1. The document provides guidance on evaluating a patient presenting with red or brown colored urine (hematuria). An initial workup includes a urine analysis and microscopy to determine the source and characteristics of the red blood cells.
2. Further evaluation depends on whether the hematuria is glomerular or extraglomerular in origin, which can be suggested by factors like RBC morphology and presence of proteinuria. Potential causes include infections, stones, tumors, and glomerular diseases.
3. If hematuria persists after initial workup, referral to nephrology or urology may be warranted for cystoscopy, imaging tests, or renal biopsy to identify the underlying cause. Thorough history and physical
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Causes and Evaluation of Red or Brown Colored Urine
1. Hematuria
Dr Muzammil Koshish
DCH, DNB Resident,
JLN Hospital and Research
Centre, Bhillai
2. Red or brown color change of urine
Intermittent red or brown color urine a/w variety of clinical setting
Medications (phenazopyridine, microbid, NSAID)
Ingestion of beets or certain dyes
Metabolities
Myoglobinuria or hemoglobinuria
Hematuria
3. Work up
Centrifuge the specimen,
Supernatant be tested for
heme (hemoglobin or myoglobin) with a urine dipstick.
4. APPROACH TO A PATIENT WITH RED OR BROWN COLOURED URINE
5. CAUSES OF HEME-NEGATIVE RED URINE
Medications Food dyes Metabolities
Doxorubicin Beets (in selected patients) Bile pigments
Chloroquine Blackberries Homogentisic acid
Desferoxamine Food coloring Melanin
Ibuprofen Methemoglobin
Iron sorbitol Porphyrin
Nitrofurantoin Tyrosinosis
Phenazopyridine Urates
Phenolphthalein
Rifampin
7. The evaluation should address the following three
questions
1. Are there any clues from the history or physical
examination that suggest a particular diagnosis?
2. Does the hematuria represent glomerular or
extraglomerular bleeding?
3. Is the hematuria transient or persistent?
8. a three-tube test may also help to
locate the source of bleeding in
selected cases.
Urethral: First 10-15 mL
Bladder: Final 10-30 mL
Upper urinary tract: Throughout
14. Physical Exam
Vital sign: BP, T, HR
Skin: Rashes, evidence of trauma, bruising
Abdomen for masses, tenderness (flank,
suprapubics), bruits
CVS: irregular irregular
Edema (especially periorbital)
Joint erythema, swelling, warmth
Paleness, jaundice
Careful inspection of external genitalia
•If BP is elevated, further evaluation is immediately warranted
15. Clues from the history and physical examination
that point toward a specific diagnosis
1. Concurrent pyuria and dysuria, indicate UTI.
2. A recent URI, raise the possibility of either post infectious
glomerulonephritis or IgA nephropathy
3. A positive family history of renal disease give suspicion of hereditary
nephritis, polycystic kidney disease, or sickle cell disease.
4. Unilateral flank pain radiating to the groin, suggesting ureteral
obstruction. Flank pain that is persistent or recurrent can also occur in
the rare loin pain hematuria syndrome.
16. Clues from the history and physical examination that
point toward a specific diagnosis
5. Recent vigorous exercise or trauma
6. History of a bleeding disorder or bleeding from multiple sites due to
coagulopathy.
7. Medications that might cause nephritis (usually with other findings,
typically with renal insufficiency).
8. All should be screened for sickle cell trait or disease, which can lead to
papillary necrosis and hematuria.
9.Sterile pyuria with hematuria, which may occur with renal tuberculosis,
analgesic nephropathy and other interstitial diseases.
21. Rare cause of Microscopic Hematuria
Arteriovenous malformations and
fistulas
Nutcracker syndrome
Loin pain-hematuria syndrome
22. Arteriovenous malformations and fistulas — An AV
malformation (AVM) or fistula of the urologic tract may be either congenital or
acquired. The primary presenting sign is gross hematuria, but high-output heart
failure and hypertension also may be seen . The latter is presumably due to
activation of the renin-angiotensin system resulting from ischemia distal to the
AVM
Nutcracker syndrome — The nutcracker syndrome refers to compression
of the left renal vein between the aorta and proximal superior mesenteric artery.
Nutcracker syndrome can cause both microscopic and gross hematuria, primarily in
children (but also adults) in Asia . The hematuria is usually asymptomatic but may be
associated with left flank pain. Nutcracker syndrome has also been associated with
orthostatic proteinuria.
Loin pain-hematuria syndrome — The loin pain-hematuria syndrome
is a poorly defined disorder characterized by loin or flank pain that is often severe
and unrelenting, and hematuria with dysmorphic red cell features suggesting a
glomerular origin. Affected patients usually have normal kidney function.
23. Extraglomerular vs Glomerular
Extraglomerular Glomerular
Color (if
Red or pink Red, smoky brown, or "Coca-Cola"
macroscopic)
Clots May be present Absent
Proteinuria <500 mg/day May be >500 mg/day
RBC morphology Normal Dysmorphic
RBC casts Absent May be present
24.
25. Dysmorphic erythrocytes are characterized by an irregular outer cell membrane and
suggest hematuria of glomerular origin.
Red blood cell casts are also associated with a glomerular cause of hematuria.
FIGURE 2. Dysmorphic erythrocytes from a urine specimen. These cells suggest a
glomerular cause of microscopic hematuria. (phase contrast microscopy, 3 100)
27. Transient hematuria
Transient microscopic hematuria is a common problem in
adults
Fever, infection, trauma, and exercise are potential causes
It is reasonable to repeat an abnormal urinalysis in a few
days
28. Persistent hematuria
When persistent hematuria is essentially the only manifestation of glomerular
disease, one of three disorders is most likely
IgA nephropathy, in which there is often gross hematuria, and sometimes a
positive family history but without any clear pattern of autosomal inheritance
Alport syndrome (hereditary nephritis), in which gross hematuria can occur
in association with a positive family history of renal failure, and sometimes
deafness or corneal abnormalities.
Thin basement membrane nephropathy (also called thin basement
membrane disease or benign familial hematuria), in which gross hematuria is
unusual and the family history may be positive (with an autosomal dominant
pattern of inheritance) for microscopic hematuria but not for renal failure .
29. Persistent hematuria
Underlying malignancy is greater in patients with persistent hematuria in
whom there is no obvious cause from the history
The primary underlying cancers are bladder, renal, and, much less
often, prostate
30. Laboratory Tests (initial work up)
• UA and microscopy to determine the number and morphology of
RBC, crystal and casts
• Consider urine Cx
• CBC, PT, INR, electrolytes, kidney function
• Serum chemistries and serologic studies for glomerular causes of
hematuria as directed by the medical history
• Repeat UA in a few days
Further urologic evaluation is warranted if more than five
RBC/phf are found on at least two of three properly
collected urine specimens or if high-grade microscopic
hematuria (more than 100 red blood cells per high-power
field) is found on a single urinalysis.17
31. Further Work up
•Glomerular causes:
Consider a refer to nephrology for further
evaluation and possible renal biopsy
32. Renal Biopsy
A biopsy is not usually performed for isolated
glomerular hematuria (i.e., no proteinuria or renal
insufficiency,) since there is no specific therapy for
these conditions
However, biopsy should be considered if there is
evidence of progressive disease as manifested by an
elevation in the plasma creatinine concentration,
increasing protein excretion, or an otherwise
unexplained rise in blood pressure, even when the
values remain within the normal range
33. Further Work up
•Non-glomerular causes:
CT, renal US, and/or IVP: to search for lesions in the
kidney, collecting system, ureters, and bladder
Consider a referral to urology for cystoscopy
34. RADIOLOGIC AND OTHER TESTS FOR THE EVALUATION OF HEMATURIA
Test Advantages Disadvantages
Excellent visualization of the May miss bladder lesions; can
Intravenous pyelogram (IVP) kidney, collecting system, and cause nephrotoxicity,
ureter idiosyncratic reactions (1/10,000)
Best way to examine the bladder,
Invasive, uncomfortable and
Cystoscopy which is not as well visualized by
expensive
IVP or ultrasound
If of good quality, as sensitive as
Less sensitive than IVP for ureter
Ultrasound IVP for renal lesions, with less
and bladder
morbidity and cost
The best test for examing the Invasive, not useful for
Retrograde pyelography ureters, can be combined with examining other parts of the
cystoscopy urinary collecting system
Sensitivity 67 percent, specificity
Useful only for cancer, mainly of
Urinary cytology 96 percent for uroepithelial
the bladder
cancer
Excellent for examining the
CT scan, DTPA, DMSA renal parenchyma and Expensive
functioning
Useful for gross hematuria when
other tests have not revealed the
Angiography Invasive, expensive
cause; the only good test for
vascular malformations
36. Reference:
1. Significance of microhaematuria in young adults. AU Froom P; Ribak J; Benbassat J SO Br Med J (Clin Res Ed)
1984 Jan 7;288(6410):20-2.
2. Asymptomatic microhematuria and urologic disease. A population-based study
3. Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. AU
Grossfeld GD; Wolf JS Jr; Litwan MS; Hricak H; Shuler CL; Agerter DC; Carroll PR SO Am Fam Physician 2001
Mar 15;63(6):1145-54.U Mohr DN; Offord KP; Owen RA; Melton LJ 3d SO JAMA 1986 Jul 11;256(2):224-9
4. The left renal entrapment syndrome: diagnosis and treatment. AU Zhang H; Li M; Jin W; San P; Xu P; Pan S SO
Ann Vasc Surg. 2007 Mar;21(2):198-203.
5. Heavy phenacetin use and bladder cancer in women aged 20 to 49 years. AU Piper JM; Tonascia J; Matanoski GM
SO N Engl J Med 1985 Aug 1;313(5):292-5.
6. Recent advances in the diagnosis and treatment of renal arteriovenous malformations and fistulas. AU Crotty KL;
Orihuela E; Warren MM SO J Urol 1993 Nov;150(5 Pt 1):1355-9.
7. Evaluation of Asymptomatic Microscopic Hematuria in Adults. TIMOTHY R. THALLER, M.D
University of Kansas Medical Center, Kansas City, Kansas LESTER P. WANG, M.D. Valley Urology
Center, Renton, Washington
8. Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.
Accessed Sept. 24, 1998.
9. Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.
Accessed Sept. 24, 1998.
10. Urothelial tumors of the urinary tract. In: Walsh PC, ed. Campbell's Urology. 7th ed. Philadelphia:
Saunders, 1998:2327-410.
11. A quick reference for urologist, AUA 2006
12. Up to date 2008
16 TI Clinical practice. Microscopic hematuria. AU Cohen RA; Brown RS SO N Engl J Med 2003 Jun 5;348(23):2330-8.
Concurrent pyuria and dysuria, which are usually indicative of a urinary tract infection, but may also occur with bladder malignancy. A recent upper respiratory infection, suggesting either postinfectious glomerulonephritis or IgA nephropathy (see "Hematuria following an upper respiratory infection"). A positive family history of renal disease, as in hereditary nephritis, polycystic kidney disease, or sickle cell disease. Unilateral flank pain, which may radiate to the groin, suggesting ureteral obstruction due to a calculus or blood clot, but can occasionally be seen with malignancy. Flank pain that is persistent or recurrent can also occur in the rare loin pain hematuria syndrome. (See "Loin pain hematuria syndrome"). Symptoms of prostatic obstruction in older men such as hesitancy and dribbling. The cellular proliferation in benign prostatic hyperplasia (BPH) is associated with increased vascularity, and the new vessels can be fragile. There is some controversy about whether hematuria is more common in these patients than in age-matched controls [11,17] . However, there is general agreement that the presence of BPH should not dissuade the clinician from pursuing further evaluation of hematuria, particularly since older men are more likely to have more serious disorders such as cancer of the prostate or bladder. Among those with gross hematuria in whom no other cause can be identified, finasteride usually suppresses the hematuria [18,19] . (See "Medical treatment of benign prostatic hyperplasia"). Recent vigorous exercise or trauma (see "Exercise-induced hematuria"). History of a bleeding disorder or bleeding from multiple sites due to uncontrolled anticoagulant therapy. In contrast, it should not be assumed that hematuria alone can be explained by chronic warfarin therapy. In one report of 243 patients prospectively followed for two years, the incidence of hematuria was similar to that in a control group not receiving warfarin [20] . Furthermore, evaluation of patients who developed hematuria revealed a genitourinary cause in 81 percent of cases. Infection was most common, but papillary necrosis, renal cysts, and several malignancies of the bladder were also found. A smaller study found significant urinary tract disease in nine of 30 patients, two of whom had bladder cancer [21] . These observations indicate that hematuria in an anticoagulated patient should generally be evaluated in the same fashion as in other patients unless there is evidence of bleeding from multiple sites with markedly abnormal coagulation studies.Cyclic hematuria in women that is most prominent during and shortly after menstruation, suggesting endometriosis of the urinary tract [22] . Contamination with menstrual blood is always a possibility, and should be ruled out by repeating the urinalysis when menstruation has ceased. Medications that might cause nephritis (usually with other findings, typically with renal insufficiency). Black patients should be screened for sickle cell trait or disease, which can lead to papillary necrosis and hematuria. (See "Renal manifestations of sickle cell disease"). Travel or residence in areas endemic for Schistosoma hematobium, or tuberculosis. Sterile pyuria with hematuria, which may occur with renal tuberculosis, analgesic nephropathy and other interstitial diseases. 22 Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-1992. A 34-year-old woman with endometriosis and bilateral hydronephrosis. N Engl J Med 1992; 327:481.