Acute Poststreptococcal

Glomerulonephritis(APSGN)

Dept. of PediatricsThe first Affiliated Hospital

Sun Yat-Sen University

Liangzhong Sunsunliangzhong@yahoo.com.c

n

Acute Glomerulonephritis

Acute Nephritic Syndrome gross hematuria (sudden onset)

Edema

Hypertension

renal insufficiency (oliguria)

Causes of Acute Glomerulonephritis

Numerous infectious organisms, include

fungi, bacteria, rickettsia, virus, especially

influenza, and parasites could induce

PAGN.

However, APSGN accounts for 80 to 90% of

such cases and is used as the prototype for

this group of disorder.

APSGN is a classic example of the acute

nephritic syndrome

Non-infectious Infectious

one of the most common glomerular causes of gross hematuria in children, surpassed only by IgA nephropathy.

Acute post-steptococcal glomerulonephritis （ APSG

N ）

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

PATHOLOGY

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.

IFM 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.

A B

Neutrophils infiltration

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 ProteinuriaRBC 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 ofstreptocacci

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.

PATHOGENESISQuestions 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.

Antecedent infection: pharyngitis 1-2 wk,

pyoderma 2-3wk (3–6 wk).

General manifestations

Typical manifestations (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)

Proteinuria 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)

Typical manifestations (4)

Clinical course

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.

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.

Subclinical, microscopic hematuria may be four times more common as

overt acute PSGN

Attention

Asympatimatic type With urine changes, but no edema or

hypertension.

Extrarenal manifestation type With edema and/or hypertension, but

mild or none urine abnormalities.

Nephrotic type with nephrotic range of proteinuria,

hypoalbuminemia, hypercholesteremia

Atypical manifestations

Laboratory Findings (1) Urinalysis

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 (2)

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.

Laboratory Findings (3) evidences of streptococcal infection

Throat or skin cultures. Antistreptolysin O (ASO) titer.

Pharyngitis (80%), skin infections (<50%).

Anti-deoxyribonuclease (DNase) B level. Pharyngitis (98%), skin infections (80%). IT’s the best single antibody titer to document cutaneous streptococcal infection .

Activation of complements Serum C3 level, decrease (90%), return

to normal within 4-8 wk. Serum C4 levels are typically normal.

DIAGNOSIS Acute Nephritic Syndrome

gross hematuria (sudden onset) Edema Hypertension renal insufficiency (oliguria)

evidences of streptococcal infection Antecedent infection: pharyngitis,

pyoderma. ASO Anti-deoxyribonuclease B level

Activation of complements C3 level

Renal biopsy

acute renal failure nephrotic syndrome absence of evidence of streptococcal

infection normal complement levels. when hematuria and proteinuria,

diminished renal function, and/or a low C3 level persist more than 2 mo after onset.

IgA nephropathy

Rapid progressive glomerulonephritis

(RPGN), include Goodpature syndrome

Nephrotic syndrome (NS,nephritic type)

Exacerbation of chronic

glomerulonephritis

Secondary glomerulonephritis ：

HS ， SLE ， HBV, ect.

Differential Diagnosis

Clinical manifestations

APSGN IgANGoodpatureSyndrome

RPGN

 Age and sex 5-12yr, rare<2 yr, 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/Antecedent infection

Latent period of 1–3 wk

Follows viral syndromes

P. HemorrhageIDA

None

Laboratory findings

↑ ASO titers (70%) ,↓C3

↑ Serum IgA (50%)

anti-GBM Ab Positive ANCA in some

  Renal pathology LM, IF

Diffuse proliferationGranular IgG,

C3

Focal proliferationDiffuse mesangial

IgA deposits

Focal diffuse ➙Proliferation with crescentsLinear IgG, C3

Crescentic GN No immune

deposits

Prognosis 95% resolvespontaneously 5% RPGN

Slow progression in 25–50%

75% stabilize or improve if treated early

75% stabilize or improve if treated early

IgA nephropathy (IgAN)

Children with IgAN present of sudden onset hematuria, usually gross hematuria. Follow a short period (usually 1-3 days ) of antecedent infect.

But hypertension, and renal insufficiency are uncommon, and C3 level is typically normal.

ASO or anti DNase B are not elevated. Pathological changes would help for

the differential diagnosis.

Nephrotic syndrome (nephritic type)

Nephritic type NS include at least one of the following manifestations: hematuria, hypertension, renal insufficiency, and decreased C3.

But no typical antecedent infection, or elevateed ASO or anti DNase B levels in NS patients

C3 decreasing in AGN is transient, but in NS, it is continued or recurrent.

Finally, the pathological changes would help for the differential diagnosis.

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

Therapeutic Principle

Treatment (1) Bed rest

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.

Treatment (2) Diet

Protein, sodium and water intake should be restricted in patients with acute renal failure.

Sodium and water restriction is also needed in treating hypertension.

Antibiotics 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) Hypertension

Salt and water restriction Diuresis usually with intravenous

Lasix, pharmacotherapy with calcium

channel antagonists, vasodilators, or ACEI.

congestive heart failure/ pulmonary congestion In this scenario, Sodium Nitroprusside

is the first choice to decrease the BP, and to relief the cardiac preload and afterload.

Diuritic therapy are always needed if it is effective

Oxygen should be given Sedation is indicated if the child is

irritated Cardiotonic drugs

Treatment of complications (2)

Hypertensive encephalopathy management of convulsion is emergent,

diazepam, midazolam Effective drugs to desrease the BP is

necessary, such as Sodium Nitroprusside, calcium channel antagonists.

Diuritic therapy and steroids which to alleviate encephaledema are indicated. But mannitol, dextrose or albumin are forbidden.

Airway should be keep clear and Oxigen should be given

Sedation, (phenobarbital, chloral hydrate )

Treatment of complications (3)

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 (4)

Treatment of complications (5) Indications for dialysis

Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy

Persistent hyperkalemia Severe metabolic acidosis

unresponsive to medical management Neurologic symptoms (altered mental

status, seizures) Blood urea nitrogen greater than 100–

150 mg/dL Calcium/phosphorus imbalance, with

hypocalcemic tetany.

Prognosis Complete recovery occurs in more than

95% of children with APSGN. Mortality in the acute stage can be

avoided by appropriate management of acute renal failure, cardiac failure, and hypertension.

Infrequently, the acute phase may be severe and lead to glomerular hyalinization and chronic kidney disease.

Recurrences are extremely rare.

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