NEPHRITIC SYNDROME Definition: Nephritic syndrome is characterized by hematuria (gross or microscopic),
dysmorphic red cells, red cell casts in the urine, azotemia and oliguria (due to decreased
glomerular filtration rate), and mild to moderate hypertension. Proteinuria and edema are
common, but they are not as severe as in the nephrotic syndrome.Acute Proliferative Glomerulonephritis
� These are immune complexes mediated diseases. The inciting antigen
may be:
n Exogenous (e.g., postinfectious glomerulonephritis, which commonly
follows streptococcal infection).
n Endogenous [e.g., systemic lupus erythematosus (SLE)].
� Characterized histologically by diffuse proliferation of glomerular
cells, and infiltration by leukocytes.
POSTSTREPTOCOCCAL (POSTINFECTIOUS)
GLOMERULONEPHRITIS
Q. Classify glomerulonephritis. Discuss the
etiopathogenesis of acute poststreptococcal
glomerulonephritis. Describe its light microscopy,
electron microscopy and immunofluorescence
findings.
Poststreptococcal glomerulonephritis is a common disorder in developing
countries.
Age group: Most frequent in children between 6 and 10 years of age, but
may develop in adults.
Etiology and Pathogenesis
Q. Describe the etiopathogenesis of acute diffuse
proliferative glomerulonephritis/poststreptococcal
glomerulonephritis.
� It follows streptococcal infection (hence poststreptococcal) rather than
direct primary infection of the kidney by streptococci.
� Primary streptococcal infection usually involves the pharynx
(pharyngitis) or the skin (impetigo/pyoderma). Skin infections are usually
associated with overcrowding and poor hygiene.
� Only certain strains of group A β-hemolytic streptococci are
nephritogenic. More than 90% are due to types 12, 4, and 1. These can
be identified by typing of M protein of the streptococcal cell wall. Main
streptococcal antigenic component responsible for immune reaction in
poststreptococcal glomerulonephritis are streptococcal pyogenic exotoxin
B (SpeB) and and streptococcal glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) in most but not all cases.
� Manifests usually after a latent period of 1–4 weeks following primary
streptococcal infection.
� It is an immunologically mediated disease. Both have an affinity for
glomerular proteins and plasmin.
Evidences to Support Immunological Basis
� Latent period: It ranges from 1–4 weeks, between the streptococcal
infection and beginning of glomerulonephritis and is compatible with the
time required for the production of antibodies and the immune
complex formation.
� Antibodies against streptococcal antigens: They are increased in
majority of patients. These antibodies includes:
n Anti-streptolysin O
n Anti-deoxyribonuclease B (anti-DNase B)
n Anti-streptokinase
n Anti-hyaluronidase
n Anti-nicotinyl adenine dinucleotidase.
� Hypocomplementemia: It is observed in more than 90% of patients,
due to activation and utilization of complement components by immune
complexes.
� Immune-complex deposits:
n Electron microscopy shows glomeruli with electron dense deposits
of immune complexes.
n Immunofluorescence shows granular fluorescence to the immune
deposits.
� Streptococcal antigens in the glomeruli: Many cationic antigens unique
to nephritogenic strains of streptococci, can be demonstrated in the
glomeruli. Examples:
n Nephritis-associated streptococcal plasmin receptor (NAPlR).
n Streptococcal pyogenic exotoxin B (SpeB) (main antigenic
determinant responsible for immune reaction in most cases of
poststreptococcal glomerulonephritis) and its zymogen precursor
(zSpeB).
n Streptococcal GAPDH.
Mechanism of Damage
� Immune complexes are formed in the circulation and gets deposited
within glomeruli.
� These immune complexes initiate inflammation by activating
complement and other humoral and cellular mediators of
inflammation (refer page 153).
� The inflammatory mediators attract and activate neutrophils and
monocytes and stimulate proliferation of mesangial and endothelial cell.
The result is hypercellular glomerulus.
MORPHOLOGY
Q. Describe the morphology of kidney in acute
diffuse proliferative glomerulonephritis.
Gross
The kidneys are enlarged and show pale capsular surface and cortex.
Q. Write a short answer on microscopy of kidney
in acute post-streptococcal glomerulonephritis.
Microscopy (Figs. 20.7A and B)
1. Glomeruli:
• Enlarged hypercellular glomerulus: It is the classical diagnostic feature, which is
seen in all glomeruli (hence called diffuse). The hypercellularity is due to:
– Infiltration by leukocytes: It includes both neutrophils and monocytes.
– Proliferation and swelling of endothelial and mesangial cells.
– Rarely proliferation of parietal cells lining Bowman’s capsule: It forms
crescent. Presence of crescents is a poor prognostic feature.
• Obliteration of glomerular capillary lumen: It is due to swelling and
proliferation of endothelial and mesangial cells + infiltration by leukocytes.
2. Tubules: It may contain red cell casts in the lumen and the tubular epithelial cells may
show degenerative changes.
3. Interstitium: It may show edema and inflammatory cell infiltrate.
4. Blood vessels: Unremarkable.
Immunofluorescence Microscopy (Fig. 20.8)
Granular deposits of IgG, IgM, and C3 in the mesangium and along the GBM →
granular fluorescence.
Electron Microscopic Findings (Fig. 20.9)
• Subepithelial deposits of discrete, amorphous, electron-dense deposits is
characteristic feature. These appear as dome-shaped “humps” → termed as ‘humps’ or
‘lumpy’ deposits. They correspond to the granular IgG and C3 demonstrated by the
immunofluorescence.
• Subendothelial, intramembranous and mesangial deposits may also be present.
Clinical Course
� Affected child develops malaise, fever, nausea, oliguria, and
hematuria (smoky or cola-colored urine) 1–2 weeks after recovery
from a sore throat.
� Periorbital edema, and mild to moderate hypertension is usually
observed.
� In adults, clinical features are atypical.
Laboratory Findings
Q. Laboratory findings in nephritic syndrome.
Blood Findings
� Raised antistreptococcal antibody titers [e.g., anti-streptolysin O
(ASO) titer], but the level may be low in GN that follows streptococcal
skin infection.
� Hypocomplementemia: Significant reduction in serum concentration
of complement (C3) components.
� Raised blood urea and serum creatinine indicate renal impairment.
Urinary Findings
Q. Write a short answer on urinary findings in acute
nephritis.
� Oliguria
� Mild (variable degree) proteinuria (usually <1 g/day).
� Hematuria (smoky or cola-colored urine): RBCs in urine.
� Microscopy: Red cell casts or dysmorphic red cells (red cells with
cellular protrusions or fragmentation).
Prognosis
� Children: Prognosis is good in children and more than 95% totally
recover.
� Adults: In adults, it is less benign. They may recover promptly or
develop rapidly progressive glomerulonephritis or progress to chronic
glomerulonephritis.
Q. A10-year-old boy was brought by the mother to
pediatric outpatient with chief complaints of puffiness
of face, particularly more marked in the morning,
mild pitting edema on both legs, malaise with nausea
and a slight fever for about one month. Mother also
complained that he passes dark brown (red or cola)
colored (smoky) urine and the urine output was
reduced (oliguria). On enquiry, mother informed that
about 2 weeks back the child had impetigo lesions on
the face (or upper respiratory tract infection). On
examination, the blood pressure was 140/100 mm Hg
(moderate hypertension). Urine examination revealed
mild (or moderate) albuminuria/proteinuria and
microscopy showed RBC ++ and RBC cast +.
Laboratory investigation showed a raised serum antistreptolysin O titer and low serum complement level.
(a) What is the most probable diagnosis? (Ans:
Nephritic syndrome due to acute poststreptococcal
glomerulonephritis)
(b) Discuss the etiopathogenesis of these lesions
(refer pages 664-5)
(c) Describe the light microscopy,
immunofluorescence and electron microscopic
findings (refer page 665)
Nephritic syndrome:
• Hematuria
• RBC casts/dysmorphic red cells in the urine
• Moderate proteinuria
• Oliguria
• Hypertension
Proliferative GN: Increased numbers of cells within the glomerulus due to proliferation of cells of
the glomeruli and/or infiltration of polymorphs and macrophages.
Acute poststreptococcal glomerulonephritis: Develops after streptococcal infection in children and
young adults. It is an immune-complex mediated disease.
Poststreptococcal glomerulonephritis:
• Diffuse cellular proliferation of endothelial and mesangial cells
• Infiltration by leukocytes
• Granular immunofluorescence
• Subepithelial deposits (humps) on EM
Acute proliferative glomerulonephritis:
• Periorbital edema
• Mild to moderate hypertension
• Cola-colored urine
(d) List the investigations. What is the prognosis of
this disease? (refer pages 665-6)
Nonstreptococcal Acute Glomerulonephritis
(Postinfectious Glomerulonephritis)
Acute proliferative glomerulonephritis may also occur in association with
other infections:
� Bacteria: Examples, staphylococcal endocarditis, pneumococcal
pneumonia, and meningococcemia.
� Virus: Examples, hepatitis (B and C), mumps, HIV infection, varicella,
and infectious mononucleosis.
� Parasite (e.g., malaria, toxoplasmosis).
The morphological changes are similar to poststreptococcal
glomerulonephritis.
Pitting edema: Does not distinguish nephritic from nephrotic syndrome.
Complement levels in poststreptococcal GN:
• Transient reduction during the disease
• Return to normal in 6–8 weeks
Hematuria with dysmorphic RBCs are seen in: Acute glomerulonephritis.
Poststreptococcal glomerulonephritis: Most affected children recover; in adults prognosis is worse.
Definition: Rapidly progressive glomerulonephritis (RPGN) is a syndrome, characterized by rapid
and progressive loss of renal function associated with severe oliguria and signs of nephritic
syndrome. If not treated, death occurs due to renal failure within weeks to months.
RAPIDLY PROGRESSIVE
(CRESCENTIC)GLOMERULONEPHRITIS
Q. Write short note on rapidly progressive
glomerulonephritis.
RPGN does not represent a specific etiologic type of glomerulonephritis.
Most common microscopic features is the presence of crescents in most of
the glomeruli. Hence the term crescentic glomerulonephritis.
Classification
Q. Write short essay on classification. Etiology and
pathogenesis of rapidly progressive
glomerulonephritis.
RPGN classified into three types based on immunological findings (Box
20.4). Each type may be idiopathic or associated with a known disorder.
Type I (Anti-GBM Antibody)
Type I RPGN is an uncommon, aggressive type caused by an anti-GBM
antibody. One of the examples is Goodpasture syndrome.
Type II (Immune Complex)
� It is due to immune complex deposition and may complicate any of the
immune complex nephritides (e.g., postinfectious glomerulonephritis,
lupus nephritis).
� Immunofluorescence: Shows granular fluorescence characteristic of
immune complex nephritis.
Type III (Pauci-immune)
� It is also known as pauci-immune type.
� It neither shows anti-GBM antibody nor immune complex by
immunofluorescence and electron microscopy.
� Majorities are idiopathic and have circulating antineutrophil
cytoplasmic antibodies (ANCAs).
RPGN: Clinical entity with features of nephritic syndrome and rapid loss of renal function.
� Some may be a component of systemic vasculitis, such as Wegener
granulomatosis.
Pathogenesis
The RPGN is a syndrome caused by primary glomerular diseases as well
as systemic diseases. Pathogenetic mechanism varies but most are
immunologically mediated and it indicates severe glomerular damage.
GOODPASTURE SYNDROME
Q. Write short essay on Goodpasture syndrome.
In Goodpasture syndrome, anti-GBM antibodies cross-react with
pulmonary alveolar basement membranes causing pulmonary hemorrhage
associated with acute renal failure.
Pathogenesis
Genetic predisposition: High prevalence of certain HLA subtypes (e.g.,
HLA-DRB1) in these patients point towards genetic predisposition to
autoimmunity.
� Anti-GBM antibodies are formed against Goodpasture antigen. This
antigen results from conformational changes in the a3 chain of type IV
collagen of GBM.
� Anti-GBM antibodies cross-react with the target antigen, which is
also expressed on pulmonary alveolar capillary basement membranes.
This results in pulmonary hemorrhages and hemoptysis, which may be
life-threatening.
MORPHOLOGY
Gross
• Kidneys are enlarged and pale (large white kidney).
• May show petechial hemorrhages on the cortical surfaces (flea bitten kidney).
Microscopy (Figs. 20.10A to C)
• Glomeruli: Its characteristic feature is crescents in most of the glomeruli. Hence, the
term crescentic glomerulonephritis.
• Crescents:
– Components: Crescents are formed by:
◆ Proliferation of the parietal epithelial cells lining Bowman capsule.
◆ Infiltration of monocytes and macrophages into the urinary space.
– Stimulus: Fibrin leaked into the Bowman space is the stimulus and is found between
the cellular layers. Fibrin is derived from fibrinogen, which escaped through the
ruptured GBM into Bowman space.
– Significance: It indicates severe glomerular injury and does not represent any
specific etiological factor.
• Tubules: The tubular lumen may show casts and red cells.
• Interstitium: It shows edema with few inflammatory cells.
• Blood vessels: Normal.
Immunofluorescence Microscopy
Goodpasture syndrome show linear GBM fluorescence (Fig. 20.11) for IgG and C3
complement.
Electron Microscopy
Ruptures in the GBM: It allows leukocytes, proteins, and inflammatory mediators to
leak into the urinary space and initiates crescent formation (Fig. 20.12).
Clinical Course
In Goodpasture syndrome, patient may present with recurrent hemoptysis
or life-threatening pulmonary hemorrhage. Other features are variable
hypertension and edema.
Urine findings: (1) Hematuria, (2) RBC casts and dysmorphic RBCs, and 
(3) moderate proteinuria.
Goodpasture syndrome: Anti-GBM disease in which anti-GBM antibodies cross-react with alveolar
basement membrane of lung.
Goodpasture antigen: A peptide within the noncollagenous portion of the α3 chain of collagen type
IV of GBM.
Epithelial crescents: Proliferation of parietal epithelial cells + monocytes and macrophages. Formed
due to fibrin leaked through ruptured GBM.
Prognosis: Milder forms may recover, but the renal involvement usually
progress within weeks and cause severe oliguria.
Uremia is the cause of death in Goodpasture syndrome.
Goodpasture syndrome:
• Anti-GBM disease
• Epithelial crescent
• Linear immunofluorescence. In concise points for exam