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Laboratory Diagnosis of

Renal Diseases
By
Dr. Marwa Abd el-Haq
Assistant Professor
Faculty of Medicine
University of Tabuk
Overview
 Functions of the kidney include:
1. Maintenance and regulation of fluid
balance, acid/base and electrolyte
balance (eg, sodium, potassium,
chloride, bicarbonate, calcium,
phosphate).
2. Excretion of waste substances.
3. Production of hormones as
erythropoietin and 1,25-
dihydroxyvitamin D.
Overview
 An important example of undesirable
substances is the end products of
protein metabolism (called non-protein
nitrogenous substances NPN), as:
- Urea and Creatinine (The most
commonly used in investigations).
- Others: Uric acid, amino acids,
creatine, nucleotides … etc.
Indications for assessment
of renal function
 To asses the functional capacity of
kidney before operation or in hospital
admitted patients.
 Early detection of possible renal
impairment (No symptoms until 50-75%
of kidney function is lost).
 Severity and progression of the
impairment.
 Monitor response to treatment.
 Monitor the safe and effective use of
drugs which are excreted in the urine.
Types of renal investigations:

 Renal function tests are divided into the


following:
1. Urine analysis
2. Blood examination
3. Glomerular Function Test
4. Tubular Function Test
BASIC RENAL PROCESS
Urine formation:
 Filtration of plasma from
glomerular capillaries into
Bowman’s space.
 Movement from the tubular
lumen to the peritubular
capillaries is called tubular
reabsorption
 Movement from the
peritubular capillaries to
tubular lumen is called
tubular secretion
Blood examination
 Performed to measure substance in
blood that are:
1. normally excreted by kidney.
2. Their level in blood increases in kidney
dysfunction.
This includes creatinine, urea (most
commonly), and uric (not commonly)
Blood urea
 Urea is major nitrogenous end product of
protein and amino acid catabolism (40%
of all NPN).
 It is a non-toxic substance synthesized
by the liver by disposing of ammonia
from protein metabolism
 Filtered freely in glomeruli  40-70% is
reabsorbed in proximal tubules (so it is
not useful in clearance tests)
Blood urea
 The reference range for serum urea of
healthy adults is 10-40 mg/dl.
 Its level is greatly influenced by diet (esp.
proteins)  so need to prevent protein
intake 24 hours before the test.
 A normal level of blood urea is often
mistakenly indicate normal kidney
function, because blood urea may not
rise beyond the upper normal range
(40mg/dl) except after >75% of the renal
function is lost.
Blood urea
 BUN is increased in:
1. Decline in the GFR (decreased cardiac
output, dehydration, shock)
2. Increased protein intake
3. Gastrointestinal hemorrhage
4. Tissue trauma or burns.
5. Severe infections
6. Renal diseases
7. Post renal obstruction
Blood urea
 BUN is decreased in:
1. Liver diseases
2. Decreased protein intake
3. Overhydration
Serum Creatinine
 Creatinine is a breakdown product of
creatine phosphate in muscles
 It is usually produced at a fairly constant
rate depending on muscle mass (which
also depends on gender “M>F” and
age).
 Normal range is 0.8-1.5 mg/dl in men
and 0.6-1.3 mg/dl in women.
 Creatinine is freely filtered and not
reabsorbed by the kidney.
Serum Creatinine
 Increased:
- Pathologically: As in azotemia or
certain drugs (e.g. co-trimoxazole and
cimetidine).
- Physiologically: As in athletes.

 Decreased:
- Pathologically: As in paraplegia,
muscular dystrophy, amputation,
rhabdomyolysis … etc.
- Physiologically: As in elderly patients.
 Measurement of plasma creatinine
provides a more accurate assessment
than urea because there are many
non renal factors that affect urea level.
BUN/creatinine ration
 It is performed in:
1. If either the creatinine or BUN
concentrations are increased above
the upper normal range.
2. In conditions associated with elevated
levels of blood urea (uremia or
azotemia) to differentiate between
them.
Azotemia (Uremia)
1. Prerenal (due to kidneys
hypoperfusion): as in dehydration,
severe hemorrhage, shock.
2. Renal (primary kidney damage): as in
GN, ATN, interstitial nephritis …).
3. Postrenal (due to blockage of urine
flow): as in prostate enlargement,
stones, congenital anomalies.
 The normal BUN/Creatinine ratio is
between 10:1-20:1. The ratio is helpful
in determining the cause of renal
impairment.
BUN/creatinine ration
 Pre-renal azotemia leads to increased
urea level, while creatinine level
remains within the normal range (ratio is
20:1 or higher).
 In renal azotemia both urea and
creatinine levels rise proportionate to
one another (ratio near 10:1)
 Post-renal azotemia both urea and
creatinine levels rise, but creatinine in a
smaller extent.
BUN/creatinine ration
 Increased:
• Pathologically in:
1. Pre-renal azotemia
2. Post renal azotemia:
3. Increased protein catabolism: as in
bleeding in the digestive tract, severe
tissue injury (as burns, trauma and
infarctions …)
4. Intraperitoneal extravasation of urine
and urinary enteric fistulas: urea goes
back to blood.
• Physiologically in:
 Increased protein intake.
BUN/creatinine ration
 Decreased:
• Pathologically in:
1. Renal azotemia: both are increased in blood
but creatinine> urea due to decreased
tubular urea reabsorption.
2. Decreased urea synthesis: as in Liver
cirrhosis.
3. Increased protein loss: as in nephrotic
syndrome.
4. Hemodialysis: semi membranes are more
leaky for urea.
• Physiologically in:
 Decreased protein intake.
 Overhydration
Glomerular Function Test
 The glomerulus is investigated by
determining:
1. Glomerular filtration rate
2. Creatinine clearance
Glomerular filtration rate
 GFR is the volume of plasma filtered from
glomerulus to Bowman’ capsule per unit time
(mL/min).
 Reference Range:
 Male = 117 ± 20 mL/min.
 Female = 95 ± 20 mL/min.
 GFR can be calculated by measuring a
substance that has a steady level in the
blood, freely filtered and neither reabsorbed
nor secreted by the kidneys.
 Creatinine is freely filtered.
 10% of the total excreted creatinine is
secreted by the tubules.
 Negligible amounts of creatinine are
reabsorbed.
Methods to measure GFR
1. Inulin  difficult to perform routinely.
2. Most commonly used method is by
measuring creatinine clearance (Ccr )
• Ccr: Creatinine clearance (ml/min)
 Ucr: Creatinine urine concentration
(mg/dl).
 Pcr: Creatinine plasma concentration
(mg/dl).
 V: Urine volume (mg/dl).
Stage GFR Comment

0 ≥90 Normal kidney function


and no proteinuria

1 ≥90 Kidney damage despite a


normal GFR

2 60-89 Mildly decreased GFR

3 30-59 Moderately decreased


GFR

4 15-29 Severely decreased GFR

5 <15 Renal failure


Dialysis or transplant is
needed
Tubular function tests
 Tubular function is assessed by:
1. Urine osmolality
2. Specific gravity
3. Fractional Excretion of Na+
4. Selectivity ratio
Tubular function tests
 Osmolality: Concentration (number) of
particles in solution, expressed in
mOsm/kg of water.
 Reference range: 60-1250 mOsm/kg.
Average 825 mOsm/kg
 Specific Gravity: Ratio of the weight of a
volume of the particles solution to the
weight of an equal volume of water.
 The ability of the kidney to concentrate
urine is a test of tubular function.
 Both osmolality & specific gravity are
used to measure the tubular function of
the kidney.
 Specific gravity is less accurate (because
it may be affected by the presence of
inactive particles as glucose, protein…)
but it is more practical.
 Isosthenuria: low fixed specific gravity
(1.008-1.012)  It indicates loss of
tubular function (as in acute tubular
necrosis [ATN]).
Fractional Excretion of Na+
• Determined by measuring both plasma
and urine concentrations of sodium and
creatinine:
FE Na = (Na urine/Na plasma)
(Cr urine/Cr plasma)
 <1% is seen in pre-renal failure:
decrease in renal perfusion  increase
aldosterone increase in sodium and
water tubular reabsorption to control
hypovolemia.
 If >2-3% it indicates tubular dysfunction
as in ATN.
Selectivity Ratio
 The ratio of the clearances of a high and a
low molecular weight protein (Ig and
albumin, respectively) assess the degree of
glomerular damage in proteinuria.
 Selective Proteinuria : intermediate sized
proteins(albumin,transferrin) leaks through
glomerulus.
 Nonselective proteinuria : different sized
proteins including larger proteins
(immunoglobulin) leak through glomerulus.
 High selectivity: < 0.15 (minimal change
glomerulonephritis).
 Poor selectivity: > 0.30 (other than minimal
change disease, e.g. membranous GN).
Laboratory findings in certain
renal diseases
 Acute glomerulonephritis
 Chronic glomerulonephritis
 Nephrotic syndrome
 Acute pyelonephritis
 Chronic pyelonephritis
Acute Glomerulonephritis:
 Acute diffuse inflammatory changes in the
glomeruli (pre-renal azotemia) with
hematuria, RBC casts, hypertension,
azotemia, mild proteinuria and edema.
 Serum:
- Elevated SUN, creatinine, uric acid …
- Elevated SUN/creatinine ratio (>20:1).
- Decreased creatinine clearance and GFR.
- Metabolic acidosis due to retention of
phosphate, sulfate, amino acids, and other
metabolic acids.
 Urine:
 Red cells in urine
* Microscopic hematuria (smoky urine).
* Macroscopic hematuria (red urine).
 Casts: Red blood cell casts (pathognomic).
 Proteinuria, mild to moderate.
Chronic Glomerulonephritis:
 A slowly progressive glomerular disease
characterized by diffuse sclerosis of glomeruli,
loss of nephrons, tubules  tubular and
glomerular dysfunction with loss of protein into
urine.
 Serum:
- Elevated SUN, creatinine, uric acid …
- Decrease SUN/creatinine ratio (<10).
- Decreased creatinine clearance and GFR.
- Metabolic acidosis.
- Hyponatremia & hyperkalemia.
- Hypocalcemia & hyperphosphatemia.
- Elevated alkaline phosphatase (hypocalcemia
increase PTH secretion increase bone
resorption).
 Urine:
 Proteinuria (Massive).
 Cylindruria (Tubular casts in the urine).
 Episodic hematuria (Red cells in urine).
 Isosthenuria
 CBC:
 Anemia (due to decrease in erythropoietin
production).
Nephrotic Syndrome:
A group of disorders characterized by
prolonged increase in glomerular
permeability (no azotemia) for proteins
leading to:
- Massive proteinuria.
- Generalized edema.
- Hypoalbuminaemia.
- Hyperlipidemia.
 Serum:
- Normal: SUN, serum creatinine, serum
SUN/creatinine ratio, creatinine clearance
and GFR.
- Low serum albumin, 1-2.5 g/dL (Normal:
3.4-4.8 g/dL).
- Increase in serum lipids (Triglycerides,
cholesterol, lipoproteins).
- Albumin / globulin ratio is decreased.
 Urine:
- Large amounts of protein, usually 3.5-10
g/d.
- Red and white cells are common.
- Casts: many hyaline and finely granular
casts due to low urine flow.
- Oval fat bodies (Epithelial cells and
macrophages loaded with fat).
Acute pyelonephritis:
 It is acute inflammation of renal pelvis
and parenchyma (no azotemia).
 It is one of the most common diseases
of the kidney.

 Serum:
- Normal serum creatinine, SUN, serum
SUN/creatinine ratio, creatinine
clearance, GFR, and uric acid.
- Leukocytosis.
 Urine:

 Pyuria (Pus in urine).


 Microhematuria (Few red cells in
urine).
 WBC casts.
 Bacteriuria (Bacteria in urine).
Tubular Dysfunction Glomerular Dysfunction
 Usualy unilateral.  Usualy bilateral.
 Glomeruli focally affected.  Glomeruli diffusely affected.
 SUN, serum creatinine,  SUN, serum creatinine,
serum SUN/creatinine serum SUN/creatinine ratio,
creatinine clearance are
ratio, creatinine clearance
ABNORMAL
are NORMAL
 GFR is normal and the
 GFR is reduced in addition
urine may contains pus
the urine may contain
cells and leucocytic casts.
RBCs casts, proteinuria,
with low specific gravity