20100603 acute glomerulonephritis


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20100603 acute glomerulonephritis

  1. 1. Acute Poststreptococcal Glomerulonephritis (APSGN) <ul><li>Dept. of Pediatrics </li></ul><ul><li>The first Affiliated Hospital </li></ul><ul><li>Sun Yat-Sen University </li></ul>Liangzhong Sun [email_address]
  2. 2. Acute Glomerulonephritis <ul><li>Acute Nephritic Syndrome </li></ul><ul><ul><li>gross hematuria (sudden onset) </li></ul></ul><ul><ul><li>Edema </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>renal insufficiency (oliguria) </li></ul></ul>
  3. 3. Causes of Acute Glomerulonephritis <ul><li>Numerous infectious organisms , include fungi, bacteria, rickettsia, virus, especially influenza, and parasites could induce PAGN. </li></ul><ul><li>However, APSGN accounts for 80 to 90% of such cases and is used as the prototype for this group of disorder. </li></ul><ul><li>APSGN is a classic example of the acute nephritic syndrome </li></ul><ul><li>Non-infectious </li></ul><ul><li>Infectious </li></ul>
  4. 4. <ul><li>one of the most common glomerular causes of gross hematuria in children, surpassed only by IgA nephropathy. </li></ul>Acute post-steptococcal glomerulonephritis ( APSGN )
  5. 5. <ul><li>APSGN follows infection of the throat or skin by certain “ nephritogenic ” strains of group A β-hemolytic streptococci </li></ul><ul><ul><li>Throat ( serotype 12 ) , cold weather months. </li></ul></ul><ul><ul><li>skin ( serotype 49 ) , warm weather months. </li></ul></ul><ul><li>APSGN is most commonly sporadic, although epidemics of nephritis have been described. </li></ul>Etiology and epidemiology
  6. 6. PATHOLOGY <ul><li>The kidneys appear symmetrically enlarged. </li></ul><ul><li>All glomeruli appear enlarged and relatively bloodless and show diffuse mesangial cell proliferation with an increase in mesangial matrix. </li></ul><ul><li>Polymorphonuclear leukocytes are common in glomeruli during the early stage of the disease. </li></ul><ul><li>Crescents and interstitial inflammation may be seen in severe cases. </li></ul><ul><li>IFM reveals lumpy-bumpy deposits of immunoglobulin and complement on the glomerular basement membrane (GBM) and in the mesangium. </li></ul><ul><li>EM: electron-dense deposits, or “humps,” are observed on the epithelial side of the GBM </li></ul>
  7. 7. Diagrams depicting the ultrastructural features of a normal glomerular capillary loop (A) , and the ultrastructural features of APSGN ( B ), Note the subepithelial hump like dense deposits and endocapillary hypercellularity. A B
  8. 8. <ul><li>Neutrophils infiltration </li></ul>LM of a glomerulus with APSGN demonstrating marked influx of neutrophils (arrows). (Masson trichrome, ×700.)
  9. 9. IF micrograph of a glomerular segment from a patient with APSGN showing coarsely granular capillary wall staining for IgG(left) and C3(right). IgG and C3 deposition
  10. 10. EM of a portion of a glomerular capillary from a patient with APSGN showing subepithelial dense deposits and a neutrophil (N) marginated against the basement membrane with no intervening endothelial cytoplasm.
  11. 11. Immune complexes, antigens Activation of Compliments Recruitment of leukocytes GBM damage, Blood ingredients leakage Hematuria Proteinuria RBC Casts Proliferation of MC and EC Blockage of renal capillaries and decreased GFR Edema hypertention heart failure encephalopathy renal failure Oliguria, sodium and water retention, hypervolemia Inflammation mediates, Cytokines, proliferative F. Infection of streptocacci PATHOGENESIS
  12. 12. <ul><li>Although morphologic studies and a depression in the serum complement (C3) level strongly suggest that APSGN is mediated by immune complexes , the precise mechanisms by which nephritogenic streptococci induce complex formation remain to be determined. </li></ul><ul><li>The finding of circulating immune complexes in APSGN is not uniform </li></ul><ul><li>Complement activation is primarily through the alternative rather than the classic (immune complex–activated) pathway. </li></ul>PATHOGENESIS Questions still unsolved
  13. 13. <ul><li>Age : APSGN is most common in children aged 5-12 yr (5-15yr) and uncommon before the age of 3 yr. </li></ul><ul><li>Sex : more common in boys than in girls, male : female ratio is 2 : 1 . </li></ul><ul><li>Antecedent infection : pharyngitis 1-2 wk , pyoderma 2-3wk (3–6 wk). </li></ul>General manifestations
  14. 14. Typical manifestations (1) <ul><li>This syndrome can present with an entire spectrum of severity from asymptomatic microscopic hematuria to oliguric acute renal failure . </li></ul><ul><li>Classically, the syndrome of APSGN presents abruptly with hematuria, proteinuria, hypertension, edema, and azotemia . </li></ul><ul><li>Nonspecific symptoms include malaise, lethargy, abdominal or flank pain, and fever. </li></ul>
  15. 15. <ul><li>Hematuria : Gross hematuria (30-50%), microscopic hematuria are more common. </li></ul><ul><li>Edema (90%): typically presents in the face and upper extremities. Ascites and anasarca may occur in children. </li></ul><ul><li>Hypertension (75% ): usually mild to moderate, and most evident at the onset of nephritis and typically subsides promptly after diuresis. </li></ul><ul><li>Oliguria and anuria : transient oliguria. Anuria is infrequent and, if persistent, may indicate the development of crescentic glomerulonephritis. </li></ul>Typical manifestations (2)
  16. 16. <ul><li>Proteinuria </li></ul><ul><ul><li>Many patients have significant proteinuria, but <5% of symptomatic patients develop frank nephrotic syndrome. </li></ul></ul><ul><ul><li>urinary protein excretion usually normalize by 4-6 wk after onset. </li></ul></ul><ul><ul><li>The long-term persistence of proteinuria may be an indication of persistence of proliferative glomerulonephritis. </li></ul></ul>Typical manifestations (3)
  17. 17. <ul><li>Clinical course </li></ul><ul><ul><li>Spontaneous improvement typically begins within 1 wk with resolution of edema in 5-10 days and hypertension in 2-3 wk, but urinalysis may be abnormal ( persistent microscopic hematuria ) for several years. </li></ul></ul>Typical manifestations (4)
  18. 18. Complications in severe cases <ul><li>Circulatory hypervolemia / Congestive heart failure Jugular venous distention, the presence of an S3 gallop, dyspnea, and signs of pulmonary congestion. </li></ul><ul><li>Encephalopathy presenting as confusion, headache, somnolence, or even convulsion. </li></ul><ul><li>Acute renal failure Usually mild, a form of rapidly progressive glomerulonephritis is unusual(<1%). Oliguria, electrolytes disorder, and acidosis. </li></ul>
  19. 19. Subclinical, microscopic hematuria may be four times more common as overt acute PSGN Attention
  20. 20. <ul><li>Asympatimatic type </li></ul><ul><ul><li>With urine changes, but no edema or hypertension . </li></ul></ul><ul><li>Extrarenal manifestation type </li></ul><ul><ul><li>With edema and/or hypertension, but mild or none urine abnormalities. </li></ul></ul><ul><li>Nephrotic type </li></ul><ul><ul><li>with nephrotic range of proteinuria, hypoalbuminemia, hypercholesteremia </li></ul></ul>Atypical manifestations
  21. 21. <ul><li>Urinalysis </li></ul><ul><ul><li>Hematuria is nearly always present in APSGN. Other findings on microscopy are those of leukocytes , red blood cell casts, and granular casts . Macroscopic hematuria typically has a rusty or tea-color. </li></ul></ul><ul><ul><li>Proteinuria is nearly always present but typically in the sub-nephrotic range. Nephrotic-range proteinuria occurs in <5% of patients. </li></ul></ul><ul><ul><li>The urine contains large amounts of fibrin degradation products , and fibrinopeptides . </li></ul></ul>Laboratory Findings (1)
  22. 22. <ul><li>GFR and Blood chemistory </li></ul><ul><ul><li>The BUN concentration is elevated in 75% of patients, and serum creatinine level is increased in one half of the patients, but profound decrease in GFR is uncommon in children. </li></ul></ul><ul><ul><li>Hyperkalemia, hypocalcaemia, hyponatremia, and metabolic acidosis are seen only in severe patients. </li></ul></ul><ul><ul><li>A mild normochromic anemia may be present from hemodilution and low-grade hemolysis. </li></ul></ul>Laboratory Findings (2)
  23. 23. <ul><li>evidences of streptococcal infection </li></ul><ul><ul><li>Throat or skin cultures . </li></ul></ul><ul><ul><li>Antistreptolysin O ( ASO ) titer. Pharyngitis (80%), skin infections (<50%). </li></ul></ul><ul><ul><li>Anti-deoxyribonuclease (DNase) B level. Pharyngitis (98%), skin infections (80%). IT’s the best single antibody titer to document cutaneous streptococcal infection . </li></ul></ul><ul><li>Activation of complements </li></ul><ul><ul><li>Serum C3 level, decrease (90%), return to normal within 4-8 wk. </li></ul></ul><ul><ul><li>Serum C4 levels are typically normal. </li></ul></ul>Laboratory Findings (3)
  24. 24. DIAGNOSIS <ul><li>Acute Nephritic Syndrome </li></ul><ul><ul><li>gross hematuria (sudden onset) </li></ul></ul><ul><ul><li>Edema </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>renal insufficiency (oliguria) </li></ul></ul><ul><li>evidences of streptococcal infection </li></ul><ul><ul><li>Antecedent infection: pharyngitis, pyoderma . </li></ul></ul><ul><ul><li>ASO </li></ul></ul><ul><ul><li>Anti-deoxyribonuclease B level </li></ul></ul><ul><li>Activation of complements </li></ul><ul><ul><li>C3 level </li></ul></ul>
  25. 25. Renal biopsy <ul><li>acute renal failure </li></ul><ul><li>nephrotic syndrome </li></ul><ul><li>absence of evidence of streptococcal infection </li></ul><ul><li>normal complement levels. </li></ul><ul><li>when hematuria and proteinuria, diminished renal function, and/or a low C3 level persist more than 2 mo after onset. </li></ul>
  26. 26. <ul><li>IgA nephropathy </li></ul><ul><li>Rapid progressive glomerulonephritis (RPGN), include Goodpature syndrome </li></ul><ul><li>Nephrotic syndrome (NS,nephritic type) </li></ul><ul><li>Exacerbation of chronic glomerulonephritis </li></ul><ul><li>Secondary glomerulonephritis : HS , SLE , HBV, ect. </li></ul>Differential Diagnosis
  27. 27. 75% stabilize or improve if treated early 75% stabilize or improve if treated early Slow progression in 25–50% 95% resolve spontaneously 5% RPGN Prognosis Crescentic GN No immune deposits Focal ➙ diffuse Proliferation with crescents Linear IgG, C3 Focal proliferation Diffuse mesangial IgA deposits Diffuse proliferation Granular IgG, C3   Renal pathology LM, IF Positive ANCA in some anti-GBM Ab ↑ Serum IgA (50%) ↑ ASO titers (70%) ,↓C3 Laboratory findings None P. Hemorrhage IDA Follows viral syndromes Latent period of 1–3 wk Other/Antecedent infection 60% 50% Very rare 50% (transient)   ARF 25% Rare 30–50% 70%   Hypertension 10–20% Rare Rare 10–20%   NS Rare Rare 50% Occasionally   Asymptomatic hematuria 90% 90% 50% 90%   nephritic syndrome Adults, 2 : 1 male 15–30 yr, 6 : 1 male 10–35 yr, 2 : 1 male 5-12yr, rare<2 yr, 2 : 1 male   Age and sex RPGN Goodpature Syndrome IgAN APSGN Clinical manifestations
  28. 28. IgA nephropathy (IgAN) <ul><li>Children with IgAN present of sudden onset hematuria, usually gross hematuria. Follow a short period (usually 1-3 days ) of antecedent infect. </li></ul><ul><li>But hypertension, and renal insufficiency are uncommon, and C3 level is typically normal. </li></ul><ul><li>ASO or anti DNase B are not elevated. </li></ul><ul><li>Pathological changes would help for the differential diagnosis. </li></ul>
  29. 29. Nephrotic syndrome (nephritic type) <ul><li>Nephritic type NS include at least one of the following manifestations: hematuria, hypertension, renal insufficiency, and decreased C3. </li></ul><ul><li>But no typical antecedent infection, or elevateed ASO or anti DNase B levels in NS patients </li></ul><ul><li>C3 decreasing in AGN is transient, but in NS, it is continued or recurrent. </li></ul><ul><li>Finally, the pathological changes would help for the differential diagnosis. </li></ul>
  30. 30. <ul><li>Treatment of APSGN is largely that of supportive care. </li></ul><ul><li>Usually, patients undergo a spontaneous diuresis within 7 to 10 days after the onset of their illness. </li></ul><ul><li>Management is directed at treating the acute effects of renal insufficiency and hypertension </li></ul>Therapeutic Principle
  31. 31. <ul><li>Bed rest </li></ul><ul><ul><li>Bed rest is indicated as long as there are clinical manifestation of active disease, such as edema, hypertension, or gross hematuria. </li></ul></ul><ul><ul><li>The acute phase generally resolves within 2-3 wk. </li></ul></ul><ul><ul><li>Children could go back school after ESR returns to normal. </li></ul></ul><ul><ul><li>But, exhausting and competive activites are prohibited until the Addis count returns to normal. </li></ul></ul>Treatment (1)
  32. 32. Treatment (2) <ul><li>Diet </li></ul><ul><ul><li>Protein, sodium and water intake should be restricted in patients with acute renal failure. </li></ul></ul><ul><ul><li>Sodium and water restriction is also needed in treating hypertension. </li></ul></ul><ul><li>Antibiotics </li></ul><ul><ul><li>A 10-day course of systemic antibiotic therapy with penicillin is recommended to limit the spread of the nephritogenic organisms. </li></ul></ul><ul><ul><li>Antibiotic therapy does not affect the natural history of glomerulonephritis. </li></ul></ul>
  33. 33. Treatment of complications (1) <ul><li>Hypertension </li></ul><ul><ul><li>Salt and water restriction </li></ul></ul><ul><ul><li>Diuresis usually with intravenous Lasix, </li></ul></ul><ul><ul><li>pharmacotherapy with calcium channel antagonists, vasodilators, or ACEI. </li></ul></ul>
  34. 34. <ul><li>congestive heart failure/ pulmonary congestion </li></ul><ul><ul><li>In this scenario, Sodium Nitroprusside is the first choice to decrease the BP, and to relief the cardiac preload and afterload. </li></ul></ul><ul><ul><li>Diuritic therapy are always needed if it is effective </li></ul></ul><ul><ul><li>Oxygen should be given </li></ul></ul><ul><ul><li>Sedation is indicated if the child is irritated </li></ul></ul><ul><ul><li>Cardiotonic drugs </li></ul></ul>Treatment of complications (2)
  35. 35. <ul><li>Hypertensive encephalopathy </li></ul><ul><ul><li>management of convulsion is emergent, diazepam, midazolam </li></ul></ul><ul><ul><li>Effective drugs to desrease the BP is necessary, such as Sodium Nitroprusside, calcium channel antagonists. </li></ul></ul><ul><ul><li>Diuritic therapy and steroids which to alleviate encephaledema are indicated. But mannitol, dextrose or albumin are forbidden. </li></ul></ul><ul><ul><li>Airway should be keep clear and Oxigen should be given </li></ul></ul><ul><ul><li>Sedation, (phenobarbital, chloral hydrate ) </li></ul></ul>Treatment of complications (3)
  36. 36. <ul><li>Acute renal failure </li></ul><ul><ul><li>Management of hypertension, hypervolemia, electrolytes disorder and metabolic acidosis. </li></ul></ul><ul><ul><li>Some patients with substantial volume expansion and marked pulmonary congestion do not respond to diuretics. In those individuals, dialytic support is appropriate </li></ul></ul>Treatment of complications (4)
  37. 37. Treatment of complications (5) <ul><li>Indications for dialysis </li></ul><ul><ul><li>Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy </li></ul></ul><ul><ul><li>Persistent hyperkalemia </li></ul></ul><ul><ul><li>Severe metabolic acidosis unresponsive to medical management </li></ul></ul><ul><ul><li>Neurologic symptoms (altered mental status, seizures) </li></ul></ul><ul><ul><li>Blood urea nitrogen greater than 100–150 mg/dL </li></ul></ul><ul><ul><li>Calcium/phosphorus imbalance, with hypocalcemic tetany . </li></ul></ul>
  38. 38. Prognosis <ul><li>Complete recovery occurs in more than 95% of children with APSGN. </li></ul><ul><li>Mortality in the acute stage can be avoided by appropriate management of acute renal failure, cardiac failure, and hypertension. </li></ul><ul><li>Infrequently, the acute phase may be severe and lead to glomerular hyalinization and chronic kidney disease. </li></ul><ul><li>Recurrences are extremely rare. </li></ul>
  39. 39. THANK YOU !