Urinalysis

The kidneys of an adult produce an average of 1-1.5 liters of urine daily, also known as urine. In this way, the fluid balance of the body is regulated. Furthermore, metabolic end products are excreted with the urine, such as urea or uric acid.Urine volume: normally, urine excretion is between 500 and 3,000 ml per day. Oliguria describes decreased urine output with a daily maximum of 500 ml. Anuria is the absence of urine excretion (maximum 100 ml/24 h). The color of urine depends on the amount of drinking and nutrition. A large amount of drinking causes the urine to be of a light water-like color. A small amount of drinking makes the urine dark to yellow-brown in color. Even a normal urine becomes slightly darker when standing. Discoloration is usually caused by specific foods (e.g., red beets (betanidin), rhubarb (anthrone derivatives), blackberries, food dyes (e.g. aniline) or drugs (chloroquine, deferoxamine, ibuprofen, imipenem/cliastatin, metronidazole, nitrofurantoin, rifampicin, phenophthalein, phenothiazines, phenytoin).A purple discoloration of the urine is present in “purple urine bag syndrome” (PUBS). This is due to a bacterial metabolite, which should be considered as an indication of a urinary tract infection and treated accordingly. Urinary turbidity (urine cloudiness) is usually harmless. These are usually salts in the urine that are soluble in fresh urine and precipitate in the cooling urine. Other causes of cloudy urine include pus (pyuria) and calcium phosphates in alkaline urine (phosphaturia). Urine odor (urine odor): Fresh urine is normally almost odorless, while stale urine takes on the pungent odor of ammonia due to bacterial transformation processes. A deviant, unusual urine odor may indicate metabolic disorders (e.g., diabetes mellitus; congenital disorders of amino acid and lipid metabolism). In severe diabetes mellitus, urine may smell of acetone; this is caused by ketoacidosis (keto bodies in the blood). Furthermore, acute diseases (e.g. fever, infections), food (e.g. asparagus, fish), medications and toxins (e.g. solvents) can lead to urine with atypical odor. Urine odor and possible causes

Urine odor	Active substance	Cause
alcoholic	various	food, urinary tract infection
Chemical	diverse	Medication
fecal	Indole, Skatole	Urinary tract infection, vesicointestinal fistula
putrid	cadaverine, choline, putrescine	Necrotizing tumor in genitourinary tract, food, drugs.
Fishy	Trimethylamine	Trimethylaminuria, bacterial infection
Musty	Phenylketones	Phenylketonuria (PKU)
Lindenblossom	Aminoacetophenone	Urinary tract infection
Sweetish	Ketone	Ketoacidosis, febrile infection, food restriction.
pungent-biting	Ammonia	Urinary tract infection, liver failure, dehydration.

Indications (areas of application)

Some diseases may affect the composition of urine. Examination of the urine provides information about:

• Condition of the kidneys as well as the urethra, ureters, and urinary bladder – e.g., acute and chronic renal failure, acute renal failure, nephrotic syndrome, injury
• Infections of the urethra (urethritis), urinary bladder (cystitis) and kidneys (glomerulonephritis, pyelonephritis).
• Kidney stone disease (urolithiasis).
• Tumors of the urinary tract – both benign and malignant neoplasms.
• Changes in urine composition as an indication of metabolic disease,
• Acid-base therapy due tolatent metabolic acidosis (metabolic acidosis).
• Diabetes mellitus (increased glucose content).
• Consumption of medicines, drugs, doping substances, etc.
• Environmental pollution

The process

Based on a urine sample, the following parameters are determined:

• PH value of the urine
• Protein content (protein content)
• Sugar content (glucose content)
• Nitrite content
• Bilirubin
• Ketones
• Urine sediment (urinary sediment)
• Bacteria

Each of these parameters provides information about any changes or diseases that may be present.

Urine collection

The following is the description of urine collection with the aim of reducing contamination/impurities. For biochemical analysis, the first morning urine is the most appropriate and the second morning urine is the most practical for ambulation:

• For an examination of urine sediment or urine culture: obtaining midstream (= midstream urine); preparatory measures:
  • Infants/toddlers:
    • “clean-catch” urine, i.e., the child is held on the lap with genitals exposed and spontaneous micturition (urination) is awaited. The urine is collected with a sterile container.
    • Catheter urine or
    • Urine by bladder puncture (suprapubic bladder puncture).
  • Woman:
    • Spreading of the labia (labia majora)
    • Careful cleaning of the meatus urethrae (outer mouth of the urethra) with water.
  • Man:
    • Careful cleaning of the glans penis (“glans”) with water.
• For an orientational urine examination (e.g., by means of test strips), cleaning of the introitus vaginae (vaginal entrance) or glans penis can be omitted.

Implementation of a three-glass sample (synonym: 3-glass sample):

• First jet urine (conclusions about germ infestation of the urethra).
• Middle jet urine (if germ detection positive, then the germ colonization has reached the urinary bladder).
• Terminal jet urine (after careful prostate massage; indication of germ status in the prostate).

Urine pH

Urine pH values in the pH daily profile (at least four measurements throughout the day) are usually between 4.5 and 8.0. Urine pH values are in the acidic range (lower) for meat diets and alkaline range (higher) for plant-based diets. Urine is slightly alkaline after lunch and acidic after midnight. Urine collected two hours after a large meal or left at room temperature for several hours tends to be alkaline. Urine pH values are characteristic in some specific clinical situations:

• Urine pH values > 7.0 in the pH daily profile = indication of a urinary tract infection (risk of infection stone formation).
• Urine pH values constantly < 6 in the pH daily profile = “acidity of urine.” [favors cocrystallation of uric acid and calcium oxalate].
• Urine pH values constant > 5.8 in the pH daily profile = indication of an underlying renal tubular acidosis (RTA), provided that a urinary tract infection is excluded

Protein content (protein level)

Under normal circumstances, protein (protein) is filtered out by the filtering apparatus of the kidney and is therefore not detectable in the urine, or only in very small amounts. However, if disorders occur, proteinuria (increased excretion of protein in the urine) can be detected. The protein test field reacts mainly to negatively charged proteins such as albumin. Microalbuminuria cannot be detected by the conventional test strips, as they only react to protein concentrations of 100 to 300 mg/liter and above. Caution. The extent and pattern of proteinuria cannot be assessed solely on the basis of a urine test strip. In such cases, quantification (total protein in urine) and differentiation (qualitative urine protein differentiation) are always required. Proteinuria is considered an independent progression factor (factor for progression) of renal insufficiency (kidney weakness). Accordingly, it indicates diseases with renal damage:

• Chronic glomerulonephritis – bilateral inflammation of the kidneys in which the renal corpuscles (glomerules) are affected first.
• Diabetes mellitus
• Gouty kidney
• Nephrotic syndrome – collective term for symptoms that occur in various diseases of the glomerulus (renal corpuscles); symptoms include: Proteinuria (excretion of protein in the urine) with a protein loss of more than 1 g/m²/body surface per day; Hypoproteinemia, peripheral edema due to hypalbuminemia of < 2.5 g/dl in serum, hyperlipoproteinemia (lipid metabolism disorder).
• Collagenoses – autoimmune diseases of the connective tissue.
• Phenacetin kidney – disease of the kidneys due to phenacetin abuse.
• Pyelonephritis (kidney-pelvis inflammation).
• Heavy metal poisoning
• Pregnancy nephropathy – kidney disease in the context of pregnancy.
• Toxic tubular damage

Proteinuria may be transient (transient) or functional (e.g., hemodynamic). It is then usually not considered indicative of renal disease. The following causes may be present:

• Fever
• Hyperthermia (overheating)
• Physical exertion (heavy physical labor).
• Emotional stress
• Cardiac insufficiency (heart failure)
• Hyperthyroidism (hyperthyroidism)
• Seizures
• Shock

Other clues

• High specific gravity and the presence of erythrocytes (red blood cells) in the urine can lead to false positive findings of microproteinuria. In such cases, proteinuria findings obtained by test strips should be verified by calculating the albumin–creatinine quotient.
• Large proteinuria may already be present without the clinical sign of nephrotic syndrome (NS; edema (water retention), oliguria, see above under urinary volume).
• A proteinuria with hematuria (blood in the urine; see below sediment) requires, especially with signs of a nephritic syndrome or presence of a systemic disease, the presentation to a nephrologist.

Glucose content (sugar content)

Glucose (sugar) is always present in small amounts in urine. Normal values are less than 15 mg/dl (0.84 mmol/l). A simple test strip can be used to measure the sugar content of urine. The glucose content of the urine is increased (glucosuria) in:

• Diabetes mellitus – clarification is then absolutely necessary.
• Debré-Toni-Fanconi syndrome – defect of renal glucose reabsorption; defect of renal glucose reuptake.
• Chronic pancreatitis (inflammation of the pancreas).
• Cancers – e.g. pancreatic cancer (pancreatic cancer).
• Cushing’s disease – group of diseases leading to hypercortisolism (hypercortisolism; excess of cortisol).
• Poisoning with heavy metals, which lead to kidney damage – e.g. lead, cadmium.
• Pregnancy

Thus, more than 50% of pregnant women have measurable sugar in the urine (glucosuria) – especially after the first three months of pregnancy. This is due to an increased glomerular filtration rate. This sugar is almost always glucose. Lactose may also be present in the last weeks of pregnancy. In rare congenital defects of metabolism (metabolism), fructose, galactose as well as pentose-1-xylose may also be present in the urine. In these cases, a glucose-specific measurement may provide information.

Nitrite content

Nitrites are only detectable in urinary tract infections because they are chemically reduced to nitrite from nitrate by some bacteria. However, the nitrite test cannot replace cultural bacterial counts and is false-negative in:

• Severe diuresis (excretion of urine).
• Lack of nitrate excretion – e.g., premature infants, neonates.
• Hunger states
• Parenteral nutrition (bypassing the intestine) or vegetable-free diet.
• Less than 105/ml urine colony forming bacteria.
• Very high bacteria count – nitrite is then reduced to elemental nitrogen
• Infection with bacteria that do not form nitrite from nitrate – e.g. staphylococci, enterococci, gonococci and pseudomonads.

Bilirubin

Bilirubin is formed during the breakdown of the red blood pigment hemoglobin and is normally passed through the bile into the intestine. However, if this is not possible because of gallstones or a tumor – due to obstruction of the bile ducts – the bilirubin accumulates in the blood and is excreted by the kidneys (bilirubinuria). Hepatitis (liver inflammation) or liver cirrhosis can also lead to elevated bilirubin levels.

Ketones

Healthy people do not have ketones or have only small amounts in their urine (normal values: 3-15 mg/dl). The cause of ketonuria (excessive concentration of ketone bodies in the urine) is due to an increase in fat metabolism to meet energy needs. This in turn is caused by a disturbance in carbohydrate metabolism and the resulting glycogen deficiency. In the case of increased fat metabolism, free fatty acids (FFS) are produced as metabolic by-products.free fatty acids; ffa) ketone bodies, especially acetone, which are excreted in the urine. Ketonuria can lead to ketoacidosis or ketoacidotic coma in a diabetic (predominantly in type 1 diabetes mellitus). In approximately 25% of cases, ketoacidotic coma is the first sign of type 1 diabetes mellitus (manifestation coma). Healthy patients may develop ketonuria transiently during catabolic metabolism (e.g., fasting, large dietary fat, fever, great physical exertion, severe trauma/injury, and prolonged vomiting such as hyperemesis gravidarum/pregnancy vomiting). In “nutritional ketosis” (nutritive ketosis), the concentration of ketone bodies is 0.5-3 mg/dl. The concentration of ketone bodies in diabetic ketoacidosis in type 1 diabetes is associated with up to ten times more ketone bodies.

Urine Sediment

This test is also known as the sediment field method. After centrifugation of 10 ml of urine, which should be no more than two hours old, unstained cells are counted at 400× magnification using a technique called bright-field microscopy. The urine sediment (synonym: urinary sediment) is used to examine for microhematuria – erythrocyturia not visible to the naked eye = excretion of red blood cells in the urine -, leukocyturia – occurrence of leukocytes in the urine -, to search for cylinders – cylindrical outpourings of the lower sections of the renal tubules – and renal epithelia, as well as for quantitative assessment of the urinary epithelia. The urine sediment can be used to distinguish whether hematuria – excretion of red blood cells (erythrocytes) in the urine – has a renal (kidney-related) or a postrenal (affecting the draining urinary tract) cause. Furthermore, lymphocytes and eosinophilic granulocytes can be identified, as well as specific bacteria and parasites – e.g., trichomonads, schistosomes, spirochetes, TB.

• Erythrocytes* * (red blood cells): normal < 0-5/ml (0-1/facial), excretion 1,500/min.
• Leukocytes* (white blood cells): normal < 0-3/ml (5/facial field), excretion 3,000/min (Caution! Isolated leukocyturia does not equate to urinary tract infection).
• Bacteria: Shape and staining behavior provide clues to the pathogen before culture.
• Epithelia* : Round and polygonal cells originate mainly from the kidney.
• Cylinder:
  • Isolated hyaline cylinders are normal, in large quantity signs of glomerular proteinuria (protein excretion in urine).
  • Leukocyte cylinders* * * in pyelonephritis, interstitial nephritis, SLE nephritis.
  • Erythrocyte or Hb cylinders are a sign of glomerulonephritis, erythrocyte cylinders* * * * are always pathological.
  • Epithelial or granular cylinders occur in acute renal failure, interstitial nephritis, rapid progressive glomerulonephritis (RPGN) and occasionally in healthy individuals.
• Crystals: rarely of clinical significance.

* For the diagnosis of urinary tract infection, significant bacteriuria with monoculture and significant leukocyturia must be present. * * An isolated hematuria (blood in the urine) requires nephrological workup and follow-up. * * * The co-occurrence of leukocyturia and leukocyte cells in the sediment indicates the presence of “interstitial nephritis”. If the interstitial nephritis is due to bacterial inflammation, it is called pyelonephritis (inflammation of the renal pelvis). * * * * The co-occurrence of hematuria and erythrocyte cylinders in the sediment indicates the presence of an intrarenal (“inside the kidney”) source of bleeding. Caution. Even a small amount of blood can cause macrohematuria.

Bacteria

Significant bacteriuria (excretion of bacteria with the urine) is said to occur when the pathogen count exceeds 105 germs per ml of urine (CFU/ml). Detection is by urine culture. A positive urine culture is followed by a resistogram, i.e. testing of suitable antibiotics for sensitivity/resistance. Criteria for microbiologic diagnosis of asymptomatic bacteriuria (presence of bacteria in urine) or urinary tract infection (UTI):

• Asymptomatic bacteriuria (ABU; ASB): pathogen counts > 105 CFU/mL of the same pathogen (and same resistance pattern) in two urine specimens in the absence of clinical signs of UTI.
• Urinary tract infection:
  • Pathogen counts > 105 CFU/ml (obtained from the “clean” midstream urine).
  • Pathogen counts of 103 to 104 CFU/ml may already be clinically relevant in the presence of clinical symptoms (symptomatic patients), provided that they are pure cultures (i.e., only one type of bacteria) of typical uropathogenic bacteria
  • Pathogen counts of 102 CFU/ml (at least 10 identical colonies); for urine culture from suprapubic urinary bladder puncture (bladder puncture).

In pregnancy

• Systematic screening for asymptomatic bacteriuria should not be performed in pregnancy (Ib-B).

In infants

• For the detection of a urinary tract infection is required: positive findings in urinalysis (leukocyturia and/or bacteriuria) and in a urine sample obtained by catheter or bladder puncture a number of > 105 CFU/ml of a uropathogenic pathogen.

Patients who are about to undergo urologic procedures.

• Screening for and treatment of asymptomatic bacteriuria is indicated.