Unit 8: Kidney Functions and disorders

Kidney Functions and disorders
Dr. Elham Sharif,PhD
Assistant professorof BiomedicalSciences
College of Health Sciences
Qatar University
Tel: 00974-4403-4788
Email: e.sharif@qu.edu.qa

Objectives
• After attending a series of lectures on kidney, the students will:
• Identify/Describethe mechanisms by which the kidney maintains fluid and
electrolytebalance in conjunction with hormones. (TL1)
• Identify/Describediseases of the glomerulus and tubules and how
laboratory tests are used in these disorders. (TL1)
• Distinguish between acute and chronic renal failure. (TL2)
• For each kidney disease discussed in this lecture, determine the
appropriate tests resolve the problem. (TL2)
• Calculate the creatinine clearance, glomerular filtration rate and estimate
the glomerular filtration rate. (TL2)
• Identify/Evaluate the clinical significance of total urine proteins, urine
albumin, microalbuminuria, myoglobin clearance, serum β2-microglobulin,
and cystatin C. (TL3)
• Identify/List the tests in a urinalysis and microscopy profile and understand
the clinical significance of each. (TL1)
• Interpret the biochemical data used in the investigation and diagnosis of
kidney disease, when given problem based case studies. (TL3)
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About this Chapter
• How filtration is regulated
• Kidney functions
• Kidney disorders
• Investigation of kidney disease
• Non protein nitrogenous compounds
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The Kidney
Figure 19-1: Anatomy Summary: The Urinary System
• Paired, bean shaped
• Partially protected by
the 11th and 12th ribs
• Right kidney slightly
lower due to liver
• Kidney
o Cortex
o Medulla
o Pelvis
o Nephrons
• Ureters connect
kidneys to urinary
bladder.
• Bladder
• Urethra leads from
bladder outside the
body.
4http://www.youtube.com/watch?v=cc8sUv2SuaY&feature=related
Basics
9/2/2019Dr Elham Sharif

Renal Anatomy
• Anatomy
o Five basic parts of nephron:
• 1) Glomerulus: a capillary tuft surrounded by expanded end of renal tubule
• 2) Proximal convoluted tubule: located in cortex
• 3) Loop of Henle: comprising descending & ascending limbs
• 4) Distal convoluted tubule: located in cortex
• 5) Collecting duct: formed by 2 or more distal convoluted tubules as they
pass through cortex & medulla
5Dr Elham Sharif
Basics
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Renal Anatomy
• Representation of a nephron and its blood supply
http://www.youtube.com/watch?v=chhNaLi9P3E
Basics

Renal Physiology
• Glomerular Filtration
o Glomerulus filters incoming blood.
o Of 1.2–1.5 liter of blood received by kidneys, the
glomerulus filters out 125–130 mL of protein-free, cell-
free fluid (glomerular filtrate).
o Glomerular filtration rate: volume of blood filtered
per minute
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Basics
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Renal Physiology (cont’d)
• Tubular Function
o Proximal convoluted tubule
• Tubular reabsorption: returns valuable substances to blood
• Tubular secretion: secretes products of metabolism
o Loop of Henle: aids in reabsorption of water, sodium,
chloride
o Distal convoluted tubule: adjusts for electrolyte & acid–
base homeostasis through hormonal control of ADH &
aldosterone
o Collecting duct
• Final site for concentrating or diluting urine
• Controls reabsorption of water, sodium, chloride, & urea
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Basics

• Elimination of Nonprotein Nitrogen Compounds (NPN)
o Urea
• Readily filtered by glomerulus & reabsorbed in collecting ducts
o Creatinine
• Readily filtered by glomerulus; not reabsorbed by tubules
o Uric acid
• Readily filtered by glomerulus
• Undergoes complex cycle of reabsorption & secretion as it courses through
nephron
9Dr Elham Sharif
Renal Physiology (cont’d) Basics
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Glomerular Filtration Rate
• Is the amount of blood filtered per minute by the
glomerulus of the kidney
• Volume of plasma filtered / unit time
• Approx. 180 L /day
• Urine output is about 1- 2 L /day
• About 99% of filtrate is reabsorbed
• Factors affecting the filtration rate at the capillary
bed are:
o Total surface area available for filtration
o Filtration membrane permeability
o Net filtration pressure

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GFR influenced by:
• Blood pressure and blood flow
• Obstruction to urine outflow
• Loss of protein-free fluid
• Hormonal regulation
o Renin – angiotensin
o Aldosterone
o ADH
o Atrial natriuretic peptide (ANP), vasodilator

Control of Filtration Rate
• 180L/day (GFR)
• Normal auto-regulation
• Changes lead to additional regulation:
o Sympathetic innervations of arterioles e.g.:
• Volume of blood drops….
• Blood pressure drops….
• Decrease in filtration rate of blood to conserve water.
• The reverse also occurs

Control of Filtration Rate Cont’d
o Renin-angiotensin system
• Juxtaglomerula apparatus
• Renin
• Angiotensinogen  angiotensin I Angiotensin II
• Aldosterone
o Stimulus:
• Drop in blood pressure
• Decreasing levels of Na+, K+. Cl-

Renin-Angiotensin System Control of Filtration Rate
Dr Elham Sharif
http://www.youtube.com/watch?v=jXR5fLw8WzU
9/2/2019

Forces that influence filtration
Filtration Pressure
1. Hydrostatic pressure of glomerulus-Glomerular
blood hydrostatic pressure
o Main force for filtration
o Positive pressure that pushes fluid out
2. Opposing forces:
• Osmoticpressureof blood plasma-Plasma colloid
osmotic pressure
o Negative pressure that prevents filtration
• Hydrostatic pressure of Bowman’s capsule-Capsular
hydrostatic pressure
o Negative pressure that prevents filtration

Glomerular Flow Rate (GFR)
Figure 19-6: Filtration pressure in the renal corpuscle
• Capillary
o Hydrostatic pressure
o Colloidal
• Capsule pressure
o Back pressure
o Net Filtration p
• GFR  180L/day (about
1% is excreted)
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Glomerular Flow Rate (GFR)
Figure 19-5: The filtration fraction 17
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Filtration Pressure
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Dr Elham Sharif
Symptoms associated with falling GFR
Normal GFR = 125-130 ml/min

• Kidney functions:
1. Filtration of blood
• Removes metabolic wastes from the body, esp. those containing nitrogen.
• Excretion: Metabolic wastes & foreign molecules
2. Regulation:
Blood volume and composition
Homeostatic regulation: ECF volume, osmolarity, ion & pH
balance.
Water, electrolyte and acid base balance.
Blood pH
Blood pressure
3. Synthesis & regulation of hormones & enzymes.
4. Other functions include:
o Gluconeogenesis during prolonged fasting
o Production of renin to help regulate blood pressure and erythropoietin to
stimulate RBC production
o Activation of vitamin D
Kidney Functions: Overview

o Water balance
• Increased plasma osmolality or decreased intervascular volume stimulates
secretion of ADH from posterior pituitary.
• ADH increases permeability of distal convoluted tubules & collecting ducts to
water, causing increased water absorption.
o Electrolyte balance
o Electrolyte conc. expressed in milliequivalents per liter (mEq/L)
o mEq/L = (concentration of ion in [mg/L]/the atomic weight of ion) x number of
electrical charges on one ion
• Sodium:Primary extracellular (EC) cation, controlled primarily by renin-
angiotensin-aldosterone hormonal system (RAAS); excreted from kidneys
• Potassium: reabsorbed & excreted by distal convoluted tubule & collecting ducts;
excretion controlled by aldosterone

o Electrolyte balance cont’d
o Chloride:
• 1ry EC anion
• Regulated by renin-angiotensin-aldosterone system
o Phosphate
• Present in equal amounts in IC & EC compartments
• Balanced determined by PTH
o Calcium
• Primary inorganic cellular messenger
• Ionised form reabsorption is controlled by PTH
• Main regulation occurs with PTH & calcitonin, control of bone resorption and absorption
from the gut
o Mg
• Acts as a enzyme cofactor
• PTH controls reabsorption in proximal tubule
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Acid base balance
1. Acid wastes excreted by the kidney include carboic acid, lactic
acid and ketoacids
2. Maintains pH by reabsorbing bicarbonate or secreting acids
3. Regeneration of bicarbonate ions: kidney generates bicarbonate
ions to replace those lost by metabolism
4. Excretion of metabolic acids: kidney excrete excess hydrogen
ions while making urine
5. Reaction with ammonia: ammonia is combined with hydrogen ions
in the kidney and excreted as the ammonium ion.
o Reactions with HPO4
-2 : this compound combines with hydrogen
ions and is excreted, can excrete until urine pH = 4.4
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Acid base balance will be discussed further later through out the course
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Endocrine functions
1. Renin
• The juxtaglomerular cells of the renal medulla secrete renin in response
to a ↓ in ECF.
• Function: catalyzes synthesis of angiotensin I and then to angiotensin II
via ACE , vasoconstrictor that ↑s the blood pressure.
2. Prostaglandins
o PGA2, PGE2, PGI2 & PG12 are secreted
o Function: increase renal blood flow, Na and water excretion & renin release;
oppose renal vasoconstriction
3. Erythropoietin
o Produced in cortex
o Regulated by oxygen levels in the blood
o Function: increase the number of RBCs
4. Viatmin D, insulin, glucagon and aldosterone metabolism occur in the
kidney.
1. vitamin D3: active form of vitamin D; determines phosphate & calcium
balance & bone calcification
Dr Elham Sharif

Kidney Disorders
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Kidney disease: 1. Acute glomerulonephritis
C. Lab results
• Microscopic hematuria (Smoky urine).
Macroscopic hematuria (Red urine).
• Anaemia
• Proteinuria (albumin < 1 g/day)
• Renal tubular epithelial
• Decreased GFR
• Increased BUN & creatinine
• Elevated uric acid
• Elevated SUN/creatinine (> 20:1)
• Decreased creatinine clearance
• Numerous hyaline, granular casts, &/or RBC
casts.
• Metabolic acidosis.
A. Mechanism
• Immune complexes (e.g. gp A
beta streptococci) settle on the
glmerular basement membrane &
trigger specific & nonsp immune
responses that damage the
basement membrane.
• Other causes include drug
exposures, SLE, & subacute
bacterial endocarditis.
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b. Symptoms
Oliguria
Water retention (swelling of ankles)
Congestive heart failure

Kidney disease: 2. chronic glomerulonephritis
• Occurs from prolonged inflammation of the glomerulus, causing
destruction of the nephron
• Uremia may be the 1st clinical sign
Lab results
• Episodic hematuria: increased RBCs, renal epithelial cells, tubular casts in the urine
• Increased proteinuria (> 2.5 g/day)
• Oliguria → anuria
• Hyponatremia
• Hyperkalemia (Secondary to potassium retention).
• Hypocalcemia (Secondary to loss of albumin into the urine and phosphate retention)
• Hyperphosphatemia (Secondary to phosphate retention)
• Decreased creatinine clearance
• Metabolic acidosis (Secondary to retention of hydrogen ion).
• Elevated alkaline phosphatase (Secondary to hypocalcemia stimulating secretion of
parathyroid hormone)
• Decreased SUN/creatinine ratio (<10:1), GFR decreased
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Kidney disease: 3. nephrotic syndrome NS
C. Lab results
• Massive proteinuria > 3 g/d
• Hypoalbuminemia
• Hyperlipidemia
• Lipiduria
• Oval fat bodies, free fat, Renal epithelial
B. Symptoms
• Swelling of the ankles, osmotically
induced hypovolemia
Mechanism: increased permeability of the glomerulus
A. Causes
•Glomerular disease
•SLE
•Renal vain thrombosis
•Syphilis
•Amyloidosis
•Sever preeclampsia
•Transplant rejection

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Sever NS
Orbital odema
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Pathophysiology of nephrotic syndrome

Nephrotic syndrome
• Comprises:
o proteinuria,
o Hypoproteinaemia
o oedema and
• can be a result of a variety of diseases affecting the glomeruli.
• The clinical and biochemical features stem from the loss of protein from
the body.
• In addition to albumin, the loss of which is responsible for the oedema,
the loss of other proteins leads to increased susceptibility to infection and
hypercoagulability.
• Uraemia may or may not be present, depending on the nature of the
underlying glomerular damage.
• Hypoproteinaemia with oedema may develop if large amounts of protein
are excreted in the urine.
• For this to occur, proteinuria must usually exceed 5 g/24 h.
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Kidney disease:4. tubular disease
1. Distal RTA, no pH gradiant
between blood and filtrate
a. Causes
• Drug or x-ray toxicity
• Methicillin hypersensitivity reaction
• Transplant rejection
• infections
2. Proximal RTA, increased
water reabsorption
b. Lab findings
• Decreased serum phosphate &uric acid
• +ve glucose & amino acids in urine
• WBC, RBCs
• Proteinuria < 2 g/day, Oliguria
Renal tubular acidosis (RTA)

Kidney disease:5. UTI/Obstruction
1. Pyelonephritis: kidney
infection
• Normal serum: Urea N,
serum creatinine, SUN,
serum SUN/creatinine ratio
(~12), creatinine clearance,
GFR, and uric acid
• Urinalysis: increased urine
WBCs, bacteria, Pyuria,
RBCs and renal epithelial.
• Hematology:
• Peripheral leukocytosis
2. Cystitis/bladder infection
• Lab findings: increased
WBCs, bacteria, RBCs and
transitional epithelium
a. UTI infection
Lab results:
•Positive nitrate for some organisms
•Positive leckocyte esterase
•Positive occult blood
•WBC casts (diagnostic for
pyelonephritis)
Symptoms
• pain or burning urination
•Back pain
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May occur in the kidney (in nephrons, collecting ducts or pelvis) in ureter or in
urethera:
Mechanisms
• Increased intratubular
pressure so nephrons die
and CRF persists.
• Facilitate frequent UTIs
Causes
• Neplasms
• Lymph node tumors
• Urethral strictures, stones
• Congenital abnormalities
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Diagnosed by:
•Radiologic imaging
Symptoms
• hematuria
•Extreme pain
b. Obstruction

Kidney disease:
6. Renal Calculi/stones - Nephrolithiasis
• Formed by crystallization of organic & inorganic substances
• Most common is calcium oxalate
• Symptoms: hematuria & extreme pain

Kidney disease: 7. Acute renal failure ARF
• Definition: sudden decline in renal function due to an insult to the kidney (GFR = <
10 ml/min), reversible, high mortality.
1. Pre-renal: occurs in blood supply before reaching the kidney, urine Na <20 mmol/L,
urine:plasma urea >20:1, urine:plasma osmolality >1.5:1.
2. Intrinsic acute renal failure Causes:
o Hemolytic transfusion reactions
o Heavy metal/solvent poisoning
o Antifreeze ingestion
o Analgesic & amino-glycoside toxicities
o Septic hemorrhagic shock, burns & cardiac failure CF
• Symptoms
o Oliguria, anuria (< 400 ml/d)
o If more water retained than Na then Hyponatremia… drowsiness, seizures, coma
& death
o Hyperkalemia leading to cardiac arrhythmias

acute renal failure ARF cont’d
• Lab results
o RBCs casts, hematuria, proteinuria, metabolic acidosis
o Uremic syndrome with increased BUN and creatinine.
o Urine Na >40 mEq/L, urine:plasma urea < 10:1 or <3, urine:plasma
osmolality <1.1:1
3. Post-renal: occurs after urine leaves the kidney, caused by lower UT
obstruction (stone, tumor)

Causes of acute renal failure

Unit 8: Kidney Functions and disorders

Biochemical changes in plasma acute
renal failure ARF
Increased
• Potassium
• Urea
• Creatinine
• Phosphate
• Mg
• Hydrogen ion
• urate
Decreased
• Na
• Bicarbonate
• calcium

Kidney Disease: chronic renal failure CRF
• Renal function is irreversibly lost;
• Causes include:
• diabetes, vascular diseases, glomerulonephritis and pyelonephritis.
• CRF usually develops slowly
• It is a progressive disease that causes a decline in renal
function over time and progresses in 4 stages:
o 1st stage: BUN and creatinine stay normal while kidney function
declines
o 2d stage: small decrease in renal function. 50 % loss of function
is when BUN and creatinine increase
o 3d stage: patients becomes acidotic and anemic
o 4th stage: uremic syndrome begins (increased BUN &
creatinine), oliguria (<400 ml/d), anuria, edema, hypertension
and CHF).

• Neurological: lethargy, peripheral neuropahty
• Musculoskeletal: growth failure, bone pain, myopathy
• Gastrointestinal: anorexia, hiccup, nausea &
vomiting, gastrointestinal bleeding
• Cardiovascular: anaemia, hypertension, pericarditis
• Dermal: pruritis/itch, pallor, purpura
• Genitourinary: nocturia, impotence
purpura

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Stages of chronic Progressive renal disease
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Kidney disease: Diabetes mellitus
• 45 % of type I patients develop diminished
kidney function 15-20 years after diagnosis
• Causes primarily glomerular problems
• Associated with glucosuria, polyuria, nocturia.
• Microalbuminemia occurs between 10-15 years
after diagnosis

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Development of Diabetic Nephropathy
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Kidney disease: renal hypertension
• Causes decreased blood flow to all or parts of
an area of the kidney or accumulation of Na
• Ischemia to the kindney triggers the renin-
angiotensin-aldosterone system which causes
vasocontriction
• Lab results:
o aldosterone, Na and renin levels are high
o Urine potassium increased
o Serum potassium is decreased, hypokalemia

• Increased levels of protein in the urine
•The glomeuli normally filter 7-10 g of protein per 24hrs
•Almost all reabsorbed by endocytosis and then
catabolised in proximal tubule PT.
•Normal urine protein excretion < 150 mg/24 hrs, approx
half of this is glycoprotein called Tamm-Horsfall protein
and < 30 mg is albumin.
•Dip stick can detect albumin > 200 mg/L in urine but less
sensitive to other proteins,
•False positive FP are found when urine:
• is alkaline,
• contaminated with antiseptics
• or contains X-ray contrast media
Kidney disease: Proteinuria

Summary
• Glomerular Diseases
o Acute glomerulonephritis
• Large, inflamed glomeruli with a decreased capillary
lumen
• Rapid onset of hematuria & proteinuria
o Chronic glomerulonephritis
• Glomerular scarring & eventual loss of functioning
nephrons
• Gradual development of uremia may be first sign.
o Nephrotic syndrome
• Associated with massive proteinuria, hypoalbuminemia,
edema, hyperlipidemia, & lipiduria

Summary cont’d
• Tubular Diseases
o Result in decreased excretion/reabsorption of certain
substances or reduced concentrating capability
o Renal tubular acidosis: disorder affecting acid–base
balance
• Urinary Tract Infection
o Infection: in either kidneys or urinary bladder
o Obstruction: in upper or lower tract
• Renal Calculi (kidney stones)
o Formed by combination of various crystallized
substances

Summary cont’d
• Renal Failure
o Acute renal failure: sudden, sharp decline in renal
function
o Chronic renal failure: gradual decline in renal
function over time
o Renal hypertension: caused by decreased perfusion
to kidney
o Therapy of acute renal failure
• Dialysis: removal of waste from blood by external, synthetic membrane
o Therapy of end-stage renal disease
• Dialysis & transplantation

Treatment of renal disease
Hemodialysis
Peritoneal dialysis
Renal transplant

Non-protein nitrogenous compounds-Urea
• Regulation:
o Urea is the major nitrogen-containing compound in the blood.
o It results from protein catabolism and is synthesized in the liver from the
deamination of amino acids.
o Urea is excreted by the kidneys.
• Clinical significance:
o Abnormal serum urea levels may be due to prerenal, renal, or postrenal disorders.
o a. Increased serum urea: Renal failure, glomerular nephritis, urinary tract
obstruction, congestive heart failure, dehydration, increased protein catabolism.
o b. Decreased serum urea: Severe liver disease, vomiting, diarrhea, malnutrition.
- Blood urea nitrogen (BUN) is an older term still in use, and the terminology was
based on previous methodology where nitrogen was measured.
To convert BUN to urea:BUN X 2.14 = Urea.
update

Non-protein nitrogenous compounds –Urea
Cont’d
Test methodology:
• Reference range: 6-20 mg/dL
update

Non-protein nitrogenous compounds: Creatinine
• 1 . Regulation:
• Creatinine is a waste product of muscle contraction that is formed from
phosphocreatine, a high-energy compound. Creatinine levels are regulated by kidney
excretion. Measurements of creatinine in serum and urine (creatinine clearance) are
used to assess the glomerular filtration rate (GFR). Creatinine levels are not changed
by diet or rate of urine flow. Creatinine is not reabsorbed by renal tubules.
• 2. Clinical significance
o a. Increased serum creatinine: Renal disease, renal failure
• 3. Test methodology
• Reference ranges: Male, 0.9-1.3 mg/dL; female, 0.6-1.1 mg/dL .
update

update

• Creatinine clearance is used to assess the GFR.
• Testing requires a plasma sample and a 24-hour urine collection.
• Creatinine clearance formula:
• C (mL/min) = (U X V/P) X 1.73 m2 SA
o a. P: plasma creatinine mg/dL, U: urine creatinine mg/dL, V: urine flow in
mL/min, and SA: body surface area; 1.73 m2 = average body surface area
• Reference ranges: Differ according to age and sex; values decrease with age
o Creatinine clearance (males): 105 ± 20 mL/min/1.73 m2
o Creatinine clearance (females): 95 ± 20 mL/min/1.73 m2 d.
• Estimated glomerular filtration rate (eGFR) uses only a blood creatinine and the
MDRD (Modification of Diet in Renal Disease) formula.
o 1) Correction for gender and race required
o 2) Results only reported as a number if <60 mL/min/1.73 m2
Non-protein nitrogenous compounds: Creatinine cont’d
update

Non-protein nitrogenous compounds: Uric Acid
• Regulation:
o Uric acid, the major waste product of purine (adenosine and guanine) catabolism,
is synthesized in the liver. Uric acid elimination from the blood is regulated by the
kidneys through glomerular filtration, and some uric acid is excreted through the
GI tract.
• 2. Clinical significance
o a. Increased serum uric acid: Gout, renal disorders, treatment of
myeloproliferative disorders, lead poisoning, lactic acidosis, toxemia of
pregnancy, Lesch-Nyhan syndrome
o b. Decreased serum uric acid: Severe liver disease as a secondary disorder,
tubular reabsorption disorders, drug induced
o a. Chemical method
o Uric acid + phosphotungstic acid + O2 —> allantoin + CO2 + tungsten blue
o b. Enzymatic urease method: Decrease in absorbance monitored at 293 nm
o Uric acid + O2 + 2H2O urease>allantoin + H2O2 + CO2
• 4. Reference ranges: Male, 3.5-7.2 mg/dL; female, 2.6-6.0 mg/dL
update

Non-protein nitrogenous compounds/ Ammonia
• 1. Regulation
o a. Ammonia produced from deamination of amino acids
o b. Hepatocytes convert ammonia to urea for excretion.
o c. With severe liver cell malfunction, blood levels of ammonia increase.
o d. Ammonia is neurotoxic.
• 2. Type of specimen and storage
o a. Venous blood free of hemolysis; place on ice immediately
o b. Blood collected in ethylenediaminetetra-acetic acid (EDTA) may be used.
o c. Centrifuge sample within 20 min of collection and remove plasma.
o d. Plasma stable up to 3.5 hr in ice bath; stable several days frozen
• 3. Clinical significance:
o Increased plasma ammonia levels seen in hepatic failure and Reye syndrome
o a-Ketoglutarate + NH+4 + NADPH  Glutamate + NADP+ + H2O (Glutamate dehydrogenase)
• 5. Interferences
o a. Incorrect handling of blood sample
o b. Ammonia contamination
• 6. Reference range: 11-32 (μmol/L)
update

Laboratory diagnosis

Analytic Procedures
• Clearance Measurements
o Evaluation of renal function depends on measurement of waste
products in blood that accumulate when kidneys begin to fail.
o Clearance: rate at which creatinine & urine are removed from
blood into urine
o Creatinine: endogenous metabolic product synthesized at a
constant rate & cleared only by glomerular filtration
o Creatinine clearance rate CCr: standard lab method to
determine glomerular filtration rate (GFR), require 24/hr urine
collection.
o Estimated glomerular filtration rate: used to predict GFR; is
based on serum creatinine, age, body size, gender, & race;
does not require urine collection

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Creatinine clearance
• Creatinine is an end product of muscle metabolism
• 20 % of muscle creatine is converted to creatinine daily.
• Is propotional to muscle mass
• Muscle mass is constant; creatinine is constant
• Normal 0.7 – 1.5 mg/ dL in plasma
• Can then be compared to creatinine in urine over 24
hour period to determine clearance.
• Not reabsorbed by the kidney
Diagnostic tests

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• Creatinine clearance is an indirect measure of GFR and
renal blood flow
• Creatinine is neither reabsorbed nor secreted, just freely
filtered.
• Amount excreted = amount filtered
• Useful to monitor changes in chronic renal function
• Increases with trauma with massive muscle breakdown.
• The most widely used biochemical clearance test is
based on measurements of creatinine in plasma and
urine.
• A small amount of creatinine is derived from meat in the
diet.

• UCr is urine creatinine clearance
• VUr is urine volume excreted in 24 hours
•PCr is serum creatinine concentration
•1.73 generally accepted average body surface in square meters.
• A is the actual body surface area of the individual determined from height and weight).
•The usual collection time is 24 h.
Creatinine clearance reference range =
Males: 97-137 mL/min per 1.73 m2
Females: 88-128 mL/min per 1.73 m2
Creatinine clearance normally decreases with age, with a decrease of about 6.5 mL/min
per 1.73 m2 for each decade of life.
Creatinine clearance (CCr) =

Estimated Glomerular Filtration Rate =
•The equation is used to predict GFR and is based on serum creatinine, age, body size,
gender, and race, without the need of a urine creatinine.
•Because the calculation does not require a timed urine collection, it should be used more
often than the traditional creatinine clearance and result in earlier detection of chronic
kidney disease

Analytic Procedures (cont’d)
• Clearance Measurements
o Urea: does not provide full clearance assessment &
is no longer widely used
o Cystatin C: a low-molecular-weight protein produced
by nucleated cells; levels remain stable if kidney
function is normal.

Blood Urea Nitrogen BUN
• Urea produced by breakdown of amino acids (proteins) -
influenced by diet, dehydration, and hemolysis.
• Kidney is the only way to excrete urea
• Normal range 10-20 mg/ dL
• Rate of urea excretion depends on;
o GFR,
o plasma renal flow &
o urine flow rate.
• If the GFR decreases due to:
o renal disease or blockage,
o or decreased blood flow to kidney
o BUN will increase
• BUN is used for general screen for abnormal renal function

Uric acid
• Major waste product of purine metabolism
• Reabsorbed and secreted by the nephron
• Formed as sodium urate in urine with pH > 5.75
• Can cause stones in urines with pH < 5.75
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• Urine Electrophoresis
o Distinguishes between acute glomerular nephropathy
& tubular proteinuria
o Screens for abnormal monoclonal or polyclonal
globulins
• 2-Microglobulin
o Used clinically to assess renal tubular function in
renal transplant patients, with elevated levels
indicating organ rejection
• Myoglobin
o Myoglobin clearance has been proposed as an
effective early indicator of myoglobin-induced acute
renal failure.

• Microalbumin
o Microalbuminuria: small amounts of albumin in urine
o Urine microalbumin measurement is important in management of
patients with diabetes mellitus, who are at risk for nephropathy.
o Type 1 diabetes: 30–45% risk; type 2 diabetes: 30% risk
o In later phase of nephropathy, increased glomerular capillary
permeability allows small amounts of albumin to pass into urine.
o If detected in early phase by microalbumin measurement,
progression to end-stage renal disease can be prevented.
o Urinary albumin concentrations of 50–200 mg/24 hours are
predictive of diabetic nephropathy.

77
Renal diagnostic procedures
• Urinalysis is non-invasive and inexpensive
• Normal properties are well known and easily measured

• Urinalysis
o Permits a detailed, in-depth assessment of renal status
with an easily obtained specimen
o Serves as a quick indicator of glucose status & hepatic-
biliary function
o Routine urinalysis includes assessment of:
• Physical characteristics
• Chemical analyses
• Microscopic examination of sediment from a urine sample
78Dr Elham Sharif
9/2/2019

79
Substances not normally present in urine
• Acetone
• Bile, bilirubin
• Glucose
• Protein – albumin
oRenal disease involving glomerulus
Dr Elham Sharif
9/2/2019

• Urinalysis
o Physical characteristics
• Specimen collection
• Visual appearance
• Odor
• Turbidity
• Volume
• Specific gravity
• Lab methods
• Disease correlation
• pH
o Chemical analyses
• Glucose &
ketones
• Protein
• Nitrite
• Leukocyte
esterase
• Bilirubin/urobilino
gen
• Hemoglobin/bloo
d

• Urinalysis
o Sediment examination
• Red blood cells
• White blood cells
• Epithelial cells
• Miscellaneous elements
• Bacteria
• Hyaline casts
• Granular casts
• Cellular casts
o Crystals
• Acid environment
• Alkaline environment
• Other
81Dr Elham Sharif
9/2/2019

Urine protein test 1
1. Urine protein increased in:
• Renal absorption defects
• Glomerular filtering problems
• Increase in serum proteins
2. Diseases markedly increased urine proteins
include:
o Acute glomerular nephropathy
o Tubular proteinemia
o Multiple myeloma MM
o Nephrotic syndrome, diabetes & systemic lupus
eythromatosus (SLE)
3. Bence Jones proteins found in MM patients
82
Diagnostic tests

Urine protein test 2
1. Β2- microglobulinemia:
o Indicator of glomerular disease in intermediate diabetic
nephropathy or renal transplant status
2. Myoglobin: used as early indicator of acute renal failure
caused by significant cardiac or skeletal muscle injury or
release of massive amount of myoglobin into the blood
3. Microalbumin:
o Monitor renal function in diabetics
o Progressive treatment and strict glucose control in
patients with high microalbumin can reduce the chances
for the diabetic to develop end stage renal failure.
o Special dipstick methods have been developed to detect
10 μg/ml

References
• Bishop., ML, Fody., E.P. Schoeff, LE , Clinical
Chemistry: Techniques, Principles, Correlations
(Bishop, Clinical Chemistry) ISBN: 978-0781790451,
Publisher: Lippincott Williams & Wilkins; Sixth
Edition, 2010.
• Marshall, W.J., Bangert, S.K.; Clinical Chemistry 6th
edition, ISBN 0-7234-3328-3 -Publisher: Mosby,
Release date: 2008.
• Christenson, R.H., Gregory, L.C., Johnson, L.J.
(2001). APPLETON & LANGES OUTLINE REVIEW
CLINICAL CHEMISTRY, ISBN 0070318476,
Publisher: McGraw Hill Companies.
Dr Elham Sharif

Unit 8: Kidney Functions and disorders

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Unit 8: Kidney Functions and disorders