Sudung O. Pardede
Department of Child Health Faculty of Medicine University of Indonesia –Cipto Mangunkusomo
HospitalJakarta
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Glomerular capillary membranes mechanism of proteinuria
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A SIZE-SPECIFIC BARRIER
A CHARGE-SPECIFIC BARRIER
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GlomerulonephritisSynonyms:
GlomerulonephropathyGlomerular diseases
Definition:A group of conditions in which inflammation in the
glomerulus occurs The mechanisms for glomerular injury are complex
more often are inisiated by an immune response
Classification of glomerulonephritis
1. Congenital or inherited:a. Alport syndromeb. Congenital NSc. Familial hematuria
2. Acquired a. Primary or idiopathic:b. Secondary:
1. infection-related2. associated with a multisystem disease3. drugs4. neoplasia5. miscellaneous
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a. Primary or idiopathic:
Minimal changesMesangial proliferative GNFocal segmental glomerulosclerosisMembranoproliferative GNMembranous glomerulonephropathyIgA nephropathyRapidly progressive GNFocal proliferative GNDiffuse proliferative GN proliferative GN
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b. Secondary:1. Infection related:
Poststreptococcal GN Subacute bacterial endocarditis Postpneumococcal GN Shunt nephritis Hepatitis B, C, HIV Malaria, leprosy, schistosomiasis, etc
2. Associated with multisystem disease Henoch-Schoenlein purpura Systemic lupus erythematosus Hemolytic uremic syndrome Collagen vascular disease: polyarteritis nodosa,
vasculitis Goodpasture syndrome, etc
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b. Secondary…………….:3. Drugs:
Penicillamine, NSAID Captopril, gold salts, Trimethadione, lithium, mercury, etc
4. Neoplasia Leukemia Lymphoma Carcinoma
5. Miscellaneous Renal transplant rejection Sickle cell disease Reflux nephropathy 9
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Classification of glomerulonephritis
Etiology: congenital x primary x secondary
According time period: acute x subacute x chronic
According renal biopsy: focal x segmental x diffuse
According number of cells: non-proliferative x proliferative
According immunofluorescence:
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EtiologyCongenital:
Intra uterinePrognosis: infaust
Primary glomerular disease:Disorders in which the glomeruli are the sole or
predominant tissue involved. Usually : idiopathic.
Secondary glomerular disease:
Glomerular injury is a feature of a systemic disease, vascular, metabolic or genetic disorders involving multiple organs or systems.
Time periode or chronology
Acute : days to weeks
Subacute/rapidly progressive:over weeks to few months
Chronic : many months to years
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Location of lesion One kidney;focal : <50% of all glomerulidiffuse : ≥50% of all glomeruli
One glomerulus:segmental : part of individual glomerulusglobal : entire glomerulus
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A B C
Fig. Penampang dalam pemeriksaan mikroskop cahaya yang memperlihatkan kelainan glomerulus yang: A. Difus; B. Fokal; C. segmental
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Pathology features
Proliferative: increased glomerular cellIntracapillary/endocapillary:
endothelial or mesangial cellsExtracapillary:
cells in Bowman’s spaceCrescent: half-moon-shaped collection of
cells in Bowman’s space
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Pathology features……
Membranous:expansion of glomerular basement membrane
as a dominant feature
Sclerosis:increased amount of homogenous non-fibrillar
extracellular material similar to GBM and mesangeal matrix
Fibrosis:deposition of type I and III collagen commonly as a consequence of healing of
crescents or tubulointerstitial inflammation
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Acute glomerulonephritis:
constellation of clinical manifestations caused by
glomerular injury and inflammation
that leads to decline in glomerular filtration rate
Etiology
InfectionsBacteria: Streptococci, pneumococci,
staphylococci, Treponema pallidum, Salmonella typhi
Virus: Hepatitis B, Echovirus, Ebstein B virus, HIV.
Protozoa: MalariaVascular-colagen disease:
Purpura Henoch Schönlein, SLE,Genetic
Alport’s syndromeDrugs
Methicillin19
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Symptoms and Signs
Hematuria (with RBC casts)ProteinuriaHypertension Renal function impairment
Oliguria Elevated plasma creatinine/Reduction in GFR
Acute fluid overload Peripheral oedema Pulmonary oedema Congestive cardiac failure
Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3 rd ed.,Oxford, Toronto, 2003,p.367-80. Bagga A. Pediatric Nephrology, 6th ed.,Wlsevier, 2009,p.815-28
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EpidemiologyActual incidence is not known, because the
majority of APSGN cases are sub clinical in nature
APSGN: schooll-aged children 5 – 15 years < 2 years : < 5% Male > female
APSGN: skin infection younger than pharingeal infection10-15% of nephritogenic infection APSGN
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Alatas A, et al. Maj Kedok Indones 1983Kazzi AA, et al. http://www.emedicine.com/emerg/topic219.htm. 2006
Parmar MS. http://www.emedicine.com/med/topic879.htm. 2006Smith JM, et al. Clinical paediatric nephrology. 2003
Etiology
Post infection of group A Streptococcus hemoliticus
Specific serotype of APSGN: Type 12: pharyngitis : onset : 10 (7-14) days
Type 49: skin infection (impetigo): onset: 21 days ( 3-6
weeks)
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Nephritogenic strains of Streptococci
Group ABeta-hemolytic Respiratory tract – M 1,2,4,12,18,25 Skin – M 49, 55, 57, 60
Group CStreptococciStreptococcus zooepidermicus
Site of infection:upper respiratory tract: pharynx, tonsilles, middle earskin
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a. Host factors: Age 5 -15 years Sex : boys > girls Genetic Nutrition Socio-economic conditions
b. Bacterial factors: M Protein
Endostreptozine Cationic protein) Streptococcal pyrogenic exotoxin B Nephritis associated plasmin receptor Streptokinase Streptolysin O Streptodornase Hyaluronidase acid Neuraminidase DNA-ase Nicotinamide adenine dinucleotidase
Pathogenesis
Hypothesis:• Circulating immune complex formation • In situ immune complex formation• Autoimmune process
Neuraminidase produced by streptococci removes sialic acid from Ig, alters endogenous IgG and
makes it autoantigenic altered IgG form circulating complexes deposited in kidney
Streptokinase:Plasminogen plasmin
Activate complement casacade
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Clinical manifestations 5 - 15 years
After pharingytis or impetigo:
-pharingytis: 7-14 days
-skin infection: 3-6 weeks
Acute nephritic syndrome: Hematuria Oedema Hypertension : headache, seizures, vision abnormality Proteinuria Oliguria/anuria
28Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
Fluid overloadgeneralized oedema: 85%acute pulmonary oedema: 14%heart failure: 2%
Hematuria: microscopic: + 100%macroscopic
Hypertension: 60-80%: encephalopathy hypertension: rareNephrotic proteinuria: < 5%Hypoalbuminemia: mild, intravascular dilutionAnaemiaAnaemia GFR: 45%Normal: 1-2 weeks
29Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
LaboratoryUrinalysis:
Hematuria Proteinuria Erythrocyte casts Leucocyturia Leucocyte casts Dysmorphic erythrocyte Normal
Streptococcus infections: Antibody for streptococcus antigen :
Titer ASO: pharingytis (80-90%), skin infection (<50%), Normal: 16-18%
Streptozyme assay: (ASO, streptokinase, hyaluronidase, DNA-se B, NADase) : pharingytis: 95%, skin infection: 80%
Serologi negative: maybe not APSGN Throat swab (normal: + 20%)
30Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
Laboratory ………
Immunology: Complement:
C3 C4 normal
renal function: Creatinine and ureum Hyperkalemia Hyperphosphatemia Acidosis Calcium and phosphate
Hematology: Mild anemia Mild thrombositopenia
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Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
Complications
Encephalopathy hypertension Acute renal failure Pulmonary oedema Congestive heart failure
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Treatment
1. Bed rest2. Antibiotic for eradicating streptococci
- Penicillin 10 days- Erythromicyn
3. Dietetic (fluid & salt restriction)- low protein 1 g/kgBW/day - low salt 1 g/day- IVFD as necesarry
4. Prolonged anuria dialysis- peritoneal dialysis- haemodialysis
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Treatment ……..
5. DiureticsFurosemide 1 mg/kgbw/dose 2x/ day
6. Symptomatic treatmenthypertensionhypertensive encephalopathycongestive heart failureacute renal failure
Indications for in-patient management of APSGN
HypertensionOedemaOliguriaMacroscopic hematuriaElevated plasma creatinineElectrolyte abnormalities
35Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3 rd ed.,Oxford, Toronto, 2003,p.367-80.
Prognosis 95 – 98% : complete resolution
: self limited disease: 1 – 2 weeks
< 3% : died in the acute phase < 1% : RPGN
Hematuria-proteinuria until 12 months: CGN
Ad vitam/for life : goodAd sanationum/for cure : goodAd fungsionum/for function : good
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Clinical course of APSGN symptoms
Oedema : subside day 3 (4,3 + 1,8)
Macroscopic hematuria : subside day 2 (5,1 + 4,2)
Hypertension : subside day 3 (4,6 + 2,4)
Oliguria : subside day 3 (3,8 + 2,6)
C3 complement normal : 6-8 weeks
ASO normal : 1-6 months
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2 weeks 4 weeks 2 months 6 months 1 year 2 years
Gross haematuria, Oliguria, azotaemia
Hypertension
Depression of C3
Persistent proteinuria
Microscopic haematuria or intermittent Orthostatic proteinuria
Fig. Natural history of APSGN
Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3 rd ed.,Oxford, Toronto, 2003,p.367-80.
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Acute non post streptococcal GN
symptoms are not similar with APSGNfamily history of glomerular diseaseunder 4 years or over 15 yearsprevious history of similar symptomsevidence of extra-renal disease
evidence of acute or chronic non streptococcal infection
evidence of chronic renal disease
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Shunt nephritis 4% of infected shunt
Hydrocephalus with VP shunt
Coagulase-negative Staphylococcus
Fever, lethargy, arthralgia, hepatomegali, purpura,
adenopathy, BW ,
Kidney: hematuria, proteinuria (30% nephrotic), azotemia,
hypertension
Lab: anemia,lecocytosis, ESR , C3 dan C4 (90%)
Therapy: - AB
- removal shunt
- supportive41
Infective endocarditis - nephritis
RareStaphylococcus aureusRenal manifestations:
Hematuria Proteinuria Hypertension Renal function
GSFS, diffuse proliferative GN, rapid progressive GN
Hypocomplementemia: 60-90%
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Hepatitis B - nephritisMembranous nephropathy, MPGN, minimal
changes, IgA nefrophaty, FSGS, diffuse proliferative GN, cresentic GN
Age: 2- 12 yearsBoy: 75-80%Renal manifestations:
oedema, Proteinuria (nephrotic) Hypertension: 25% Hematuria Hypocomplementemia: 15-64%
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Hepatitis C - nephritis
MPGN, acite proliferative GN, mebranous nephropathy
RareRenal manifestations:
proteinuria renal function C3 and C4
Therapy: Antiviral: ribavarine -interferon: proteinuria
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HIV Nephritis
Urinalysis: routineFSGS, minimal changes, IgA nephropathyRenal manifestations:
Proteinuria nephrotic Hematuria: not significant Normotension Hypocomplementemia
Therapy: antiviral ACE inhibitor: proteinuric effect
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Others glomerulonephritis
Henoch Schoenlein purpura nephritisIgA nephritisMembranoproliferative
glomerulonephritisLupus nephritisANCA positive nephritis
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APSGN Henoch-SchönleinPurpura
IgANephropathy
MPGN SLE ANCA-positive vasculitis
Mean age (years)Antecedent infectionGross haematuriaNephrotic syndrome*Serum C3Serum C4Diagnostic serologyExtrarenal disease
5-15
Yes
30%
5%
LowNormal***ASOT; streptozymeRare
4-14
35%
20%
5-10%
NormalNormalNo
Yes
10-20
Concurrent common50-80%
<10%
NormalNormalNo
Rare
8-12
Common
20-50%
30-50%
LowNormal/lowNo
Rare
15-20
Rare
<10%
0-50%**
LowLowANA, anti- dsDNACommon
12-20
Flu-like prodrome common30%
< 10%
NormalNormalANCA
Common
Table: presenting clinical features of paediatric glomerular diseases that may mimic APSGN
* Some of these values are estimates, as good epidemiological data are not published** Incidence depends upon the histological class of lupus nephritis*** A small number of cases presenting early in the clinical course of the disease may have very transiently depressed C4 levels.