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Hematuria refers to the presence of blood in the urine. This abnormality is usually detected on routine urinalysis when the condition is microscopic and asymptomatic. Patients with gross or symptomatic hematuria will usually present to their physician requesting evaluation. Asymptomatic hematuria in a young male patient is often benign. In patients older than 40 years of age, asymptomatic hematuria may be an indicator of underlying malignancy and warrants a more aggressive and complete evaluation. Common causes of hematuria include trauma, exercise, infections, malignancies, calculi, and IgA nephropathy (Bergers disease). Once detected by urinalysis or on gross exam, hematuria needs to be confirmed by microscopic examination of the urine. The finding of 1 to 3 red cells/high-power field (RBC/HPF) is considered normal and does not warrant further workup.
If the patient presents with macroscopic hematuria but the urinalysis is negative for blood this would be indicative of either porphyria or contamination of the urine with certain dyes, foods (beets, rhubarb), or medications (phenazopyridine, phenindione, phenothiazine, rifampin, phenytoin, quinine, sulfasalazine). If the urine dipstick is positive for blood but the microscopic exam is negative for urinary red blood cells, then one of several conditions may exist: either the urine specimen is too old and the urinary red cells have autolyzed, or the dipstick was positive owing to either myoglobinuria or hemoglobinuria and not hematuria. False-positive results on urine dipstick testing are seen in the presence of povidone-iodine and oxidizing agents whereas false-negative results are seen in persons who have ingested large amounts of vitamin C or when dipsticks have had prolonged exposure to air.
Once the diagnosis of hematuria is confirmed by the presence of greater than 3 RBC/HPF, it is necessary to determine whether the hematuria is persistent or a transient abnormality. Transient hematuria is a common finding in young men and is most often benign. However, in older patients, the risk of underlying disease increases and significant concern must be given to the possibility of urinary tract malignancies. The possibility of urinary contamination by menstrual blood loss should always be considered in premenopausal females. Contamination from vaginal, cervical, or endometrial hemorrhage should be considered in women of all ages. Collection and examination of a catheterized urine specimen will eliminate the reproductive organs as the source of bleeding in female patients.
A good history will help direct the work-up or may reveal important clues as to the etiology. The history should include questions as to recent trauma, exercise habits, a family history of hematuria (cystic kidney disease, Alport syndrome), deafness (Alport syndrome), end-stage renal disease (Alport syndrome), a history of bleeding from other sites (bleeding diathesis or thrombocytopenia), recent pharyngeal, skin (PSGN) or upper respiratory tract infections (Bergers disease), oral ulcerations, photosensitivity, skin rashes (SLE), and recent travel history. It is important to ask about travel as infestation with Schistosoma haematobium is a common cause of hematuria in certain parts of the world; however, the most common cause of hematuria is IgA nephropathy.
The first step in the workup of hematuria is determining the source. The potential sites of bleeding may be divided into four broad categories: hematologic (bleeding diathesis, thrombocytopenia, sickle-cell disease, sickle-cell trait, sickle-cell thalassemia, etc.), glomerular renal disease, non-glomerular renal disease, and post renal causes (benign prostatic hypertrophy; prostatitis; tumors of the prostate, bladder, urethra, or ureter; cystitis, etc). Dysmorphic red blood cells noted on microscopic examination indicate a glomerular source of bleeding but may be seen with other conditions such as post renal biopsy or in persons with renal tumors. The finding of heavy proteinuria and the presence of red blood cell casts in the urine sediment more specifically implicate glomerular bleeding.
The workup of hematuria secondary to a non-glomerular origin should include the following studies when appropriate: urine culture (although the absence of nitrites or leukocytes on urinalysis and microscopic exam makes bacterial infection unlikely), CBC, prothrombin time, partial thromboplastin time, sickle cell prep or hemoglobin electrophoresis, KUB, PPD, urine AFB, urine cytology, 24-hour urine determination of protein and creatinine, 24-hour urine determination of calcium and uric acid levels, serum PSA testing, digital rectal examination, intravenous pyelogram (IVP), renal ultrasonography, cystoscopy, computed tomographic scanning, and renal angiography. Strong consideration should be given to renal tuberculosis or Chlamydia trachomatis urethritis when there is concomitant sterile pyuria. When the preliminary workup does not lead to a diagnosis but the source of bleeding is believed to be renal, then renal biopsy may prove useful. A full list of etiologies to consider is listed under the differential diagnosis; however, some common causes of non-glomerular renal hematuria include: infections (bacterial and tuberculous), neoplasm, trauma, nephrolithiasis, and crystalluria (hypercalciuria and hyperuricosuria). Non-glomerular renal hematuria may be further divided into two broad categories: tubulointerstitial and vascular diseases.
As stated above, a glomerular source for hematuria is implied when there is concomitant proteinuria, red blood cell casts, or dysmorphic red blood cells noted on further study of the patients urine. Once the source has been localized to the glomerulus, determination of the serum complement (C3) will help narrow the differential diagnosis. A low serum complement level is seen with glomerular disease secondary to systemic lupus erythematosus, poststreptococcal glomerulonephritis, cryoglobulinemia, membranoproliferative glomerulonephritis, hepatitis C, infectious endocarditis, and ventriculoatrial shunt infections. In patients with a normal complement level, further testing should include: C-ANCA (Wegener's granulomatosis), P-ANCA (polyarteritis nodosa), anti-glomerular basement membrane antibodies (Goodpastures syndrome), and renal biopsy if indicated.
If the source of hematuria is non-glomerular renal or post renal, urologic consultation is indicated if preliminary studies are not rewarding. Urine should be collected for cytologic evaluation in appropriate cases. If urine cytology is negative, intravenous pyelography (IVP) may reveal pathology of the renal pelvis or ureters; however, some physicians advocate KUB along with renal ultrasonography over IVP for the initial radiologic evaluation. If the preliminary radiologic evaluation is unrewarding, cystoscopy will allow visualization of the urethra, bladder, and distal openings of the ureters. If no pathology is noted in the urethra and bladder on cystoscopy, the occurrence of unilateral bleeding from a ureter will help direct which side to perform the renal biopsy.