Hematuria can be either gross or microscopic. Gross hematuria is the presence of red or brown urine. In the initial evaluation of a patient with gross hematuria, it must be determined whether the urine discoloration is truly secondary to pathologic bleeding within the urinary tract. Patients who are menstruating or postpartum should not be evaluated for hematuria. In the absence of actual bleeding the urine may appear grossly red following the intake of certain medications, such as rifampin, phenothiazine, or phenazopyridine (analgesic), or the intake of beets in certain predisposed individuals. It is also important to differentiate hematuria from other causes of red urine such as hemoglobinuria and myoglobinuria. The latter is usually seen in those with acute rhabdomyolysis.
Microscopic hematuria is defined as the presence of more than two red blood cells (RBCs)/hpf. It is usually detected incidentally by urine dipstick examination.
Careful history taking is of paramount importance in the evaluation of patients with hematuria. Important historical information usually provides diagnostic clues. For instance, the occurrence of concomitant flank pain with radiation to the ipsilateral testicle or labia suggests underlying nephrolithiasis, burning on urination or dysuria may point to possible urinary tract infection, and a recent upper respiratory tract infection may suggest either postinfectious glomerulonephritis or even IgA nephropathy. A family history of hematuria is also vital, as certain diseases tend to run in families, such as polycystic kidney disease or even sickle cell nephropathy. Likewise, thin basement membrane disease and benign familial hematuria tend to occur in families, and notably have a rather benign course despite the presentation. Exercise-induced hematuria is seen in adolescents who exercise vigorously.
In elderly individuals, or those above 50 years of age, the finding of gross or microscopic (even transient) hematuria should trigger an extensive evaluation to rule out malignancy involving the genitourinary tract. The incidence of bladder cancer and other malignancies involving the kidneys and the ureters is significantly elevated, particularly in those with a prolonged history of chronic smoking and analgesic use. The occurrence of symptoms of increased urgency and frequency with hematuria in this population should suggest urinary tract obstruction secondary to either benign prostatic hypertrophy (BPH) or prostatic malignancy.
Using urine microscopy, the presence of dysmorphic RBCs or RBC casts should suggest glomerular disorders as the primary etiology of hematuria. This is one of the indications for performing a percutaneous renal biopsy.
Normal urine protein excretion is 150 mg/day. Anything above this value is considered overt proteinuria. Proteinuria usually implies that there is a defect in glomerular permeability. In general, proteinuria can be classified into three types: (1) Glomerular, (2) tubular, or (3) overflow.
Glomerular proteinuria includes diabetic nephropathy and other common glomerular disorders (see Chapters 36, 37, 38, 39, and 40). It is usually caused by increased filtration of albumin across the glomerular capillary wall. There are also causes of glomerular proteinuria that have a rather benign course, such as orthostatic and exercise-induced proteinuria. These latter causes are characterized by significantly lower degrees of proteinuria, <2 g/day.
Tubular proteinuria is usually seen in those with underlying tubulointerstitial diseases. They often have defective reabsorptive capacities in the proximal tubules, such that the proteins, instead of being normally reabsorbed, are excreted in the urine. In contrast to glomerular proteinuria, whereby macromolecules such as albumin are leaked out, in tubular proteinuria, it is mostly low-molecular-weight proteins, such as immunoglobulin light chains.
Lastly, overflow proteinuria is exemplified by multiple myeloma, where there is an overabundance of immunoglobulin light chains secondary to overproduction. Simply put, proteinuria occurs because the amount of protein produced basically exceeds the maximum threshold for reabsorption in the tubules.
Whereas both glomerular and tubular proteinuria are secondary to abnormalities involving the glomerular capillary and tubular walls, respectively, in overflow proteinuria, the problem is the overproduction of certain proteins.
When performing a urinalysis, the dipstick examination can detect only albumin, and not the low-molecular-weight proteins. In fact, it can detect it only when proteinuria is >300–500 mg/day. Hence, one of its most important limitations is its inability to detect microalbuminuria, which corresponds to the earliest phase of diabetic nephropathy. However, the sulfosalicylic acid test (SSA) can detect all types of proteins in the urine, including low-molecular-weight proteins.
Quantification of the degree of proteinuria is accomplished by performing a 24-hour urine collection, which can be cumbersome, especially in elderly individuals or those with concomitant fecal or urinary incontinence.
The urine protein-to-creatinine (using a random urine specimen) ratio has been shown to have a good correlation with 24-hour urine protein determination.
Orthostatic or postural proteinuria, by definition, is characterized by increased urine protein excretion in the upright position and normal urine protein excretion in the supine position. It is a benign condition, seen mostly among adolescents, the mechanism of which is not clearly understood. The diagnosis is established by performing a split urine collection, the protocol for which is as follows: (1) The first morning void is discarded, (2) a 16-hour upright collection is obtained between 7 am and 11 pm, with the patient performing normal activities and finishing the collection by voiding just before 11 pm (the times can be adjusted according to the normal times at which the patient awakens and goes to sleep), (3) the patient should assume a recumbent position 2 hours before the upright collection is finished to avoid contamination of the supine collection with urine formed when in the upright position, and (4) a separate overnight 8-hour collection is obtained between 11 pm and 7 am.
Patients with orthostatic proteinuria do not progress to end-stage renal disease; in fact, proteinuria resolves spontaneously in the majority of affected patients.