrogen content of blood is called azotaemia
Serum creatinine

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? Creatinine is a breakdown product of creatine

phosphate in muscle, and is usually produced at a

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fairly constant rate by the body depending on muscle

mass

? Creatinine is filtered but not reabsorbed in kidney.

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? A small amount of creatinine is secreted into tubules

and its secretion is increased with the increasing level

of plasma creatinine.

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? Normal range is 0.8-1.3 mg/dl in men and 0.6-1 mg/dl

in women

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? Not increased above normal until GFR<50 ml/min .
Increased serum creatinine

? Impaired renal function

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vDrugs:

? Anabolic steroid users

? Probenecid

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? Vary large muscle mass:

? Cimetidine

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body builders,

? Triamterene

acromegaly patients

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? Trimethoprim

? Rhabdomyolysis/crush

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? Amiloride

injury

? Athletes taking oral

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creatine

Determination of serum creatinine gives a useful
indication of the degree of renal failure

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II. GLOMERULAR FILTRATION BARRIER

INTEGRITY TEST

Glomerulus acts as a selective filter of the blood passing

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through its capillaries

A. PROTEINURIA

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? Proteinuria is the first sign of glomerular injury

before any decrease in GFR.

? The glomeruli of kidney are not permeable to

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substances with molecular weight more than 69,000
& plasma proteins are absent in normal urine
PROTEINURIA

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? When glomeruli are damaged or diseased, they become

more permeable & plasma proteins may appear in urine.

? The smaller molecules of albumin pass through damaged

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glomeruli more readily.

? Albuminuria is always pathological
If total protein excretion > 150 mg/day

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Or

Albumin excretion > 30 mg/day

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Indicative of glomerular damage
MICRO-ALBUMINURIA

? It

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is

also

called

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minimal

albuminuria

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or

paucialbuminuria.

? It is an early indicator of onset of nephropathy due to

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microvascular glomerular damage.

? Micro albuminuria is an early indication of nephropathy

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in patients with diabetes mellitus & hypertension.

? It is identified, when small quantity of albumin (30-300

mg/day) is seen in urine.

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? It is also expressed as albumin creatinine ratio. Albumin

creatinine ratio ? 30-300mg albumin /gm of creatinine
URINARY PROTEIN ELECTROPHORESIS

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? Urine protein electrophoresis separates the proteins

according to charge and allows classification of the type

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of renal injury.

? Protein patterns are interpreted and classified as

glomerular, tubular, or mixed patterns

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In minimal glomerular damage



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Low molecular weight protein such as albumin,

1- AT, and transferrin are excreted


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In severe glomerular damage


other proteins having high molecular weight

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like immunoglobulin are excreted into urine
TUBULAR PROTEINURIA occurs when the renal tubules
cannot reabsorb low molecular weight proteins

Tubular

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proteinuria

is ? This

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protein

pattern

associated with

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reveals protein bands in

? Drug toxicity

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the

i.

aminoglycosides,

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? alpha 2 region (alpha 2

ii. cephalosporins,

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microglobulin,

retinol

binding protein), and

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iii. Cyclosporine

? one band in the beta 2

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?

Pyelonephritis,

region

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(beta

2

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?

Interstitial nephritis,

microglobulin)

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?

Renal vascular disease,

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and

?

Transplant rejection.

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Overflow proteinuria

? It is caused by high plasma protein

concentrations that exceed the reabsorptive

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capacity of the tubules.

? Common examples include Bence-Jones

Proteins

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(multiple

myeloma)

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and

myoglobinuria.

? In hemolytic conditions, hemoglobin can

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appear in urine (hemoglobinuria)
B. HEMATURIA

? An earliest sign of glomerular damage before the

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overt decrease in GFR.

? Intact glomerulus does not allow the passage of RBC.
When severe glomerular damage

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RBC leakage occurs
? Detection of microscopic hematuria or RBC casts

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confirm glomerular damage


TUBULAR FUNCTION TEST

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? These tests are based on tubular reabsorption and

secretion function of kidneys.

? The tubular epithelial cells of nephrons are highly

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specialized structure, which selectively reabsorb
water and some substances and secrete other.
1. Specific gravity of urine

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? The simplest test of tubular function is the measurement of

specific gravity of urine by a urinometer.

? Normal 1.015-1.025

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? This is an indication of osmolality.
? Incase of proteinuria S.G. elevated.
? Earliest manifestation of renal disease may be difficulty in

concentrating the urine.

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? Sp.gr.-- excessive water intake, ch.nephritis, Diabetes

Insipidus

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? Sp.gr.-- diabetes mellitus, nephrosis, Ch.Renal failure.
? Fixed sp.gr. at 1.010 isosthenuria -- earliest

manifestation of tubular disease / chronic renal failure.

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? A defect in concentrating capacity is termed

hyposthenuria.

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? The inability to excrete the waste products may be

counterbalanced by large urine output.

? Thus the earliest manifestation of the renal disease

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may be difficulty in concentrating urine.
2. Urine Osmolality

? Osmolality of urine varies from 50 mosm/kg in

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condition of excessive fluid intake to 1200 mosm/kg in
low fluid intake.

? Random urine sample = 850-900 mosm/kg.

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? It is found that the urine (without any protein or high

molecular weight substance) with an osmolality of 800
mosm/kg has a specific gravity of 1.020

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? Therefore, measurement of urine osmolality will also

help to assess tubular function

? Plasma osmolality is 285-295 mOsm/kg.

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3. WATER DEPRIVATION TEST OR URINE

CONCENTRATION TEST

? 99% of water of glomerular filtrate is reabsorbed during

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its passasge through different segment of renal tubule.

Fluid intake is withheld overnight preferably 18 hours

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osmolality of 1st urine sample in the morning

If osmolality > 850 mosmol/kg , Sp.Gv- 1.022

Renal concentrating ability is normal/good

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? In low ADH activity ( hypothalmic / pituitary

disorder) or nephrogenic diabetes insipidus (lack of

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response to ADH)

Osmolality is low and rarely exceeds 300 mosm/kg

(Sp. Gr. 1.010)

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4. Urine dilution test

? A normal kidney produce a dilute urine following excessive

water intake.

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After an overnight fast and fluid deprivation

Bladder is emptied at 7 am and water load (1200 ml over

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the next 30 min) is given

Hourly urine samples are collected for next four hours

The specific gravity of at least one sample should fall to

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1.003 and osmolality to 50 mOsm/kg


? Normal person will excrete all the water load with in

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4 hours

? Kidneys which are severely damaged cannot excrete a

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urine of lower specific gravity than 1.010 or a volume
above 400 ml in this time.

? This test is more sensitive and less harmful than

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concentration test

? The test should not be done if there is oedema or renal

failure; water intoxication may result

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5. Ammonium chloride loading test or

Urinary Acidification test

? It is indicated in unexplained hyperchloremic

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metabolic acidosis

? Acidification defects may occur due to generalized

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tubular defects or due to genetically determined
defects in ion pumps

? Enteric coated capsules containing ammonium

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chloride at a dose of 0.1 g / kg body wt is given

? In the liver, NH3 is converted to urea and HCl is

produced which is excreted by kidney.

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? Urine is collected hourly from 2 to 8 hours after

ingestion.

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? At least one sample should have a pH of 5.3
? In type I distal renal tubular acidosis, urinary pH

rarely falls below 6 and never falls below 5.3.

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? Liver disease is a contraindication to perform this

test.

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FRACTIONAL EXCRETION OF SODIUM

It is a measure of

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the percentage of
sodium that gets
excreted in the urine
over

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the

total

filtered sodium by

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the kidney


URINE ANALYSIS

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URINE ANALYSIS