APSGN follows infection of the throat or skin by certain “ nephritogenic ” strains of group A β-hemolytic streptococci
Throat ( serotype 12 ) , cold weather months.
skin ( serotype 49 ) , warm weather months.
APSGN is most commonly sporadic, although epidemics of nephritis have been described.
Etiology and epidemiology
The kidneys appear symmetrically enlarged.
All glomeruli appear enlarged and relatively bloodless and show diffuse mesangial cell proliferation with an increase in mesangial matrix.
Polymorphonuclear leukocytes are common in glomeruli during the early stage of the disease.
Crescents and interstitial inflammation may be seen in severe cases.
IF reveals lumpy-bumpy deposits of immunoglobulin and complement on the glomerular basement membrane (GBM) and in the mesangium.
EM: electron-dense deposits, or “ humps, ” are observed on the epithelial side of the GBM
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.
LM of a glomerulus with APSGN demonstrating marked influx of neutrophils (arrows). (Masson trichrome, ×700.)
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
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.
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
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.
The finding of circulating immune complexes in APSGN is not uniform
Complement activation is primarily through the alternative rather than the classic (immune complex – activated) pathway.
PATHOGENESIS Questions still unsolved
Age : APSGN is most common in children aged 5-12 yr (5-15yr)and uncommon before the age of 3 yr.
Sex : more common in boys than in girls, male : female ratio is 2 : 1 .
This syndrome can present with an entire spectrum of severity from asymptomatic microscopic hematuria to oliguric acute renal failure .
Classically, the syndrome of APSGN presents abruptly with hematuria, proteinuria, hypertension, edema, and azotemia .
Nonspecific symptoms include malaise, lethargy, abdominal or flank pain, and fever.
Hematuria : Gross hematuria (30-50%), microscopic hematuria are more common.
Edema (90%): typically presents in the face and upper extremities. Ascites and anasarca may occur in children.
Hypertension (75% ): usually mild to moderate, and most evident at the onset of nephritis and typically subsides promptly after diuresis.
Oliguria and anuria : transient oliguria. Anuria is infrequent and, if persistent, may indicate the development of crescentic glomerulonephritis.
Typical manifestations (2)
Many patients have significant proteinuria, but <5% of symptomatic patients develop frank nephrotic syndrome.
urinary protein excretion usually normalize by 4-6 wk after onset.
The long-term persistence of proteinuria may be an indication of persistence of proliferative glomerulonephritis.
Typical manifestations (3)
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.
Typical manifestations (4)
Complications in severe cases
Circulatory hypervolemia / Congestive heart failure Jugular venous distention, the presence of an S3 gallop, dyspnea, and signs of pulmonary congestion.
Encephalopathy presenting as confusion, headache, somnolence, or even convulsion.
Acute renal failure Usually mild, a form of rapidly progressive glomerulonephritis is unusual(<1%). Oliguria, electrolytes disorder, and acidosis.
With urine changes, but no edema or hypertension .
Extrarenal manifestation type
With edema and/or hypertension, but mild or none urine abnormalities.
with nephrotic range of proteinuria, hypoalbuminemia, hypercholesteremia
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.
Proteinuria is nearly always present but typically in the sub-nephrotic range. Nephrotic-range proteinuria occurs in <5% of patients.
The urine contains large amounts of fibrin degradation products , and fibrinopeptides .
Laboratory Findings (1)
GFR and Blood chemistory
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.
Hyperkalemia, hypocalcaemia, hyponatremia, and metabolic acidosis are seen only in severe patients.
A mild normochromic anemia may be present from hemodilution and low-grade hemolysis.
Clinical manifestations APSGN IgAN Goodpature Syndrome RPGN Age and sex All ages, 2 : 1 male 10–35 yr, 2 : 1 male 15–30 yr, 6 : 1 male Adults, 2 : 1 male nephritic syndrome 90% 50% 90% 90% Asymptomatic hematuria Occasionally 50% Rare Rare NS 10–20% Rare Rare 10–20% Hypertension 70% 30–50% Rare 25% ARF 50% (transient) Very rare 50% 60% Other Latent period of 1–3 wk Follows viral syndromes P. Hemorrhage IDA None Laboratory findings ↑ ASO titers (70%) ,↓C3 ↑ Serum IgA (50%) anti-GBM Ab Positive ANCA in some Renal pathology LM, IF Diffuse proliferation Granular IgG, C3 Focal proliferation Diffuse mesangial IgA deposits Focal ➙ diffuse Proliferation with crescents Linear IgG, C3 Crescentic GN No immune deposits Prognosis 95% resolve spontaneously 5% RPGN Slow progression in 25–50% 75% stabilize or improve if treated early 75% stabilize or improve if treated early
Treatment of APSGN is largely that of supportive care.
Usually, patients undergo a spontaneous diuresis within 7 to 10 days after the onset of their illness.
Management is directed at treating the acute effects of renal insufficiency and hypertension
Bed rest is indicated as long as there are clinical manifestation of active disease, such as edema, hypertension, or gross hematuria.
The acute phase generally resolves within 2-3 wk.
Children could go back school after ESR returns to normal.
But, exhausting and competive activites are prohibited until the Addis count returns to normal.
Protein, sodium and water intake should be restricted in patients with acute renal failure.
Sodium and water restriction is also needed in treating hypertension.
A 10-day course of systemic antibiotic therapy with penicillin is recommended to limit the spread of the nephritogenic organisms.
Antibiotic therapy does not affect the natural history of glomerulonephritis.
Treatment of complications (1)
Salt and water restriction
Diuresis usually with intravenous Lasix,
pharmacotherapy with calcium channel antagonists, vasodilators, or ACEI.
Hypertensive encephalopathy or congestive heart failure
Sodium Nitroprusside is the first choice.
Acute renal failure
Management of hypertension, hypervolemia, electrolytes disorder and metabolic acidosis.
Some patients with substantial volume expansion and marked pulmonary congestion do not respond to diuretics. In those individuals, dialytic support is appropriate
Treatment of complications (2)
Treatment of complications (3)
Indications for dialysis
Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy
Severe metabolic acidosis unresponsive to medical management