NEPHRITIC SYNDROME

Oleh : Yeni Ayu Prihastuti

Moderator: Dr. dr. Hani Susianti, Sp.PK(K)
INTRODUCTION
Glomerulonephritis
 Inflammation of the glomerular capillaries

• Etiology:
– genetic mutations – hypertension
– infection – emboli
– toxin exposure – thrombosis
– autoimmunity – diabetes mellitus
– atherosclerosis – unknown (idiopathic)
INTRODUCTION
Glomerulonephritis
• Patients usually have some hematuria with varying degrees
of proteinuria
• can be isolated to the kidney (primary) or is part of systemic
disease (secondary)
INTRODUCTION
Spectrum of Glomerular Disease
ACUTE NEPHRITIC
SYNDROMES
CLASSIFICATION

1. Poststreptococcal
glomerulonephritis

2. Endocarditis-associated
glomerulonephritis

Acute Nephritic
Syndromes 3. Lupus Nephritis

4. Antiglomerular basement
membrane disease
CLASSIFICATION
5. IgA Nephropathy

6. Henoch-Schönlein Purpura

Acute Nephritic 7. ANCA small-vessel vasculitis

Syndromes

8. Membranoproliferative
glomerulonephritis

9. Mesangioproliferative
glomerulonephritis
CLINICAL PRESENTATION
Classically present with:
• hematuria • Renal insufficency
• red blood cells casts • variable proteinuria

Extensive inflammatory damage to glomeruli:

 a fall in GFR
 uremic symptoms with salt and water retention
 edema & hypertension
1. POSTSTREPTOCOCCAL
GLOMERULONEPHRITIS
PATHOPHYSIOLOGY
• Suggested as an immune-complex disorder
• Follows streptococcal infection with only certain strains of
streptococci (nephritogenic streptococci)
– M protein
 Skin infection: M types 47, 49, 55, 2, 60, and 57
 Throat infection: M types 1, 2, 4, 3, 25, 49, and 12
– Nephritis-associated plasmin receptor (NAPlr)
– Streptococcal pyrogenic exotoxin B (SPEB)
PATHOPHYSIOLOGY
• 1. Soluble Antigen-Antibody Complex  NAPlr

• 2. Insitu Formation  SPEB

PRESENTATION
• History
– Usually affected children between the ages of 2 and 14 years
– A history suggestive of preceding streptococcal infection
(pharyngitis, tonsillitis, pyoderma)
– Dark-colored urine
– Periorbital edema
– Oliguria
– Nonspecific symptoms (malaise, weakness, anorexia)
• Physical Examination
– Edema
– Hypertension
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria
– Urine sediment: dysmorphic red blood cells, red blood cell
casts, white blood cells, granular casts, white blood cell casts
– Elevated BUN & creatinine values
– Elevated ASO or anti-DNAase B titers
– Hypocomplementemia (C3)
PRESENTATION
• Renal Biopsy

 Diffuse proliferative glomerulonephritis with neutrophil and

monocyte infiltration of the glomeruli. Severe cases may
show glomerular crescents
WORKUP
• Laboratory Studies
– ASO and anti-DNAase B titers
– BUN & Creatinine
– Urinalysis
– Complement

• Renal Biopsy
Is not indicated unless there are characteristics that make the
diagnosis doubtful or have prognostic significance and
therapeutic implications
 2. ENDOCARDITIS-
ASSOCIATED
GLOMERULONEPHRITIS
PATHOPHYSIOLOGY
• A complication of subacute bacterial endocarditis
• Caused by the development of immune complex-mediated
injury  diffuse deposition of immunoglobulin, depression of
complement, and electron-dense deposits
• Glomerulonephritis unusual in acute settings because it takes
10 – 14 days to develop immune complex-mediated injury
PRESENTATION
• History
– Patients with subacute bacterial endocarditis who remain
untreated for a long time, have negative blood cultures, or
have right-sided endocarditis
– Clinical presentation may vary from an indolent illness to few
systemic manifestations
• Physical Examination
– Heart murmurs
– Petechiae
– Subungual hemorrhages
– Osler’s nodes 
– Janeway lesions 
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria
– Pyuria
– Urine sediment: dysmorphic red blood cells, red blood cell
casts
– Normochrom normocytic anemia
– Elevated rheumatoid factors titer
– Presence of mixed cryoglobulins
– Elevated C-Reactive Protein
– Hypocomplementemia
WORKUP
• Laboratory Studies
– Urinalysis
– Complete blood count
– Complement
– Mixed cryoglobulins
– C-Reactive Protein
– Rheumatoid Factors
3. LUPUS NEPHRITIS
PATHOPHYSIOLOGY
• Caused by production of autoantibodies directed against
nuclear element (nephritogenic autoantibodies):
– Antigen specificity directed against nucleosome or dsDNA
– Higher-affinity autoantibodies may form intravascular
immune complexes
– Cationic autoantibodies have a higher affinity for the anionic
glomerular basement membrane
– Autoantibodies of certain isotype (IgG1 & IgG3) readily
activate complement
CLASSIFICATION
ISN/RPS 2003
Class I Minimal mesangial lupus nephritis
Class II Mesangial proliferative lupus nephritis
Class III Focal lupus nephritisa,b
Class IV Diffuse segmental (IV-S) or global (IV-G) lupus nephritis
Class V Membranous lupus nephritisc
Class VI Advanced sclerosing lupus nephritis
a indicatethe proportion of glomeruli with active and sclerotic lesions
b indicatethe proportion of glomeruli with fibrinoid necrosis and with cellular crescents
c class V may occur in combination with class III or IV in which case both will be

diagnosed
PRESENTATION
• History
– Symptoms of active SLE: fatigue, fever, rash, arthritis,
serositis, or CNS disease
– Can be asymptomatic

• Physical Examination
– Rash
– Oral/nasal ulcers
– Peripheral edema
– Hypertension
– Ascites
– Pleural/pericardial effusions
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria
– Urine sediment: red blood cell casts
– Elevated BUN & creatinine values
– Elevated ANA titer
– Elevated anti-dsDNA titer
– Elevated C-Reactive Protein
– Hypocomplementemia
WORKUP
• Laboratory Studies
– BUN & Serum creatinine
– Creatinine clearance
– Urinalysis
– ANA
– Anti-dsDNA
– Complement (C3, C4, CH50)
– C-Reactive Protein

• Renal Biopsy
 4. ANTIGLOMERULAR
BASEMENT MEMBRANE
DISEASE
PATHOPHYSIOLOGY
• Also called Goodpasture Syndrome (triad of glomerulonephritis,
pulmonary hemorrhage and anti-GBM antibodies)
• An autoimmune disease
• Characterized by the presence of circulating pathogenic
autoantibodies directed against proteins in the glomerular and
alveolar basement membranes
• Anti-GBM antibodies are directed against an epitope located at
the NC1 domain at the C-terminal of the alpha-3 chain of type
IV collagen
PATHOPHYSIOLOGY
Anti-GBM antibodies bind to specific GBM antigen

Complement is activated

Proinflammatory cells and CD4+ and CD8+ are recruited to the site

Proinflammatory cytokines, chemokines, and proteolytic enzymes are

released

Endothelial damage, endothelial cell detachment from the underlying

GBM & fibrin accumulation beneath the disrupted endothelial cells

Breaks develop in GBM, plasma proteins and cells leak into the
Bowman space  crescents develop
PRESENTATION
• History
– Prodromal: flulike illness, arthralgia, myalgia, arthritis
– Pulmonary manifestations: hemoptysis, acute respiratory
failure, asphyxia
– Renal manifestations: tea-colored urine, oliguria/anuria

• Physical Examination
– Tachycardia
– Cyanosis
– Pale (due to anemia)
– Respiratory distress
– Chest exam: fine rales and dullness to percussion
– Hemorrhagic shock
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria, usually modest
– Urine sediment: dysmorphic red blood cell, red cell casts
– Low hemoglobin and hematocrit levels
– Elevated BUN & creatinine values
– Positive circulating ANCA (25-30% patients)
– Positive circulating anti-GBM antibodies, usually IgG/IgM/IgA
(>95% patients)
PRESENTATION
• Renal Biopsy

 glomeruli with segmental necrosis, leakage of blood into

Bowman’s space, and crescent formation
WORKUP
• Laboratory Studies
– Urinalysis
– Complete Blood Count
– BUN & Serum creatinine
– ANCA
– Anti-GBM antibodies

• Chest X-ray
• Renal Biopsy
5. IgA NEPHROPATHY
PATHOPHYSIOLOGY
• The most common form of glomerulonephritis
• An immune-complex mediated glomerulonephritis
• IgA nephropathy represents abnormal polyclonal IgA
production, specifically a post-translational defect
• Abnormal glycosilation impairs the normal clearance from
bloodstream of the circulating IgA molecules
 IgA deposition in the glomerular mesangium
PATHOPHYSIOLOGY
PRESENTATION
• History
– Episodic painless gross hematuria
associated with upper RTI (‘synpharyngitis) and other
infections
– Persistent microscopic hematuria

• Physical Examination
– Hypertension
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria, usually mild
– Urine sediment: dysmorphic red blood cell, red blood cell
casts
– Low hemoglobin and hematocrit levels
– Elevated BUN & creatinine values
– Elevated serum IgA
PRESENTATION
• Renal Biopsy

 segmental areas of increased mesangial matrix and

cellularity; globular mesangial IgA deposits
WORKUP
• Laboratory Studies
– Urinalysis
– Complete Blood Count
– BUN & Serum creatinine
– Creatinine clearance
– GFR assessment

• Renal Biopsy
6. HENOCH-SCHÖNLEIN
PURPURA
PATHOPHYSIOLOGY
• A vasculitis with IgA dominant immune deposits affecting small
vessels and typically involving the skin, gut, and glomeruli and
associated with arthralgias or arthritis
• Suggested as the multisystem form of primary IgA nephropathy
• Why IgA deposition leads to systemic vasculitis and extrarenal
manifestations in HSP and not in isolated IgAN is unknown.
PRESENTATION
• History
– Rash
– Arthralgias
– Abdominal pain (colic, sometimes associated with GI
bleeding)
• Physical Examination
– Palpable purpura
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria, usually mild
– Urine sediment: red blood cell, cellular casts
– Normal coagulation tests and platelet counts
– Normal or elevated creatinine values
– Elevated serum IgA
WORKUP
• Laboratory Studies
– Urinalysis
– BUN & Serum creatinine

• Skin Biopsy
• Renal Biopsy
 7. ANCA SMALL
VESSEL VASCULITIS
ANCA SMALL VESSEL VASCULITIS
Anti-Neutrophilic Cytoplasmic Antibodies (ANCA)
• Specific antibodies for antigens in cytoplasmic granules of
neutrophils and monocyte lysosome
Vasculitis
• Inflammation of the blood vessel walls

ANCAs directed to proteinase 3 (PR3-ANCA) or

myeloperoxidase (MPO-ANCA) is strongly associated with
small-vessel vasculitis & glomerulonephritis
CLASSIFICATION
Wegener’s Microscopic Churg-Strauss
Granulomatosis Polyangitis Syndrome
Classic triad: Clinically similar to Three phases:
1.UTI –sinusitis, Wegener’s granulomatosis 1. Alergic rhinitis &
nasal ulcers, otitis asthma
Rarely have significant
media, hearing 2. Eosinophilic
UTI symptoms
loss infiltrative disease
2.Lungs Kidney are the most resembling
3.Kidneys commonly affected organs pneumonia
Most common: 3. Systemic small
Definitive diagnostic:
40 – 70 years old vessel vasculitis
Lung biopsy
with granulomatous
Peak incidence: inflammation
4th decade
Onset:
15 – 70 years old
PRESENTATION
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria, usually moderate
– Urine sediment: dysmorphic red blood cell, red blood casts
– Eosinophilia (Churg-Strauss Syndrome)
– Positive ANCA
WORKUP
• Laboratory Studies
– Urinalysis
– Complete blood count
– ANCA titers

• Lung Biopsy
• Renal Biopsy
WORKUP
8. MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
PATHOPHYSIOLOGY
• Also known as mesangiocapillary glomerulonephritis
• Caused by deposits in kidney glomerular mesangium and
basement membrane thickening
• Associated with immune-complex mediated disease,
autoimmune disease, chronic infections, thromobotic
microangiopathies, paraprotein deposition, malignant
neoplasms
CLASSIFICATION
Based on histopathologic findings
Type I Idiopathic Characterized by
Subacute bacterial endocarditis subendothelial deposits
SLE
Hepatitis C ± cryoglobulinemia
Mixed cryoglobulinemia
Hepatitis B
Cancer: lung, breast, ovary
Type II Idiopathic Charcterized by dense-
C3 nephritic factor-associated deposits in the glomerular
Partial lipodystrophy basement membrane
Type III Idiopathic Characterized by subepithelial
Complement receptor deficiency & subendothelial deposits
PRESENTATION
• History & Physical Examination

Patients may present in 1 of 5 ways:

– Asymptomatic proteinuria and hematuria
– Nephrotic syndrome: periorbital/dependent/anasarca edema
– Acute nephritic syndrome: oliguria
– Recurrent episodes of gross hematuria
– Azotemia: fatigue
PRESENTATION
• Laboratory Examination
– Hematuria
– Proteinuria
– Urine sediment: dysmorphic red blood cell, red blood cell
casts
– Normocytic normochromic anemia
– Elevated BUN & creatinine values
– Decreased GFR
– Hypocomplementemia
PRESENTATION
• Renal Biopsy

 lobular appearance of the glomerulus, diffuse

hypercellularity, and thickening of the capillary wall
WORKUP
• Laboratory Studies
– Urinalysis
– Complete Blood Count
– BUN & Serum creatinine
– Lipid profile
– ANA test
– Hepatitis screening
– Cryoglobulins
– Complement

• Renal Biopsy
9. MESANGIOPROLIFERATIVE
GLOMERULONEPHRITIS
PATHOPHYSIOLOGY
• Characterized by expansion of the mesangium, sometimes
associated with mesangial hypercellularity; thin, single
contoured capillary walls; and mesangial immune deposits
• May be seen in IgA nephropathy, malaria, resolving
postinfectious glomerulonephritis, and class II lupus nephritis
• Clinically can present with varying degrees of proteinuria and
hematuria
SUMMARY
REFERENCES
1. Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL,
Lameson JL, et al, editors. Harrison’s Principles of
Internal Medicine, 17th ed. New York: McGraw-Hill. 2008.
2. Lerma EV, Berns JS, Nissenson AR, editors. CURRENT
Diagnosis and Treatment: Nephrology & Hypertension,
1st ed. New York: McGraw-Hill. 2009.
THANK YOU