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Nephrogenic diabetes insipidus

Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine. DI is caused by a deficiency of antidiuretic hormone, or by an insensitivity of the kidneys to that hormone. more...

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Signs and symptoms

Excessive urination and extreme thirst (especially for cold water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of severely deranged diabetes mellitus, with the distinction that the urine is not sweet and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. However, there is a continuous risk of dehydration.


In order to distinguish DI from other causes of excess urination, blood glucose, bicarbonate and calcium need to be tested. Electrolytes can show substantial derangement; hypernatremia (excess sodium levels) are common in severe cases. Urinalysis shows low electrolyte levels, and measurement of urine osmolarity (or specific gravity) is generally low.

A fluid deprivation test helps determine whether DI is caused by:

  1. excessive intake of fluid
  2. a defect in ADH production
  3. a defect in the kidneys' response to ADH

This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.

To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in central DI. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.

If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma) is affecting pituitary function.


Electrolyte and volume homeostasis is a complex mechanism that balances the body's requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.

The regulation of urine production is the hypothalamus, which produces antidiuretic hormone (ADH or vasopressin) in the posterior lobe of the pituitary gland. In addition, it regulates the sensation of thirst as perceived by the cortex.


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From Gale Encyclopedia of Medicine, 4/6/01 by Maureen Haggerty


Urinalysis is a diagnostic physical, chemical, and microscopic examination of a urine sample (specimen). Specimens can be obtained by normal emptying of the bladder (voiding) or by a hospital procedure called catheterization.


Urinalyses are performed for several reasons:

  • General evaluation of health.
  • Diagnosis of metabolic or systemic diseases that affect kidney function.
  • Diagnosis of endocrine disorders. Twenty-four-hour urine studies are often ordered for these tests.
  • Diagnosis of diseases or disorders of the kidneys or urinary tract.
  • Monitoring of patients with diabetes.
  • Testing for pregnancy.
  • Screening for drug abuse.


Voided specimens

Urinalysis should not be performed while a woman is menstruating or having a vaginal discharge. A woman who must have a urinalysis while she has a vaginal discharge or is having her period should insert a fresh tampon before beginning the test. She should also hold a piece of clean material over the entrance to her vagina to avoid contaminating the specimen.

Patients do not have to fast or change their food intake before a urine test. They should, however, avoid intense athletic training or heavy physical work before the test because it may result in small amounts of blood in the urine.

The following drugs can affect urinalysis results. The patient may be asked to stop taking them until after the test:

  • Nitrofurantoin (Macrodantin, Furadantin). Nitrofurantoin is prescribed for infections of the urinary tract and other bacterial infections.
  • Phenazopyridine (Pyridium). This medication is used to relieve burning and pain caused by urinary-tract infections.
  • Rifampin (Rifadin). This medication is prescribed to treat tuberculosis, prevent the spread of meningitis, and treat other infections.

Bladder catheterization

Bladder catheterization is sometimes used to collect urine samples from hospitalized patients. It should not, however, be used to collect specimens from males with acute inflammation of the prostate or from a patient of either sex with a fractured pelvis.


Collecting a urine sample from emptying the bladder takes about two or three minutes. The sample can be collected at home as well as in a doctor's office. Urine specimens are usually collected early in the morning before breakfast. Urine collected eight hours after eating and at least six hours after the most recent urination is more likely to indicate abnormalities. Some people may be asked to void into a clean container before getting out of bed in the morning.

Specimen containers

The doctor or hospital will supply a sterile container for a specimen being collected for a colony count. A colony count is a test that detects bacteria in urine that has been cultured for 24-48 hours. It is used instead of a routine urinalysis when a patient's symptoms suggest a urinary tract infection. Nonsterile containers can be used for routine specimens that will not be tested immediately after being collected. An ordinary open-necked jar may be used after it and its lid have been soaked in very hot water for 15-20 minutes and then air-dried.

Laboratory procedures


Urine specimens should not remain unrefrigerated for longer than two hours. A urine specimen that cannot be delivered to a laboratory within two hours should be stored in a refrigerator. The reason for this precaution is that urine samples undergo chemical changes at room temperature. Blood cells begin to dissolve and the urine loses its acidity.

Visual examination

A doctor, nurse, or laboratory technician will look at the specimen to see if the urine is red, cloudy, or looks unusual in any way. He or she will also note any unusual odor.

Testing techniques

Urine samples are tested with a variety of different instruments and techniques. Some tests use dipsticks, which are thin strips of plastic that change color in the presence of specific substances. Dipsticks can be used to measure the acidity of the urine (its pH) or the presence of blood, protein, sugar, or substances produced during the breakdown of fatty acids (ketones). A urinometer is used to compare the density of the urine specimen with the density of plain water. This measurement is called specific gravity.

The urine specimen is also examined under a microscope to determine whether it contains blood cells, crystals, or small pieces of fibrous material (casts).


Voided specimens

Most urine specimens from adults or older children are collected by the patient's voiding into a suitable container. Soaps and disinfectants may contaminate urine specimens and should not be used. The doctor or laboratory may supply a special antiseptic solution that won't irritate the skin. The method for collection varies somewhat according to age and sex.

Women and girls

Before collecting a urine sample, a woman or girl should use a clean cotton ball moistened with lukewarm water to cleanse the external genital area. Gently separating the folded skin (labia) on either side of her vagina, she should move the cotton ball from the front of the area to the back. After repeating this process several times, using a fresh piece of cotton each time, she should dry the area with a clean towel.

To prevent menstrual blood, vaginal discharge, or germs from the external genitalia from contaminating the specimen, a woman or girl should release some urine before she begins to collect her sample. A urine specimen obtained this way is called a midstream clean catch.

Men and boys

A man or boy should use a piece of clean cotton, moistened with antiseptic, to cleanse the head of his penis and the passage through which urine leaves his body (the urethral meatus). He should draw back his foreskin if he has not been circumcised. He should move the cotton in a circular motion away from the urinary opening, using a fresh piece of cotton each time. After repeating this process several times, he should use a fresh piece of cotton to remove the antiseptic. After the area has been thoroughly cleansed, he should begin urinating and collect a small sample in a container without interrupting the stream of urine.


A parent, nurse, or doctor should cleanse the child's genitals and as much of the surrounding area as will fit into the sterile urine-collection bag provided by the hospital. When the area has been thoroughly cleansed, the bag should be attached to the child's genital area and left in place until the child has urinated. It is important to remember not to touch the inside of the bag and to remove it as soon as a specimen has been obtained.

Bladder catheterization

Bladder catheterization is a hospital procedure used to collect uncontaminated urine when the patient cannot void. A catheter is a thin flexible tube that the doctor inserts through the urethra into the bladder to allow urine to flow out. To minimize the risk of infecting the patient's bladder with bacteria, many doctors use a so-called Robinson catheter, which is a plain rubber or latex tube that is removed as soon as the specimen is collected.

Suprapubic bladder aspiration is a technique that is sometimes used to collect urine from infants younger than six months. The doctor withdraws urine from the bladder into a syringe through a needle inserted through the skin over the bladder. This technique is used only when the child cannot void because of an abnormal urethra or if he or she has a urinary tract infection that has not responded to treatment.


The patient may return to normal activities after collecting the sample and may start taking medications that were discontinued before the test.


There are no risks associated with voided specimens. The risk of bladder infection from catheterization with a Robinson catheter is about 3%.

Normal results

Contents and appearance

Normal urine is a clear straw-colored liquid. It has a slight odor. It contains some crystals, a small number of cells from the tissues that line the bladder, and transparent (hyaline) casts. Normal urine does not contain sugars, yeast cells, protein, ketones, bacteria, or parasitic organisms.

The time of day a urine sample is collected can make a difference in the appearance of the specimen. Some foods and medicines, including red beets, asparagus, and penicillin, can affect the color or smell of urine. Although most color variations are harmless, they sometimes indicate the presence of serious disease. A doctor, nurse, or laboratory technician should be notified if the urine is red or cloudy or looks unusual in any way.


The pH of normal urine is 4.5-8.0. Its specific gravity is 1.0005-1.035.

Abnormal results


Urine may be cloudy (turbid) because it contains red or white blood cells, bacteria, fat, mucus, digestive fluid (chyle), or pus from a bladder or kidney infection.


Foul-smelling urine is a common symptom of urinary-tract infection. A fruity odor is associated with diabetes mellitus, starvation and dehydration, or ketone formation. Other distinctive odors are present in the urine of patients with maple syrup urine disease or phenylketonuria (PKU).

Specific gravity

The specific gravity of urine can be affected by a range of diseases and disorders. Low specific gravity (below 1.005) is associated with diabetes insipidus, nephrogenic diabetes insipidus, acute tubular necrosis, and inflammation of the upper urinary tract (pyelonephritis). In fixed specific gravity, the specific gravity of the urine remains at 1.010 no matter how much fluid the person drinks. This condition occurs in patients who have chronic inflammation of the small blood vessels in the kidneys (glomerulonephritis) and serious kidney damage. High specific gravity (above 1.035) occurs in patients who are in shock or who suffer from nephrotic syndrome, dehydration, acute glomerulonephritis, congestive heart failure, or liver failure.


A pH factor greater than 7 (more alkaline) may result from Fanconi's syndrome, urinary tract infections, or metabolic or respiratory alkalosis. A pH factor below 7 (more acid) may be due to fever, PKU, the secretion of homogentisic acid in the urine (alkaptonuria), and acidosis.

Blood and tissue cells

Red blood cells in the urine can be due to vigorous exercise or exposure to toxic chemicals. Bloody urine can also be a sign of bleeding in the genitourinary tract as a result of systemic bleeding disorders, various kidney diseases, bacterial infections, parasitic infections including malaria, obstructions in the urinary tract, scurvy, subacute bacterial endocarditis, traumatic injuries, and tumors.

A high number of white blood cells in the urine is usually a symptom of urinary tract infection. A large number of cells from tissue lining (epithelial cells) can indicate damage to the small tubes that carry material into and out of the kidneys.


Casts are small fibrous objects that are formed when protein and other materials settle in the kidney tubules and collecting ducts. Casts are dislodged by normal urine flow. A large number of them in a urine specimen is a sign of kidney disease.


There are several different chemicals in body fluids that can form crystals that appear in urine. Some of these appear in normal urine, such as calcium oxalate or uric acid crystals. A large number of calcium oxalate crystals, however, may be a sign of abnormally high levels of calcium in the blood (hypercalcemia). Other crystals, including tyrosine, leucine, and cholesterol, are abnormal. The presence of cystine crystals is a symptom of excessive urinary secretion of cystine (cystinuria). Cystine is an acid found in many proteins and normally reabsorbed by the kidney tubules.


Protein in the urine can be a symptom of kidney stones, inflammation of the kidneys, degenerative kidney disease, or multiple tumors.


A high level of glucose and other sugars in the urine (glycosuria) is often a symptom of diabetes mellitus. Glycosuria can also be caused by advanced kidney disease, Cushing's syndrome, impaired tubular reabsorption, shock, a rare tumor of the adrenal gland (pheochromocytoma), or cancer of the pancreas.

Milk in the urine is normal if a woman is pregnant, has just given birth, or is breastfeeding. On the other hand, rare hereditary metabolic disorders are indicated when urine contains fruit sugar (fructose), milk sugar (galactose), or a simple sugar called pentose.


The presence of abnormally high numbers of ketones in the urine (ketonuria) usually results from uncontrolled diabetes mellitus. Ketonuria can also be caused by prolonged diarrhea or vomiting that results in starvation.


Bilirubin is an orange-yellow pigment found in bile, a fluid secreted by the liver. When it is found in urine, bilirubin may be a symptom of liver disease caused by the formation of fibrous tissue, medications that damage the liver, or obstructive jaundice.


Bacteria in the small intestine can convert bilirubin to urobilinogen, which is excreted in the feces, in bile, or in urine. An accumulation of urobilinogen in the urine may be a sign of severe infection, liver damage, or diseases that destroy red blood cells. Low levels of urobilinogen in the urine may be a result of antimicrobial therapy, inflammatory diseases, kidney disease, severe diarrhea, or blocked bile ducts.

Other findings

The presence of bacteria, parasites, or yeast cells in the urine may be a symptom of urinary tract infection or contamination of the external genitalia. Other factors that may affect urinalysis results include failure to collect a specimen during the day's first voiding; frequent urination; large dietary intake of vitamin C; and urine with a pH value lower than 6.

Key Terms

A condition of the blood in which bicarbonate levels are below normal.
A condition of the blood and other body fluids in which bicarbonate levels are higher than normal.
Small fibrous objects formed from materials that collect in the kidney tubules and are washed out by normal urine flow.
A thin flexible tube inserted through the urethra into the bladder to allow urine to flow out.
Clean catch specimen
A urine specimen that is collected from the middle of the urine stream after the first part of the flow has been voided.
Colony count
A measurement of the growth of bacteria in a urine sample that has been cultured for 24 to 48 hours.
Fanconi's syndrome
A rare disorder caused by vitamin D deficiency or exposure to heavy metals.
Substances produced during the breakdown of fatty acids. They are produced in excessive amounts in diabetes and certain other abnormal conditions.
Nephrotic syndrome
A condition characterized by water retention, little or no protein in urine, and high blood cholesterol.
A chemical symbol used to describe the acidity or alkalinity of a fluid, ranging from 0 (more acid) to 14 (more alkaline).
The duct that carries urine from the bladder to the outside of the body.

Urinalysis (plural, urinalyses)
The diagnostic testing of a urine sample.
Another word for emptying the bladder or urinating.

Further Reading

For Your Information


  • "Laboratory Diagnosis: Urine Studies." In Clinician's Pocket Reference, edited by Leonard G. Gomella. Norwalk, CT: Appleton & Lange, 1993.


  • American Association of Kidney Patients. 100 S. Ashley Drive, Suite 280, Tampa, FL 33260. (800)749-2257.
  • American Kidney Fund. 6110 Executive Blvd., Suite 1010, Rockville, MD 20852. (301)881-3052.
  • National Kidney and Urologic Diseases Information Clearinghouse. 3 Information Way, Bethesda, MD 20892-3580.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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