Kidney function tests by moustafa rizk

Interpretation
of
Kidney Function
ByBy
Dr. Moustafa RizkDr. Moustafa Rizk
Prof. of Clinical PathologyProf. of Clinical Pathology
Faculty of Medicine, University of Alexandria.Faculty of Medicine, University of Alexandria.

Objectives:Objectives:
 Describe the physiologic role of the kidney.Describe the physiologic role of the kidney.
 State the laboratory tests used to assessState the laboratory tests used to assess
glomerular function.glomerular function.
 Discuss the concept of renal clearance and howDiscuss the concept of renal clearance and how
it is measured.it is measured.
 State the laboratory tests used to assessState the laboratory tests used to assess
tubular function.tubular function.
 Record laboratory biochemical findings in someRecord laboratory biochemical findings in some
renal disorders.renal disorders.

Interpretation of Kidney Function

Functional unit of the kidney is the
NEPHRON (pleural (NEPHRA)
1.2 x 106
nephra per kidney.
Each nephron about 50 mm long.
Combined lengths about 145 km (85 miles)
Renal corpuscle.
Proximal convoluted tubule (PCT)
Loop of Henle
Distal convoluted tubule (DCT).

Glomerular Filtration Rate (GFR)
Kidneys receive 25% of the cardiac output
GFR = the amount of filtrate that forms in both
kidneys every minute.
In adults GFR is about :
 105 ml.min-1
in females
 125 ml.mi-1
in males
Daily volume of glomerular filtrate
 150 L in females
 180 L in males

Tubular Reabsorption: One of the important
nephron functions
99% of glomerular filtrate reabsorbed.
1% leaves body: 1-2 L per day.
Cuboidal epithelial cells with microvilli.
Osmosis, diffusion, active transport.
Materials reabsorbed include:
 Water
 Glucose
 Amino acids, urea.
 Na+
, K+
, Ca2+
, Cl-
, HCO3
-

Reabsorption of Selected Substances
Conserve valuable nutrients, e.g.
 Amino acids
 Glucose
Abnormally, glucose, amino acids, blood,
ketones, leukocytes, kidney stones, etc. might be
found in urine.

Fluid Compartments

Regulates blood volume and blood pressure
Adjust the amount of water lost or retained
 Energy dependent NA+ extrusion
 Antidiuretic hormone (ADH, or vasopressin)
Blood volume related to blood pressure
Regulation of blood pressure and blood flow
 Renin-angiotensin-aldosterone pathway
 Flow-rate through kidney can be adjusted.

Renal Functions : Acid-Base balance
Stabilizes blood pH (in company
with buffer systems and regulation
of [CO2]
 Regulates loss of H+ ions (acid)
 Regulates loss of HCO-3 ions
(base)
Normal plasma pH
7.35-7.45
Acidosis
pH < 7.35
Alkalosis
pH > 7.45

Regulates plasma concentrations of electrolytes
(e.g. Na+
, K+
, Cl-
, and other ions)
Water retained or lost in response to plasma osmolality
(normal plasma osmolality 290 mOsm/kg H2O).
 ADH mechanism
Controls loss in urine
Contributes to plasma [Ca2+] regulator by vitamin D
(calcitriol) regulation
 Renal activation of calcitriol increases Ca2+
uptake
from gut.

Juxtaglomerular Apparatus

Rennin-Angiotensin-aldosterone

Overall function of urine
production is to
maintain homeostasis
by regulating the
volume and
composition of blood.
Re-absorption of selected
substances
Acid-base balance
Electrolyte balance
Red blood cell formation
Regulate activated
vitamin D production

Laboratory tests aiding in the evaluation
of kidney functions
1. General characteristics of urine.
2. Tests measuring glomerular filtration rate
Clearance tests (urea,inulin,creatinin)
Non protein nitrogenous compounds
3. Tests measuring tubular function
Urinary acidification test
Sodium and potassium excretion tests
Specific gravity of the urine
Osmolality of urine and serum
Concentration and dilution tests

•Volume: (N: 700 – 2500 ml / day)
•Specific gravity: (N: 1.015 – 1.025)
•Osmolality: The number of dissolved solutes
/ kg body H2O.
(N: 500 – 800 mosmol /
kg body H2O)
•Protein.
•Microscopic examination: (cells and casts)
A-A- Complete Urine Examination:Complete Urine Examination:

S. CreatinineS. Creatinine
 S. ureaS. urea
S. CreatinineS. Creatinine
 S. ureaS. urea
B-Glomerularfunction tests
 GFRGFR
 glomerularglomerular
permeabilitypermeability
(selectivity index)(selectivity index)
 GFRGFR
 glomerularglomerular
permeabilitypermeability
(selectivity index)(selectivity index)
DirectDirectDirectDirect
IndirectIndirectIndirectIndirect

Test to estimate Glomerular Filtration Rate
(GFR)
1. GFR at which ultrafiltrate of plasma is formed; is
a “true” physiological estimate of renal function.
It assumes no secretion from blood into tubule
and no reabsorption once it is in tubule.
2. Inulin: is an inert carbohydrate that is not
metabolized, secreted or reabsorbed; thus ideal
agent for GFR determination; thus is used mainly
for research since not practical.

Glucose Urea
Creatinine
Inulin
PAHA
A B C D
Different ways by which renal tubules can handle
substances freely filtered at glomeruli.

Creatinine Clearance (90-140 ml/min/1.73 m2
)
1. Creatinine is primarily excreted via glomerualr
filtration with about 10-15% eliminated by active
tubular secretion.
2. CrCl is estimate of GFR
3. Clinical uses for obtaining CrCl :
Assessing kidney function in patients with acute or
chronic renal failure
Monitoring patients on nephrotoxic drugs.
Determining dosage adjustments for renally
eliminated drugs.

Definition of Clearance ( C ):
( ml / min)
It is the hypothetical volume of
plasma, that is completely cleared
from a certain substance per unit time
(minute).

Calculating Creatinine Clearance
Direct measurement:
CrCl = (UV) (Ucr) / (SCr) (1440) x 1.73 m2
/ BSA
- UV = 24 hour urine volume in ml.
- Ucr = urinary creatinine conc. in mg/dl.
- SCr = serum creatinine in mg/dl at midpoint of
urine collection.
- 1440 is number of minutes per day
- CrCl is in ml/min.

Criteria for an ideal GFR markerCriteria for an ideal GFR marker
 Produced inside the body i.e. Endogenous.Produced inside the body i.e. Endogenous.
 Constant production rate .Constant production rate .
 Elimination only via glomerular filtration with noElimination only via glomerular filtration with no
reabsorption or secretion.reabsorption or secretion.
 No laboratory interference for its measurment.No laboratory interference for its measurment.

1- Inulin clearance:
- Reference clearance method.
- Not suitable for routine investigation.
- Exogenous material I.V. infused in such a
way to maintain plasma level steady during the
period of the test.
(N: 125 ml / min).
GFR can be measured by:GFR can be measured by:

2- Creatinine clearance:
- It is widely used in routine work.
- An endogenous substance.
- Its value correlates fairly closely with inulin
clearance.
- Plasma creatinine is used as a day to day indication of
changes in GFR. It is superior to creatinine clearance
( error in all analysis based upon timed collection of
urine).
♂105 ± 20 ml/min
♀ 95 ± 20 ml/min
GFR can be measured by:GFR can be measured by:
N:

3- Urea clearance:
• Not used nowadays.
• It is 70% of GFR because part of urea in the
glomerular filtrate diffuses back into the
tubular cells and the amount reabsorbed
varies inversely with urine flow rate.

Clearance ( C ) =
U X V
P
1.73
A
X = 75 ml/min
Clearance ( C ) =
U X√ V
P
X = 54 ml/min
1.73
A
• Maximum urea clearance:
If the volume of urine / min = > 2 ml/min
• Standard urea clearance:
If the volume of urine / min = < 2 ml/min

•Para-amino hippuric acid ( PAHA ) is a substance
that can be filtered at the glomeruli and excreted by
the tubules.
•Such substance when infused at a low plasma
concentration, its clearance is very high.
•It measures the effective renal blood flow (RBF).
(N: 650 ml/min).
4- PAHA clearance:4- PAHA clearance:

5-Cystatin C ( New marker for GFR)5-Cystatin C ( New marker for GFR)
 Specific and sensitive parameter for
glomerular filtration rate (GFR).
 Independent of muscle mass, age and sex.
 Only eliminated via filtration.
 Not influenced by acute phase reaction.
 Independent from urine collection, only one serum
sample.
 quick, simple and reliable.

Assessment of Glomerular permeability
A. Selective proteinuria: the glomerular membrane has
still the ability to prevent filtration of proteins of large
MW and allow the filtration of small MW proteins
( Albuminuria).
B. Non selective proteinuria: as the damage proceeds ;
proteins of larger molecular sizes pass through the
membrane.
 Selectivity is measured by comparing the clearance of 2
proteins of different MW; albumin or transferrin versus
larger IgG.
 Selectivity ratio = Clearance of IgG
Clearance of albumin
Lower ratio <0.16 = more selective proteinuria.

Creatinine (0.7-1.5 mg/dl)
Is normal metabolic product of creatine
and phosphocreatine which are
constituents of skeletal muscle.
The daily production of creatinine is
determined by person’s muscle mass; in
normal patients, the rate of creatinine
production equal its excretion.

Cause of true changes in S. creatinine
Unlike BUN, SCr is not influenced by changes in
renal blood flow or diet
A rise in SCr almost always indicates worsening
renal function (decreased GFR)
Since creatinine is byproduct of muscle
metabolism, severely decreased muscle mass
(cachexia) may decrease SCr
Vigorous exercise may temporarily increase SCr by
0.5 mg/dly

Cause of false serum creatinine
Depends on the test that lab uses.
If using Jaffe assay, larger amounts of non
creatinine chromogens (uric acid, glucose,
acetone, acetoacetate, pyruvic acid, ascorbic
acid) can increase the results of the test.

Age-adjusted Standards for CrCl
CrCl declines with age at any given SCr.
An elderly with a “normal” SCr does not have
normal CrCl.
Estimate age-adjusted normal values of CrCl :
 Males : CrCl = 133 - (0.64 X age)
 Females : takes 93% of this value

Blood Urea Nitrogen (BUN) (8-20 mg/dl)
Is concentration of nitrogen within urea in serum;
produced in liver.
Serum concentration depends on urea production
(liver) and tubular reabsorption as well as
glomerular filtration;
Thus by itself is not a useful indicator of GFR.
Used with other lab data; can assess hydration
status, renal function, protein tolerance, &
catabolic process

Elevated BUN
Pre-renal causes
1. Decreased renal perfusion
Dehydration
Shock
Diuretics
Blood loss
Severe CHF
Note : BUN follows
sodium & water, if
increased reabsorption
of sodium & water then
BUN reabsorption also
increases
Note : BUN follows
sodium & water, if
increased reabsorption
of sodium & water then
BUN reabsorption also
increases

Elevated BUN
Pre-renal causes
2. Increased protein breakdown
GI bleeding
High protein diets

Elevated BUN
Renal causes of elevated BUN :
• Acute renal failure : drugs such as :
aminoglycosides, amphotricin B, cisplatin.
• Chronic renal failure : diabetes,
pyelonephritis. Chronic analgesics abuse
Post-renal causes of elevated BUN :
• Obstruction of ureter, bladder or urethra.

•GF passes through tubules;
where:
1.Reabsorption of water and solute.
2.Excretion of certain substances.
3.Exchange of ions across cell wall.
•As a result, urine is excreted carrying waste
products and maintaining body homeostasis.
•The urine finally excreted has an entirely
different composition from GF.
C- Tubular FunctionC- Tubular Function
TestsTests::

GFGF UrineUrine
VolumeVolume 120120ml/minml/min 1.01.0ml/minml/min
OsmolalityOsmolality 300300mosmol/kgmosmol/kg 800800mosmol/kgmosmol/kg
pHpH 7.47.4 6.86.8
ProteinProtein PresentPresent AbsentAbsent
UreaUrea ------mg/dlmg/dl ------g/dlg/dl
Amino acidsAmino acids PresentPresent AbsentAbsent
GlucoseGlucose PresentPresent AbsentAbsent

Tests to assess tubular function
1. Urine concentration test (14-16 h water restrict)
• N. SG > 1.025 & > 800 mOsmol/kg
• Decreased RF < 1.020 & 400-600 mOsmol
• Severe Renal impairment , SG approaches
1.010 &< 400 mOsmol

2. If failure to concentrate urine to 800 mOSmol/kg
We do DDAVD test IM. Injection
(1-deamino 8-D-Arginint Vasopressin test)
• To distinguish causes of polyuria (inability
to concentrate urine)
DDAVPDDAVP Fluid deprFluid depr
CentralCentral ResponseResponse No responseNo response
PsychogeniPsychogeni
cc
ResponseResponse ResponseResponse
RenalRenal No responseNo response No responseNo response

3-Urinary acidification test:
[H+
] of urine is normally > [H+
] of blood & of GF.
In order to achieve this degree of acidification, the Kidney:
- Reabsorbs [HCO3-
].
- Excretes [H+
] partly as free [H+
] and partly as NH4
Salt or in combination with anions principally inorg Ph.

Urine acidification test
• 0.1 g/kg body weight of ammonium chloride
(NH4Cl) given by mouth.
• Urine collected/h. for 8 hours – falls below
(pH<5.3) in at least one specimen.Blood
specimens are collected befor the test and
2 hours after ammonium chloride intake for
measuring total CO2 to ensure satisfactory
acidosis.

Sodium and Potassium excretion:
♦ Sodium excretion:
- About 70% of Na in the GF is reabsorbed by the PCT
(active reabsorption).
Serum Na:(N:135-145 mmol/L)
Urinary Na:(N: 40-220 mmol/d)
♦ Potassium excretion:
- About 90% of K in GF is normally reabsorbed in the PCT
while the DCT secretes K.
Serum K: (N: 3.5-5.5 mmol/L)
Urinary K: (N: 25-125 mmol/d)

4. Na excreation
• Giving diet containing 20 mmol Na+
/day.
• Normally urinary sodium falls within a week
to the amount present in the diet.
• In diseased kidney, when dietary Na+
↑ →
Na+
and water retained, by contrast when
dietary Na+
↓ → Na+
depletion → ↓ GFR
→ aggravate the condition.

Renal diseases commonly present with
proteinuria.
Since glomeruli filter 5 - 7 g of protein / 24 h
and only < 150 mg is excreted in urine / 24 h,
therefore, tubular reabsorption must be very
efficient.
ProteinuriaProteinuria

♦ Mechanisms of Proteinuria:
1- Overflow.
2- Glomerular:
due to glomerular permeability,
e.g. albumin.
3- Tubular:
due to tubular reabsorption,
e.g. β2-microglobulin.

1. Orthostatic: (proteinuria after standing or walking).
2. Transient: (during pyrexia, CHF or intense exercise).
3. Systemic diseases: e.g. DM, SLE, MM….etc.
4. Renal disease: acute & chronic GN and NS.
Causes of proteinuriaCauses of proteinuria::
- Mild 1.0 g /d
- Moderate 3.0 g /d
- Severe > 3 g /d
Grades of proteinuriaGrades of proteinuria::

♦ Selective and non-selective proteinuria:
The concept of selectivity derives from the fact
that glomerular permeability to a plasma protein
depends largely on its MW; small molecules being
cleared more rapidly than large molecules.
Selective: High MW proteins ( IgG & α2-MG ) tend to
be retained.
Non-selective: Both high, moderate (albumin) & low
( transferrin) MW proteins are excreted.

Biochemical Findings in SomeBiochemical Findings in Some

Laboratory findings in tubular dysfunction
Plasma:
Metabolic acidosis (↓ pH & ↓ HCO3
-
).
↓ K+
↓ Phosphorus
↓ Uric acid
↑ Osmolality
Normal urea and creatinine.
Urine
↑ volume
↓ osmolality
↑ sodium content

Acute Renal Failure
• Prerenal conditions (shock, hemorrhage, heart failure).
• Renal (acute tubular necrosis, glomerulonephritis).
• Post-renal (bladder obstruction).
60%of cases occur during or immediately
after surgery.
10%associated with obstetric problems.
30%medical conditions

Early stage findings
• Scanty urine <50 ml/day.
• Usually bloody with ↑ specific gravity.
• Urine sodium >50 mmol/L.
• BUN ↑ by > 50 mg/dl/day.
• Creatinine, uric acid ↑
• Hypocalcemia.
• Metabolic acidosis.

Second week findings
• Urine becomes clear after several days with a
small daily increase in volume.
• Daily volume of 400 ml indicates onset of
recovery.
• BUN continues to rise after onset of diuresis.
• Metabolic acidosis ↑
• Serum K ↑ (tissue injury – acidosis – failure of excretion).
• Na is ↓.

Diuretic Stage
• Urine sodium is 50-70 mmol/L.
• Large urinary potassium excretion may
casue decreased serum potassium.
• Serum Na and Cl may ↑ due to dehydration
resulting from large diuresis if replacement
of water is inadequate.

Chronic Renal Failure (CRF)
• It is the end result of progressive and
gradual destruction of the nephrons
e.g. chronic GN, chronic
pyelonephritis, chronic obstructie
uropathy.

Biochemical features of renal failure
• Increased serum urea.
• Increased serum creatinine.
• Capacity of the kidney to concentrate urine is impaired.
• Capacity of the kidney to dilute urine remains unaffected.
• Serum sodium tends to be low especially if Na+
intake is
diminished but in severe case → sodium retention
occurs.
• Serum potassium: raised level is uncommon expect when
large load of K is given.

• Metabolic acidosis.
• Decreased serum Ca due to:
 Decreased serum albumin.
 Improper activation of Vit. D.
• Increased serum phosphorus.
We can susbect that patient with CRF can maintain Na+
, K+
and water balance normal if that dietary load remains close
to normal daily requirement.

Nephrotic Syndrome (NSNephrotic Syndrome (NS))
Diagnostic criteriaDiagnostic criteria::
1.1.Proteinuria ( > 3 g / dProteinuria ( > 3 g / d).).
2.2.Hypoalbuminemia ( < 3 g/dlHypoalbuminemia ( < 3 g/dl).).
3.3.EdemaEdema..
EtiologyEtiology::
I- Primary NSI- Primary NS::
--Minimal change lesionMinimal change lesion..
--Membranous nephropathyMembranous nephropathy..
--Proliferative GNProliferative GN..
II- Secondary NSII- Secondary NS::
Secondary to systemic disease e.g. SLE,Secondary to systemic disease e.g. SLE,DMDM
and amyloidosisand amyloidosis..

Nephrotic Syndrome (NSNephrotic Syndrome (NS))
 Biochemical findings:Biochemical findings:
Serum:Serum:
-- Hyperlipidemia: CHOL & TG.Hyperlipidemia: CHOL & TG.
-- Albumin.Albumin.
-- αα22 - macroglobulin &- macroglobulin & ββ- globulins.- globulins.
-- N.N. Urea & creatinine at presentation.Urea & creatinine at presentation.
Urine:Urine:
-- Proteinuria ( > 3 g/d ).Proteinuria ( > 3 g/d ).
-- Mild MP hematuria.Mild MP hematuria.
N.B: Patients with NS who have selective proteinurina respond to
steroid therapy more than those with non-selective proteinuria.

Conclusions
• The urinary system is more than a waste disposal
system.
• It regulates plasma volume and composition from
minute to minute.
• This in turn results in constant composition for all
the other fluid compartments.
• The three fundamental mechanisms of kidney
function are filtration, secretion and reabsorption.

Kidney function tests by moustafa rizk

Kidney function tests by moustafa rizk

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