Hematuria

1. Hematuria For Surgical Board... Dr. M. El-Shazly MD Urology

2. Hematuria is a frequent reason for physician consultation in clinical practice up to 8-20% of urology consultations (Messing et al., 2006).

3. Definition • Macroscopic (gross) Hematuria (VH) • visible to the human eye (Red Urine) • Microscopic Hematuria (NVH) • >3RBC/hpf from two of three urinary sediments without a urinary tract infection, or menstruation on microscopic evaluation (Grossfeld et al., 2001)

4. Hematuria can be caused by a variety of urothelial, vascular, glomerular, interstitial disorders.

6. The main focus in the workup of hematuria is tumor detection, either urothelial cell cancer or renal cell carcinoma (RCC).

7. Definition of positivity • Urine dipstick of a fresh voided urine sample, containing no preservative, is considered a sensitive means of detecting the presence of haematuria. • Routine microscopy for confirmation of dipstick haematuria is not necessary.

8. Significant haematuria is considered to be 1+ or greater. Trace haematuria should be considered negative

9. Trace versus 1+ • Significant haematuria is considered to be 1+ or greater. • Trace haematuria should be considered negative

10. What is significant haematuria? • a) Any single episode of VH. • b) Any single episode of s-NVH (in absence of UTI or other transient causes). • c) Persistent a-NVH (in absence of UTI or other transient causes). Persistence is defined as 2 out of 3 dipsticks positive for NVH.

11. Transient causes to be excluded: • Urinary tract infection (UTI) - A negative dipstick result for both leucocytes and nitrites. Otherwise an MSU negative for pyuria and culture are required. • • Exercise induced haematuria or rarely myoglobinuria • • Menstruation.

12. Urological referral • The following patients require direct referral to urology for further investigation. • • All patients with visible haematuria (any age). • • All patients with s-NVH (any age). • • All patients with a-NVH aged ≥40 yrs.

14. Glomerular Hematuria • brown, tea colored urine • proteinuria • deformed urinary RBCs • RBC casts

15. RENAL IgA nephropathy Alport syndrome Thin glomerular BM disease Post infectious MPGN MULTI-SYSTEM SLE nephritis HSP nephritis Wegener syndrome Goodpasture syndrome HUS Sickle cell Disease Glomerular Hematuria

16. W/u for Glomerular Hematuria • CBC • C3,C4 • antistreptolysin-O titer, streptozyme titer • serum electrolytes, BUN, serum Cr, serum albumin • test for lupus • Hep B • antinuclear cytoplasmic antibody titer

17. Extraglomerular Hematuria • Hematuria from lower urinary tract • terminal hematuria • blood clots • nl urinary RBCs • minimal proteinuria

18. UPPER URINARY TRACT pyelonephritis ATN papillary necrosis nephrocalcinosis thrombosis malformation SCD tumor PCKD LOWER URINARY TRACT cystitis urethritis urolithiasis trauma coagulopathy heavy excersise UPJ obstruction ureterocele Munchausen, MBP Extraglomerular Hematuria

19. Nephrological referral • Evidence of declining GFR (by >10ml/min at any stage within the previous 5 years or by >5ml/min within the last 1 year) • • Stage 4 or 5 CKD (eGFR <30ml/min) • • Significant proteinuria • • Isolated haematuria with hypertension in those aged <40. • • Visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection

20. Nephrologic Causes of Hematuria • Nephrologic causes of hematuria should be considered early in the workup of both microscopic and macroscopic hematuria because up to 10% of cases of hematuria can be nephrologic (Khadra et al., 2000). • The most frequent causes include IgA nephropathy and thin basement membrane nephropathy.

21. Nephrologic Causes of Hematuria • There is no simple test to differentiate urologic from nephrologic hematuria. Most tests depend on pattern recognition and urinalysis, especially the urine sediment. The most important clues include the presence of hypertension, reduced renal function, proteinuria, and the presence of dysmorphic erythrocytes in the urine sediment.

22. Nephrologic Causes of Hematuria • If the percentage of dysmorphic erythrocytes increases above 20%, a glomerular cause is likely; if the percentage of dysmorphic erythrocytes is above 80%, a glomerular cause is almost certain

23. The Clinical Picture: Microscopic Versus Macroscopic Hematuria • The traditional risk factors for malignancy include macroscopic hematuria, smoking, age, sex, micturition complaints, urothelial cancer, radiotherapy of the pelvis, and working with aromatic amines in the chemical industry

24. Macroscopic Hematuria • The risk for malignancy is high. Malignancy can be found in 10–28% of cases overall and in up to 10% of patients younger than 40 years [Booman et al., 2001)). • In the study of Edwards et al. [13], upper urinary tract urothelial cell cancer was found in 0.5% and RCC in 2% of patients, and 16.5% of patients were diagnosed with bladder cancer (90%).(Edwards et al., 2006)

25. Recurrent Microscopic Hematuria • The risk of urologic malignancy is much lower with microscopic than with macroscopic hematuria. Depending on the population studied, in up to 8.9% of patients with recurrent microscopic hematuria, a malignancy was found [ Interestingly, In the largest cohort studied, upper urinary tract urothelial cell cancer was found in 0.2%, RCC in 1%, and bladder cancer

26. Glomerular Brown or tea-colored RBC cast, cellular cast Tubular cells Proteinuria >2+ Dysmorphic erythrocytes Erythrocyte volume <50 um3 Non-glomerular Red-pink urine Blood clots No proteinuria or <2 Normal morphology of erythrocytes Erythrocyte volume > 50 um3 Localization of Hematuria

27. Hematuria • Patient comes to your office complaining that their urine is reddish in color... • What is your first step?

28. Laboratory Diagnosis of Hematuria • Urinalysis : • Even though most urine samples are early morning urine, for analysis of corpuscular elements, the so-called “second morning urine” is more suitable and recommended. • Analysis should follow rapidly, preferably within 1 hour for sediment analysis and 2 hours for dipstick testing.

29. Urine Cytology • The sensitivity of urine cytology for the diagnosis of urothelial cell cancer is low, and a negative result does not exclude patients from further testing (Rodgers et al., 2006]. • It has been shown in multiple studies that the addition of urine cytology in the primary analysis of hematuria does not contribute to diagnosis [Hovius et al., 2008], which is usually made by cystoscopy or imaging.

30. Urine Culture • The addition of cultures of urine may be indicated if the sediment shows leukocytes.

31. Clinical Chemistry • Important to support a nephrologic diagnosis • RFT • Coagulation profile

32. Cystoscopy • Flexible cystoscopy remains the reference standard for diagnosis of hematuria of the lower urinary tract

33. Cystoscopy • The American Urological Association best practice policy suggests that, in patients at low risk for urothelial cancer, cystoscopy may be avoided [4, 5]. Imaging of the bladder should preferably precede cystoscopy, so it can aid the urologist and improve diagnostic yield.

34. Ureterorenoscopy • Upper tract gross hematuria • (Unilateral hematuria) • Urothelial tumors ofupper urinary tract if imaging is not conclusive and negative cytology

35. Radiologic Diagnosis of Hematuria • Radiologic imaging plays a pivotal role in the diagnosis of hematuria • No specific diagnostic algorithm for hematuria

36. Abdominal Radiographs • Its overall sensitivity for renal and ureteral stones is only 45–60% in multiple studies (Ege et al., 2004)

37. Non-contrast CT • It is now the reference standard for stone detection, and even very-low-dose unenhanced CT techniques with a radiation dose comparable to that of abdominal radiographs have shown better results (Kluner et al., 2006)

38. Ultrasound • Ultrasound is suitable as first-line diagnostic test • In comparison with excretory urography, ultrasound showed a higher sensitivity for bladder tumors and equal (i.e., moderate) sensitivity for upper urinary tract tumors. Ultrasound alone is not sensitive (19–32%) for stone detection,

39. Excretory Urography • For hematuria, multiple studies have now shown the superiority of CT urography over excretory urography. There is also a low sensitivity (< 60%) for renal tumors smaller than 3 cm for excretory urography

40. Retrograde Ureteropyelography • However, with the increasing use of MDCT urography and ureterorenoscopy, its role has diminished significantly. It has been shown that, in high-risk patients, CT urography is equivalent to retrograde ureteropyelography in the upper urinary tract

41. CT Urography • For identification of the cause of hematuria, the overall sensitivity is 92–100%, and the specificity is 89–97% (Albani et al.,2007 & Sudakoff et al., 2008)

42. Radiation Exposure • KUB =0.2–0.7 mSv • CTKUB =(2–3 mSv) • CTU=(9-16 mSv)

43. Imaging is key in the analysis of hematuria, but it should be realized that CT urography is a high-dose examination, upper urinary tract urothelial cell cancer is a rare disease, and the risk for malignancy in many patients with microscopic hematuria is relatively low. Therefore, the use of CT urography should be justified by weighing benefits versus risks, and CT urography protocols should be optimized to radiation dose.

44. Therefore, the use of CT urography should be justified by weighing benefits versus risks, and CT urography protocols should be optimized to radiation dose.

45. This can be accomplished well by this risk-based approach to the work-up of hematuria, whereby initial screening is performed with ultrasound and CT urography as a first-line modality is reserved for patients at high risk of malignancy.

46. MR Urography (MRU) • MRU has inherent advantages in that it does not require ionizing radiation, has a high contrast resolution, has good sensitivity for contrast media, and has the possibility for better tissue characterization than other imaging techniques do

47. MR Urography (MRU) • However, MRU is costly, technically demanding, and not widely practiced. Therefore, MRU expertise is available only in specific dedicated centers. • It is good for pediatric diseases and for the evaluation of obstructive disease (Silverman et al., 2009)

48. A Vision for the Future • Validated Scoring System

49. Quiz Time Let’s see who has been paying attention...

50. Quiz time #1 • 10 yr old boy coming in for school physical. Found to have 30 RBC/hpf on microscopic analysis. • Family Hx reveals uncle used to have “blood in his urine” • What is your diagnosis?