1. Hematuria Katie Townes MD, PGY2

2. Case 8 year old male with episodic hematuria, initially thought to be due to trauma, but persisted for weeks and recurred with fevers. Also with severe anemia requiring multiple blood transfusions. Hematuria seemed to occur when he was febrile……

3. What is hematuria? >5 RBCs per high power field Microscopic vs. gross hematuria Multiple differentials of hematuria

4. RBCs in urine microscopy Library.med.utah.edu

5. Foods or medicines that turn the urine red? Urate crystals in diapers Myoglobinuria? -positive heme on dipstick -no RBCs seen on microscopy -cause? -muscle breakdown from rhabdomyolysis (crush injury, burns, asphyxia) Hemoglobinuria can be caused by hemolysis, but again, no RBCs seen on microscopy Things that are NOT Hematuria

6. Urate Crystals in Diaper From newborns.stanford.edu

7. Differentials Glomerular disease Tubular disease UTI Schistosomiasis Trauma Tumors Stones Polycystic kidney disease

8. Glomerulonephritis History -coca-cola colored or smoky urine -edema -malaise Physical -hypertension -edema Labs -renal failure -microscopy RBC casts and dysmorphic RBCs Cyberrounds.com

9. Formation of RBC casts -GBM is damaged -RBCs can get through GBM -Going through the tubule, the stick together, forming casts that appear in the urine Library.med.utah.edu

10. Casts and dysmorphic RBCs Library.med.utah.edu

11. Glomerulonephritis Causes post-strep GN membranoproliferative GN RPGN IgA nephropathy SLE Alport’s disease (not really GN…)

12. Glomerular Disease- Treatment Post-Strep GN usually self-resolves in kids Kidney biopsy RPGN, Membranoproliferative GN, IgA nephropathy, SLE- immunosuppressives (steroids, cyclophosphamide) Supportive treatment: anti-HTN, fluid restriction, Lasix Many will develop ESRD and need HD or transplant

13. Tubular disease ATN -anoxic injury -rhabdomyolysis -certain medications/toxins? -sometimes reversible with supportive care Cortical necrosis -usually due to severe anoxia -often irreversible AIN -urine eosinophils elevated -usually related to medications- sulfa, ibuprofen -reversible when stopped

14. UTI Causative organisms? History -dysuria, frequency, urgency- lower UTI -Fever, back pain, vomiting- upper UTI Physical -fever- upper -suprapubic pain -CVA tenderness- upper Labs -CBC -U/A? -urine culture Catsmeowvets.com

15. UTI WBC- see nuclei WBC cast in pyelonephritis Library.med.utah.edu

16. UTI Treatment (WHO book) Cotrimoxazole 4mg TMP/20mg sulfa per kg PO BID x 5d if no signs of upper tract infection Alternatives: Ampicillin, Amoxicillin, Cephalexin, Ciprofloxacin If signs of pyelo or in young infants (<2 months), give parenteral Ampicillin and Gentamicin or cephalosporin x10-14 days Consider sepsis or perinephric abscess if no resolution with antibiotics

17. Schistosomiasis-Pathophys Larval parasites penetrate cutaneously Migrate hematogenously to portal system, where mating occurs over 1-3 months S. hematobium organisms migrate to venous channels in bladder and lay eggs Eggs breach vessel walls and enter the bladder, causing inflammatory response and urinary symptoms Eggs are then passed back into the water by urination, completing the cycle

18. Schisto- Clinical Acute sx -fevers -pruritic rash (swimmer’s itch) -LAN -abdominal pain Chronic sx -terminal hematuria -dysuria -obstructive uropathy -Chronic inflammation can cause malnutrition, poor growth Diagnosis: urine microscopy to look for eggs (only in chronic stage) Treatment- Praziquantel, education (avoid fresh water!)

19. Schistosomiasis commons.wikimedia.org

20. Trauma History -trauma to the back -flank pain Physical -evidence of trauma -flank bruising Labs: hematuria without casts

21. Tumors? Wilms tumor (nephroblastoma) ◦Most common pediatric renal malignancy ◦Median age 3-3.5 years, M=F ◦History: hematuria, abdominal mass, fever, abd pain ◦Physical: palpable abdominal mass Treatment: surgery +/- chemoradiation Rhabdomyosarcoma

22. Wilms Tumor www.szote.u-szeged.hu/radio/retr/ret4c.gif

23. Stones Uncommon in children History: flank pain, gross hematuria Physical: writhing in pain, flank pain, abdominal pain, can’t get comfortable Labs: Urinalysis with positive heme and positive RBCs (no casts) Treatment: pain control, fluids. Stones can usually pass on their own if not too big Complications: obstruction causing UTI, abscess, sepsis if stone doesn’t pass

24. Stones Most common places to obstruct: 1)Renal pelvis 2)Crossing the pelvic brim 3)Entering the bladder Staghorn calculus Calcium oxalate All images from google images

25. Polycystic kidney disease Autosomal dominant PKD doesn’t affect children (renal failure usually 4 th -5 th decade) Autosomal recessive PKD affects children, can be variable (infants-adolescent presentation). Depending on category, liver disease also part of the syndrome Clinical- renal failure, palpable flank masses, cystic kidneys on ultrasound Treatment- ARPKD eventually progresses to ESRD, needing HD or transplant

26. PKD-Images Healthjockey.com nature.com

27. Hemoglobinuria Due to hemolysis (sickle cell, G6PD def, malaria, TTP, DIC, HUS) U/A shows positive heme, but no RBCs Hemoglobin is toxic to kidneys, causes ATN

28. Paroxysmal Nocturnal Hematuria Rare, autosomal dominant mutation of RBC membrane protein (GPI-anchor), leads to complement deposition and intravascular hemolysis Clinical triad of intravascular hemolytic anemia, venous thrombosis, and pancytopenia Median age 46, but children can be affected Children tend to have aplastic anemia Hematuria most noticeable in AM when urine is concentrated, but can occur anytime

29. Paroxysmal Nocturnal Hematuria History -Fatigue and jaundice (hemolytic anemia) -coca cola colored urine -abdominal pain, headache, SOB (clots) -bleeding, infections, fatigue (BM failure) Physical -signs of hemolytic anemia (pallor, tachy, jaundice) -usually no spleen, because intravascular hemolysis -abdominal pain may suggest hepatic or portal vein thrombosis -petechiae or fevers to suggest pancytopenia

30. Paroxysmal Nocturnal Hematuria Treatment -medial survival is 10 years, death usually due to thrombosis -immunosuppression with steroids can help with hemolytic anemia -Folic Acid for all children with hemolytic anemia. Why? -beware infection risk….

31. Back to the case: So what diagnosis makes the most sense? -UTI? -Trauma? -Glomerulonephritis? -Myoglobinuria? -Paroxysmal nocturnal hemoglobinuria? -Sickle cell anemia?

32. References Besa, Emmanuel. “Paroxysmal Nocturnal Hematuria.” emedicine.com. March 2009 library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.ht ml#2 library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.ht ml#2 Nelson’s Essentials of Pediatrics. 5 th Edition. Chapter 163, page 757-759. Young, B. Y. et al. Autosomal Recessive Polycystic Kidney Disease. Emedicine.com. April 28, 2010. www.szote.u-szeged.hu/radio /retr/ret4c.gif