nephritic syndrome / apsgn in children

Acute Poststreptococcal Glomerulonephritis

(APSGN)

Dr. Muhammad Sajjad Sabir

MBBS, DCH, MCPS, FCPS Assistant Professor of Paediatrics

Acute Nephrit ic Syndrome

Acute Nephrit ic Syndrome

1. Gross hematuria (sudden

onset)

2. Edema

3. Hypertension (HTN)

4. Renal insufficiency (oliguria)

Feature NEPHROTIC NEPHRITIC

ONSET Insidious Abrupt

OEDEMA ++++ ++

BLOOD PRESSURE Normal High

JVP Normal Raised

Proteinuria ++++ ++

Hematuria May/ may not +++

RBC Cast Absent Present

Serum Albumen Low Normal 4

Causes of Nephritic Syndrome• IgA nephropathy • APGN• HUS• HSP• SLE nephritis• MPGN• RPGN

Acute Poststreptococcal Glomerulonephritis （ APSGN ）

Classic example of the acute nephritic syndrome characterized by sudden onset of:

Gross hematuriaEdemaHypertension, and Renal insufficiency

2nd most common glomerular causes of gross hematuria in children (1st IgA nephropathy) 6

• 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.

BUT

• APSGN is most commonly sporadic

• Epidemics of nephritis -reported

Etiology and epidemiology

PATHOLOGY• Kidneys →symmetrically enlarged • Light microscopy, • All glomeruli appear enlarged & relatively bloodless • Diffuse mesangial cell proliferation • Increase mesangial matrix• Polymorphonuclear leukocytes in glomeruli • Crescents and interstitial inflammation• These changes are not specific for

poststreptococcal glomerulonephritis8

(A) ultrastructural features of a normal glomerular capillary loop , (B)ultrastructural features of APSGN, Note the subepithelial hump like dense deposits and endocapillary hypercellularity

A B

Neutrophils infiltration

PATHOLOGY

 Immunofluorescence microscopy Lumpy-bumpy deposits of immunoglobulin complement on glomerular basement membrane (GBM) in the mesangium.Electron microscopyElectron-dense deposits, or "humps," on the epithelial side of the GBM

EM glomerular capillary -APSGN showing subepithelial dense deposits and a neutrophil (N) marginated

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

Inf lammation mediates, Cytokines,

proliferative F.

Infection ofstreptocacci

PATHOGENESIS

Although

• Morphologic studies &• ↓(C3) level

strongly suggest →mediated by immune complexes

Questions still unsolved• Precise mechanisms→ UNKNOWN

14

PATHOGENESIS

Clinical Manifestations

15

General manifestations• Age: • most common in children aged 5-12 yr • uncommon before the age of 3 yr.

• Sex: more common in boys than in girls,

(M:F 2 : 1)

• Antecedent infection:

• 1-2 wk after pharyngitis

• 3-6 wk after pyoderma

Typical manifestations Severity of renal involvement varies

from asymptomatic microscopic hematuria to oliguric acute renal fai lure

Nonspecific

symptoms malaise, lethargy, abdominal /

f lank pain fever

Classically, abrupt onset

hematuria, proteinuria, hypertension, edema, and

azotemia.

• Hematuria: • Gross hematuria (30-50%), • microscopic hematuria - more

common• Edema (90%): • Puffy face • Ascites and • Anasarca may occur• Hypertension (75% ): usually mild to moderate

Typical manifestations

• Oliguria and anuria : • transient ol iguria. • Anuria is infrequent• Proteinuria

–Many patients have significant proteinuria

–<5% - frank nephrotic syndrome.

Typical manifestations

Subclinical, microscopic hematuria may be four times more common as overt acute

PSGN

Attention

Clinical course– Spontaneous improvement begins within 1 wk

– Edema-- resolves in 5-10 days

– Hypertension-- normalize by 4-6 wk after onset

– Proteinuria -- normalize by 4-6 wk

• Acute phase resolves within 6-8 wk.

• Microscopic hematuria may persist 1-2 yr

INVESTIGATIONS

22

• Urinalysis – demonstrates red blood cells (RBCs), – RBC casts – Proteinuria – ↑WBC

• CBC– Mild normochromic anemia (due to hemodilution and

low-grade hemolysis)

23

Laboratory Findings

Laboratory Findings

• Activation of complements– Serum C3 level, decrease (90%), – return to normal within 4-8 wk – Serum C4 levels -- typically normal• Urea / creatinine ↑

• Blood chemistory– Hyperkalemia– hypocalcaemia– hyponatremia–Metabolic acidosis

Clinical diagnosis of APSGN likely with:

1.Acute nephritic syndrome

2.Evidence of recent streptococcal infection– Positive throat culture

– Rising titer to streptococcal antigen(s)

3. Low C3 level 25

DIAGNOSIS

Antibodies to streptococcal antigen(s)

• Anti-streptolysin O titer (ASOT) >333 TOD Units

• COMMONLY elevated after a pharyngeal infection but • RARELY increases after streptococcal skin infections.

• Anti deoxyribonuclease (DNase) B antibodies(best single antibody titer to document cutaneous

streptococcal infection)

• Anti-hyaluronidase antibodies• Anti-streptokinase antibodies

Renal biopsy • Acute renal failure• Nephrotic syndrome• Absence of evidence of streptococcal

infection• Normal complement levels

ALSO if

• Hematuria and proteinuria, diminished renal function, and/or low C3 level persist > 2 mo after onset

Differential Diagnosis• IgA nephropathy

• Rapid progressive glomerulonephrit is

(RPGN)

• Nephrotic syndrome (NS,nephrit ic

type)

• Exacerbation of chronic

glomerulonephrit is

• Secondary glomerulonephrit i– HSP,

– HUS ，

– SLE ，

– HBV, ect.

Complications Acute renal dysfunctionHypertension → 60% of patients Hypertensive encephalopathy → 10%casesHeart failureHyperkalemiaHyperphosphatemiaHypocalcemiaAcidosis Seizures 29

• 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 i l lness.

• Management is directed at treating the acute effects of renal insufficiency and hypertension

Therapeutic Principle

Treatment

Management is directed at

• Treat renal insufficiency • Treat hypertension•Antibiotic therapy

Diet Protein, sodium and water intake

-ARF Salt and water restriction -HTN

Treat renal insufficiency Careful intake and output record Daily weight measurementMonitor & treat HTN Water and sodium restriction Protein restriction Potassium and phosphate restriction Adjust medication dosages

32

TREAT if any HyperkalemiaHyponatremiaSeizuresAcidosisHypocalcemia

Treat hypertension (HTN)

• Sodium restriction• Diuresis (I .V Lasix)• Calcium channel antagonists, • Vasodilators• Angiotensin -converting enzyme

(ACE) inhibitors 33

Antibiotics

Systemic antibiotic therapy to limit spread of nephritogenic organisms

10-day course of systemic antibiotic therapy with Penicillin OR

Single I.M Inj Benzathin Penicillin

NOTE: Antibiotic therapy does not affect natural history of glomerulonephritis  

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 .

PrognosisComplete recovery ≥95%

Infrequently, acute phase severe

chronic renal insufficiency

Recurrences -- extremely rare

Mortality ??? LOW

MortalityCan be avoided by appropriate

management of:

•Acute renal failure •Cardiac failure •Hypertension

37

Prevention ?? • Early systemic antibiotic therapy for

streptococcal throat and skin infections does not eliminate the risk of glomerulonephritis

• Family members of patients with acute glomerulonephritis should be cultured for group-A β-hemolytic streptococci and treated if culture positive 38

IgA nephropathy (IgAN)

• Recurrent painless gross hematuria. • Preceded by (usually 1-3 days ) infections

(URTI , Ac GE). • HTN & renal insufficiency --- uncommon• C3 level ----- normal• ASO or anti DNase B ---- not elevated

Henoch-Schonlein Purpura (HSP)

Purpuric rash on buttocks , lower extremities Normal platelet countAbdominal painGastrointestinal bleedingHematuria Proteinuria Arthralgias

HUS• Mostly <4yrs age• Follows gastroenteritis by E.coli 0157.• Micro-angiopathic hemolytic anemia• Hematuria • Oedema • Oliguria• Hypertension• Variable proteinuria (usually < 3 g/day)• Azotemia→ARF

THANK YOU！