Renal Function

Tests
DR. BILAL IQBAL
ASSISTANT PROFESSOR PATHOLOGY
Segment wise
• Test for
• glomerular function= creatinine clearance, Cystatin C
• Tubular function= glycosuria, aminoaciduria, B2b micro,
RBP, a1micro. N-acetyl-b-glucosaminidase,
• Distal tubular function= fluid deprivation test
Kidneys
Biological functions:
1. Excretion
anuria(<100 mL/day), oliguria(<400 mL/day),polyuria(>3 L/day or 50 mL/kg body
weight/day)
2. Homeostatic regulation
Electrolyte and water homeostasis
3. Endocrine
Primary because the kidneys are endocrine organs producing hormones like
erythropoietin, Prostaglandins, thromboxanes, Renin, 1,25(OH)Vit D
Secondary because kidneys are site of action for hormones produced or activated
elsewhere. Site for degradation for hormones like insulin and aldosterone.

Glomerular filtrate has similar composition to plasma except that it is free of large proteins.
Q:1 The substance which is neither absorbed nor
secreted in the renal tubules:

a. Albumin
b. Creatinine
c. Inulin
d. Paramino hippuric acid
e. Urea

Best answer:
c. Inulin
 Inulin
• Inulin is a substance which is neither
absorbed nor secreted and is an exact
indicator of GFR
• It is not part of normal human
metabolism and has to be injected
externally
Q:2: Renal Clearance of a substance

a. 24 hour urinary clearance of that substance

b. Amount of that substance excreted through kidney in one
minute
c. Concentration of the substance in urine
d. Ratio of urinary concentration of that substance to urinary
creatinine
e. Volume of plasma cleared of that substance in one minute

Best answer:
e. Volume of plasma cleared of that substance
in one minute
 Renal Clearance of a substance

• Clearance of substance is defined as

volume of plasma cleared of that
substance in one minute (or second).
• It is expressed as ml/min or ml/sec
Q:3 The test which is MOST effected by extra-renal
conditions in the absence of a renal disease:

a. Creatinine calculated by Modification of Diet in Renal

Disease (MDRD) formula
b. Creatinine clearance
c. Serum creatinine
d. Serum urea
e. Urinary creatinine

Best answer:
d. Serum urea
 The test which is MOST effected by extra-renal conditions
(without renal disease):

 Serum Urea can go upto 60 mg/dl (10

mmol/L) due to increased protein diet
 It can go upto 120 mg/dl (20 mmol/L) due to
dehydration etc.
 Increased urea= high prot,dehydration, GI
bleed, muscle wasting, stasis
 Decreased = low protein intake, dialysis,
severe liver disease
Q:4 The test which gives the poorest indication of
glomerular function is:

a. Calculation of eGFR
b. Creatinine clearance
c. Iohexol Clearance
d. Serum creatinine
e. Serum cystanin C

Best answer:
d. Serum Creatinine
 Kidney Damage
Kidney damage includes pathologic abnormalities in
the native or transplanted kidney. Kidney damage is
identified in most cases by the presence of one of the
following clinical markers :
1. Albuminuria − In clinical practice, albuminuria is the
most frequently assessed marker of kidney
[Link]-to-creatinine ratio (ACR) in an
untimed "spot" urine is the best method to measure it.
 Kidney Damage (cont)
2. Urinary sediment abnormalities − Urinary sediment
abnormalities such as red or white blood cell casts may
indicate the presence of glomerular injury or tubular
[Link]-Cast-proliferative glomerulonephritis and
WBC cast in pyelonephritis and intersitial diseases
3. Imaging abnormalities − Kidney damage may be detected
by the presence of imaging abnormalities such as polycystic
kidneys, hydronephrosis, and small and echogenic kidneys.
 Kidney Damage (cont)
4. Pathologic abnormalities − A kidney biopsy may
reveal evidence for glomerular, vascular, or
tubulointerstitial disease.
5. Kidney transplantation − Patients with a history of
kidney transplantation are assumed to have kidney
damage whether or not they have documented
abnormalities on kidney biopsy or markers of kidney
damage.
[Link] disorders – Electrolyte and other
abnormalities due to tubular disorders
 Decreased GFR
• GFR is generally considered to be the best index of overall kidney function
• Declining GFR is the hallmark of progressive kidney disease. Measured GFR
varies in normal individuals by :
• age
• sex
• dietary protein intake
• Race-ethnicity
• Threshold defining a decreased GFR is less than 60 mL/min per 1.73 m2
• Kidney failure is defined as a GFR <15 mL/min per 1.73 m2 or treatment by dialysis
• GFR is reduced to less than 60 before sign and symptoms of kidney failure are
observed.
Uremic (Azotemia) Syndrome
Group of sign and symptoms and abnormal findings that result from
failure of kidneys to maintain adequate excretory, regulatory and
endocrine function.
Signs
Progressive weakness, fatigue,loss of apetite, nausea,
vomiting,muscle wasting,tremors, abnormal mental function,
metabolic acidosis, stupor, coma.
Pts with CKD stage 5 will generally exhibit signs & symptoms of
uremia and need RRT.
 Measuring Renal Function
• Glomerular filtration rate(GFR describes the flow rate
of filtered fluid through the kidney
• GFR is a measure of the efficiency with which the
kidneys remove waste products from the blood stream
• Normal GFR is 80-120ml/min
• There are two types of GFR
• Calculated/estimated GFR
• Measured GFR with creatinine clearance
 Measured GFR
• A number of methods are used to measure
GFR
• Most involve the kidney’s ability to clear either
an exogenous or endogenous marker
• Most common is CrCl
• Problem with creatinine clearance is that it
has lots of variations and poor
reproducibility.
 Contd
• GFR can be calculated by measuring any
chemical that has a steady level in the blood, and
is freely filtered but neither reabsorbed nor
secreted by the kidneys
• The rate therefore measured is the quantity of the
substance in the urine that originated from a
calculable volume of blood
 Accurate plasma and
urine measurement
• For a reliable plasma measurement
substance must have reached steady state
concentration
• For a reliable urine collection urine flow must
be adequate, collection period long enough
and complete bladder emptying achieved
 Markers of GFR
• Exogenous
• Endogenous
 Criteria for GFR Markers
• Freely filterable at the glomerular barrier
• Not reabsorbed by the tubules
• Not secreted by the tubules
• Not synthesized by the tubules
• Not metabolized by the kidneys
• Present at a stable plasma concentration
• Physiologically inert
 Endogenous Markers
• Creatinine
• Urea
• Beta2-Microglobulin
• Retinol-binding protein
• Alpha1-Microglobulin
• Cystatin C
 Advantages
• No injection required
• Only a single blood sample needed
• Simplifies the procedure for the patient, clinician
and laboratory
• These proteins are entirely eliminated from the
circulation
Disadvantages

• There are many factors, which affect GFR estimation by simply

measuring concentration of endogenous filtration markers including
generation, renal tubular reabsorption, secretion and extra renal
elimination of these markers.
• These factors are collectively known as non-GFR determinants.
 Serum Creatinine
• Measuring serum creatinine is a simple test and it is the most
commonly used indicator of renal function
• Lower in women, elderly malnutrition muscle paralysis and smaller
persons
• Higher in high intake of meat , exercise, coricosteroids, ketoacidosis
• Affected by drugs like cimetidine and trimethoprim reduce GFR.
• A better estimation of kidney function is given by the creatinine
clearance test
• Optical interferences like hemolysis,icterus, lipemia, and also it does
not address the interindividual variability of non-creatinine
chromogens.
 Creatinine Clearance
• Is a renal function test based on the rate of
excretion by the kidneys of metabolically produced
creatinine
• Amount of creatinine produced by endogenous
creatine metabolism is constant
• It is directly proportional to the body surface area
 Creatinine Clearance (cont)
• Advantages;
• Creatinine is freely filtered at the glomerulus
• Not absorbed by the tubules
• Actively secreted by the renal tubules in very
small amounts such that creatinine clearance
overestimates actual GFR by 10-20%.
 Creatinine Clearance (cont)
• A 24 hour urine collection is performed but shorter
collection periods are acceptable
• A blood sample is drawn during the urine
collection period
• Height
• Weight
 Calculation of Creatinine Clearance
• Creatinine clearance(ml/min)=UCrV/PCr
• Since the product of urine concentration and urine
flow rate yields creatinine's excretion rate,
creatinine clearance is also said to be its excretion
rate (UCr×V) divided by its plasma concentration
• To allow comparison of results between people of
different sizes, the CCr is often corrected for the
body surface area and expressed compared to the
average sized man as mL/min/1.73 m2.
• Only valid for a steady state that is when renal
function is not changing rapidly.
Creatinine Co-efficient/ Completeness of
Collection: (C.C)
• It is the ratio of mg of creatinine in urine in 24 hour/ Body weight
in Kg.
C.C. = Urinary Creatinine in mg/dl x 24 h Volume
100 Body Weight
Male: 17.6-26.8; Female: 13.4-21.0
• Significance: it depends on muscle mass and remains fairly
constant. Since muscle mass is constant in the given individual, the
creatinine coefficient serves as a reliable index of the adequacy of
a 24- hours urine collection.
 eGFR
eGFR formulae are based on serum or plasma
creatinine. Urine sample NOT required
They take into account age, gender, ethnicity and
BMI of the patient.
Three formulae are used:
1. Cockcroft and Gault: requires BMI.
2. MDRD: Not suitable for mild CKD and in obese
patients
3. CKD-EPI: Suitable throughout the CKD range.
 Biomarkers of Acute Kidney Injury
Ideal Biomarker (imp)
Highly organ specific/sensitive
Allow recognition of etiology of AKI
Allow early detection and no overlap b/w diseased patients and healthy
individuals
Is site specific to detect early injury
Correlate with histological findings
Correlate with degree of tubular damage
Predict outcome of AKI
Noninvasive, TAT-low
Test be simple, quick, accurate, reliable , inexpensive and commonly available
Not subjected to interference by drugs and endogenous substances
BIOMARKERS OF CKD BIOMARKERS OF
NEPHROTOXICITY
• Cystatin C • N acetyl glucosaminidase (NAG)
• Beta trace protein • Glutathione-s-transferase (GST)
• N-GAL • GGT
• KIM-1 • Alanine aminopeptidase (AAP)
• L-FABP • LDH
• Asymmetric dimethylarginine
• Uromodulin
• microRNA
 URIC ACID
 Acute urate nephropathy
 Marker of Imminent onset of AKI
 Diagnostic marker
 Active indicator of intra-renal
injury to microvasculature
 Potent regulator of endothelial
NO levels
 Inhibitor of proliferation and
migration of epithelial cells
 Urine as Clinical material for AKI
1. Urinary enzymes of renal origin
2. Urinary low molecular weight
proteins-macromolecules
3. Gene products - AKI markers
specially produced in the Kidney
Proteinuria
 Normal urinary protein excretion
 In normal adult, normal urinary protein excretion
should be < 150 mg/day
 Normal rate of albumin excretion is < 20 mg/day (15
mcg/min), increases with age and higher body
weight
 In general proteins of molecular weight greater than
albumin are retained by glomerulus and are termed
as high mol weight proteins
 Proteins found in urine are IgG, Albumin, a1-
micro,RBP, Cystatin C,b2 micro
 Abnormal proteinuria
 Previously, abnormal proteinuria was defined as excretion of protein >
150 mg/day
 However, early renal disease is reflected by lesser degrees of
proteinuria
 It occurs due to increase in filtered load, increased circulation of LMW
proteins, decrease in reabsorptive capacity.
 Persistent albumin excretion between 30 and 300 mg/day (20 to 200
mcg/min): high albuminemia (formerly called microalbuminuria)
 Albumin excretion > 300 mg/day (200 mcg/min): overt proteinuria or very
high albuminuria (formerly called macroalbuminuria)
 Tam horse fall protein(protein secreted by tubules)
 Proteiuria above 1000mg/day implies glomerular proteinuria.
 Types of proteinuria
 Glomerular proteinuria: increased filtration of macromolecules (such as albumin)
across the glomerular capillary wall.

 Tubular proteinuria: excretion of low-molecular-weight proteins, such as beta2-

microglobulin, immunoglobin light chains, retinol-binding protein and polypeptides
derived from breakdown of albumin

 Overflow proteinuria: increased excretion of low-molecular-weight proteins; almost

always due to immunoglobin light chains in multiple myeloma, lysozymes in AML, or
myoglobin in rhabdomyolysis

 Post-renal proteinuria: inflammation in the urinary tract (UTI), excreted proteins

are generally non-albumin (IgA or IgG)

 Functional: fever and exercise

 Orthostatic: posture related (upright posture increases protein loss)
Thank you