RENAL FUNCTIONS TESTS & RENAL

DISORDERS
Prepared by : Nermeen Zakaria

PB704/ BIOC 421

By the end of this chapter, we will be able to know:
1-Anatomy of Nephrons.
2 Functions of the Kidney.
3 The most significant Kidney functions tests and their
interpretation.
4 Most common kidney disorders.
5 Acute Renal Failure.
6 Chronic Renal Failure.
Anatomy:
The functional unit of the kidney is the Nephron. Each
kidney contains about one million nephrons.

The Kidney is bean shaped divided into lobes that consists

of: 1) outer cortex: It is composed of the glomeruli,
proximal and distal convoluted tubules.
2) The Medulla: which consists mainly of loop of Henle,
vasa recta (elongated vessels accompany the loop of
Henle) and collecting ducts. The urine is collected in the
pelvis, flow through the ureter that carry the urine
into the urinary bladder, where it is stored until emptied
through the urethra.
NEPHRON Structure:
1 The glomerulus: a capillary clump surrounded by the Bowman’s the
Bowman’s capsule. Each glomerulus is supplied
by an afferent arteriole carrying the blood in and
an efferent arteriole carrying the blood out.
2. The proximal convoluted tubule:
carries the Glomerular filtrate away from the
Bowman’s capsule.
3. Loop of Henle: composed of descending limb and
the ascending limb.
4. distal convoluted tubule: carries the filtrate from
loop of Henle to be drained in the collecting ducts.
5. The collecting ducts: collect urine draining from each Nephron.
Collecting ducts merge & empty their contents into the renal pelvis.
Main Functions of the Kidney
* Excretion: of unwanted materials from plasma (both waste and excess
products) through urine formation.
*Homeostasis: of water, electrolytes, acid-base balance status, and regulation
of blood ions concentration and pH.

* Endocrine Function and Participation in hormonal regulation: by producing

number of hormones (EPO, calcitriol, and rennin), and being controlled by
other hormones as vasopressin (AVP), aldosterone, and parathyroid hormones.
Homeostatic function of the Kidney:
• Water is the main component of all body fluids making up to 75% of the
total body weight.
• Solutes include: 1) electrolytes as: inorganic salts, all acids and bases and
some proteins. 2) Non-electrolytes: as glucose, lipids creatine, and urea.
*Extracellular Fluids (ECF): sodium is the main cation, and chloride is the main
anion.
*Intracellular Fluids (ECF): potassium is the main cation, and phosphate is the
main anion.
**The kidney is highly sensitive to any disturbance in this balance and
responds quickly to maintain homeostasis (reabsorption, retention,
excretion).
Homeostasis maintenance by kidney regulation
Endocrine Function and hormonal regulation:
1 Hormones produced by the Kidney
a) Erythropoietin:
It is a peptide hormone that acts on bone marrow for the production of RBCS.
It is stimulated by bleeding or moving to high altitudes.
b) Renin:
It catalyzes the formation of Angiotensin I from angiotensinogen. Angiotesin I is
converted to Angiotensin II , by the action of Angiotensin converting enzyme (ACE),
which stimulates aldosterone hormone synthesis by the adrenal cortex leading to
increased s o d i u m r e a b s o r p t i o n a n d i n c r e a s e d blood pressure through
cascades of stimulus.

c) Calcitriol:
It is the active form of Vitamin D (Vitamin D3) , which is derived from calciferol. It is
converted into the active form in 2 steps: in the liver and then in the kidney.
Endocrine Function and hormonal regulation:
2 Hormones produced by other endocrine glands and act on the
kidney
a) Vasopressin (AVP): It is also called anti-diuretic
hormone (ADH), which is secreted from the posterior lobe of the pituitary
gland. It acts on collecting ducts to stimulate water reabsorption through
different mechanisms: i) reduction of water output of the kidney, ii)
decrease Glomular filtration rate, iii) Increase permeability to water by
increase water reabsorption through making the collecting ducts cells
porous or permeable to water.
b) Parathyroid Hormone: Promotes tubular reabsorption of calcium,
phosphate excretion, and the synthesis of calcitriol, which regulates
calcium absorption by the gut.
Excretory Function and urine formation:
Urine formation occurs through three steps in the Nephron:

1. Glomerular filtration: It is the first step in urine formation. About 25% of the cardiac
output received by the kidneys .The blood passes through the glomerulus is filtered out.
The glomerular filtrate has the same composition of the blood without most of the
proteins more than about 63 KDa and cells (macromolecules).
2. Selective Tubular reabsorption: Occurs in proximal tubules, to remove useful solutes
from the filtrate and return them back to circulation.
* Useful solutes subjected to reabsorption : glucose,
sodium (80% reabsorbed), Potassium (80% reabsorbed), Bicarbonates, Phosphates
, amino acids, water and chloride.
Excretory Function and urine formation: continued
3. Tubular secretion: Removes additional wastes from the blood through the
peritubular capillaries and add them to the filtrate. The urine is
concentrated by increasing the concentration of waste elements.
4. Collecting ducts: Urine is then collected in the collecting ducts to be drained as
described previously.
 Urine analysis evaluation:
Urine analysis involves the assessment of urine by physical observation, chemical and
microscopic examination.
1. Physical examination-
• Normal urine output – 800-2000 ml/day
• Anuria and oliguria can be because of various conditions like, diminished perfusion of kidney
due to diminished blood volume, renal diseases like tubular necrosis, pre-renal obstruction.
• Anuria - <100 ml/day
• Oliguria - <400 ml/day
• Polyuria - >2000 ml/day
• Polyuria can be caused by various conditions like glucosuria in diabetes mellitus, ADH
deficiency in diabetes insipidus.
Urine analysis evaluation:
Color of urine-
• Normally urine is Amber yellow in color.
• Hematuria or hemoglobinuria may result in dark brown colored urine.
• Pyuria, pale or turbid urine is due to infections.
• Dark yellow colored urine may be due to Jaundice, intake of B complex
vitamins or reduced intake of water (less than 2 liters/day)

pH of urine – It is usually acidic pH6 (4.5-8-pH )

specific gravity – Normally varies from 1.016 to 1.025

Osmolality –
On average fluid intake, it ranges from 300 to 900 mosmol/kg

Odour – Foul smell indicates bacterial infection

Renal Functions evaluation:
Signs and symptoms related to kidney problems are:

• Blood in urine (reddish urine)

• Lethargy and weakness.
• Dry and itching skin.
• Increase urge to urinate (specially at night)
• Foamy urine (due to presence of protein in urine)
• Persistent puffiness of body ( especially around eyes)
• Poor appetite.
• Muscles cramping.
• Discomfort during urination.

Co-morbidities such as diabetes and hypertension usually cause chronic kidney diseases
over a long term so it is important to screen the kidney functions.
Renal Functions Tests:
1) Glomerular filtration rate (GFR) and, Glomerular integrity:
- Inulin
Clearance (Exogenous marker)
- Creatinine Clearance
- Serum creatinine and urea
- BUN (Blood Urea Nitrogen)
- ** Glomerular Integrity : Proteinuria detection.

II) Renal tubular function: About 180 liters of fluid passes into glomerular filtrate
daily, and more than 99% is recovered. Water, glucose, sodium, glucose & amino acids should be
reabsorbed.
-Concentration test (osmolality test).
-The water deprivation test.
-Vasopressin test (ADH).
-Glucosuria test.
-Proteinuria and -Aminoaciduria.
A) GFR Tests
Glomerular filtration rate (GFR) is defined as: the volume of plasma which is
filtered by the glomeruli per unit time (ml/min ≈ 125-140 ml/min).

GFR is usually constant. However, some variables can affect the

physiological GFR such as: the body size, muscle mass (higher in males), age
(decrease in elderly individuals), renal blood flow and pressure, protein
intake and obesity.

ANP (Atrial natriuretic peptide): is a hormone that is produced in the

heart and whose secretion increases in response to increased plasma
volume. ANP promotes natriuresis (increased sodium excretion), increases
GFR, decreases Na+ reabsorption.
 GFR Tests
Clearance is defined by: the volume of plasma which is cleared from a
given substance per unit time (ml/min.).
For accurate evaluation of GFR, It is very important to select a substance that
is completely filtered by the glomerulus from the blood and is not
excreted, reabsorbed or metabolized by the renal tubules.
GFR is Reduced in cases such as: * low blood pressure,
hemorrhage, dehydration or cardiac failure, renal artery stenosis (pre-renal
uremia).
*obstruction in the urinary tract: stones, tumors of urinary bladder or prostatic
enlargement (Post-renal uremia).
Glomerulonephritis: (damage in the glomerulus).

**GFR is Increased cases such as: Hypoproteinemia, High blood pressure.

 Methods of GFR estimation:
1.Inulin Clearance
Inulin is a plant polysaccharide that is used as an exogenous marker for
estimating GFR, because it is not metabolized nor reabsorbed by the
tubules, therefore the excreted inulin is equal to the injected.
The test is done by infusion of known amount of inulin into the blood.
Then the urine is collected through 24 hours.

2- Creatinine Clearance (Endogenous marker):

It is the golden standard to measure GFR.
3. Serum creatinine and urea concentration : less sensitive measures of
GFR:
*GFR often must fall to its half normal value, before clinically rise in the serum
creatinine and urea is detected.
*Serum creatinine is increased with age and body size (Cockroft-Gault
formula), while it is decreased by starvation, after surgery or increased
corticosteroids.
*Serum urea: about 40% of the urea is reabsorbed in the tubules, and its
concentration is affected by protein intake, severe liver disease, infection, surgery,
and trauma.
Also , urea clearance is highly dependent on urine flow, it is increased in hydrated
flow (high urine flow rate), and decreased in dehydrated state (urine flow is low).
4. BUN (Blood Urea Nitrogen)
Catabolism of proteins and nucleic acids, results in the formation of
what is known as: non- protein nitrogenous compounds.
The BUN test measures the amount of nitrogen in the blood.
A normal BUN: 6 - 20 mg/dL.
A high BUN value may be caused by:
-kidney disease.
-Blockage of the urinary tract. (kidney stone or tumor)
-Dehydration or heart failure.
-High-protein diet, tissue damage (such as from severe burns), or from bleeding
in the gastrointestinal tract.
A low BUN value : Very low protein diet, malnutrition, or severe liver damage.
B. Glomerular integrity tests (proteinuria):
The glomerular membrane does not allow passage of albumin and
macromolecules. (large proteins).
However, small amounts of albumin less than 25 mg/24 hours is found in urine.
If larger amount are detected, this means significant damage to the glomerular
membrane has been occurred.
Excess protein in urine (Proteinuria) indicates significant damage to the
glomerular membrane or insufficient reabsorption.

* Presence of RBCs in urine is strongly suggest glomerular integrity problem.

*Damaged nephrons results from Diabetes may develop proteinuria (increase
excretion).
 Renal Tubular Functions:
1. Concentration test (specific gravity):
The main function of the kidney is to concentrate the urine with waste products and excrete
them. If the tubules and collecting ducts are working efficiently, they will be able to reabsorb
water and to concentrate the urine.
Osmolality of the serum: is the measurement of the osmotic concentration of serum
electrolytes, glucose, ketone bodies and urea.
Osmolality (mmol/L)= 2X(Na+) + (urea) + (glucose)
Osmolality should be measured in urine and serum and the results compared, in addition to
the ratio between them.
Interpretation of the results:

* Urine/serum ratio: the ratio in normal individual should be 3 or above; which means that
the urine is more concentrated than the serum.
 Renal Tubular Functions:
* However if the ratio is 1 or less, this means that the renal tubules are not reabsorbing
water efficiently, leading to polyuria due to one of the following: 1) primary polydipsia
(increased water intake, due to dry mouth sensation. It is mainly due to mental disorder as
schizophrenia.
2) increased osmotic load due to diabetes mellitus.
3) Diabetes insipidus (nephrogenic DI) : Defective ADH receptors or receptor binding
mechanism or inability of the kidney to respond to ADH.
4) hypercalcemia, and finally 4) renal failure.

So Differential diagnosis of polyuria is done by the following laboratory tests:

Blood glucose: if it is high so, polyuria is due to D.M.
Plasma creatinine: if high, therefore, polyuria is due to renal failure.
Serum calcium: if high so, the polyuria is due to hypercalcemia.
*
IF the above mentioned three tests are normal, so, the polyuria is may be due to diabetes
insipidus (DI), or primary polydipsia. Differential diagnosis is then done by water
deprivation test.
 Renal Tubular Functions:
2- Water deprivation test: Normally: response to water deprivation is water
retention, which decreases plasma osmolality.
Test Procedure:
- allow fluids intake overnight and then light breakfast in the morning with no
fluids intake, and no smoking.
For the next 8 hours, no fluids are allowed. Urine is collected at this period every
2 hours.After 8 hours, blood sample is collected and the patient is allowed to
drink, and osmolality is measured in serum and urine.

Interpretation : *If the urine: serum osmolality ratio of 2 or above, &

serum osmolality > 600 mmol/kg:This indicates primary polydipsia.
*If urine to serum ratio ranges from 0.2 to 0.7 & serum osmolality is
less than 300 mmol/kg, this indicates Diabetes insipidus (DI). So,
Vasopressin test should be done.
 Renal Tubular Functions:
3.Vasopressin (ADH) test:
Defects in concentrating urine is a feature of tubular disorders such as:
nephrogenic diabetes insipidus or central diabetes insipidus.

4.Glucosuria test:
Glucose is reabsorbed by the renal tubules and normally urine contains no
glucose.
If blood glucose level is normal and there is (glucosuria), this indicates inability of
tubules to reabsorb glucose: Fanconi syndrome, which is characterized by:
polyuria, polydipsia, dehydration, acidosis, and hypokalemia and renal glucosuria.
 Renal Tubular Functions:
5.Proteinuria tests:
In this test, the first morning urine specimen is used.
*Albumin/Creatinine ratio is detected or specific proteins tests in 24 hours
urine).
• ** Specific proteins that indicate renal tubular dysfunction are: ß2
macroglobulin and ɑ1 micro globulins.
• because they are small proteins which are filtered at the glomeruli and
reabsorbed by the tubular cells.Therefore, increase in their urine
concentrations is a sensitive indicator of renal tubular cell damage.

6. Aminoaciduria:
Amino acids are normally reabsorbed. Detection of aminoaciduria indicates failure
of normal tubular reabsorption, which may be due to : inherited metabolic
disorder, cystinuria, or acquired renal damage.
RENAL FAILURE:
It is the loss or cessation of the kidney function.
*Acute Renal Failure (ARF):
It is a sudden failure of the kidney function over a period of hours or days, and the normal
renal function may be regained, when the causes have been treated. It is also defined as a
reduction in GFR sufficient to impair the homeostatic functions of the kidney
Clinical findings:
1.GFR: decreases by 25% or more in children & young people in the past 7 days.
2-Increased levels of serum urea and creatinine.
3-Oligouria: Urine output decreases to less than 0.5 mL/kg/hour for more than 6
hours in adults & more than 8 hours in children and young people.
Less than 400 ml/24 hour urine.
4- Metabolic acidosis: due to failure of the kidney to excrete hydrogen ions.
5-Hyperkalemia: (potassium retention).
6- Hyponatremia:This is due to decrease in water excretion and increase in
water intake.
RENAL FAILURE:
*Acute Renal Failure (ARF):Types:
1 Pre-renal:
The kidney fails to receive proper blood supply,
due to severe hypotension, reduced cardiac output,
decrease in blood volume due to hemorrhage,
prolonged vomiting, or diarrhea.
All these clinical disorders lead to decrease in GFR.
2 Post-renal:
Due to Obstructed urine flow.The obstruction
may be in the urethera, bladder, renal stones,
enlarged prostate.

3 Integral renal failure: Intrinsic damage to

the kidney tissues.
RENAL FAILURE:
*Acute Renal Failure (ARF):
Acute RENAL FAILURE:
Diagnosis:
1- Serum and urea creatinine increased. 2-Decreased GFR 3.Metabolic acidosis.
4.Hyperkalemia:The fastest to appear in ARF.
5.Kidney Biomarkers: elevated within hours of the event: NGAL (neutrophil
gelatinase-associated lipocalin) and KIM-1 (kidney injury molecule).

Treatment: 1-Correction of pre-renal factors, if present.

2-Care should be taken that the patient does not become fluid overloaded.
• 3-Treatment of the underlying disease (e.g. to control infection).
• Biochemical monitoring: body fluid volume, Serum creatinine and Potassium
should be monitored closely.
• Dialysis: Is needed only in cases of a rapidly rising serum potassium
concentration, severe acidosis and fluid overload.
RENAL FAILURE:
*Chronic Renal Failure (CRF):
CRF develops over more than 3 months and persists as a progressive irreversible
destruction of kidney tissues.
If not treated by dialysis or transplant, it will result in death of the patient.

*loss of the nephrons functions lead to major effects of the renal failure.
CRF is identified when complications occurs as a result of CRF, such as:
cardiovascular diseases, anemia, decreased ability of kidney to excrete wastes and
appearance of proteins and/or RBCs in the urine.

** Blood tests and renal biopsy are used to classify the severity of the CRF which
are classified from stage 1 to stage 5.
Stages of Chronic Renal Failure:
Clinical Findings in CRF:
1 High serum creatinine and proteinuria.
2- Increased blood pressure: (Aldosterone-renin- angiotensin system)
increasing the risk of developing heart failure.
3. Impairment in glucose and amino acids reabsorption, and hence, decrease their
concentrations in the blood.
4. Hyperkalemia with potentially fatal cardiac arrhythmias.
5. Anemia due to impaired failure of erythropoietin synthesis by the kidney.
6. Hyperphosphatemia due to decreased excretion of phosphate
(phosphate retention) that inhibits production of vitamin D3(active form) leading to
hypocalcemia that may progress due to hyperparathyroidism.

*If these changes are not prevented they will lead to renal osteodystrophy (metabolic bone
disease) and vascular calcification leading to impaired cardiac function.
7. Metabolic acidosis: due to mainly retention of hydrogen ions.
Complications of Chronic Renal Failure:
 Uremia : azotemia with symptoms or signs of renal failure and
biochemical abnormalities: fatigue, nausea, anorexia,
 pruritis, altered taste sensation, hiccups.
 Metabolic and endocrine alterations
 anemia, malnutrition, change in plasma level of PTH,
insulin,glucagon, sex hormone, prolactin.
 Renal osteodystrophy, uremic gastroenteritis, carditis, peripheral
neuropathy, dermatological changes.
Chronic RENAL FAILURE:

* uremic frost
Management:
The goal is to slow down the progress of CKD to stage 5 by controlling all
the consequences of the CRF.

Renal replacement therapy: either dialysis or kidney

transplantation ( However, in kidney transplantation, patients need to take
long term immune suppression drug as cyclosporine which is
nephrotoxic at high concentration so, monitoring of both creatinine and
cyclosporine is necessary).
Thank You