nephritic syndrome / apsgn in children
TRANSCRIPT
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
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PATHOGENESIS
Clinical Manifestations
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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
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• Urinalysis – demonstrates red blood cells (RBCs), – RBC casts – Proteinuria – ↑WBC
• CBC– Mild normochromic anemia (due to hemodilution and
low-grade hemolysis)
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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
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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
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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
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