pH. The normal urine pH range is 4.5 to 8 (usually 5-7). A urine pH higher than 5.3 in the presence of metabolic acidosis raises the possibility of renal tubular acidosis (RTA). A very high urine pH (>8) suggests the presence of urea-splitting organisms (e.g., Proteus), in which cases production of ammonia (NH₃) will raise the urine pH.

Specific gravity. The specific gravity is the weight of urine relative to distilled water and reflects the number and size (weight) of particles in urine. Osmolality is dependent on just the number of particles (solute concentration) in urine. Specific gravity is usually directly proportional to osmolality. However, iodinated contrast and, to a lesser extent, glucose and protein will increase specific gravity, but have little effect on osmolality. The normal range of urine specific gravity is 1.001 (very dilute) to 1.030 (very concentrated). Since the specific gravity of plasma is normally 1.010, a urine specific gravity of 1.010 indicates that the urine is neither concentrated nor dilute (isosthenuria). In an oliguric patient, a specific gravity of more than 1.020 suggests normal ability to concentrate urine and thus prerenal failure (decreased renal blood flow), whereas a specific gravity of about 1.010 suggests loss of tubular function (acute tubular necrosis/acute kidney injury). In a hyponatremic patient, an inappropriately high specific gravity (>1.010) suggests antidiuretic hormone (ADH) secretion, whereas in a hypernatremic patient, an inappropriately low specific gravity (<1.010) suggests diabetes insipidus (central or nephrogenic).

Protein. The dipstick for protein detects primarily albumin. Normal urine usually has no protein by dipstick, but occasionally very concentrated urine will be trace or even 1+ positive for protein in healthy individuals. A positive dipstick should lead to a quantitative measurement. Classically, this was done by a 24-hour urine collection, but
since creatinine is excreted at a constant rate, the UACR or UPCR is sufficient in most patients (see Chapter 4). Simultaneous measurement of both UACR and UPCR is a good screening test for the presence of paraproteinuria, as in myeloma, in which case there will be a much more marked increase in urine total protein relative to urine albumin.

Blood. A positive test indicates heme is present, which can be due to red blood cells (RBCs), myoglobinuria, or hemoglobinuria. Microscopic hematuria is hematuria in the absence of a visual change in color of the urine. As few as 2 to 3 RBCs/high-power field (hpf) may make the dipstick positive.

Glucose. Normal urine does not contain glucose because of the reabsorption of filtered glucose by the proximal tubule. Glycosuria with elevated blood glucose indicates diabetes mellitus. Glycosuria with normal blood glucose indicates renal glycosuria, which may be isolated or associated with other evidence of proximal tubular dysfunction (phosphaturia, aminoaciduria, bicarbonaturia) (Fanconi syndrome).

Ketones. Normally, there are no ketones in the urine. Ketonuria without ketoacidosis suggests starvation, low carbohydrate (such as Atkins) diet, or isopropyl alcohol ingestion. Ketonuria with ketoacidosis suggests diabetic or alcoholic ketoacidosis. Note that in some patients with ketoacidosis, the dipstick may be negative due to the reduction of acetoacetate to beta-hydroxybutyrate.

Bilirubin. Normally, there is no bilirubin in the urine. If present, this suggests hepatobiliary disease (failure to conjugate and/or excrete bilirubin into the gut) or hemolysis (increased production of bilirubin from heme).

Urobilinogen. Bilirubin is secreted in bile into the gut, where it is metabolized by microorganisms into urobilinogen. Urobilinogen is then absorbed and partially excreted into the urine. In the presence of liver disease, urobilinogen can accumulate in plasma and appear in the urine. Bilirubin without urobilinogen in the urine suggests biliary obstruction.

Leukocyte esterase. This is an enzyme found in white blood cells (WBCs) and indicates the presence of pyuria, which can be due to either urinary tract infection (UTI) or inflammation (such as interstitial nephritis).

Nitrite. Enterobacteria convert urinary nitrate to nitrite and therefore a positive test suggests UTI. Note that not all organisms make nitrite, so UTI may be present with a negative nitrite.

RBCs (Fig. 1.1). Hematuria requires evaluation if there are more than 3 RBCs/hpf on two out of three urinalyses, or more than 100 RBCs/hpf on one urine sample, or gross hematuria. In the absence of infection, if there is coexisting proteinuria, glomerulonephritis or renal vasculitis should be suspected.

WBCs (Fig. 1.2). This is usually due to bacterial infection, but if sterile pyuria, one should exclude interstitial nephritis, nonbacterial infection, prostatitis, nephrolithiasis, and glomerulonephritis. Eosinophiluria suggests interstitial nephritis.

Squamous epithelial cells. Squamous epithelial cells from the skin surface or from the outer urethra or vagina in females can appear in urine, indicating possible contamination of the specimen with skin flora.

Bacteria (Fig. 1.3). The presence of bacteria indicates possible infection depending on culture results.

Yeast. These can indicate infection or colonization. The presence of pseudomycelia suggests infection. Risk factors include indwelling catheters, recent antibiotics, immunosuppression, and diabetes.

Crystals. A number of different kinds of crystals can appear in the urine, including calcium oxalate dihydrate (envelopes) (Fig. 1.4), monohydrate (dumbbells), and calcium phosphate (amorphous—form in alkaline urine; in large amounts, may be associated with calcium phosphate kidney stones as may be seen in distal RTA). Uric acid crystals form in acid urine (pleomorphic, yellow/brown) (Fig. 1.5); when in large amounts, it suggests uric acid kidney stones or nephropathy. Cystine (hexagons) indicates cystinuria (Fig. 1.4). Magnesium ammonium phosphate (triple phosphate) (“coffin lids”) can form struvite stones (a urea-splitting organism must be present to produce NH₃ and elevate urine pH) (Fig. 1.6).