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

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

6. Hematuria
Microscopic hematuria
> 50 RBCs / μl ( 5 RBCs / HPF )
Gross hematuria
> 2500 RBCs / μl
•American Urological Association

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

9. History and Physical
Examination

10. History
 Abdominal or flank pain
􀂄 Dysuria, frequency, urgency
􀂄 Trauma
􀂄 Strenuous exercise
􀂄 Menstruation
􀂄 Recent URI/ sore throat
􀂄 Skin rashes/ skin infection
􀂄 Diarrhea (especially bloody)
􀂄 Joint pains/swellings
􀂄 Medications/toxins
􀂄 h/o sickle cell disease or sickle trait

11. Family history
 Hematuria ,
Hearing loss,
HTN,
Stones,
Renal disease,
Dialysis or transplant,
Sickle cell trait
Coagulopathy,

12. Medication Hx
Substances and Medications Affecting Urine Color
Artificial food coloring
Beets
Berries
Chloroquine (Aralen)
Furazolidone (Furoxone)
Hydroxychloroquine (Plaquenil)
Nitrofurantoin (Furadantin)
Phenazopyridine (Pyridium)
Phenolphthalein
Rifampin (Rifadin)
Information from Restrepo NC, Carey PO. Evaluating hematuria in adults.
Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood:
Colo.: Micromedex, Inc., 1999. Accessed Sept. 24, 1998.

13. MECHANISM BY WHICH SELECTED DRUGS CAN CAUSE HEMATURIA
Interstitial nephritis Captopril (Capoten)
Cephalosporins
Chlorothiazide (Diuril)
Ciprofloxacin (Cipro)
Furosemide (Lasix)
NSAIDs
Olsalazine (Dipentum)
Omeprazole (Prilosec)
Penicillins
Rifampin (Rifadin)
Silver sulfadiazine (Silvadene)
Trimethoprim-sulfamethoxazole (Bactrim, Septra
Papillary necrosis Acetylsalicylic acid (aspirin)
NSAIDs
Hemorrhagic cystitis Cyclophosphamide (Cytoxan)
Ifosfamide (Ifex)
Mitotane (Lysodren)
Urolithiasis Carbonic anhydrase inhibitors
Dichlorphenamide (Daranide)
Indinavir (Crixivan)
Mirtazapine (Remeron)
Ritonavir (Norvir)
Triamterene (Dyrenium)

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.

17. Glomerular or Extra Glomerular bleeding?

18. Microscopic hematuria DDx
Glomerular
 primary nephritis (post streptococcal glomerulonephritis, Ig A
nephropathy, Anti-GBM disease)
 IInd nephritis (SLE, goodpasture’s syndrome, ANCA related
vasculitis)
 Alport’s syndrome (hereditary nephritis)
 Thin basement membrane nephropathy (benign familial hematuria)
•

19. Microscopic hematuria DDx
Non-glomerular
 Renal
 Malignancy
 vascular disease (malignant hypertension, AVM,
nutcracker syndrome, renal vein
thrombosis, sickle cell trait/disease,
papillary necrosis)
 infection (pyelonephritis, TB, CMV, EBV)
 Hypercalciuria
 hereditary disease (polycystic kidney disease, medullary
sponge kidney)

20.  Nonrenal
 Nephrolithiasis
 Coagulopathy
 Trauma

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

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)

26. Transient or persistent hematuria

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

35. SCREENING FOR HEMATURIA
Not recommended

36. Reference:
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2. Asymptomatic microhematuria and urologic disease. A population-based study
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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
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SO N Engl J Med 1985 Aug 1;313(5):292-5.
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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:
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11. A quick reference for urologist, AUA 2006
12. Up to date 2008

37. Thank you