Hematuria of Unknown Origin

1. HEMATURIA OF UNKNOWN
ORIGIN
(Case Discussion)
Dr Shuah Ullah
Resident

2. Case History :
Patient Asma Inayat, 28 years old female, Known case of HTN, married
(2017), resident of Baldia Town, presented first time at SIUT in Jan 2012
with complains of :
Recurrent Gross Hematuria
Bilateral Flanks Pain

3. According to her, she had multiple episodes of hematuria for last one
year (2011) and she has been catheterized at local hospital for clot
retention.
On presentation at SIUT, she has B/L Flanks Pain, which was mild, non
radiating, associated with urinary retention.

4. She was recently diagnosed as hypertensive and BP was well controlled
on anti-HTN.
No other significant clue was found in history for DM, TB, Jaundice,
Malignancy and Hematological Disorders.
No any addiction.
Transfusion hx was positive in last one year.

6. Investigations at SIUT :
Blood CP : HB 8.9 S. Cre 0.70
PCV 30.6 ESR 11
MCV 82.6 RBC Morphology Uniform
TLC 7.9 (P 56.4% L 33.6%)
PLT 286000
LFT : T.Bil 0.6 (Direct 0.1)
SGOT 29
SGPT 23
GGT 36
ALK PHOSP. 69
INR 1.07

7. Urine DR : Albumin 3+
RBC Numerous
Pus Cells Numerous
Rest all were negative.
Urine CS : Insignificant Bacterial Growth.
ULTRASOUND : Bilateral normal kidneys. No Stone. No HDN.
Urinary Bladder, normal wall thickness, partially filled.

8. Urethrocystoscopy and four quadrant biopsy was done on 28-01-2012.
Operative Findings :
Normal urethra
Raised Bladder neck.
Bladder wall mildly trabeculated, otherwise normal.
Both ureteric orifices clearly visualized and there was no bleeding or oozing
from the orifice.
Good flow of urine after filling the bladder.

10. Cystourethroscopy was again done on 27-08-12, as patient keeps on visiting for hematuria
after first cystoscopy.
Findings :
Normal Urethra.
No visible growth.
No Hematuria.
B/L normal ureteric orifices.
Mildly Trabeculated Bladder.
No Biopsy was taken.

11. Patient remain symptomatic with intermittent hematuria.
CT Abdomen Triphasic was done on 09-05-2013.

13. Renal Biopsy was planned after consultation with Nephrology and
Internal medicine team.

15. Histopathologist was unable to rule out thin membrane disease on EM.
But Nephrology team ruled out possibility of thin membrane disease as
hematuria with clots is not a feature of this disease.

17. Patient repeatedly visited opd and ER with intermittent gross
hematuria, and lower tract pathology was already ruled out so planned
for B/L Ureteroscopy.
B/L Ureteroscopy + B/L Ureteric catheterization was done on 14-05-
2015.

18. Operative findings include :
B/L normal ureter upto PUJ
No growth or erythematous areas seen.
Cystoscopy also showed no growth or erythema.
Urine cytology was sent from B/L ureteric catheter, which turned out to
be negative for any malignant cells and show mixed inflammatory cells
infiltrate.

19. Planned for CT Angiogram as patient remain symptomatic, which was
done on 18-01-2016.

26. In March 2017, steroid therapy was initiated by nephrology team.
Serological test including Hep B, Hep C, C3, C4 levels were all normal
and patient didn’t respond on steroid and advised to taper but pt. keep
on taking on her own.

30. • On detail discussion with radiologist, he advised to repeat CT
Triphasic as SMA abnormality was suspected on reviewing last year
CT.
• CT Triphasic was repeated on 21-12-2017.

43. CURRENT STATUS
• Admitted on 23-04-2018 with complains of vertigo, blackouts,
syncope, SOB on walking.
• Found to be anemic, so optimized via blood and iron supplements
and discharged on 27-04-18

44. Discussion
• Thin Membrane Disease
• Loin Pain Hematuria Syndrome
• Nutcracker Syndrome

45. LOIN PAIN HEMATURIA SYNDROME
• The loin pain-hematuria syndrome (LPHS) was first described in 1967 in a
report of three young women (20 to 28 years of age) who had recurrent
episodes of severe unilateral or bilateral loin (flank) pain that were
accompanied by gross or microscopic hematuria.
• The major causes of flank pain and hematuria, such as nephrolithiasis and
blood clot, were not present. Renal arteriography suggested focally
impaired cortical perfusion, while renal biopsy showed interstitial fibrosis
and arterial sclerosis.

46. • Classified as rare disease with highest reported cases in central Ohio
i.e. 200 cases in 2 Million population.
• Characterized by recurrent or persistent loin (flank) pain and
hematuria that appears to represent glomerular bleeding.
• Affected patients are typically young (mean age of 31 years in one
review, with some cases occurring in teenage children) women (70 to
80 percent in most series).

47. Cause :
• One theory proposes that it is caused by a thin glomerular basement membrane
and RBC renal tubular congestion that leads to swelling of the kidney and
distension of the renal fascia resulting in pain.
• May be due to blood vessel diseases of the kidney, spasms of the kidney vessels,
or other bleeding disorders (coagulopathy).
• The hematuria in LPHS may be due to an abnormal (thick or thin) glomerular
basement membrane. An abnormal glomerular basement membrane may allow
red blood cells into the urinary space.
• Kidney stones are common in people with LPHS, crystals in the kidney tubules
may also play a part in bleeding and pain

48. Classic loin pain-haematuria syndrome
Some patients have none of the underlying cause.
In these cases there may be minor abnormalities on a kidney biopsy.
Angiogram tests to look at the blood vessels in the kidney may show abnormal
blood flow, perhaps causing a cramp like pain.
The cause is not fully understood. It more common in women than in men, and
there may be hormonal influences.
Some women find the pain is worse at different times of their menstrual cycle, or
comes on during pregnancy, or if they are taking
oral contraceptives.

49. Diagnosis :
• LPHS is considered a diagnosis of exclusion. The syndrome presents
with hematuria and flank pain which can result from a number of
causes.
• Non glomular bleeding (e.g., urinary infection, tumor, or
nephrolithiasis) must be excluded.
• Obstruction of the urinary tract should not be present, confirmed by
at least two imaging procedures while pain is present.

50. Protein is also commonly found in the urine of patients with LPHS.
Kidney biopsies are sometimes performed to look for evidence of glomerular
hematuria, excess red blood cells in the kidney tubules, and to assess the
width of the glomerular basement membrane.
Hematuria (more than 5 red blood cells per high power field) should be
present in virtually every urinalysis and is typically characterized by
dysmorphic red cells.
Recurrent or persistent severe pain for six months or more, occurring in the
costovertebral angles

51. TREATMENT :
Standard of care does not exist.
Pain Management with opioids and non-opiate.
Angiotensin converting enzyme inhibitors are thought to be beneficial
as they reduce intra-glomerular pressure and reduce renal tubular
congestion with RBCs.

52. NUTCRACKER SYNDROME
Compression of the left renal vein,
most commonly between the
aorta and the superior mesenteric
artery, with impaired blood
outflow often accompanied by
distention of the distal portion of
the vein.

53. Symptoms :
• Hematuria is the most commonly reported symptom and is attributed to
rupture of thin-walled varices, due to elevated venous pressure, into the
collecting system.It varies from microhematuria to macrohematuria.
• Pain is the next most common symptom. Characterized by abdominal or
flank pain that occasionally radiates to the posteromedial thigh and
buttocks.
• Varicoceles almost always occur on the left side and affect up to 9.5% of
men.

54. • To rule out more common renal conditions, diagnostic methods include
blood examinations, urinalysis, urine culture, cytology, urethrocystoscopy,
CT urography, and renal biopsy.
• In cases of hematuria, the number of isomorphic erythrocytes, suggesting
nonglomerular origin, may be variable, and this finding is unreliable.
• Doppler ultrasonography is a helpful, noninvasive modality and should be
the first assessment after NCS is suspected. Sensitivity of DUS ranges from
69% to 90%, and specificity from 89% to 100%

55. Treatment :
• Management options range from observation to nephrectomy,
depending on the severity of symptoms.
• Angiotensin inhibitors may be helpful in improving orthostatic
proteinuria in patients with NCS.
• Interventions should be considered only when symptoms are severe
or persistent, including severe unrelenting pain, severe hematuria,
renal insufficiency, and failure to respond to conservative treatment
after 24 months.

56. A variety of surgical approaches have been used, including
Medial nephropexy with excision of renal varicosities.
LRV bypass.
LRV transposition with or without Dacron wedge insertion between SMA and
aorta.
SMA transposition.
Renal-to-IVC shunt.
Renal autotransplant.
Gonadocaval bypass,and even nephrectomy for persistent hematuria.

57. THANK YOU