Sudung O.

Pardede
Department of Child Health Faculty of Medicine University of Indonesia Cipto Mangunkusomo Hospital Jakarta

Glomerular capillary membranes mechanism of proteinuria

A SIZE-SPECIFIC BARRIER A CHARGE-SPECIFIC BARRIER

Glomerulonephritis
Synonyms:
Glomerulonephropathy
Glomerular 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 syndrome b. Congenital NS c. Familial hematuria

2. Acquired
a. Primary or idiopathic: b. Secondary: 1. infection-related 2. associated with a multisystem disease 3. drugs 4. neoplasia 5. miscellaneous

a. Primary or idiopathic:
Minimal changes Mesangial proliferative GN Focal segmental glomerulosclerosis

Membranoproliferative GN
Membranous glomerulonephropathy IgA nephropathy

Rapidly progressive GN
Focal proliferative GN Diffuse 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

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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Etiology
Congenital: Intra uterine Prognosis: 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.

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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 : diffuse :
One glomerulus: segmental : global : <50% of all glomeruli 50% of all glomeruli

part of individual glomerulus entire glomerulus

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Fig. Penampang dalam pemeriksaan mikroskop cahaya yang memperlihatkan kelainan glomerulus yang: A. Difus; B. Fokal; C. segmental

Pathology features
Proliferative:
increased glomerular cell

Intracapillary/endocapillary: endothelial or mesangial cells

Extracapillary: cells in Bowmans space

Crescent: half-moon-shaped collection of cells in Bowmans 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

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Etiology
Infections
Bacteria: Streptococci, pneumococci, staphylococci,

Treponema pallidum, Salmonella typhi Virus: Hepatitis B, Echovirus, Ebstein B virus, HIV. Protozoa: Malaria

Vascular-colagen disease:
Purpura Henoch Schnlein, SLE,

Genetic
Alports syndrome

Drugs
Methicillin
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Symptoms and Signs

Hematuria (with RBC casts)

Proteinuria
Hypertension

Renal function impairment

Oliguria Elevated plasma creatinine/Reduction in GFR

Peripheral oedema Pulmonary oedema Congestive cardiac failure
Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80. Bagga A. Pediatric Nephrology, 6th ed.,Wlsevier, 2009,p.815-28

Acute fluid overload

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Epidemiology
Actual 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 infection 10-15% of nephritogenic infection APSGN

Alatas A, et al. Maj Kedok Indones Kazzi AA, et al. http://www.emedicine.com/emerg/topic219.htm. Parmar MS. http://www.emedicine.com/med/topic879.htm. Smith JM, et al. Clinical paediatric nephrology.

1983 2006 2006 2003

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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 A
Beta-hemolytic Respiratory tract M 1,2,4,12,18,25 Skin M 49, 55, 57, 60

Group C
Streptococci

Streptococcus zooepidermicus

Site of infection: upper respiratory tract: pharynx, tonsilles, middle ear skin
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a. Host factors:

Age 5 -15 years Sex : boys > girls Genetic

Nutrition Socio-economic conditions

b. Bacterial factors:
Endostreptozine Cationic protein) Streptococcal pyrogenic exotoxin B Nephritis associated plasmin receptor Streptokinase Streptolysin O Streptodornase Hyaluronidase acid Neuraminidase DNA-ase Nicotinamide adenine dinucleotidase
M Protein

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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

28 Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79

 Fluid overload generalized oedema: 85%

acute pulmonary oedema: 14%

heart failure: 2%

Hematuria: microscopic: + 100%

macroscopic

Hypertension: 60-80%: encephalopathy hypertension: rare Nephrotic proteinuria: < 5% Hypoalbuminemia: mild, intravascular dilution Anaemia GFR: 45% Normal: 1-2 weeks
29 Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79

Laboratory
Urinalysis:

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%)

Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3 rd ed., Oxford, 2003;h.3-79

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Laboratory
Immunology:

Complement:

C3 C4 normal

renal function:

Creatinine and ureum Hyperkalemia Hyperphosphatemia Acidosis Calcium and phosphate Mild anemia Mild thrombositopenia

Hematology:

Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3 rd ed., Oxford, 2003;h.3-79

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Complications
Encephalopathy hypertension
Acute renal failure Pulmonary oedema Congestive heart failure

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Treatment
1. Bed rest 2. 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. Diuretics Furosemide 1 mg/kgbw/dose 2x/ day

6. Symptomatic treatment hypertension hypertensive encephalopathy congestive heart failure acute renal failure

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Indications for in-patient management of APSGN

Hypertension
Oedema Oliguria

Macroscopic hematuria
Elevated plasma creatinine Electrolyte abnormalities

Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80.

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Prognosis
95 98% : complete resolution : self limited disease : 1 2 weeks : died in the acute phase : RPGN

< 3% < 1%

Hematuria-proteinuria until 12 months: CGN

Ad vitam/for life Ad sanationum/for cure Ad fungsionum/for function

: good : good : good

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Clinical course of APSGN symptoms

Oedema Macroscopic hematuria

: subside day 3 (4,3 + 1,8) : subside day 2 (5,1 + 4,2)

Hypertension
Oliguria C3 complement normal ASO normal

: subside day 3 (4,6 + 2,4)

: subside day 3 (3,8 + 2,6) : 6-8 weeks : 1-6 months

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Gross haematuria, Oliguria, azotaemia

Hypertension

Depression of C3 Persistent proteinuria Microscopic haematuria or intermittent Orthostatic proteinuria

2 weeks 4 weeks 2 months 6 months 1 year 2 years

Fig. Natural history of APSGN

Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80.
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Acute non post streptococcal GN

symptoms are not similar with APSGN
family history of glomerular disease under 4 years or over 15 years

previous history of similar symptoms

evidence 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 - supportive

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Infective endocarditis - nephritis

Rare Staphylococcus aureus Renal manifestations:

Hematuria Proteinuria Hypertension Renal function

GSFS, diffuse proliferative GN, rapid progressive GN Hypocomplementemia: 60-90%

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Hepatitis B - nephritis
Membranous nephropathy, MPGN, minimal changes, IgA

nefrophaty, FSGS, diffuse proliferative GN, cresentic GN Age: 2- 12 years Boy: 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 Rare Renal manifestations:

proteinuria renal function C3 and C4

Therapy:
Antiviral: ribavarine -interferon: proteinuria

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HIV Nephritis
Urinalysis: routine
FSGS, minimal changes, IgA nephropathy Renal manifestations:

Proteinuria nephrotic Hematuria: not significant Normotension Hypocomplementemia

Therapy:

antiviral ACE inhibitor: proteinuric effect

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Others glomerulonephritis
Henoch Schoenlein purpura nephritis IgA nephritis Membranoproliferative glomerulonephritis Lupus nephritis ANCA positive nephritis

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Table: presenting clinical features of paediatric glomerular diseases that may mimic APSGN APSGN HenochSchnlei n Purpura 4-14 35% 20% 5-10% Normal Normal No Yes IgA Nephropat hy MPGN SLE ANCA-positive vasculitis

Mean age (years) Antecedent infection Gross haematuria Nephrotic syndrome* Serum C3 Serum C4 Diagnostic serology Extrarenal disease

5-15 Yes 30% 5% Low Normal*** ASOT; streptozym e Rare

10-20 Concurrent common 50-80% <10% Normal Normal No Rare

8-12 Common 20-50% 30-50% Low Normal/lo w No Rare

15-20 Rare <10% 0-50%** Low Low ANA, antidsDNA Common

12-20 Flu-like prodrome common 30% < 10% Normal Normal ANCA Common

* 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. 47