Proper urine collection is necessary for accurate interpretation of urinalysis or culture. All tests must be performed on a freshly voided specimen. Urine that has been left standing becomes alkaline, with lysis of red blood cells, disintegration of casts, formation of crystals, and proliferation of bacteria. If it is not possible to examine the urine promptly, it should be refrigerated.

Color and appearance should be noted. Normal urine is pale urine but is affected by the patient’s hydration status. A cloudy or milky appearance can be due to the precipitation of phosphates (phosphaturia) in alkaline urine, pyuria, or, rarely, chyluria. Amorphous phosphates are frequently seen in the urine grossly and microscopically after meals.

Specific gravity (SG), measured by hydrometer or refractometer, can give a good estimate of the patient’s hydration, barring significant renal impairment. The normal range is 1.003 to 1.030. Glucose, protein, or intravenous contrast agents in the urine can cause a falsely elevated value. An SG >1.020 indicates concentrated urine and a fixed SG of 1.010 indicates renal insufficiency.

The urine dipstick permits simultaneous performance of a battery of useful chemical tests in <2 minutes. These are screening tests, and positive results generally need confirmation by other more precise tests. Faulty dipstick results can be caused by mixing of chemicals from adjacent pads as a result of excess urine on the dipstick or holding the dipstick in a vertical position. Do not use outdated dipsticks or allow them to sit out exposed to air or light for extended periods.

Serum creatinine is a simple measurement that accurately reflects the glomerular filtration rate (GFR). Creatinine is a metabolic product of creatine phosphate in the skeletal muscle. The daily production is relatively stable for a given individual and is proportional to muscle mass. Creatinine clearance occurs mainly by glomerular filtration (90%) and, to a lesser extent, by tubular secretion (10%). Thus, creatinine clearance approximates GFR, and a doubling of serum creatinine indicates a 50% reduction in GFR. As individual nephrons (out of the 1,000,000/kidney) are lost to disease, the remainder hypertrophy, and single nephron GFR increases to maintain the overall GFR. A loss of 40% to 50% of renal mass is required before GFR begins to fall and creatinine rises. Note—a normal creatinine in a term infant is only 0.1 to 0.4 mg/dL because of low muscle mass.

Urea is a metabolic product of protein catabolism that is excreted by the kidneys. Blood levels tend to reflect GFR but can be influenced by dietary protein intake, hydration, gastrointestinal bleeding, and glucocorticoids. The blood urea nitrogen/creatinine ratio, which is normally 10:1, can be a useful indicator.

Acid phosphatase is an enzyme produced by various body tissues; however, the prostate is noted to be the most concentrated source. Human prostatic acid phosphatase (PAP) is a glycoprotein of 102,000 MW. Routine enzymatic serum assays specific for PAP utilize thymolphthalein phosphate as substrate. Blood samples should be chilled immediately after collection to avoid loss of enzyme activity. An elevated serum enzymatic PAP suggests metastatic disease. Routine use of PAP has been essentially replaced by prostate-specific antigen (PSA).

PSA is a 34-kDa glycoprotein found only in the cytoplasm of prostatic epithelial cells. It is a protein product of the human kallikrein gene family identified as hKLK3 or hK3. It is believed to function as a neutral serine protease that lyses seminal coagulum. It can be detected in the semen and serum of males with prostate tissue. It cannot be detected in females. PSA exits in serum both free and complexed (cPSA) to protease inhibitors.

PSA is specific only for prostate tissue and cannot differentiate benign from malignant prostate conditions. However, levels correlate with prostate size and the presence of prostate cancer. In addition, men with prostate cancer have a greater fraction of PSA complexed to serum proteins (cPSA). Normal levels of PSA are age dependent (see chart) and can be affected by androgen levels. In addition to prostate cancer, serum PSA levels can be elevated by acute prostatitis, vigorous prostatic manipulation or surgery, and markedly enlarged benign prostate glands. Serum PSA has been utilized extensively in prostate cancer for early detection, staging, and monitoring response to therapy. Serum PSA screening remains the best means for detecting early prostate cancer. PSA levels above 10 ng/mL are highly suspicious for the
presence of prostate cancer, even in males with a normal digital rectal examination. However, 20% of men with prostate cancer have a normal PSA.

The percent free PSA is a useful adjunct for differentiating a benign from malignant source of PSA when the PSA level is between 4.0 and 10.0 ng/mL. A low percent free PSA (<10%) increases the likelihood that prostate cancer is present while a high percent free PSA (>30%) favors a benign prostate. Direct measurement of cPSA levels provides equivalent prostate cancer detection specificity.

The rate of change of PSA or PSA velocity has been shown to be useful for early detection of prostate cancer. A PSA velocity >0.7 ng/mL per year averaged over at least 18 months with three repeated PSA measurements is associated with an increased detection of prostate cancer.

The ratio of serum PSA to prostate volume measured by prostate ultrasound is related to the chance of detecting prostate cancer on biopsy. A PSA density >0.1 has been suggested to be a useful marker for indicating prostate biopsy.

Alkaline phosphatase is an enzyme produced by many tissues, especially bone, liver, intestine, and placenta. Most enzymes present in normal serum is derived from metabolic activity in the
bone. Prostate cancer metastatic to the bone causes an elevation in alkaline phosphatase secondary to increased metabolic activity in the bone surrounding the metastatic lesion. When an elevated total alkaline phosphatase is in question, the bone derived isoenzyme can be isolated by its heat lability (bone burns). If the enzymatic activity of the heated fraction is <30% of the total, it suggests bone as the origin (bone isoenzyme is inactivated by heating).

Lactic acid dehydrogenase (LDH) is a cellular enzyme found in a number of different tissues. Elevated LDH can be found in germ cell tumors (GCTs).

A 24-hour collection is often necessary for the workup of stone-forming patients and for an accurate assessment of renal function or proteinuria in a patient with renal disease. The most common reason for inaccuracy of values obtained from a 24-hour urine collection is due to incomplete collection. An incomplete collection is suggested by an inadequate amount of total creatinine in the sample because the total amount of creatinine excreted in 24 hours is dependent on muscle mass and is generally constant. The normal production of creatinine is 1.0 mg/kg/hour.

Spot urinary sodium (Na) and potassium (K) measurements can be a valuable tool in diagnosing hypovolemia or prerenal azotemia. The kidney has an impressive capacity to hold onto sodium.

Human chorionic gonadotropin (hCG) is a 38,000 MW doublechain glycoprotein with α- and β-subunits normally secreted by the syncytiotrophoblastic cells of the placenta. The α-subunit of hCG resembles that found in leutinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone. The β-subunit is structurally unique and is used for antigenic detection. hCG is normally secreted during pregnancy. It has a metabolic half-life of 24 to 36 hours, and normal adult levels should be <5 mIU/mL. Elevated levels of hCG are detected in patients with GCTs: all patients with choriocarcinoma, in 40% to 60% of embryonal carcinomas, and in 5% to 10% of pure seminomas.

α-Fetoprotein (AFP) is a 70,000 MW single-chain glycoprotein normally secreted by the fetal yolk sac. It is also produced by trophoblastic cells of embryonal carcinoma and yolk sac tumors. It is not made by pure choriocarcinoma or seminoma. Elevated AFP is found in 50% to 70% of nonseminomatous testis tumors.
It has a half-life of 5 to 7 days, and normal adult levels should be <40 ng/mL (see Chapter 26).

X-rays are electromagnetic waves of energy created when highspeed electrons hit the tungsten target of an x-ray tube. They are invisible because they have a shorter wavelength than visible light, which also gives them their greater penetrating ability. X-rays can produce an image on photographic film or fluorescent detectors, which accounts for their value in medical imaging. An x-ray is ionizing energy or radiation owing to its ability to liberate electrons from atoms and thus can have a detrimental affect on biologic matter.