RENAL FUNCTION TESTS...Clinical Chemistry Renal Function Tests - Lecture Ideal Marker for GFR...

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Clinical Chemistry Renal Function Tests - Lecture

#Clinical Chemistry

RENAL FUNCTION TESTS - Lecture

Dr. Kakul Husain

# The Kidney

Kidneys are bean-shaped organs, each about the size of fist, located near the

middle of the back, just below the ribs cage.

Produces urine

Transports urine

towards bladder

Temporarily store

urine

Conducts urine to

exterior

Kidneys work as filters for the waste products and extra water from the

blood and produce urine as a result.

Urine flows to Bladder through Ureters; Bladder stores the urine which will

pass through the Urethra in the process of urination.

Dr. Kakul Husain Firoz

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# Functions of the Kidney

Urine Formation

4 Processes:

Glomerular Filtration

Ultrafiltration of plasma in the glomerulus producing cells- and protein -

free filtrate which passes to the Bowman’s capsule.

Tubular Reabsorption

Reabsorption of important molecules back to the blood (water, a.a. glucose

and ions).

Tubular Secretion

Secretion of waste and toxic substances into the tubules.

Urine Excretion


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Excretion of harmful/toxic substances:

Non-nitrogenous substances

*Bilirubin *Metabolites *Drugs/Toxins

Non-protein nitrogenous NPN substances

*Urea *Creatinine *Uric Acid

Production of Hormone:

- Erythropoietin (EPO) Secreted in response to low blood oxygen content. It

acts on bone marrow, stimulating the production of RBCs.

- Renin Regulates blood pressure and fluid and electrolyte balance via the

Renin-Angiotensin-Aldosterone System (RAAS).

Homeostasis:

- Acid/Base Balance

- Electrolytes Balance

Notice >>

Glomerular filtration, tubular reabsorption, and tubular secretion permit rapid

removal of toxic substances and entire plasma filtration about 60 times/day.

Each of these processes is regulated according to the body needs.

e.g. when there is excess sodium in the body, the rate at which sodium is

filtered increases and a smaller fraction of the filtered sodium is reabsorbed,

resulting in increased urinary excretion of sodium.

Dr. Kakul Husain Firoz 3

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# Why Testing Renal Function..??

Laboratory evaluation may be the only way of detection because

patients with kidney disease have few signs and symptoms early in

disease course.

For early detection to allow corrective therapy especially to high risk

people.

To follow up renal disease progression.

To assess appropriate dosing for different medications.

# Signs and Symptoms of Kidney Disorders

Early Symptoms

Weight loss

Nausea, vomiting

General ill feeling

Fatigue

Headache

Frequent hiccups

Generalized itching (pruri

tus)

Late Symptoms

Increased or decreased urine output

Need to urinate at night

Easy bruising or bleeding

Decreased alertness

Muscle cramps

Decreased sensation in the hands an

d/or feet.

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# Types of Renal Disorders

Acute Renal Failure (ARF)

Occurs quickly and suddenly as a result of kidney injures. It results

from pre-, renal, or post-renal causes.

May lead to permanent loss of kidney function.

Can be reversed if kidneys are not seriously damaged.

Physiologic impact includes:

Retention of water (edema), electrolytes (hypertension), and metabolic

bi-products (neurotoxicity).

In severe cases, complete anuria occurs.

Death may occur in 8 to 14 days.

Pre-renal causes:

Reduced perfusion due to:

Blood loss (hemorrhage)

Cardiac failure

Peripheral vasodilation resulting in hypotension (e.g. anesthesia)

Renal artery Obstruction

Stenosis, embolism, or thrombosis.

Renal causes:

Acute Glomerulonephritis due to:

Infections (e.g. post-streptococcal infection)

Autoimmune disorders (e.g.systemic lupus erythematosus SLE)

Acute Tubular Necrosis due to:

Renal Ischemia (↓O2). ■ Hemolysis (Hb degradations interfere tubules

Toxins or Medications (e.g. carbon tetrachloride CCl4, insecticides, etc.)


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Post-renal causes: Obstruction of renal flow due to:

Renal Calculi.

Benign or malignant masses (e.g. BPH, bladder and prostate cancer)

Normal kidney function can be restored if the basic cause is corrected.

Chronic obstruction of the urinary tract, lasting for several days or

weeks, can lead to irreversible kidney damage.

Chronic Renal Disease (CRD)

Occurs gradually and slowly as a result of a long-term disease, such as

high blood pressure or diabetes which slowly damages the kidneys and

reduces their function over time.

May remain asymptomatic for years.

Patients with CRD are susceptible to heart attacks and strokes due to

electrolyte imbalance.

Most kidney disorders are included under this category.

Common causes and predisposing factors:

*Diabetes *Increased Blood Pressure*Poisons *Certain drugs

*Recurrent urinary tract infection UTI

Physiologic Impact

Anaemia (↓EPO hormone)

Metabolic acidosis (Accumulation of acids)

↓Active form of Vit. D → ↓Ca intestinal absorption →2ry

HPT

Osteomalacia

End-Stage Renal Disease (ESRD)

If CRD cannot be controlled, total or nearly total permanent loss of

kidney function will occur.

Dialysis or transplantation is necessary at this stage


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# Classes of Renal Function Tests

Glomerular Function

Serum Urea, Creatinine and Uric acid

Clearance Tests

Proteinuria

Hematuria

Tubular Function

Specific Gravity

Urine Analysis

Physical, Chemical and Microscopic Examination of urine.

# Biochemical Tests of Renal Function

Blood Urea Nitrogen (BUN) 7.0 - 20 mg/dl

Urea is produced in the liver as a result of protein metabolism. It is

transported in the blood to the kidneys, where it is excreted.

Since urea is cleared from the blood stream by the kidneys, measurement

of the level of urea nitrogen in the blood is an appropriate test of renal function, specifically that of glomerular function.

High Blood Urea Nitrogen (BUN)

Renal impairment

- Glomerulonephtitis

- Obstructive uropathy


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High protein diet

Catabolic states: (Protein catabolism e.g. fever, severe infections, etc.)

Dehydration: (increased tubular reabsorption of urea)

Drugs: Steroids, Diuretics, etc.

Low Blood Urea Nitrogen (BUN)

Diet inadequate in protein

Liver failure

Malnutrition

Serum Uric Acid

♂ 3.6–8.5 mg/dL

♀ 2.3–6.6 mg/dL

Uric acid is produced by the breakdown of purines, chemicals that are

the building blocks for DNA and RNA.

Excess serum uric acid can become deposited in joints and soft tissues,

causing gout, an inflammatory response to the deposition of the urate

crystals.

High Serum Uric Acid

Conditions of rapid turnover of cells due to cell damage (e.g. Malignant

conditions – Leukemias)

Gout

Glomerulonephritis

Chronic renal disease


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Serum Creatinine

♂ 0.8–1.4 mg/dL

♀ 0.6–1.2 mg/dL

Chidren 0.2–1.0 mg/dL

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.

Liver Muscle

Kidney → excretion

High Serum Creatinine

Increased levels of creatinine indicate a slowing of the glomerular

filtration rate which indicates to a renal disorder.

Decreased Serum Creatinine

Muscle Atrophy


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A


lthough BUN and Creatinine are routine tests of kidney function,

their values start to abnormally increase only when more than 60% of kidney

function is impaired..!!

Thus, if kidney disease is suspected but standard blood tests (BUN and

Creatinine) are normal, more specific tests of kidney function should be

performed to assess the Glomerular filtration rate (GFR).

# Estimation of Glomerular Filtration Rate GFR

GFR is the volume (mL) of fluid filtered from the glomeruli into

Bowman's capsule per unit time (min).

Avg Normal Value: “100 ml/min” in average-sized (70kg).

GFR is directly proportional to number of intact nephrons.

GFR can be estimated by Clearance Tests.

Clearance Tests “Clearance” means the blood volume (ml) from which a marker substances is totally cleared in unit time (minute) “ml/min”

GFR = Clearance of a Substance =

(USubs/SSubs) x Urine flow rate (Urine Vol. (ml)/24 h

USubs = Conc. of the marker substance in Urine mg/dl

SSubs = Conc. of the marker substance in Plasma mg/dl

*Marker substance used to measure GFR may be Exogenous (e.g. Inulin) or

Endogenous (e.g. Creatinine)


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Ideal Marker for GFR Measurement:

Constant rate of production (endogenous) or of delivery (i.v.) (exogenous).

Freely filtered in the glomerulus i.e. no protein binding.

Metabolically inactive

No tubular reabsorption

No tubular secretion

Can be estimated in the Lab

Inulin Clearance

Inulin is a fructose polysaccharide that gives very accurate estimations

of GFR since it meets all the criteria mentioned above.

A loading dose of inulin can be administered iv, followed by a

sustaining infusion (usually for 3 hr)

Inulin concentration in urine and plasma is determined and hence

GFR can be calculated.

Inulin clearance is infrequently used in clinical lab.

Creatinine Clearance

♂ 95–135 mL/min

♀ 85–125 mL/min Children Lower values than adults

Creatinine clearance test is a more sensitive indicator of kidney

function than serum creatinine and BUN alone.

Creatinine clearance normally decreases with aging due to a decline in

the glomerular filtration rate (Above age 30 y, normal range decreases

6.5 ml/min every 1decade).


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G


Creatinine clearance test consists of 2 components:

I. 24 -hour urine sample to:

Determine Urinary creatinine (mg/dl)

Determine Urine flow rate (Urine volume/1440 min)

II. Blood sample to:

Determine Seum creatinine (mg/dl)

Creatinine Clearance (ml/min) =

Ucreat / Screat x Urine flow rate (Vol. /1440 min)

lomerular filtration membrane retains blood cells and large molecules.

Thus, the presence of RBCs and/or protein in the urine strongly suggest

a kidney disorder**

Hematuria

It is the presence of Red blood cells (RBCs) in urine detected by

microscopic examination of urine.

Proteinuria (Albuminuria)

It is the presence of protein (albumin) in urine. It can be detected by

several ways that differs in their accuracy:

- Dipsticks (qualitative)

- Microalbuminuria (MA) (Normal: < 30 mg/l)

- Albumin/Creatinine ratio (UACR)

UAlbumin mg/dl/Ucreat g/dl → (mg/g creatinine)

In contrast to the other detection methods, UACR is unaffected by urine

dilution and concentration and can be detected in random urine sample. Dr. Kakul Husain Firoz

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Urine Analysis

The urinalysis is a routine screening test which is usually done as a part of a

physical examination, during preoperative testing, and upon hospital admission. It is used in the diagnosis of infections of the kidneys and urinary tract and also in the diagnosis of diseases unrelated to the urinary system.

It involves 3 examinations:

Physical Exam.

Chemical Exam.

Microscopic Exam.

Physical Exam.

Appearance (Normal: Clear A)

Cloudy (turbid) B: bacteria and/or pyuria→UTI-urinary tract infection

Smoky C: red blood cells→ Hematuria “Crystalluria/renal calculi”

A B C


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Color (Normal: Light to amber yellow)

*Pale yellow (Polyuria) *Deep yellow (Oliguria) *Greenish yellow

(Bacterial infection or drugs)

Chemical Exam.

Urine Dipstick

Glucose

Bilirubin

Ketones

Specific Gravity

Blood

pH

Protein

Urobilinogen

Nitrite

Leukocyte Esterase


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Specific Gravity → Normal: 1.010–1.025

The specific gravity is a measure of the concentration of the urine

compared to the concentration of water, which is 1.000. The value of this test

is an indication of the kidney tubules ability to concentrate and excrete urine.

↓Sp.Gr (Diluted urine) → Causes include: High fluid intake, Diuretics,

ADH deficiency (diabetes insipidus), and Chronic pyelonephritis.

↑Sp.Gr (Concentrated urine) → Causes include: Fluid loss, DM, ↑ADH

and acute glomerulonephritis.

pH → Normal: Acidic

Alkaline → UTI and Chronic renal failure.

Protein → Normal: Nil (i.e. not found)

Proteinuria → renal dysfunction (e.g. glomerulonephritis)

“Detection of proteinuria (albuminuria) was previously mentioned page 12”

Microscopic Exam.

Red blood cells (Hematuria) → Urinary tract injury

Leukocytes (Pyuria) → Urinary tract infection

Crystals (Crystaluria) → Renal stone

The accumulation of certain substances in the urine leads to the formation

of crystals resulting in the formation of renal stones. For example, numerous

calcium oxalate crystals, resulting from hypercalcemia, may form calcium

oxalate stones.

Casts → Chronic renal disease

Casts are collections of gel-like protein material which result from the

agglutination of cells and cellular debris. They take the shape of the renal

tubules.

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Urine Pus Cells - Pyuria Urine RBCs - Hematuria

Urine Crystals – Crystalluria

Urinary crystals.

(A) Calcium oxalate crystals; (B) uric acid crystals; (C) triple phosphate

crystals with amorphous phosphates; (D) cystine crystals.


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Urine Casts

Red blood cell cast White blood cell cast

Urinary casts.

(A) Hyaline cast

(B) Erythrocyte cast

(C) Leukocyte cast

(D) Granular cast

kakulhusain @gmail.com

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