1. Hematuria in Children Alok Kalia, MD Director, Division of Pediatric Nephrology University of Texas Medical Branch Galveston, TX 77555-0373

2. Hematuria in Children Red or brown urine- Is it hematuria? - dipstick examination positive and red blood cells on microscopy: hematuria - dipstick examination positive but no red blood cells on microscopy: hemoglobinuria or myoglobinuria - dipstick examination negative: a dye or pigment other than hemoglobin or myoglobin is present

3. Hemoglobinuria and Myoglobinuria - hemolytic anemias - mismatched blood transfusion - drugs and toxins (Pamaquin, snake bite, spider bite, etc) - paroxysmal nocturnal hemoglobinuria - freshwater drowning - cardio-pulmonary bypass - crush injuries/muscle trauma - drug induced muscle injury

4. Red or Brown urine with negative dipstick Pink, red, brown, or burgundy: - beets - blackberries - nitrofurantoin - rifampin - urates Dark brown or black: - alkaptonuria - homogentisic aciduria - methemoglobinuria - tyrosinosis

5. Hematuria in Children Laboratory tests for hematuria: 1. Dipstick: Uses the peroxidase-like activity of hemoglobin to effect a color change. - The test can be false positive if other oxidizing agents are present in the urine, such as bleach (hypochlorite) used for cleaning urinals. - The test can false negative in the presence of reducing agents, such as ascorbic acid, or if the urine is highly concentrated.

6. Hematuria in Children Laboratory tests for hematuria: 2. Urine microscopy: Red blood cells (RBCs)/high power field (HPF). a) centrifuge 10 ml of urine for 5 minutes b) decant the supernatant c) re-suspend the sediment in 0.5 ml of urine d) place on a slide with a cover slip e) count the number of RBCs in 20 fields and report the average Positive test: 5 or more RBCs/HPF

7. Hematuria in Children Laboratory tests for hematuria: 3. Urine microscopy: Red blood cells per cu. mm (microliter) - place uncentrifuged urine in a counting chamber (the same one as is used for WBC and RBC count) - read and report results as RBCs/microliter Positive test: > 5 RBCs/cu mm

8. Hematuria in Children Clinical presentations of hematuria: - microhematuria, incidentally discovered - microhematuria, with symptoms - microhematuria, with intermittent gross hematuria - intermittent or continuous gross hematuria -hematuria with proteinuria

9. Hematuria in Children Prevalence of asymptomatic microhematuria Dodge et. al, Galveston: - 12,000 schoolchildren in 1st, 2nd, or 3rd grade - tested once every year for 5 years (5 or more RBCs/HPF) - 6070 children tested all 5 years - 50% of children who had hematuria one one specimen did not have hematuria on the 2nd or 3rd specimen The prevalence of hematuria, if defined as the presence of blood on at least 2/3 specimens, was 1% in girls and 0.5% in boys

10. Hematuria in Children Prevalence of asymptomatic microhematuria Vehaskari et. al, Finland: - 8954 children, 8-15 years old - 4 specimens from each child (6 or more RBCs/cu. mm.) - 305 had blood (without protein) - of these, 222 had blood only in one collection - 83 had blood on more than one collection - of these 8 had a known etiology - of the remaining 72, only 43 had blood 1 month later and only 27 at 4- months. The prevalence of hematuria, if defined as the presence of blood on at least 2/4 specimens, was 1.1%

11. Hematuria in Children Sites of origin of hematuria: - Glomerular - Renal, but not glomerular - Non-renal

12. Hematuria in Children Renal Non-Renal Color of the urine: Brown Red RBC casts: Present Absent Protein: May be+ No RBC shape: Distorted Normal None of these features are present all the time

13. Hematuria in Children Causes of glomerular hematuria: - Post-infectious nephritis - IgA nephropathy - Henoch-Schonlein purpura - Hereditary nephritis - Benign familial hematuria - Membranoproliferative glomerulonephritis - Lupus nephritis - Others...

14. Hematuria in Children Discussion of selected diagnoses:

15. Hematuria in Children Causes of Renal, Non-glomerular hematuria: - Nephrocalcinosis - Interstitial nephritis, drug induced or other - Pyelonephritis - Renal vein thrombosis - Hemoglobin S - Malformation: aneurysm, hemangioma, arterio-venous fistula - Wilm’s tumor - Renal cell carcinoma -Cystic diseases (Polycystic disease, simple cysts) - Others...

16. Hematuria in Children Discussion of selected diagnoses:

17. Hematuria in Children Causes of Post-renal hematuria: - Urolithiasis - Hypercalciuria - Papillary necrosis (infections, diabetes, HbS) - Trauma - Infection (bacterial or viral) - Drugs (cyclophosphamide) - Prostatitis - Exercise-induced hematuria - Vascular malformation - Foreign body - Others...

18. Hematuria in Children Discussion of selected diagnoses:

19. Hematuria in Children Clinical approach to hematuria: Could this be something serious, and should start doing some tests or send the child to a specialist, or should I wait and see what happens?

20. Hematuria in Children Some questions to ask in the history… - duration and pattern of hematuria - family history (hematuria, renal failure, deafness, urolithiasis) - pharyngitis, upper respiratory infection - dysuria or other symptoms of urinary infection - rash (Henoch-Schonlein purpura) - abdominal pain (infection, stone, Henoch-Schonlein purpura) - drugs (methicillin, anticoagulants etc.) - others...

21. Hematuria in Children Some clues to look for in the physical examination… - hypertension, edema, pallor - rash, impetigo - ecchymoses, petechiae, hemangiomas - abdominal mass (tumors) - abdominal or flank tenderness (infection) - evidence of abdominal trauma - external genitalia for trauma or bleeding - rectal examination for prostatitis - growth pattern - hearing test

22. Hematuria in Children Review urinalysis carefully or do fresh urinalysis to look for: - shape of RBCs - presence of RBC casts - presence of protein - presence of white blood cells - presence of crystals - repeat urinalysis to see if hematuria persists

23. Hematuria in Children If hematuria is persistent: - Obtain serum creatinine level - Perform urine culture if indicated - Perform urine calcium/creatinine ratio if indicated - Obtain other specific tests if indicated by the history or physical examination (ASO titer, serum complement levels, anti-nuclear antibody, etc.)

24. Hematuria in Children At this stage, one will be able to decide if the child has: a) a specific diagnosis such as post-streptococcal nephritis, hereditary nephritis, urinary tract infection, hypercalciuria, etc. Appropriate investigations can be ordered and management strategies pursued. Continued...

25. Hematuria in Children Or, the child has: b) no specific diagnosis, but the presence of indicators such as gross hematuria, hypertension, edema, significant proteinuria, or growth failure indicate the need for further investigation. Renal function should be assessed, imaging studies undertaken, and other specific tests performed until a diagnosis is made. Continued...

26. Hematuria in Children Or: c) neither “a” nor “b” is applicable. This is known as isolated or asymptomatic hematuria. No further investigation is necessary, but the child should be monitored carefully for any change in the clinical condition Continued...

27. Hematuria in Children If a child has isolated hematuria, one of three outcomes will be seen during follow-up: 1. Hematuria will disappear. If the disappearance is permanent, no further action is necessary. Or 2. New symptoms will emerge, indicating the need for further investigation. Or 3. Hematuria will persist. The child need to be followed regularly with clinical examination, urinalysis, and serum creatinine. Ultimately, a renal biopsy might be necessary.