2. HematuriaHematuria Transient phenomenon of little significance Transient phenomenon of little significance Sign of serious renal disease Sign of serious renal disease

3. Classification of hematuria Macroscopic - Microscopic Symptomatic - Symptomless Transient - Persistent

5. Normal erythrocyte excretion rate * 0 – 425.000/12 h. ( mean – 65.750 ) T.Addis; J.of Clin Invest, 1926 Upper limit in children * 500.000 - 2.000.000/24h.

6. Detection & quantification of hematuria Screening test ( dipsticks ) - 0.02-0.03 mg/dL of Hb, myoglobin - ~5-20 RBC/mm³ Semiquantitative estimation - centrifugation of 10-15 ml of urine - resuspention of sediment in 1 ml of residual urine - high-power microscopy Counting chamber - the number of cells in 1 microliter of unspun urine

7. Microscopic Hematuria Definition > 3-5 RBC/HPF > 5 RBC/mm³ > 8000 RBC/ml Definition > 3-5 RBC/HPF > 5 RBC/mm³ > 8000 RBC/ml

11. Glomerular versus extraglomerular bleeding Urinary findingGlomerularExtraglomerular Red cell castsMay be presentAbsent Red cell morphology DysmorphicUniform ProteinuriaMay be presentAbsent ClotsAbsentMay be present ColorMay be red or brown May be red

16. Causes of Hematuria Kidney disease Lesions along the urinary tract Conditions unrelated to kidney and urinary tract

17. Hematuria not representing kidney or urinary tract disorder Following exercise Febrile disorders Gastroenteritis with dehydration Contamination from external genitalia

20. Renal causes of Hematuria Glomerular - Acute Postinfectious Glomerulonephritis - IgA Nephropathy - Hereditary Nephritis ( Alport syndrome) - Benign Recurrent or Persistent Hematuria ( Thin Membrane Disease ) 1.Sporadic 2.Familial - Membranoproliferative Glomerulonephritis - Crescentic Glomerulonephritis - Lupus Nephritis - Nephritis of Henoch-Shönlein Purpura - Focal Glomerulosclerosis - Hemolityc-Uremic Syndrome

21. Acute nephritic syndrome Acute nephritic syndrome Hematuria Proteinuria Reduced renal function Edema Hypertension

22. Renal causes of Hematuria Non-glomerular - Infection ( Pyelonephritis ) - Interstitial Nephritis - Metabolic ( Uric Acid, Nephrocalcinosis ) - Renal Malformation ( Cystic Kidney ) - Tumors ( Wilm’s, Acute Leukemia) - Idiopatic Hypercalciuria - Trauma

23. Causes of urinary tract related Hematuria Infection Urolithiasis Obstruction ( UPJ Stenosis ) Trauma Drugs ( Cyclophosphamide ) Tumors

24. Isolated Hematuria (microscopic) No other urinary abnormalities No renal insufficiency No evidence for systemic disease Incidence ( school-aged children ) 4-6% - single urine examination 0.5-1% - repeated testing over 6-12 months

25. Etiologies of isolated Hematuria Glomerular - Benign Recurrent or Persistent Hematuria 1.Sporadic 2.Familial - IgA Nephropathy - Alport syndrome - PSAGN Non-glomerular - Idiopathic Hypercalciuria - Cystic Kidneys - Urinary Tract obstruction - Tumors - Trauma

26. Hematuria with familial association Glomerular - Benign Familial Hematuria - Alport syndrome Non-glomerular - Idiopathic Hypercalciuria - Polycystic Kidney Disease - Urolithiasis - Tumors

27. Idiopathic Hypercalciuria Definition: Calcium excretion > 4 mg/kg/day Urinary Ca/Creatinine > 0.2 Possible mechanism of hematuria: microcrystals damaging the tubular or mucosal epithelia. Resolution of hematuria with anticalciuric therapy

28. Alport syndrome - hereditary disorder of GBM X-linked dominant Autosomal recessive Autosomal dominant

29. Renal disease Macro /Microhematuria Proteinuria Nephrotic syndrome Hypertension Renal failure- males Progressive or juvenile – 20 y Nonprogressive – 40 y

30. Hearing defects Sensorineural bilateral Never congenital Boys- 85%. Girls – 18% < 15y Progression of hearing loss parallels renal impairment

31. Diagnosis of Alport syndrome Hematuria with or without proteinuria Hypertension Renal failure Ocular defects – anterior lenticonus Familial hematuria Sensorineural hearing loss Progression to renal failure occurring in at least one affected subject

33. ALPORT’S SYNDROME

34. Familial benign essential hematuria Familial hematuria without proteinuria and without progression to renal failure or hearing defect Diffuse attenuation of the GBM is usually considered the hallmark of the condition It’s non pathognomonic of FBEH

35. Continue Autosomal dominant trait Normal antigenicity of the GBM

36. Thin basement membrane nephropathy Hematuria Proteinuria Attenuation of the GBM In children may be Alport In adults m/p benign disorder

38. HEREDITARY NEPHROPATHY Benign Familial Hematuria Alport Syndrome Overlap of histological findings The prognosis appears to be depend more on the degree of clinical expression in other members of the family and less on the histological findings

39. Evaluation of Hematuria History Detailed review of family history hematuria proteinuria renal insufficiency deafness stones Precipitating factors infection exercise Abdominal pain HSP hydronephrosis pyelonephritis urolithiasis

40. Evaluation of Hematuria Physical Examination Growth failure Hypertension Pallor Edema Rash Abdomen: search for a mass or tenderness External genitalia: bleeding infection trauma

41. Work-up of a child with Hematuria Phase I: Urinalysis ( sediment examination ) RBC’s morphology Urine culture BUN, Creatinine, Proteins, Electrolytes Antibodies against strept. & other antigens Complement, ANF, Immunoglobulins Renal US Urinalysis of 1 st degree relatives 24h urine collection: Ca, Creat.,Protein, UA Phase II: Hearing test Cystoscopy Renal biopsy

42. Isolated hematuria The child needs to be monitored for the appearance of new clinical signs: hypertension proteinuria changes in the pattern or severity of hematuria If there is no change in the first year,observation at yearly intervals is adequate

43. Isolated hematuria Possible outcome Isolated hematuria Possible outcome Disappearance of hematuria Hematuria will persist - follow-up should be continued The hematuria will no longer be “isolated” - further investigation

44. HematuriaHematuria Transient phenomenon of little significance Transient phenomenon of little significance Sign of serious renal disease Sign of serious renal disease