NEPHRITIC SYNDROME / APSGN IN CHILDREN

NEPHRITIC SYNDROME / APSGN IN CHILDREN

1. Acute Poststreptococcal
Glomerulonephritis
(APSGN)
Dr. Muhammad Sajjad
Sabir
MBBS, DCH, MCPS, FCPS
Assistant Professor of Paediatrics

2. Acute Nephritic
Syndrome

3. Acute Nephritic Syndrome
1.Gross hematuria (sudden
onset)
2.Edema
3.Hypertension (HTN)
4.Renal insufficiency (oliguria)

4. Feature NEPHROTIC NEPHRITIC
ONSET Insidious Abrupt
OEDEMA ++++ ++
BLOOD PRESSURENormal High
JVP Normal Raised
Proteinuria ++++ ++
Hematuria May/ may not+++
RBC Cast Absent Present
Serum AlbumenLow Normal
4

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

6. Acute Poststreptococcal Glomerulonephritis
（APSGN）
Classic example of the acute nephritic syndrome
characterized by sudden onset of:
Gross hematuria
Edema
Hypertension, and
Renal insufficiency
2
nd
most common glomerular causes of gross
hematuria in children (1
st
IgA nephropathy) 6

7. •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

8. 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 glomerulonephritis
8

9. (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

10. Neutrophils infiltration

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

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

13. 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

14. Although
•Morphologic studies &
•↓(C3) level
strongly suggest →mediated by
immune complexes
Questions still unsolved
•Precise mechanisms→ UNKNOWN
14
PATHOGENESIS

15. Clinical
Manifestations
15

16. 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

17. Typical manifestations
Severity of renal involvement varies
from asymptomatic microscopic
hematuria to oliguric acute renal failure

Nonspecific
symptoms
malaise,
lethargy,
abdominal /
flank pain
fever
Classically, abrupt
onset
hematuria,
proteinuria,
hypertension,
edema, and
azotemia.

18. •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

19. •Oliguria and anuria :
•transient oliguria.
•Anuria is infrequent
•Proteinuria
–Many patients have significant
proteinuria
–<5% - frank nephrotic syndrome.
Typical manifestations

20. Subclinical, microscopic
hematuria may be four times
more common as overt acute
PSGN
Attention

21. 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

22. INVESTIGATIONS
22

23. •Urinalysis
–demonstrates red blood cells (RBCs),
–RBC casts
–Proteinuria
–↑WBC
•CBC
–Mild normochromic anemia (due to hemodilution and
low-grade hemolysis)
23
Laboratory Findings

24. 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

25. 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

26. 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

27. 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

28. Differential Diagnosis
•IgA nephropathy
•Rapid progressive glomerulonephritis
(RPGN)
•Nephrotic syndrome (NS,nephritic
type)
•Exacerbation of chronic
glomerulonephritis
•Secondary glomerulonephriti
–HSP,
–HUS，
–SLE，
–HBV, ect.

29. Complications
Acute renal dysfunction
Hypertension → 60% of patients
Hypertensive encephalopathy → 10%cases
Heart failure
Hyperkalemia
Hyperphosphatemia
Hypocalcemia
Acidosis
Seizures
29

30. •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

31. Treatment
Management is directed at
•Treat renal insufficiency
•Treat hypertension
•Antibiotic therapy

Diet

Protein, sodium and water intake
-ARF

Salt and water restriction -HTN

32. Treat renal insufficiency
Careful intake and output record
Daily weight measurement
Monitor & treat HTN
Water and sodium restriction
Protein restriction
Potassium and phosphate restriction
Adjust medication dosages
32
TREAT if any
Hyperkalemia
Hyponatremia
Seizures
Acidosis
Hypocalcemia

33. Treat hypertension (HTN)
•Sodium restriction
•Diuresis (I.V Lasix)
•Calcium channel antagonists,
•Vasodilators
•Angiotensin -converting enzyme
(ACE) inhibitors
33

34. 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
 

35. 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.

36. Prognosis
Complete recovery ≥95%
Infrequently, acute phase severe
chronic renal insufficiency
Recurrences -- extremely rare
Mortality ??? LOW

37. Mortality
Can be avoided by appropriate
management of:
•Acute renal failure
•Cardiac failure
•Hypertension
37

38. 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

39. 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

40. Henoch-Schonlein Purpura (HSP)
Purpuric rash on buttocks , lower extremities
Normal platelet count
Abdominal pain
Gastrointestinal bleeding
Hematuria
Proteinuria
Arthralgias

41. 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

42. THANK YOU ！