C H A P T E R

Approach to Hematuria

31 PP Varma, T Mohanty

DEFINITION membranes of glomerulus and different osmolality. Some

Hematuria implies blood in the urine. If the urine is of these RBCs can be ring shaped with vesicle shaped
reddish to naked eye, it is called macroscopic hematuria protrusions on their surface and are called acanthocytes
and if blood is detectable only by microscopy it is called (G1 cells). Dysmorphic RBCs are best seen by phase
microscopic hematuria. Even one ml of blood in a litre contrast microscopy/ scanning microscope. Presence of
of urine is enough to result in reddish urine. Microscopic dysmorphic RBCs is s/o glomerular origin however level
hematuria is defined as presence of three or more red of cut off required for dRBCs is not clear. In a study by
blood cells (RBCs) per high-power field. For urine analysis Crop.et al, at a 40% cutoff point the sensitivity of urinary
urine should be freshly voided, should be midstream, dRBC for excluding glomerular disease in patients with
clean catch and not the first morning specimen. Urine urological diseases was 100%,while still 78% of the patients
samples collected following strenuous exercise, trauma, with a glomerular cause of hematuria had less than
sexual intercourse, during febrile illness and during 40% dRBC. None of the patients with proven urological
menstruation can show transient hematuria and hence be disease showed dRBC above the cutoff of 40%. Another
better avoided. study suggests that presence of >80% dysmorphic RBC
or presence of >5 % acanthocytes is highly suggestive of
URINE TESTING glomerular and >80% normal RBCs is suggestive of lower
Analysis of urine should be performed as early as tract bleeding.
possible following collection. Dip stick is very sensitive
and can detect microscopic hematuria of 1-5 RBCs/hpf INCIDENCE AND ETIOLOGY
with a sensitivity of 100 % & specificity of 99 %. The In five population based studies, the prevalence of
dipstick actually detects haemoglobin/ myoglobin and asymptomatic hematuria varied from 0.19- 16.1%. This
can show false positive results in case of hemoglobinuria wide variation is due to difference in age, sex, amount of
and myoglobinuria. Therefore a positive dipstick reading follow up and number of screening studies performed.
merits microscopic examination for confirmation.A In older population with risk of urologic diseases the
negative dip stick test virtually excludes hematuria. prevalence was as high as 21%.
One needs to keep in mind that in dilute urine (urine Etiology of hematuria varies with age, sex and race.
osmolality <308 mosm/l) RBCs lyse, thereby reducing the Common causes of hematuria are: urinary tract
quantumof microscopic hematuria. infections, stones, BPH, trauma, tumours, cyst rupture
Significance of hematuria in patients following catheterization etc. Glomerular diseases form an important cause of both
macroscopic and microscopic hematuria.
or on anticoagulant drugs
Studies performed by testing pre and post bladder In a study of 105 young men referred to a hospital with
catheterization urine samples for microscopic hematuria, asymptomatic hematuria (mean age 24.8 years [range
revealed that a microscopic hematuria following 18-53], 10% of the participants were > 40 yrs), 46.7% (49
catheter related urothelial trauma was indeed rare. patients) had abnormal findings; 24.8% had nephrological
Likewise control studies of patients on anticoagulants causes and in another 21.9% hematuria was of urologic
also show that anticoagulants don’t increase the risk origin.
of hematuria. Hence it seems prudent not to outright
In a study by Messing et al involving healthy males >50
neglect microhematuriain catheterised patients or those
yrs of age,1340 men were screened at home for hematuria
on anticoagulants. However exceptions can be there in
with dipstick. 21.1% had at least 1 episode of hematuria. Of
patients with clotting or bleeding abnormality or difficult
the 192 hematuria positive men who received a complete
catheterizations.
urological evaluation, 16 (8.3%) had urological cancers
Significance of Dysmorphic RBCs in differentiating upper or and 47 (24.5%) had other hematuria-causing diseases that
lower tract bleeding required immediate treatment.
Isomorphic RBC are normal dumbbell shaped and have In children between8 to 15 years, Bergstein et al observed
smooth round outline. Their presence implies bleeding microscopic hematuria in 4.1% of the participants and
from lower tract. Dysmorphic RBCs (as name implies) among adults the frequency of hematuria was reported
are distorted, broken, less hemoglobinised. This change between 2.4% to 31.1%; with higher rates in males over
of shape occurs due to passage of RBCs through slit 60 yrs.
 2.3 years). Interestingly 15 patients (17%) had complete 163
Table 1: Adult population (18-53 yrs) N= 105
resolution of hematuria. Hence, there is no consensus
Abnormalities frequency regarding the need and timing of renal biopsy in patients
Glomerular Disease 26 (16.6%) with asymptomatic microscopic hematuria. One can say
IgA nephropathy 16 that renal biopsy should not be the first investigation
in these patients. We feel that all patients with isolated
PSGN 3
hematuria should be followed up. Those with persistent
Thin basement membrane disease 2 hematuria should have urological check. Renal biopsy
MPGN 2 should be resorted only if, hematuria is progressive or
Interstitial nephritis 1 there is fresh appearance of proteinuria or renal functions
are getting deranged.
Urological Disease 23 (14.6%)
UTI 5 Urologic evaluation principles1

CHAPTER 31
All patients with asymptomatic microscopic hematuria
Trigonal Cystitis 5 require evaluation. In older individuals even transient
Congenital Hydronephrosis 3 hematuria should raise the suspicion of malignancy.
Urethral Stricture 3 Hence, even a single episode of microscopic hematuria
should prompt evaluation.
Renal Scarring 3
Renal Calcifications 1 Radiologic evaluation is to be performed in all age
groups. Following are the American Urology Association
Cancer Of Renal Pelvis 1
guidelines-
Ureteric Stone 1
For Upper tract- (kidney +Pelvis & Ureter urothelium)-CT
Bladder Cancer 1 urography is recommended.
Table 1 depicts the cause of asymptomatic microscopic When CT is contraindicated in the patient, MR
hematuria as observed in an academic centre based study Urography can be done to delineate the upper urinary
(involving referred patients). tract. When both CT and MRI are not possible, then USG
and retrograde pyelogram may be performed for upper
Should all cases of asymptomatic microscopic hematuria be urinary tract evaluation.
evaluated?
For Lower tract (Bladder + Urethra) cystoscopy is the
Hematuria without formed elements (blood cells casts)
recommended modality.
or proteinuria is called “isolated hematuria. In a study
by Ritchie et al, among the 76 patients with microscopic Cystoscopy is also recommended in all patients >35 years
hematuria who underwent some further investigations of age or patients younger than 35 years but having risk
(all investigations excepting cystoscopy), abnormalities factors for urothelial malignancy**.
were found in 21 (28%); and among those who were
Evaluation-includes evaluation of both upper and lower
fully investigated by examination of midstream urine,
tract urothelium.
intravenous urography, and cystoscopy, abnormalities
were found in 12 (50%). These included bladder neoplasms **Risk Factors for Urinary Tract Malignancy -
(two), epithelial dysplasia (one), staghorn calculi (one),
Male gender,
and chronic reflux nephropathy (one). Hence All subjects
with asymptomatic microscopic hematuria should be Age (> 35 years)
investigated. Past or current H/O smoking,
Role of kidney biopsy in asymptomatic microscopic hematuria History of irritative voiding symptoms
A Japanese study by Hoshino et al. on patients with
asymptomatic hematuria found 62% of the participants History of pelvic irradiation
to have IgA nephropathy while 13% had Thin Basement Occupational or other exposure to chemicals or dyes
Membrane Disease. However, in the study methodology (benzenes or aromatic amines),
there was no mention of any urologic evaluation prior
to the renal biopsy. Majority of these did not warrant Analgesic abuse,
any specific therapy. Hence the role of renal biopsy in History of gross hematuria,
the management of these patients is contentious. In
another study on the long term outcome of asymptomatic History of urologic disorder or disease
microscopic hematuria, only 28 of the total 90 patients History of chronic urinary tract infection
underwent renal biopsy- the most common finding was a
History of exposure to known carcinogenic agents or
normal glomerulus while the second and 3rd most common
chemotherapy such as alkylating agents
finding were thin basement membrane disease (9/28) and
IgA nephropathy (8/28) respectively. After a mean follow History of chronic indwelling foreign body
up of 5 years only one patient developed CKD (after
In patients with persistent microhematuria following
 An algorithm for hematuria is shown in Fig 1.
164

HEMATURIA

RULE OUT
FEVER
STRENUOUS EXERCISE
MENSTRUATION
RECONFIRM

IF HEMATURIA STILL PERSISTS

DETAILED URINE
ANALYSIS+USS
NEPHROLOGY

ASSOCIATED ISOLATED
CYSTIC H/O FLANK STONE
WITH HEMATURIA(NO
DISEASEeg PYURIA + PAIN OR LOIN /OBSTRUCTION/
PROTEINURIA OR MINIMAL
ADPKD TO GROIN PAIN SOL
/RBC CASTS PROTEIN)
IF USS NEG

AGE >35 YRS

REFER TO URINE PROTEIN TO URINE C/S CT SCAN FOR REFER TO
NEPHROLOGIST CREATININE POSITIVE STOENE RISK OF UROLOGIST
RATIO/DYSMORPHIC MALIGNANCY
RBCS
N Y
IF YES
CULTURE 6 MONTHLY UROLOGY
REFER TO
CULTURE POS REPEATEDLY FOLLOW UP (FOR REFERRAL FOR
REFER TO UROLOGIST
NEG HTN,↑CREAT & CYSTOSCOPY
NEPHROLOGIST ↑PROTEINURIA
FOR RENAL
BIOPSY

LOOK FOR TB,

UTI
STONE ETC

REPEAT URINE R/E

AFTER 6 WKS TO
CONFIRM
RESOLUTION

Fig. 1: An algorithm for hematuria

a negative work up or those with other risk factors for of gross hematuria for urological cancers was found to
carcinoma in situ (e.g.irritative voiding symptoms, be 0.22 while the same in people older than 40 yrs was
current or past tobacco use, chemical exposures) urine 0.44. According to AUA any adult with gross hematuria
cytology may be useful. must receive a complete evaluation (CT Urography and
Cystoscopy) for urological malignancy irrespective of
Follow up of patients with a negative urologic workup age. There are only five glomerular conditions which can
Conclusion
For persistent asymptomatic microhematuria after cause gross hematuria-IgA nephropathy, post infectious
negative urologic work up, yearly urinalyses should be glomerulonephritis, pauciimmune glomerulonephritis,
Microscopic
conducted. hematuria
For persistentis aor common urinary abnormality
recurrent asymptomatic across all age groups. Etiology
Alport’s Syndrome and thin basement membrane disease.
microhematuria after initial negative urologic work-up,
varies with
repeat age and
evaluation sexthree
within but toInfections, stonebedisease
five years should APPROACHandTO prostate related diseases
A CASE OF MICROSCOPIC HEMATURIAare
considered. Step 1
dominant causes. Patients with proteinuria, freshly diagnosed hypertension
Confirm presence or deranged
of hematuria. renal
Fever, mensturation,
Approach to gross hematuria
exercise etc are common causes of transient hematuria.
functions have to
The approach generally an identifiable
gross hematuria causetheandUrine
remains practically needshould
renal be
biopsy.
retestedEvery
after patient with
fever/ mensturation
same as that to microscopic hematuria. The only difference
persistent hematuria
is that here the emphasisneeds thorough
shifts to from subsides.
evaluation.
urological causes Despite thorough evaluation a large
the glomerular causes. In a study in pediatric population Scenario 1
proportion
2/4 th ofstill
the remain undiagnosed
participants were found and need
to have periodic
urologic followhasup.
If patient dysuria, fever, increased frequency and urine
causes,1/4th had glomerular causes and in ¼ th the cause shows WBCs/WBC casts- urine culture should be done
remained undiagnosed. Buntinx et al performed a meta- and patient be treated with suitable antibiotics on lines
analysis to find out the diagnostic value of gross hematuria. of UTI. A positive urine culture confirms the diagnosis
Most of the studies included only adults. The pooled PPV of UTI. However, a negative urine culture does not rule
out the same because administration of antibiotics rapidly biopsy. Every patient with persistent hematuria needs 165
makes the urine culture sterile. However, if the suspicion thorough evaluation. Despite thorough evaluation a large
of UTI is clinically low, then the patient should be proportion still remain undiagnosed and need periodic
evaluated for sterile pyuria which involves both urologic follow up.
(for stone/tumor/genitourinary TB) and nephrology
(acute interstitial nephritis) work up. REFERENCES
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Scenario 2 Leveillee RJ, et al. Diagnosis, evaluation and follow-up
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groin, s/o nephrolithiasis, patients be subjected to USS/CT guideline. The Journal of Urology 2012; 188(6 Suppl):2473-81.
scan and referred to urologist. Recurrent stone formers 2. Vehaskari VM, Rapola J, Koskimies O, Savilahti E, Vilska
should undergo metabolic evaluation. CT is much better J, Hallman N. Microscopic hematuria in school children:
modality for picking stone vis a vis USS. epidemiology and clinicopathologic evaluation. The Journal

CHAPTER 31
of Pediatrics 1979; 95(5 Pt 1):676-84.
Scenario 3 3. Messing EM, Young TB, Hunt VB, Roecker EB, Vaillancourt
If patient is passing blood clots, it is most likely a urological AM, Hisgen WJ, et al. Home screening for hematuria:
problem e.g. bladder tumour, trauma, bladder stone etc. results of a multiclinic study. The Journal of Urology 1992;
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Scenario 4 Significance of the evaluation of asymptomatic microscopic
If urine shows dysmorphic RBCs, proteinuria, RBC casts haematuria in young men. British Journal of Urology 1994;
etc. glomerular pathology is likely. A proteinuria of >2 74:723-9.
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Emergency Medicine 1986; 4:14-6.
Scenario 5
If patient has isolated hematuria or insignificant 6. Hockberger RS, Schwartz B, Connor J. Hematuria induced
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exclude urology cause. Many such patients have
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disease or Alport’s Syndrome and are unlikely to require haematuria found at screening. British Medical Journal
(Clinical Research Ed) 1986; 292:681-3.
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need to be followed up periodically. R. Diagnostic value of urinary dysmorphic erythrocytes in
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CONCLUSION 9. Hoshino Y, Kaga T, Abe Y, Endo M, Wakai S, Tsuchiya K, et
Microscopic hematuria is a common urinary abnormality al. Renal biopsy findings and clinical indicators of patients
across all age groups. Etiology varies with age and sex with hematuria without overt proteinuria. Clinical and
but Infections, stone disease and prostate related diseases Experimental Nephrology 2015; 19:918-24.
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diagnosed hypertension or deranged renal functions isolated microscopic haematuria: long-term follow-up.
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