The document discusses the evaluation of hematuria. It defines macroscopic and microscopic hematuria and provides a classification. Important clues from the history and physical exam are outlined that can point to specific diagnoses. Distinguishing between glomerular and extraglomerular bleeding is important. Common causes of hematuria are reviewed including those related to the kidney, urinary tract, and unrelated conditions. Transient versus persistent hematuria is an important distinction to make in guiding evaluation and workup. Recommended initial laboratory tests and potential radiologic tests are presented.

1. Evaluation of the Hematuria,
 MUHAMMAD Y EBRAHIM, MD.
 Consultant Nephrologists SRMC & MBH
 Director of inpatient dialysis at SRMC, SRCH & MBH.
 Co-medical director at out patient dialysis unit at
Dialysis & Clinics Inc DCI.
 Chief Department of Nephrology at SRMC.

3. HEMATURIA
Transient phenomenon
of little significance
Sign of serious
renal disease

4. Definition
 Macroscopic (gross) Hematuria
 any discolored urine visible to the human eye
 Microscopic Hematuria
 >5 RBC/hpf seen under microscope

5. Classification of hematuria
Macroscopic - Microscopic
Symptomatic - Symptomless
Transient - Persistent
According to the act of void:
-Initial.
-Terminal.
-Total.

6. MicroscopicHematuria
Definition > 3-5 RBC/HPF
> 5 RBC/mm³
> 8000 RBC/ml

7. Glomerular or Extra Glomerular bleeding?

8. Glomerular versus extra glomerular
bleeding
Urinary finding Glomerular Extraglomerular
Red cell casts May be present Absent
Red cell
morphology
Dysmorphic Uniform
Proteinuria May be present Absent
Clots Absent May be present
Color May be red or
brown
May be red

9. Glomerular Vs extra glomerular

10. Causes of Hematuria
Kidney disease
Lesions along the urinary tract
Conditions unrelated to kidney and
urinary tract

11. Hematuria not representing
kidney or urinary tract disorder
Following exercise
Febrile disorders
Gastroenteritis with dehydration
Contamination from external
genitalia

12. Exercise inducedhematuria:

13. Exercise inducedhematuria

14. Renal causes of Hematuria
Glomerular
- Acute Post infectious Glomerulonephritis
- IgA Nephropathy
- Hereditary Nephritis ( Alport syndrome)
- Benign Recurrent or Persistent Hematuria (Thin Membrane
Disease )
1.Sporadic
2.Familial
- Membranoproliferative Glomerulonephritis
- Crescentic Glomerulonephritis
- Lupus Nephritis
- Nephritis of Henoch-Shönlein Purpura
- Focal Glomerulosclerosis
- Hemolityc-Uremic Syndrome

15. Renal causes of Hematuria
Non-glomerular
- Infection ( Pyelonephritis )
- Interstitial Nephritis
- Metabolic ( Uric Acid, Nephrocalcinosis )
- Renal Malformation ( Cystic Kidney )
-Tumors (Wilm’s, Acute Leukemia)
- Idiopatic Hypercalciuria
-Trauma

16. Causes of urinary tract
related Hematuria
Infection
Urolithiasis
Obstruction ( UPJ Stenosis )
Trauma
Drugs ( Cyclophosphamide )
Tumors

17. Isolated Hematuria
(microscopic)
No other urinary abnormalities
No renal insufficiency
No evidence for systemic disease
Incidence ( school-aged children )
4-6% - single urine examination
0.5-1% - repeated testing over 6-12 months

18. Etiologies of isolated
Hematuria
Glomerular
- Benign Recurrent or Persistent Hematuria
1.Sporadic
2.Familial
- IgA Nephropathy
- Alport syndrome
- PSAGN (post strep)
Non-glomerular
- Idiopathic Hypercalciuria
- Cystic Kidneys
- UrinaryTract obstruction
-Tumors
-Trauma

19. Hematuria with familial
association
Glomerular
- Benign Familial Hematuria
- Alport syndrome
Non-glomerular
- Idiopathic Hypercalciuria
- Polycystic Kidney Disease
- Urolithiasis
-Tumors

20. Gross hematuria:
Suspected if a 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
If pass clot, indicate lower urinary source

21. Work up
Centrifuge the specimen,
Supernatant be tested for heme (hemoglobin or myoglobin)
with a urine dipstick.

22. Causes of heme-negative red urine
Medications Food dyes Metabolities
Doxorubicin
Beets (in selected
patients)
Bile pigments
Chloroquine Blackberries Homogentisic acid
Deferoxamine Food coloring Melanin
Ibuprofen Methemoglobin
Iron sorbitol Porphyrin
Nitrofurantoin Tyrosinosis
Phenazopyridine Urates
Phenolphthalein
Rifampin

23. Approach to the patient with red or
brown urine

24. Definitionof MicroscopicHematuria
More than three red blood cells are found in
centrifuged urine per high-power field microscopy ( > 3
RBC/HP).

25. Microscopic hematuria:
Accidental finding from UA or urine dipstick
3 or more RBC/hpf in spun urine sediment.
No "safe" lower limit below which significant disease can be excluded
Often asymptomatic
The degree of hematuria does not correlate with the seriousness of the
underlying cause of the bleeding.

26. Diagnosis:
The urine sediment is the gold standard for the detection of
microscopic hematuria
Dipsticks for heme are as sensitive as urine sediment examination,
but result in more false positive tests due to the following
 Semen is present in the urine after ejaculation
An alkaline urine with a pH greater than 9 or contamination with oxidizing
agents used to clean the perineum.
The presence of myoglobinuria.
A positive dipstick test must always be confirmed with microscopic
examination of the urine

27. 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?

28. Urethral: First 10-15 mL
Bladder: Final 10-30 mL
Upper urinary tract:Throughout
a three-tube test may also help to locate
the source of bleeding in selected cases.

29. History and Physical

30. Important questions to ask in patients History
•Has there been any signs of a UTI as dysuria & frequency? Any suprapubic pain?
•Has there been any recent URI symptoms or sore throat?
•Has there been any type of skin rashes or sores?
•Any abdominal pain or colicky pain?
•Are the stools loose or bloody?
•Has there been any recent trauma?
•Has there been any joint pains or swellings?
•Is there any history of sickle cell disease or trait?
•Is there any family history of renal disease, transplants, or dialysis? Is there a
family history of hearing deficits?
•What medications does the child take?

31. Family history:
Hematuria ,
Hearing loss, (Alports)
HTN,
Stones,
Renal disease,
Dialysis or transplant,
Sickle cell trait *:
Coagulopathy,

32. Substances and Medications Affecting Urine
Color
Artificial food coloring
Beets
Berries
Chloroquine (Aralen)
Furazolidone (Furoxone)
Hydroxychloroquine (Plaquenil)
Nitrofurantoin (Furadantin)
Phenazopyridine (Pyridium)
Phenolphthalein
Rifampin (Rifadin)
.
Medication Hx

33. MechanismsbyWhichSelectedDrugsMayCauseHematuria
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)
Medication History:

34. Important areas to check on the physical examination
•Blood Pressure
•Check for edema, especially around the eyes
•(Esp in the morning)
•Careful inspection of the external genitalia
•Look for any rashes, evidence of trauma and bruising, petechiae
•Exam all joints for signs of arthritis-red, warm, or swollen
•Feel the abdomen carefully for any masses or tenderness. Check for CVA
tenderness.
•Try to feel for enlarged kidneys.
•Check for evidence of paleness or jaundice
•Accurately measure length and weight and plot on growth chart.

35. PhysicalExaminationFindingsand
AssociatedCausesofHematuria
Physical examination finding Cause of hematuria
General (systemic) examination
Severe dehydration Renal vein thrombosis
Peripheral edema Nephrotic syndrome, vasculitis
Cardiovascular system
Myocardial infarction Renal artery embolus or thrombus
Atrial fibrillation Renal artery embolus or thrombus
Hypertension Glomerulosclerosis with or without
proteinuria
Abdomen
Bruit Arteriovenous fistula
Genitourinary system
Enlarged prostate Urinary tract infection
Phimosis Urinary tract infection
Meatal stenosis Urinary tract infection

36. 1. Concurrent pyuria and dysuria, indicateUTI, may also occur with bladder
malignancy.
2. A recentURI, 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 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.
5. Symptoms of prostatic obstruction in older men such as hesitancy and
dribbling.The cellular proliferation in BPH is associated with increased
Clues from the history that point toward a
specific diagnosis:

37. 6. Recent vigorous exercise or trauma
7. History of a bleeding disorder or bleeding from multiple sites due to
uncontrolled anticoagulant therapy.
8. Cyclic hematuria in women that is most prominent during and shortly after
menstruation, suggesting endometriosis of the urinary tract .
9. Medications that might cause nephritis (usually with other findings,
typically with renal insufficiency).
10. AA should be screened for sickle cell trait or disease, which can lead to
papillary necrosis and hematuria.
11.Travel or residence in areas endemic forSchistosoma hematobium .
12.Sterile pyuria with hematuria, which may occur with renal tuberculosis,
analgesic nephropathy and other interstitial diseases.
Clues from the history that point toward a specific diagnosis:

38. Glomerular or Extra Glomerular bleeding?

39. Glomerular
ARF
primary nephritis (post streptococcal glomerulonephritis, Ig A
nephropathy, Anti-GBM disease)
2nd nephritis(SLE, goodpasture’s syndrome, ANCA related
vasculitis)
Alport’s syndrome (hereditary nephritis) thin basement membrane
nephropathy (benign familial hematuria)
•
Microscopic hematuria DDx

40. Rare cause of Microscopic Hematuria
Arteriovenous malformations and fistulas
Nutcracker syndrome
Loin pain-hematuria syndrome

41. 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.

42. Transient or persistent hematuria

43. Exception:
Malignancy risk in older patients with transient
hematuria
In older patients, even transient hematuria carries an appreciable
risk of malignancy (assuming no evidence of glomerular bleeding)
The risks includes : age >50, smoker and Hx of analgesic abuse.
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

44. 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 autonomic dominant pattern of
inheritance) for microscopic hematuria but not for renal failure
.

45. LaboratoryTests (initial work up)
• Repeat UA in a few days
•UA and microscopy to determine the number and morphology of RBC, crystal and
casts,Consider urine Cx
• CBC, PT, INR, electrolytes, kidney function
•Further urologic evaluation is warranted if more than three RBC/phf are found on at
least 2 of 3 properly collected urine specimens or if high-grade microscopic hematuria
(>than 100 red blood cells per high-power field) is found on a single urinalysis.17
• Serum chemistries and serologic studies for glomerular causes of hematuria as
directed by the medical history ANA, C3 , C4, Hepatitis B and C, HIV, ESR, Anti DNA
and other lupus studies, ASO, ANCA, AntiGBM antibodies,SPEP, UPEP, M spike.
• Imaging stuidies like US kidney and Bladder . CT Scan, MRI , MRA, Renal angiogram ,
IVP, Cystoscopy, Retrograde Pyelogram, kidney biopsy
• Consultation to Nephrologist or Urologist

46. Radiologicandothertestsfortheevaluationofhematuria
Test Advantages Disadvantages
Intravenous pyelogram (IVP)
Excellent visualization of the
kidney, collecting system, and
ureter
May miss bladder lesions; can
cause nephrotoxicity,
idiosyncratic reactions (1/10,000)
Cystoscopy
Best way to examine the bladder,
which is not as well visualized by
IVP or ultrasound
Invasive, uncomfortable and
expensive
Ultrasound
If of good quality, as sensitive as
IVP for renal lesions, with less
morbidity and cost
Less sensitive than IVP for ureter
and bladder
Retrograde pyelography
The best test for examing the
ureters, can be combined with
cystoscopy
Invasive, not useful for examining
other parts of the urinary
collecting system
Urinary cytology
Sensitivity 67 percent, specificity
96 percent for uroepithelial
cancer
Useful only for cancer, mainly of
the bladder
CT scan
Excellent for examining the renal
parenchyma
Expensive
Angiography
Useful for gross hematuria when
other tests have not revealed the
cause; the only good test for
vascular malformations
Invasive, expensive

47. 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, unless the patient is considering
becoming a kidney donor
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.
Renal Biopsy:

48. InitialEvaluationofAsymptomaticMicroscopicHematuria*

49. --Approaching to the patient–
(Harrison’s Principle of Internal
Medicine,14th Ed)
HEMATURIA
proteinuria (>500mg/24h)
Dysmorphic RBC or RBC casts
Pyuria,WBC casts urine culture
eosinophils serologic and hematologic
evaluation: blood culture, anti-
GBM Ab, ANCA, complement,
cryoglobulin
HBV,HCV,VDRL,HIV,ASLO
renal biopsy
Hb electrophoresis, urine cytology, UA
of family member, 24h urinary
calcium/uric acid
IVP+/-renal
ultrasound
As indicated:
retrograde
pyelography or
arteriogram of cyst
aspiration
cystoscopy
CT scan
biopsy
open renal biopsy
follow
(-)
(-)
(-)
(-)
(-)
(-)
(+)
(+)
(+)
(+)
(+) ANCA:antineutrophil cytoplasmic
antibody,VDRL:venereal dis. research
laboratory, ASLO: antisteptolysin O,

50. Hematuria and Proteinuria combined:
Dipstick detects mostly ALBUMIN
negative (0 mg/dL)
trace (10-20 mg/dL)
1+ (30 mg/dL)
2+ (100 mg/dL)
3+ (300 mg/dL)
4+ (1000-2000 mg/dL)

51. Thank you for your attention!