1. بسم الله الرحمن الرحيم

2. ABDULLAH AL SALLOUM Professor and Consultant of Pediatric Nephrology College of Medicine King Saud University King Khalid University Hospital Riyadh, Saudi Arabia HEMATURIA

3. Hematuria is a common finding on urinalysis with a prevalence rate between 1% and 2%, and is more common in girls. Majority is benign. Is the presence of blood in the urine and not only the color. Is the main presentation of patient with renal disease.

4. HEMATURIA Presentations of Hematuria Gross hematuria Microscopic hematuria with clinical symptoms Asymptomatic microscopic (isolated) hematuria Asymptomatic microscopic hematuria with proteinuria (most alarming). Proteinuria is always an indication of a serious condition. – Any patient with proteinuria and hematouria should be dealt with immediately because the protein is toxic to the kidney.

5. HEMATURIA Diagnosis: Dipstick (urine strip test). – The most sensitive test for detecting the presence of blood in the urine, is abnormal urine strip test. – Up to 3 RBC/HPF can be detected (2-5RBC/HPF). – Can give you a false positive or false negative if it has high specific gravity but rarely. – Should be done in the nephrology ward because if you do it in the lab it will lyse and give you a wrong reading. – > 5 RBC/HPF in children or 10 in adults is significant for hematuria. Check it on 3 different occasions. Must check it again in 3 weeks if positive then it is pathological. And if positive you have to confirm by microscopy.

6. HEMATURIA Urine Strip Test: The reagent utilizes the pseudoperoxidaze activity of hemoglobin (or myoglobin) to catalyze a reaction between hydrogen peroxide and the chromogen tetramethylbenzidine to produce an oxidized chromogen, which has a green blue color.

7. HEMATURIA Urine Strip Test: Strips can detect concentration of 2-5 RBC/HPF

8. HEMATURIA False negative urine dipstick: High specific gravity urine High ascorbic acid concentration in the urine. False positive urine dipstick: Delayed reading Cross contamination of urine from other chemicals such as oxidized agent, (household bleach)

9. HEMATURIA Confirmation of hematuria Urine Microscopy: Centrifuge 10 ml of urine for 5 minute Decant the supernatant Re-suspend the sediment in 0.5 ml of urine Place on a slide with a cover slip Count the number of RBC. In 20 fields and report the average – Positive Test: > 5 RBC/HPF

10. HEMATURIA Definition of hematuria: 5 RBC’s /HPF in three of three consecutive, fresh, centrifuged urine specimens obtained at least 1 week apart.

11. HEMATURIA Localization of hematuria: Limits diagnostic possibilities for patients and prevent unnecessary testing. Must know if the blood is coming from the kidney or lower tract (ureter, urethra, bladder). If blood comes from the kidney (parenchyma and calyces), it is mostly associated with proeinuria and blood clots. Lower tract is rarely associated with proteinuria usually fresh blood.

12. HEMATURIA Classification: Glomerular hematuria (most serious). Non-Glomerular hematuria (mostly benign in children unlike in adults where it mostly indicate malignancy)

13. HEMATURIA Glomerular hematuria, Clinical presentation: Oliguria (<1 ml/kg/hr). – Polyuria (>5 ml/kg/hr), normal urination (2-4 ml/kg/hr), and anuria (no urine). These are not normally seen in glomerular hematuria. Presents with edema due to protein interstitial leak and retention and activation of the renin angiotensin system. – Systemic disease like SLE and HSP (more common in children. Presents with arthritis, skin rash, and hematuria). Hypertension due to renin angiotensin aldosterone activation. Symptoms of systemic disease (e.g. arthritis, rash).

14. HEMATURIA Glomerular hematuria: Brown tea, cola-colored urine. – Brown because the blood is old because it goes a long path and is sequestered epithelium Concomitant proteinuria Cellular cast (collection of RBC or WBC in a protein mesh), always indicates serious pathology (glomerular hematuria) Dysmorphic erythrocytes in phase-contrast microscopy (which is a special test). > 15% abnormal RBC is significant for glmerularnephritis not cystitis or urethritis. (golmerular disease). Low MCV of erythrocyte by automated analyze

17. HEMATURIA RBC CASTS: RBC casts are best visualized at the edges of the cover slip and tend to dissolve in urine of high PH.

19. HEMATURIA Causes of Glomerular hematuria: 1.Post-infectious glomerulonephritis (most common). 2.IgA nephropathy (common in Asians, only renal presentation unlike HSP which is systemic). 3.Henoch-Schönlein purpura (systemic presentation: kidneys + joints + vessels). 4.Hereditary nephritis or Alport syndrome ( most develop RF around the age of 20) 5.Benign familial hematuria (presents with microscopic hematuria) 6.Membranoproliferative glomerulonephritis 7.Lupus nephritis

20. HEMATURIA Differential diagnosis of RBC cast glomerulonephritis with low C3: Acute post-streptococcal (infectious) glomerulonephritis comprises 80%. Lupus nephritis (SLE), in children 80% have a renal presentation unlike adults. Membrane proliferative glomerulonephritis.

21. A child presenting with generalized edema (including peri-orbital and scrotal edema), hypertension, oligouria and gross hematuria is seen in any glomerulonephritis, most commonly acute post infectious. Minimal change: no hematuria.

22. HEMATURIA Postinfectious GN: Begins 7-21 days after group A beta-hemolytic streptococcal infection. Antibiotic treatment for the infections will not prevent the nephritis (hypertension, oliguria, edema, and high creatinine). Present with tea colored urine, edema and hypertension. May present with only microscopic hematuria, and the presence of edema is serious.

23. HEMATURIA Postinfectious GN (cont.) ASO may be negative early in the course, but is positive in 1-2 weeks. C 3 low in 90% of patients for 6 weeks caused by complement activation (alternative pathway) and its consumption. C 4 normal After recovery, gross hematuria might disappear but microscopic hematuria my persist for 2 years, but the edema resolves. glomerulonephritis has a good prognosis, 95% of the cases resolve.

24. HEMATURIA IgA nephropathy: The most common chronic GN in Europe and Asia. The most common cause of hematuria in children 15% of children with Prolonged hematuria (> 1 year) will have IgA nephropathy Present with gross hematuria during viral illness usually presents 1 day after the common cold. Very serious condition almost 40% will end in renal failure and even with transplant most are rejected and there is also an increased risk of recurrence.

25. HEMATURIA IgA nephropathy (cont.) Microscopic hematuria present between episodes of gross hematuria. Recurrent disease unlike post infectious it happens only once because of immunity. There is no laboratory test diagnostic of GN. Recurrent hematouria is suggestive. Its a clinical Diagnosis confirmed by histopathologic demonstration of mesangial deposition of IgA 25% of children with IgA nephropathy will progress to chronic renal insufficiency. Poor outcome: cresentic GN, older age group, hypertension, nephrotic range proteinuria.

26. HEMATURIA Which patients will progress to ESRD: 1.Age above 8. 2.Male. 3.Heavy (nephrotic range) proteinuria in addition to hematuria. 4.Hypertension. 5.Needs aggressive management.

27. HEMATURIA Alport hereditary nephritis: Episodes of recurrent or persistent micro and macroscopic hematuria. X-linked dominant disease resulting in a defect in collagen IV synthesis, and the basement membrane is disrupted- thick.. Organs affected are kidney (Glomerulonephritis, ESRD), ears (deafness), eyes. They develop renal failure early in life, usually in 2 nd to 3 rd decade. Family History: Family history of deafness especially in females. Male individuals with nerve deafness and progression to ESRD. Females usually have a milder form of the disease, and don’t progress to RF.

28. HEMATURIA Alport hereditary nephritis (cont.) The diagnosis is confirmed by renal biopsy. Hearing test should be done regularly to prevent speech or educational handicap, and family members should be screened for hearing problems. Patients must be transferred to special schools for hearing loss and renal failure. Good-pasture diseases post transplant (small risk). Female may have a hearing deficit without any urinary abnormalities.

29. HEMATURIA Benign Familial Hematuria: Thin glomerular basement membrane nephropathy unlike thick BM in alport. Occurs in at least 1% of the population. Inherited as AD or AR manner. Absence of proteinuria (its presence excludes benign familial hematuria), renal failure, hearing deficits, or ophthalmologic abnormalities. Persistent Microscopic hematuria (unlike alport recurrent), dysmorphic RBC’s. Rarely progress to renal failure vs. alport which develops it. It’s a diagnosis of exclusion and if the patient has a family history of hematuria then it’s alport.

30. HEMATURIA Rapidly Progressive GN: It is not a disease itself, but it’s the result of any renal disease within 2-5 weeks. Presents with symptoms and signs similar to APIGN, but continuous rising in renal proteins. In APIGN the proteinuria will go back within 1 week. Require the urgent attention of a Pediatric Nephrologist. Laboratory Studies show ARF Untreated RPGN can result in ESRD in a few weeks. Normal patient who develops seizures due to uremia and severe hypertension.

31. Renal biopsy is mandatory to assess the percentage of dead tissue and is done immediately and demonstrates glomerular crescent (dead tissue). – If > 50% dead tissue, transplant is required. – If < 50% can give them immune-suppressant therapy and steriods.

32. HEMATURIA Causes of non-Glomerular hematuria in order of its incidence in SA Hypercalciuria Infections (bacterial or viral) Papillary necrosis (HbS) Urolithiasis Trauma Foreign body Exercise-induced hematuria

33. HEMATURIA Hypercalciuria: Increased urinary excretion of Ca despite normal s. Ca Present in 5% of healthy children Most frequent cause of isolated hematuria in non- glomerular hematuria patients.

34. HEMATURIA Idiopathic Hypercalciuria: Renal hypercalciuria: result from a tubular leak of calcium. Absorptive hypercalciuria : results from increased gastrointestinal absorption of calcium.

35. HEMATURIA Idiopathic Hypercalciuria: There is often a family history of renal stones. Symptoms include dysuria, suprapubic pain, renal colic.

36. HEMATURIA Idiopathic Hypercalciuria: Present with microscopic hematuria and episodic gross hematuria. Urine RBC’s are shaped normally with no cast. The mechanism of the hematuria involve irritations to the renal tubules by ca-containing crystals. High risk of development of renal stones.

37. HEMATURIA Idiopathic Hypercalciuria: Screening for hypercalciuria: spot urinary ca/ creatinine ratio. A ration of > 0.21 is indicative of hypercalciuria. Ratio of urinary calcium to creatinine from an early morning sample. Confirmation of hypercalciuria by collecting a timed (either 12 or 24 hours) urine for ca excretion. An excretory rate of greater than 4 mg/kg/day is abnormal.

38. HEMATURIA Idiopathic Hypercalciuria treatment : Increase fluid intake to dilute the urine and improve hypertension. Severe ca restriction should be avoided because they are growing children. Hydrochlorothiazide (HCT) decrease urinary ca excretion but should not be given routinely unless there is a family history of stones. HCT in a child with isolated hematuria with no previous nephrolithiasis is not recommended.

39. HEMATURIA History clues: Duration and pattern of hematuria Family history (hematuria, renal failure, deafness, urolithiasis) Pharyngitis, URTI Dysuria or other symptoms of urinary infections Rash (HSP) Abdominal pain (infections, stone, HSP) Drugs (anticoagulant)

40. HEMATURIA Physical examinations clues: Hypertension always mandatory, edema, pallor Rash, impetigo Abdnominal or flank tenderness (infection) Abdominal mass (tumors) such as Wilm’s tumor. Child abuse Ecchymoses, petechiae, hemangiomas Evidence of abdominal trauma External genitalia for trauma or bleeding to rule out foreign body. Growth pattern because early presentation of RF is failure to thrive. Hearing test

41. HEMATURIA Basic Laboratory Evaluation: Urine culture CBC for anemia Serum creatinine for kidney function Aso titre for APIGN Urine ca: creatinine ratio Urine protein: creatinine ratio for severe proteinuria. C3 levels to r/o lupus, membrane proliferative, or APIGN.

42. HEMATURIA Renal ultrasonography for size, solitary kidney, stones (nephrocalcinosis), cysts, and tumors – If no clear cause, screen 1 st degree relatives urine test with dipstick. – If still no clear cause, refer to the Pediatric Nephrologist initially for immune studies rather than to the Pediatric Urologist.

43. HEMATURIA Other evaluation procedures: Renal biopsy Cystoscopy Renal angiography (rarely indicated)

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