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Red urine is not always caused by hematuria. A variety of medications, food dyes, and metabolites can cause heme-negative red urine, or pigmenturia (Table 21-1). Furthermore, not all dipstick tests positive for blood are due to hematuria. In addition to detecting heme in intact red blood cells (RBCs), urine dipsticks detect free hemoglobin and myoglobin, hence leading to false-positive tests for hematuria.
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Whenever the urine dipstick is positive for blood, and the microscopic exam of the urine does not show RBCs, myoglobinuria and hemoglobinuria should be considered.
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True macroscopic (visible) hematuria is always pathologic. Microscopic (nonvisible) hematuria may be transient, spurious, or persistent. Transient causes of microscopic hematuria include urinary tract infections (UTIs) (which sometimes also cause macroscopic hematuria) and strenuous exercise; hematuria due to these causes would be expected to resolve on repeat testing after 48 hours of treatment or after discontinuing exercise for 72 hours. Spurious causes include urinary contamination from menstruation and sexual intercourse in women. This chapter will focus on persistent, true hematuria.
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All patients with hematuria should have a urine culture performed, regardless of the likelihood of infection.
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The differential diagnosis of hematuria is often divided into microscopic hematuria or macroscopic hematuria. Microscopic hematuria is present when microscopic inspection of at least 2 properly collected urine specimens show > 3 RBCs per high-powered field (hpf). Macroscopic hematuria is red or brown urine, sometimes with blood clots. However, there is considerable overlap in the causes of microscopic and macroscopic hematuria, and it may be more practical to first consider whether the hematuria is glomerular in origin. Pivotal points that help distinguish glomerular hematuria from nonglomerular hematuria include dysmorphic RBCs (acanthocytes), red cell casts, new or acutely worsening hypertension or proteinuria, and increased creatinine. While these abnormalities may also be seen in some of the interstitial and vascular causes of hematuria, they will not be found when hematuria is caused by a renal structural abnormality or an abnormality distal to the kidneys. Visible blood clots, which are never due to a glomerular cause, are another pivotal point, indicating a lower urinary tract source of the hematuria.
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Renal
Glomerular
IgA nephropathy
Alport disease and thin basement membrane nephropathy (TBMN)
Other primary and secondary glomerulonephritides
(1) Postinfectious or infection-related
(2) Systemic lupus erythematosus
(3) Goodpasture syndrome
(4) Henoch-Schünlein purpura (HSP) and other small or medium vessel vasculitides
(5) Hemolytic uremic syndrome (HUS)
Nonglomerular
Neoplastic
Tubulointerstitial
Vascular
(1) Arterial embolus or thrombosis
(2) Arteriovenous malformation or arteriovenous fistula
(3) Renal vein thrombosis
(4) Nutcracker syndrome (compression of left renal vein)
(5) Malignant hypertension
Metabolic (hypercalciuria, hyperuricosuria)
Extrarenal
Ureter
Mass: benign polyp or malignancy
Stone
Stricture
Bladder
Transitional cell or squamous cell carcinoma
Noninfectious cystitis (radiation or medication [cyclophosphamide])
Infectious cystitis
Stone
Urethra
Urethritis
Urethral diverticulum
Traumatic catheterization
Urethral stricture
Prostate
Benign prostatic hypertrophy (BPH)
Prostate cancer
Post prostatic procedure
Prostatitis
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Figures 21-1 and 21-2 reorganize the differential diagnosis using pivotal points and outline the diagnostic approach to hematuria.
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Mr. A reports several episodes of painless visible hematuria over the last several days, along with occasional mild lower abdominal discomfort. He is feeling well otherwise and has no other complaints. His medical history is significant for chronic kidney disease (CKD) stage 3, hypertension treated with hydrochlorothiazide and enalapril, and a remote appendectomy. He has no family history of kidney stones, but his father did have prostate cancer. He has smoked 1 pack per day of cigarettes for 35 years. He is a philosophy professor, and has no known toxin exposures. Initial urinalysis shows many nondysmorphic RBCs, with no WBCs, bacteria, casts, or proteinuria.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?