Laboratory Evaluation of
Kidney Function Tests
Rajendra Dev Bhatt, PhD Scholar
Asst. Professor
Clinical Biochemistry & Laboratory Medicine
Dhulikhel Hospital-Kathmandu University Hospital
Fellow: Translational Research (2018-2022) in CVD in Nepal,
NIH, USA
The main function of the kidney is excretion of water
soluble waste products from our body
The kidney has various filtration, excretion and
secretary functions.
Derangement of any of these function would result in
either decreased excretion of waste products and hence
their accumulation in the body or loss of some vital
nutrient from the body.
We are able to accurately calculate the kidney's ability
to perform its various tasks based on the concentration
of these excretory products and nutrients in the blood
and urine.
The functional unit of the kidney is called a nephron. It
consists of two main parts, the glomerulus and the
tubular system.
The glomerulus is composed of a bowman’s capsule
and a tuft of leaky blood vessels encapsulated by the
bowman’s capsule.
The primary purpose of the glomerulus is filtrations.
The leaky vessels filter into the glomerulus almost all
the water, electrolytes, small proteins, nutrients such as
sugar etc and excretory products such as urea etc.
The Tubular system is responsible for re-absorption of
most of the water, electrolytes, nutrients as well as
excretion of the remaining nutrients by means of
secretion into the tubules. These tubules are responsible
for the concentration of urine.
Renal Functions
• Excretory Functions:
Formation and excretion of urine
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion
Excreting toxic substances in synergy with
liver
Renal Functions
• Homeostatic function
Regulation of blood volume
Regulation of blood pH
Regulation of serum electrolytes; Na, K, Cl
and Ca
Reabsorption of essential nutrients
Renal Functions
• Endocrine function
Erythropoietin
Renin Angiotensin system
Vitamin D activation
Degradation of hormones like insulin and
aldosterone
• Metabolic function
Along with liver site for gluconeogenesis
Why Renal Function Tests needed?
To assess functional capacity of kidneys
To diagnose renal impairment
To assess the severity and progression of renal
impairment
To assess the effectiveness of treatment
Causes of renal disease
• Pre-renal
Any condition that results in reduced blood flow
to kidneys
Severe blood loss
Hemolysis
• Renal
Damage to renal tissue, glomerular basement
membrane or tubules
Glomerulonephritis
Diabetic or hypertensive nephropathy
Tubular damage due to toxic substances
• Post Renal
Obstruction to urine outflow
Ureteric or urethral stone
Prostatic cancer
This list is not complete, these are only few
common causes of renal disease
Renal function test
Can be divided into two categories:
 Test for glomerular function
 Serum Urea
 Serum Creatinine
 Clearance tests
 Tests for tubular function
 Urine concentration test
 Dilution test
 Para amino hippuric acid clearance test
 Acidification test
 Urine examination: Important for assessing both glomerular
and tubular function
Test for glomerular function
The following parameters are commonly included in
assessing glomerular function
• Serum Urea ( 10-45 mg/dl)
• Serum Creatinine (0.6 –1.2 mg/dl)
• Serum Uric acid (males 3.5-7.2 mg/dl, females 2.6-6 mg/dl)
• Total protein (6.0-8.0 g/dl)
• Serum albumin (3.0-5.0 g/dl)
• Serum electrolytes
 Na (135-150 mEq/L)
 K (3.5-5.0 mEq/L)
 Cl (96-106 mEq/L)
 Phosphate (2.8-4 mg/dl)
 Calcium (8.0-10.2 mg/dl)
Glomerular Filtration Rate (GFR)
Glomerular filtration rate (GFR) represents the flow of
plasma from the glomerulus into Bowman's space over a
specified period.
Glomerular filtration rate (GFR) is an important indicator
of the filtering capacity of kidneys and is considered the
best overall index of renal function currently used.
Estimated glomerular filtration rate (eGFR) is the most
important variable in the assessment of patients with
suspected or known kidney disease in clinical practice.
GFR measures the rate at which the kidneys' two million
glomeruli filter plasma in order to process it and remove
waste products from it.
GFR is decreased when BP is below 80 mm of
mercury. The GFR is reduced when there is
obstruction to the renal flow (calculi, enlarged
prostate, etc.).
It also decreases with age. The renal blood flow is
about 700 mL of plasma or 1200 mL of blood per
minute.
The glomerular filtration rate (GFR) is 120–125 mL
per minute in a person with 70 kg body weight.
Glomerular filtrate formed is about 170 to 180 liters
per day, out of which only 1.5 liters are excreted as
urine.
This means that most of the water content of
glomerular filtrate is reabsorbed.
Markers for GFR
Ideal characteristics:
• Freely filtered at the glomerulus
• No tubular secretion or reabsorption
• No renal/tubular metabolism
Exogenous or endogenous:
Exogenous – not normally present in the body:
• Inulin
Endogenous – normally present in the body
• Creatinine
Advantages:
• Endogenous
• Produced at relatively constant rate per day
• Routinely measured
• Freely filtered at glomerulus
• Not reabsorbed or metabolized by renal tubules
• Assays are standardized
Disadvantages:
• Estimate of GFR
• Is secreted by renal tubules
Direct Measures of GFR:
Creatinine Clearance
C = (U x V)/P
• C = clearance
• U = urinary creatinine concentration
• V = urinary Volume
• P = plasma creatinine concentration
• Clearance = GFR
Inulin Clearance
Gold standard for renal clearance :
• Freely filtered at glomerulus
• No tubular metabolism
• No tubular reabsorption or secretion
Protocol:
• IV infusion
• Blood samples
• Urine catheter
Limitations :
• Expensive, hard to obtain
• Difficult to assay
• Invasive
Estimated Glomerular Filtration Rate (eGFR)
Modification of Diet in Renal Disease (MDRD):
The original Modification of Diet in Renal Disease (MDRD)
equation was based on 6 variables: age, sex, ethnicity, serum
creatinine, urea, and albumin (often referred to as MDRD 6).
Subsequently, the MDR was simplified to a 4-variable
version (MDRD-4) that included age, sex, ethnicity, and
serum creatinine.
This 4-variable version was later re-expressed using serum
creatinine values that were standardized to reference
methods. The equation shown here is the re-expressed 4-
variable MDRD equation.
GFR in mL/min per 1.73 m2 = 175 x SerumCr-1.154 x age-
0.203 x 1.212 (if patient is black) x 0.742 (if female)
Urine Albumin
Reference interval:
• Urine micro-albumin<30 mg/d
• Albuminuria = Micro-Albumin to creatinine
ratio (ACR) >30 mg/g
Cystatin C
Cystatin C is a relatively small protein that is
produced throughout the body by all cells that
contain a nucleus and is found in a variety of
body fluids, including the blood.
It is produced, filtered from the blood by the
kidneys, and broken down at a constant rate.
This test measures the amount of cystatin C in
blood to help evaluate kidney function.
The rate at which the fluid is filtered is called the
glomerular filtration rate (GFR). A decline in
kidney function leads to decreases in the GFR
and to increases in cystatin C and other measures
of kidney function, such as creatinine and urea in
the blood. In normal it is around 0.8-1.2mg/L
Serum Urea
 Urea is the end-product of protein metabolism.
 Normal value is 15 to 45 mg/dl.
 Serum urea is increased in all forms of kidney
diseases. In acute glomerulonephritis values may
be as high as 300 mg/dl.
 In early stages of nephrosis, serum urea may be
normal, but in late stages serum urea increases
along with decreasing renal functions.
 Urea concentration in serum may be low in late
pregnancy, in starvation, in diet grossly deficient in
proteins and in hepatic failure.
Serum Creatinine
• Creatinine is the waste product of creatine phosphate,
a compound found in the skeletal muscle tissue.
• It is excreted entirely by the kidneys.
• The creatinine level is affected primarily by renal
dysfunction and is thus very useful in evaluating renal
function.
• Increased levels of creatinine indicate a slowing of the
glomerular filtration rate.
• Female: 0.6–1.2 mg/dL
• Male: 0.8–1.4 mg/dL
• Possible Meanings of Abnormal Values:
• Congestive heart failure
• Glomerulonephritis
• Nephritis
• Pyelonephritis
• Renal failure
• Urinary obstruction
• Dehydration
Serum Uric acid
• Uric acid is produced by the breakdown of purines,
chemicals that are the building blocks for DNA
and RNA.
• Most uric acid is excreted in the urine
• Excess serum uric acid can become deposited in
joints and soft tissues, causing gout, an
inflammatory response to the deposition of the
urate crystals.
• Female: 2.3–6.6 mg
• Male: 3.5–7.2 mg/dL
Possible Meanings of Abnormal Values:
Increased (hyperuricemia)
Congestive heart failure
Glomerulonephritis
Alcoholism
Gout
Dehydration
Decreased (hypouricemia)
Liver disease
Renal tubular defects
Total protein and albumin
• Both serum total protein and albumin is
decreased in chronic kidney disease (CKD)
due to increased proteinuria
• Even though proteinuria may also be seen in
acute kidney disease but it usually does not
alter the total protein and albumin
Serum electrolytes
• Sodium is decreased (hyponatremia) and
potassium is increased (hyperkalemia) in
chronic kidney disease (CKD) as kidney
reabsorb sodium in exchange of potassium
• Chloride and phosphate is increased in CKD
• Calcium is decreased as vitamin D is deficient
Tests for tubular function
Specific Gravity of Urine:
• Specific gravity depends on the concentration of solutes,
whereas osmolality depends on the number of osmotically
active particles.
• Hence in cases of proteinuria, the specific gravity is
elevated considerably, but osmolality is only mildly
elevated.
• Normal specific gravity of urine is 1.015–1.025.
• The specific gravity will be decreased in excessive water
intake, and in diabetes insipidus.
• It is increased in diabetes mellitus, in nephrosis
Review Questions
1. Which of the following conditions is
associated with an elevated blood urea
nitrogen (BUN) level?
a. Dehydration
b. Liver cirrhosis
c. Hyperthyroidism
d. Hypoalbuminemia
Dehydration
2. Which renal function test is used to evaluate
the concentrating ability of the kidneys?
a. Serum creatinine
b. Blood urea nitrogen (BUN)
c. Urine specific gravity
d. Serum sodium
Urine specific gravity
3. Which of the following electrolyte
abnormalities is commonly associated with renal
failure?
a. Hyperkalemia
b. Hyponatremia
c. Hypocalcemia
d. Hypomagnesemia
Hyperkalemia
4. Which of the following substances is normally
not present in the urine?
a. Urea
b. Creatinine
c. Glucose
d. Albumin
Glucose
THANK YOU

5. Renal Function Tests.pptx

  • 1.
    Laboratory Evaluation of KidneyFunction Tests Rajendra Dev Bhatt, PhD Scholar Asst. Professor Clinical Biochemistry & Laboratory Medicine Dhulikhel Hospital-Kathmandu University Hospital Fellow: Translational Research (2018-2022) in CVD in Nepal, NIH, USA
  • 2.
    The main functionof the kidney is excretion of water soluble waste products from our body The kidney has various filtration, excretion and secretary functions. Derangement of any of these function would result in either decreased excretion of waste products and hence their accumulation in the body or loss of some vital nutrient from the body.
  • 3.
    We are ableto accurately calculate the kidney's ability to perform its various tasks based on the concentration of these excretory products and nutrients in the blood and urine. The functional unit of the kidney is called a nephron. It consists of two main parts, the glomerulus and the tubular system. The glomerulus is composed of a bowman’s capsule and a tuft of leaky blood vessels encapsulated by the bowman’s capsule.
  • 4.
    The primary purposeof the glomerulus is filtrations. The leaky vessels filter into the glomerulus almost all the water, electrolytes, small proteins, nutrients such as sugar etc and excretory products such as urea etc. The Tubular system is responsible for re-absorption of most of the water, electrolytes, nutrients as well as excretion of the remaining nutrients by means of secretion into the tubules. These tubules are responsible for the concentration of urine.
  • 6.
    Renal Functions • ExcretoryFunctions: Formation and excretion of urine  Glomerular filtration  Tubular reabsorption  Tubular secretion Excreting toxic substances in synergy with liver
  • 7.
    Renal Functions • Homeostaticfunction Regulation of blood volume Regulation of blood pH Regulation of serum electrolytes; Na, K, Cl and Ca Reabsorption of essential nutrients
  • 8.
    Renal Functions • Endocrinefunction Erythropoietin Renin Angiotensin system Vitamin D activation Degradation of hormones like insulin and aldosterone • Metabolic function Along with liver site for gluconeogenesis
  • 9.
    Why Renal FunctionTests needed? To assess functional capacity of kidneys To diagnose renal impairment To assess the severity and progression of renal impairment To assess the effectiveness of treatment
  • 10.
    Causes of renaldisease • Pre-renal Any condition that results in reduced blood flow to kidneys Severe blood loss Hemolysis • Renal Damage to renal tissue, glomerular basement membrane or tubules Glomerulonephritis Diabetic or hypertensive nephropathy Tubular damage due to toxic substances
  • 11.
    • Post Renal Obstructionto urine outflow Ureteric or urethral stone Prostatic cancer This list is not complete, these are only few common causes of renal disease
  • 12.
    Renal function test Canbe divided into two categories:  Test for glomerular function  Serum Urea  Serum Creatinine  Clearance tests  Tests for tubular function  Urine concentration test  Dilution test  Para amino hippuric acid clearance test  Acidification test  Urine examination: Important for assessing both glomerular and tubular function
  • 13.
    Test for glomerularfunction The following parameters are commonly included in assessing glomerular function • Serum Urea ( 10-45 mg/dl) • Serum Creatinine (0.6 –1.2 mg/dl) • Serum Uric acid (males 3.5-7.2 mg/dl, females 2.6-6 mg/dl) • Total protein (6.0-8.0 g/dl) • Serum albumin (3.0-5.0 g/dl) • Serum electrolytes  Na (135-150 mEq/L)  K (3.5-5.0 mEq/L)  Cl (96-106 mEq/L)  Phosphate (2.8-4 mg/dl)  Calcium (8.0-10.2 mg/dl)
  • 14.
    Glomerular Filtration Rate(GFR) Glomerular filtration rate (GFR) represents the flow of plasma from the glomerulus into Bowman's space over a specified period. Glomerular filtration rate (GFR) is an important indicator of the filtering capacity of kidneys and is considered the best overall index of renal function currently used. Estimated glomerular filtration rate (eGFR) is the most important variable in the assessment of patients with suspected or known kidney disease in clinical practice. GFR measures the rate at which the kidneys' two million glomeruli filter plasma in order to process it and remove waste products from it.
  • 15.
    GFR is decreasedwhen BP is below 80 mm of mercury. The GFR is reduced when there is obstruction to the renal flow (calculi, enlarged prostate, etc.). It also decreases with age. The renal blood flow is about 700 mL of plasma or 1200 mL of blood per minute. The glomerular filtration rate (GFR) is 120–125 mL per minute in a person with 70 kg body weight. Glomerular filtrate formed is about 170 to 180 liters per day, out of which only 1.5 liters are excreted as urine. This means that most of the water content of glomerular filtrate is reabsorbed.
  • 16.
    Markers for GFR Idealcharacteristics: • Freely filtered at the glomerulus • No tubular secretion or reabsorption • No renal/tubular metabolism Exogenous or endogenous: Exogenous – not normally present in the body: • Inulin Endogenous – normally present in the body • Creatinine
  • 17.
    Advantages: • Endogenous • Producedat relatively constant rate per day • Routinely measured • Freely filtered at glomerulus • Not reabsorbed or metabolized by renal tubules • Assays are standardized Disadvantages: • Estimate of GFR • Is secreted by renal tubules
  • 18.
    Direct Measures ofGFR: Creatinine Clearance C = (U x V)/P • C = clearance • U = urinary creatinine concentration • V = urinary Volume • P = plasma creatinine concentration • Clearance = GFR
  • 19.
    Inulin Clearance Gold standardfor renal clearance : • Freely filtered at glomerulus • No tubular metabolism • No tubular reabsorption or secretion Protocol: • IV infusion • Blood samples • Urine catheter Limitations : • Expensive, hard to obtain • Difficult to assay • Invasive
  • 20.
    Estimated Glomerular FiltrationRate (eGFR) Modification of Diet in Renal Disease (MDRD): The original Modification of Diet in Renal Disease (MDRD) equation was based on 6 variables: age, sex, ethnicity, serum creatinine, urea, and albumin (often referred to as MDRD 6). Subsequently, the MDR was simplified to a 4-variable version (MDRD-4) that included age, sex, ethnicity, and serum creatinine. This 4-variable version was later re-expressed using serum creatinine values that were standardized to reference methods. The equation shown here is the re-expressed 4- variable MDRD equation. GFR in mL/min per 1.73 m2 = 175 x SerumCr-1.154 x age- 0.203 x 1.212 (if patient is black) x 0.742 (if female)
  • 21.
    Urine Albumin Reference interval: •Urine micro-albumin<30 mg/d • Albuminuria = Micro-Albumin to creatinine ratio (ACR) >30 mg/g
  • 22.
    Cystatin C Cystatin Cis a relatively small protein that is produced throughout the body by all cells that contain a nucleus and is found in a variety of body fluids, including the blood. It is produced, filtered from the blood by the kidneys, and broken down at a constant rate. This test measures the amount of cystatin C in blood to help evaluate kidney function.
  • 23.
    The rate atwhich the fluid is filtered is called the glomerular filtration rate (GFR). A decline in kidney function leads to decreases in the GFR and to increases in cystatin C and other measures of kidney function, such as creatinine and urea in the blood. In normal it is around 0.8-1.2mg/L
  • 24.
    Serum Urea  Ureais the end-product of protein metabolism.  Normal value is 15 to 45 mg/dl.  Serum urea is increased in all forms of kidney diseases. In acute glomerulonephritis values may be as high as 300 mg/dl.  In early stages of nephrosis, serum urea may be normal, but in late stages serum urea increases along with decreasing renal functions.  Urea concentration in serum may be low in late pregnancy, in starvation, in diet grossly deficient in proteins and in hepatic failure.
  • 26.
    Serum Creatinine • Creatinineis the waste product of creatine phosphate, a compound found in the skeletal muscle tissue. • It is excreted entirely by the kidneys. • The creatinine level is affected primarily by renal dysfunction and is thus very useful in evaluating renal function. • Increased levels of creatinine indicate a slowing of the glomerular filtration rate. • Female: 0.6–1.2 mg/dL • Male: 0.8–1.4 mg/dL
  • 27.
    • Possible Meaningsof Abnormal Values: • Congestive heart failure • Glomerulonephritis • Nephritis • Pyelonephritis • Renal failure • Urinary obstruction • Dehydration
  • 28.
    Serum Uric acid •Uric acid is produced by the breakdown of purines, chemicals that are the building blocks for DNA and RNA. • Most uric acid is excreted in the urine • Excess serum uric acid can become deposited in joints and soft tissues, causing gout, an inflammatory response to the deposition of the urate crystals. • Female: 2.3–6.6 mg • Male: 3.5–7.2 mg/dL
  • 29.
    Possible Meanings ofAbnormal Values: Increased (hyperuricemia) Congestive heart failure Glomerulonephritis Alcoholism Gout Dehydration Decreased (hypouricemia) Liver disease Renal tubular defects
  • 30.
    Total protein andalbumin • Both serum total protein and albumin is decreased in chronic kidney disease (CKD) due to increased proteinuria • Even though proteinuria may also be seen in acute kidney disease but it usually does not alter the total protein and albumin
  • 31.
    Serum electrolytes • Sodiumis decreased (hyponatremia) and potassium is increased (hyperkalemia) in chronic kidney disease (CKD) as kidney reabsorb sodium in exchange of potassium • Chloride and phosphate is increased in CKD • Calcium is decreased as vitamin D is deficient
  • 32.
    Tests for tubularfunction Specific Gravity of Urine: • Specific gravity depends on the concentration of solutes, whereas osmolality depends on the number of osmotically active particles. • Hence in cases of proteinuria, the specific gravity is elevated considerably, but osmolality is only mildly elevated. • Normal specific gravity of urine is 1.015–1.025. • The specific gravity will be decreased in excessive water intake, and in diabetes insipidus. • It is increased in diabetes mellitus, in nephrosis
  • 34.
    Review Questions 1. Whichof the following conditions is associated with an elevated blood urea nitrogen (BUN) level? a. Dehydration b. Liver cirrhosis c. Hyperthyroidism d. Hypoalbuminemia Dehydration
  • 35.
    2. Which renalfunction test is used to evaluate the concentrating ability of the kidneys? a. Serum creatinine b. Blood urea nitrogen (BUN) c. Urine specific gravity d. Serum sodium Urine specific gravity
  • 36.
    3. Which ofthe following electrolyte abnormalities is commonly associated with renal failure? a. Hyperkalemia b. Hyponatremia c. Hypocalcemia d. Hypomagnesemia Hyperkalemia
  • 37.
    4. Which ofthe following substances is normally not present in the urine? a. Urea b. Creatinine c. Glucose d. Albumin Glucose
  • 38.