Kidney function tests by moustafa rizk

Moustafa Rezk
Moustafa RezkProffessor of Clinical Pathology , Faculty of Medicine, Alexandria University, Egypt en Faculty of Medicine, Alexandria University, Egypt
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
Interpretation of Kidney Function
Interpretation of Kidney Function
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).
Interpretation of Kidney Function
Interpretation of Kidney Function
Interpretation of Kidney Function
Interpretation of Kidney Function
Interpretation of Kidney Function
Kidney function tests by moustafa rizk
Interpretation of Kidney Function
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
Interpretation of Kidney Function
Interpretation of Kidney Function
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
-
Interpretation of Kidney Function
Interpretation of Kidney Function
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
Fluid Compartments
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
Interpretation of Kidney Function
Juxtaglomerular Apparatus
Interpretation of Kidney Function
Rennin-Angiotensin-aldosterone
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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).
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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
Interpretation of Kidney Function
Elevated BUN
Pre-renal causes
2. Increased protein breakdown
GI bleeding
High protein diets
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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)
Interpretation of Kidney Function
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.
ProteinuriaProteinuria
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.
ProteinuriaProteinuria
Biochemical Findings in SomeBiochemical Findings in Some
Interpretation of Kidney Function
Laboratory findings in tubular dysfunction
Plasma:
Metabolic acidosis (↓ pH & ↓ HCO3
-
).
↓ K+
↓ Phosphorus
↓ Uric acid
↑ Osmolality
Normal urea and creatinine.
Urine
↑ volume
↓ osmolality
↑ sodium content
Interpretation of Kidney Function
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
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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 ↓.
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
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.
Interpretation of Kidney Function
Chronic Renal Failure (CRF)
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.
Interpretation of Kidney Function
Chronic Renal Failure (CRF)
• 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.
Interpretation of Kidney Function
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
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Kidney function tests by moustafa rizk

  • 1. 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.
  • 2. 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.
  • 6. 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).
  • 13. Interpretation of Kidney Function 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
  • 15. Interpretation of Kidney Function 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 -
  • 18. Interpretation of Kidney Function 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.
  • 19. Interpretation of Kidney Function Fluid Compartments
  • 20. Interpretation of Kidney Function 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.
  • 21. Interpretation of Kidney Function 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
  • 22. Interpretation of Kidney Function 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.
  • 24. Interpretation of Kidney Function Juxtaglomerular Apparatus
  • 25. Interpretation of Kidney Function Rennin-Angiotensin-aldosterone
  • 26. Interpretation of Kidney Function 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
  • 27. Interpretation of Kidney Function 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
  • 28. •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:
  • 29. 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
  • 30. Interpretation of Kidney Function 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.
  • 31. Glucose Urea Creatinine Inulin PAHA A B C D Different ways by which renal tubules can handle substances freely filtered at glomeruli.
  • 32. Interpretation of Kidney Function 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.
  • 33. 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).
  • 34. Interpretation of Kidney Function 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.
  • 35. 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.
  • 36. 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:
  • 37. 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:
  • 38. 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.
  • 39. 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
  • 40. •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:
  • 41. 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.
  • 42. 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.
  • 43. Interpretation of Kidney Function 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.
  • 44. Interpretation of Kidney Function 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
  • 45. Interpretation of Kidney Function 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.
  • 46. Interpretation of Kidney Function 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
  • 47. Interpretation of Kidney Function 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
  • 48. Interpretation of Kidney Function 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
  • 49. Interpretation of Kidney Function Elevated BUN Pre-renal causes 2. Increased protein breakdown GI bleeding High protein diets
  • 50. Interpretation of Kidney Function 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.
  • 51. •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::
  • 52. 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
  • 53. Interpretation of Kidney Function 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
  • 54. Interpretation of Kidney Function 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
  • 55. 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.
  • 56. Interpretation of Kidney Function 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.
  • 57. 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)
  • 58. Interpretation of Kidney Function 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.
  • 59. 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
  • 60. ♦ Mechanisms of Proteinuria: 1- Overflow. 2- Glomerular: due to glomerular permeability, e.g. albumin. 3- Tubular: due to tubular reabsorption, e.g. β2-microglobulin. ProteinuriaProteinuria
  • 61. 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::
  • 62. ♦ 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. ProteinuriaProteinuria
  • 63. Biochemical Findings in SomeBiochemical Findings in Some
  • 64. Interpretation of Kidney Function Laboratory findings in tubular dysfunction Plasma: Metabolic acidosis (↓ pH & ↓ HCO3 - ). ↓ K+ ↓ Phosphorus ↓ Uric acid ↑ Osmolality Normal urea and creatinine. Urine ↑ volume ↓ osmolality ↑ sodium content
  • 65. Interpretation of Kidney Function 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
  • 66. Interpretation of Kidney Function 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.
  • 67. Interpretation of Kidney Function 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 ↓.
  • 68. Interpretation of Kidney Function 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.
  • 69. Interpretation of Kidney Function 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.
  • 70. Interpretation of Kidney Function Chronic Renal Failure (CRF) 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.
  • 71. Interpretation of Kidney Function Chronic Renal Failure (CRF) • 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.
  • 72. 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..
  • 73. 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.
  • 74. Interpretation of Kidney Function 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.