Proteinuria & Hematuria


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Proteinuria & Hematuria

  2. 2. Proteinuria and Nephrotic Syndrome <ul><li>Occurrence of proteinuria in a single urine is relatively common. </li></ul><ul><li>Will present in 5% to 15% of normal children in a random urine specimen. </li></ul>
  3. 3. <ul><li>-Proteinuria is a marker of renal disease. </li></ul><ul><li>-The dilemma for the PCP is to differentiate the child with transient or any other benign forms of proteinuria from children with renal disease. </li></ul>
  4. 4. <ul><li>PATOPHYSIOLOGY AND CLASSIFICATION </li></ul><ul><li>Normal protein excretion </li></ul><ul><li>normal child <100 mg/m2/day or 150mg/day </li></ul><ul><li>neonates is higher up to 300 mg/m2 </li></ul><ul><li>(reduced reabsorption of filtered protein) </li></ul>
  5. 5. <ul><li>The normally low rate of urinary protein excretion is: </li></ul><ul><li>-Restriction of the filtration </li></ul><ul><li>-Reabsorption of freely filtered low molecular weight protein </li></ul>
  6. 6. <ul><li>Abnormal protein excretion </li></ul><ul><li>Urinary protein excretion in excess of 100 mg/m2/day or 4mg/m2/hr </li></ul><ul><li>Nephrotic range proteinuria is defined as >1000 mg/m2/day or 40mg/m2/hr </li></ul>
  7. 7. <ul><li>Three main mechanism: </li></ul><ul><li>Glomerular (increase filtration) </li></ul><ul><li>Tubular (increase excretion- decrease reabsorption) </li></ul><ul><li>Overflow (marked overproduction of a particular protein) </li></ul>
  8. 8. <ul><li>Measurement of urinary protein </li></ul><ul><li>Urine dipstick </li></ul><ul><li>negative </li></ul><ul><li>trace between 15-30mg/dl </li></ul><ul><li>1+ 30-100 mg/dl </li></ul><ul><li>2+ 100-300mg/dl </li></ul><ul><li>3+ 300-1000mg/dl </li></ul><ul><li>4+ >1000mg/dl </li></ul>
  9. 9. <ul><li>Quantitative assessment </li></ul><ul><li>Measurement of 24-hour protein excretion or total protein/creatinine ratio </li></ul><ul><li>in a spot urine in the morning </li></ul><ul><li> normal in children : </li></ul><ul><li> <0.2mg protein/mg creatinine (+2 years) </li></ul><ul><li> <0.5mg protein/mg creatinine (6-24-month) </li></ul>
  10. 10. <ul><li>Qualitative assessment </li></ul><ul><li>May be necessary to differentiate glomerular from tubular protein </li></ul>
  11. 11. <ul><li>Approach to the child with proteinuria </li></ul><ul><li>Transient or Intermittent </li></ul><ul><li>Orthostatic </li></ul><ul><li>Persistent </li></ul>
  12. 13. <ul><li>History and physical </li></ul><ul><li>Thorough history and physical </li></ul><ul><li>change in urine volume or color </li></ul><ul><li>edema </li></ul><ul><li>increase BP </li></ul><ul><li>recent strep infection </li></ul><ul><li>family history for renal disease and hearing loss (Alport disease) </li></ul>
  13. 15. The Need for Renal Biopsy <ul><li>The key indication for biopsy in any renal disorder are the need to make specific diagnosis for therapeutic reasons or to provide a prognosis. </li></ul>
  14. 16. Neprotic Syndrome <ul><li>Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia; the most common presenting symptom is edema. </li></ul>
  15. 17. Introduction <ul><li>The annual incidence of Nephrotic syndrome in healthy children is 2 to 7 new case per 100,000 children younger than 18 years of age. </li></ul><ul><li>The peak age lf onset is at 2 to 3 years. </li></ul>
  16. 18. Definition <ul><li>The diagnosis of NS is the presence of urinary protein, with the albumin disproportionately greater than globulin. </li></ul>
  17. 19. Clinical Diagnostic Criteria <ul><li>1- Generalized edema </li></ul><ul><li>2- Hypoproteinemia <2 g/dL (disproportionately low albumin in relation to globulin) </li></ul>
  18. 20. <ul><li>3-Urine protein to urine creatinine ratio in excess of 2 (first A.M. void) or a 24- hour urine that exceeds 50mg/Kg body weight </li></ul><ul><li>4-Hypercholesterolemia (>200 mg/dL) </li></ul>
  19. 23. <ul><li>The mechanisms for edema include: </li></ul><ul><li>-Transudation of fluid from the intravascular space into the intestitium secondary to decreased albumin and </li></ul><ul><li>- Increased renal tubular reabsorption of sodium and water </li></ul>
  20. 25. <ul><li>The hyperlipidemia is secondary to: </li></ul><ul><li>-Increase in lipoprotein synthesis by the liver and </li></ul><ul><li>-Decrease in lipid catabolism resulting from reduced activity of the enzyme lipoprotein lipase and lecithin cholesterol acetyltransferase. </li></ul>
  21. 26. <ul><li>INCIDENCE FOR UNDERLYING PATHOLOGY </li></ul>
  22. 30. <ul><li>TREATMENT </li></ul>
  23. 33. Complications <ul><li>One true complication of NS is the tendency to developed infections. </li></ul><ul><li>IgG antibody is lost in the urine, and complement activation is impaired by concomitant loss of factor B. </li></ul>
  24. 34. <ul><li>Marked intravascular depletion causes diminished splachnic blood flow and hypoxia, and a marked tendency to thrombosis cause microinfarction, lowering resistance of the bowel wall to bacteria passage. </li></ul>
  25. 35. <ul><li>Peritonitis is a major contributor to the 1% to 2% mortality in NS </li></ul><ul><li>The second major contributor is Thromboembolism, however anticoagulant therapy is not justified during remission. </li></ul>
  26. 36. <ul><li>Growth is often impaired in NS </li></ul><ul><li>There may be losses of IGF-binding protein, which could account for the depressed serum concentration of IGF-I and IGF-II. </li></ul>
  27. 38. Prognosis <ul><li>Mortality in minimal-change NS is approximately 2% </li></ul><ul><li>Of the remaining 98%, most are steroid-responsive </li></ul><ul><li>about 2/3 experience 1/3 possible </li></ul><ul><li>single relapse developing protracted series of relapses </li></ul>
  28. 39. Hematuria and Glomerulonephitis
  29. 40. Introduction <ul><li>Recognition, definition, differential diagnosis, and orderly evaluation of hematuria in infants and children is often an important issue in pediatric practice </li></ul>
  30. 41. Definition <ul><li>Hematuria is defined by the presence of an abnormal quantity of red blood cells in the urine </li></ul><ul><li>Macroscopic: grossly visible </li></ul><ul><li>Microscopic: only upon urinalysis </li></ul><ul><li>>5-10 RBC’s per high power field </li></ul>
  31. 42. <ul><li>A large number of benign and serious conditions can cause hematuria in children. </li></ul>
  32. 43. <ul><li>Gross hematuria </li></ul><ul><li>UTI </li></ul><ul><li>Irritation of the meatus or perineum </li></ul><ul><li>Trauma </li></ul><ul><li>Nephrolithiasis </li></ul><ul><li>Sickle cell disease/trait </li></ul><ul><li>Post infectious glomerulonephritis </li></ul><ul><li>IgA nephropathy </li></ul>
  33. 44. <ul><li>Microscopic hematuria </li></ul><ul><li>Glomerulopathies </li></ul><ul><li>Hypercalciuria </li></ul><ul><li>Microlithiasis </li></ul><ul><li>UTI </li></ul>
  34. 45. <ul><li>Children with hematuria may present in one of three way </li></ul><ul><li>1-Onset of gross hematuria </li></ul><ul><li>2-Onset of urinary or other symptoms with incidental finding </li></ul><ul><li>3-Incidental finding during a health evaluation </li></ul>
  35. 46. <ul><li>Historical clues </li></ul><ul><li>The color of the urine </li></ul><ul><li>Glomerulonephritis may be brown and/or frothy urine, </li></ul><ul><li>while bleeding is suggested by the presence of blood clots, or pink or clearly red urine </li></ul>
  36. 47. <ul><li>The timing of the hematuria </li></ul><ul><li>Initial (urethral bleeding) </li></ul><ul><li>Terminal (bladder) </li></ul><ul><li>Throughout (no localizing value) </li></ul>
  37. 48. <ul><li>Circumstances associated </li></ul><ul><li>History of trauma, pain, micturating symptoms, systemic signs including fever and skin and nasopharyngeal infection </li></ul>
  38. 49. <ul><li>Age of onset </li></ul><ul><li>Periodicity </li></ul><ul><li>Blood on diapers of underwear </li></ul><ul><li>Exposure to medications </li></ul><ul><li>Relation with exercise </li></ul><ul><li>Flank pain (loin pain hematuria syndrome) </li></ul>
  39. 50. Physical examination <ul><li>Should Include </li></ul><ul><li>Blood Pressure measurement </li></ul><ul><li>Assessment for edema or weight gain </li></ul><ul><li>Close skin examination </li></ul><ul><li>Direct visualization of the genitals </li></ul><ul><li>Abdominal mass or discomfort </li></ul>
  40. 51. Laboratory evaluation <ul><li>-Urinalysis, urine culture, and urinary excretion studies </li></ul><ul><li>-Glomerular bleeding evaluation </li></ul><ul><li>(24-hour urinary protein excretion/creatinine ratio, excretion of casts, protein excretion, blood clots) </li></ul>
  41. 52. <ul><li>Imaging studies </li></ul><ul><li>USD of the kidney and bladder. </li></ul><ul><li>Cytoscopy </li></ul><ul><li>Is rarely indicated. May be useful to determine if the bleeding comes from bladder or one or both ureters. </li></ul>
  42. 54. Etiology <ul><li>The causes of gross and microscopic hematuria are extensive. </li></ul>
  43. 55. <ul><li>A natomical abnormalities </li></ul><ul><li>B ladder and kidney infection </li></ul><ul><li>C oagulation/hematology </li></ul><ul><li>D rugs </li></ul><ul><li>E xercise </li></ul><ul><li>F amilial hematuria </li></ul><ul><li>G lomerulonephritis </li></ul><ul><li>H ypercalciuria-hyperuricosuria-urolithiasis </li></ul><ul><li>I nterstitial nephritis </li></ul><ul><li>T rauma and tumors </li></ul>
  44. 56. <ul><li>Extrarrenal causes </li></ul><ul><li>Usually gross hematuria, no proteinuria, and RBC’s that are suggestive of nonglomerular origin. </li></ul>
  45. 57. <ul><li>-Neprholithiasis </li></ul><ul><li>-UTI </li></ul><ul><li>-Adenovirus </li></ul><ul><li>-Kidney tumor </li></ul><ul><li>-Polycystic kidney </li></ul><ul><li>-Urethral irritation </li></ul>
  46. 58. <ul><li>-Obstructive uropathy </li></ul><ul><li>-Post-traumatic kidney </li></ul><ul><li>-Onset of menarche </li></ul><ul><li>-Exposure to cyclophosphamide </li></ul><ul><li>-Thrombogenic condition </li></ul><ul><li>-Sickle cell trait </li></ul>
  47. 59. <ul><li>-Vascular bleeding </li></ul><ul><li>-”Nutcracker syndrome” </li></ul><ul><li>-Left renal vein entrapment </li></ul><ul><li>(Also orthostatic proteinuria) </li></ul><ul><li>-Loin pain hematuria syndrome </li></ul><ul><li>-Urethrovesical bleeding </li></ul>
  48. 60. <ul><li>Renal Causes ( Glomerular causes) </li></ul><ul><li>Most patients also have proteinuria, red cell casts, and/or renal insufficiency. The clinical context is also suggestive. </li></ul>
  49. 61. <ul><li>-Postinfectious glomerulonephritis </li></ul><ul><li>-Henoch-Schonlein purpura </li></ul><ul><li>(tetrad: rash, arthralgias, abdominal pain and renal disease) </li></ul><ul><li>-IgA nephropathy persistent </li></ul><ul><li>-Alport Syndrome hematuria </li></ul><ul><li>-Thin base membrane disease </li></ul><ul><li>(heterozygote carrier) </li></ul>
  50. 62. <ul><li>-Systemic diseases </li></ul><ul><li>Lupus </li></ul><ul><li>Shunt nephritis </li></ul><ul><li>Hemolitic-uremic syndrome </li></ul>
  51. 63. <ul><li>Unexplained hematuria </li></ul><ul><li>- Factitious hematuria </li></ul>
  52. 67. <ul><li>Poststreptococcal glomerulonephritis </li></ul><ul><li>The most common type in children results through immunologic process, from A Beta-hemolytic streptococcus. </li></ul>
  53. 69. <ul><li>Immunoglobulin A nephropathy </li></ul><ul><li>The most common variety of primary glomerulonephritis. Usually negative family history. </li></ul><ul><li>Mesangial IgA deposition is the most prominent finding on renal biopsy. </li></ul>
  54. 70. <ul><li>Alport Syndrome </li></ul><ul><li>Its classically X-linked form, suggested by hematuria in a male. </li></ul><ul><li>Positive family history of hematuria, deafness, and renal failure. </li></ul><ul><li>Abnormal collagen IV composition. </li></ul>
  55. 71. <ul><li>Thin base membrane disease </li></ul><ul><li>Also called benign familial hematuria , transmitted in a dominant fashion but, in most cases a heterozygous form of autosomal recessive Alport syndrome. </li></ul>
  56. 72. Treatment <ul><li>General management </li></ul><ul><li>Salt and water restriction. </li></ul><ul><li>Specific treatment </li></ul><ul><li>Depends of the etiology or severity of the disorder. </li></ul>