GLOMERULONEPHRITIS

Lecturer prof. Yu.R. Kovalev

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 DEFINITION AND CLASSIFICATION
Glomerulonephritis is diffuse bilateral
immune-mediated glomerular injury
1. Acute Primary – pathologic process is
2. Subacute (rapidly confirmed into the kidneys
progressive) (poststreptococcal
3. Chronic glomerulonephritis or Ig A
nephropathy)
Secondary glomerulonephritis is
associated with systemic
diseases
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 COMMON CAUSES
1. poststreptococcal acute glomerulonephritis;
2. other postinfective acute nephritic syndroms —
following staphylococcal, pneumococcal and viral
infections;
3. collagen disorders — systemic lupus
erythematosus and periarteritis nodosa;
4. miscellaneous groups — Henoch-Schonlein
syndrome, infective endocarditis, hypersensitivity
angiitis, and early stages of Goodpasture's
syndrome.
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 TYPES OF NEPRITIS
Etiology Histopathology Patho-
genesis
Acute (postinfectious) glomerulonephritis Light: Diffuse proliferative Immune
–Streptococci, other bacteria glomerulonephritis complexes
Immunofluorescence: IgG; C3,
granular pattern

IgA nephropathy – Light: Mesangioproliferative Unknown

In association with viral upper respiratory glomerulonephritis
tract infections; gastrointestinal infection or Immunofluorescence: IgA (with
flu-like syndrome or without IgG, C3)

Rapidly progressive glomerulonephritis – Light: Crescentic Immune

Postinfection, lupus erythematosus, glomerulonephritis complexes,
Goodposture’s syndrome (if lung Immunofluorescence: IgG, IgA; anti-GBM
hemorrhage), subacute infective C3 granular pattern autoanti-
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bodies
endocarditis, shunt infections; idiopathic.
 PATHOGNESIS AND PATHOLOGY OF
POSTSTREPTOCOCCAL GN
The streptococcal antigens of nephritogenic
strain of -hemolytic strepococcus of group A
stimulate the production of antibodies. (M
types are 1,2,4,12 a.o.) The antigens and
antibodies combine to form immune
complexes. These get deposited in the kidney
and initiate acute inflammatory reaction in the
glomerulus. The kidneys are enlarged. The
glomeruli are swollen and show proliferation
of the endothelial cells. Capillares of
glomeruli and mesangium or infiltrated by 5
 PATHOGENESIS AND PATHOLOGY OF
POSTSTREPTOCOCCAL GN

In addition to the proliferation, electron dense

deposits are seen under electron microscopy.
These are the immune complex deposits.
Immunofluorescence microscopy shows a
granular pattern of distribution of immune
complexes in the glomeruli.

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 CLINICAL FEATURES
Acute nephritic syndrome is characterised by
hematuria with or without dysmorphic red
cells, red blood cell casts, proteinuria,
oliguria, hypertension, fluid retention and
edema. Acute renal failure sometimes may
occur.
The illness starts about 10 days after
streptococcal pharyngitis; less often after
skin lesions (impetigo). In this case latent
period is more prolonged and consists 7 2
 CLINICAL FEATURES
It is more common in children but can occur
in any age. Both sexes are affected. The onset
is often abrupt with puffiness of the face,
oliguria, reddish smoky urine, hypertension,
and edema. Severity of the disease is variable.
Mild cases may go unnoticed (subclinical
type). Severe cases present with life-
threatening complications like hypertensive
encephalopathy, acute left ventricular failure
or acute renal failure.
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 URINE EXAMINATION
Urine volume is reduced, it is reddish-brown and
contains protein. At this stage the specific gravity is
normal or raised. Numerous red cells are seen. The
presence of red cell casts indicates active
glomerulonephritis.
After a variable period, the activity of the disease
ceases and the urine output and renal functions
improve. Urinary abnormalities also clear up.
Though erythrocytes and casts disappear promptly,
microhematuria and proteinuria may persist for up to
6 months.
The blood pressure promptly returns to normal in
most cases with recovery. 9
 BLOOD EXAMINATION
The blood chemistry is altered depending on
the severity of the disease. The
antistreptolysin O (ASO) titre is significantly
elevated and this suggests recent
streptococcal infection. The serum
complement levels are reduced during the
active stage of the disease.
During the oliguric phase elevation of
creatinine level may be evident but it usually
rapidly falls to normal values. 10
 DIAGNOSIS
Any patient presenting with puffiness of face,
oliguria, hematuria hypertension and edema should
be investigated to exclude acute nephritic syndrome.
Diagnosis should be confirmed by urinary findings
and biochemical examination of blood. Etiological
diagnosis is made by estimating serum complement
levels, isolation of the infection agent, estimation of
ASO titre and if necessary renal histology.
Reduction in serum complement levels and
demonstration of immune complexes in histological
specimens by immunofluorescence microscopy are
diagnostic of immune complex nephritis.
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 DIAGNOSIS
Renal biopsy is indicated under the following
conditions:
•failure rises promptly (rapidly progressive
glomerulonephritis);
•presence of hypertension, azotemia and hematuria
for a long time (1 month and more);
•possibility of systemic diseases like vasculitis and
collagen diseases.

It is contraindicated in cases of bleeding disorders,

thrombocytopenia, uncontrolled hypertension. 12
 COURSE AND PROGNOSIS
In 90 per cent of children the recovery is
uneventful and complete. The proteinuria and
microscopic hematuria may persist for a few
weeks or months. Some children develop
nephrotic syndrome or chronic
glomemlohephritis. Chronic renal failure may
develop in 2-5 per cent of cases the acute
phase. During recovery any intercurrent
infection may precipitate transient
exacerbation of the clinical and urinary
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abnormalities.
 COURSE AND PROGNOSIS
In adults uneventful recovery occurs only in
50 per cent of subjects. Many develop renal
failure, hypertension, nephrotic syndrome or
chronic glomerulonephritis slowly
progressing to renal failure.
Less than 5% of adults will develop a rapidly
progressive glomerulonephritis, and a smaller
percentage will progress to end-stage renal
disease.
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 MANAGMENT

Bed rest during 3-4 weeks or more (persistent

hematuria and/or proteinuria)
Restriction of fluid consists 500 ml + volume
of diuresis of previous day
Restriction of NaCl – 0,5 – 2,0 g a day
Protein restriction - 0,5 g a day for 3-4 weeks
Adequate nutrition (more carbohydrate and
fat calories)

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 MANAGMENT

Moderate or severe arterial hypertension

requires ACE inhibitors or angiotensin II
receptor blocking agents
Hard edema – diuretics (lasix, etacrinic acid)
Acute renal failure – hemodialysis or
peritoneal dialysis

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 IgA NEPHROPATHY
IgA nephropathy (Berger's disease) is a primary
renal disease of IgA deposition in the glomerular
mesangium. IgA nephropathy may also be
associated with hepatic cirrhosis, celiac disease,
and infections such as with CMV; gastrointestinal
adenocarcinoma as well
IgA nephropathy is the most common form of
acute glomerulonephritis in the United States and
is even more prevalent worldwide, particularly in
Asia. It is most commonly seen in children and
young adults, with males affected two to three
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times more commonly than females.
 CLINICAL FEATURES
•nephritic syndrome - gross hematuria often
developing in 24 – 48 h after pharyngeal or
gastrointestinal infection, vaccination or
strenuous exercises
•gastrointestinal symptoms (10%),
•flu-like illness (15%)
•no significant latent period
•nephrotic syndrome is rare
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The urine becomes red or cola-colored 1-2
days after onset. In contrast to postinfectious
glomerulonephritis, this feature has been
called "synpharyngitic hematuria" since there
is no significant latent period. Other findings
include asymptomatic microscopic hematuria
as an incidental finding and the nephroric
syndrome. Approximately one-third of
patients will experience a clinical remission.

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 DIAGNOSIS
The serum IgA level is increased in up to 50%
of patients, and for that reason a normal
serum IgA does not rule out the disease.
Serum complement levels are usually normal,
and renal biopsy is the standard for
diagnosis. Glomeruli show a focal
glomerulonephritis with diffuse mesangial IgA
deposits and proliferation of mesangial cells.

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 COURSE AND PROGNOSIS
Forty to 50 percent of patients will have
progressive renal insufficiency. The
remainder will show chronic microscopic
hematuria and a stable serum creatinine. The
most unfavorable prognostic indicator is
proteinuria > 1 g/d. Others include
hypertension, persistent microscopic
hematuria and proteinuria,
glomerulosclerosis, and abnormal renal
function.
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 MANAGEMENT
Treating of acute nephritic syndrome is the
same as an acute poststreptococcal
glomerulonephritis. In a case of severe form,
or nephrotic syndrome, or rapidly progressive
variant high doses of glucocorticoids
sometimes with cytotoxic agents have to be
prescribed
In patients with recurrent tonsillitis a
tonsillectomy may reduce proteinuria and
hematuria

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 Rapidly progressive glomerylonephritis
(RPGN)
Extracapillary (crescentic) GN
Hematuria
Nephritic urinary sediment
Subnephrotic proteinuria
Rapidly progressive renal failure over weeks (with or
without pulmonary hemorrage)
Hipertension is unusual (20% on cases)
Serologic marcers – circulation anti-GBM antibodies
Prognosis for renal function is poor (without
immunosuppressive therapy greates then 80% developed
ESRD within 1 year.
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 Treatment of RPGN

Plasmapheresis
Pulses Prednisolone 1-2 g/d for 3 day
then1mg/kg/d
Ciclophosphamide 2-3 mg/kg/d
Dialysis
Renal transplantation

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 CHRONIC NEPHRITIS
Chronic glomerulonephritis is characterized
chiefly by persistent urinary abnormalities
(proteinuria, hematuria) and by slowly
progressive impairment of renal function,
eventuating by hypertension, contracted
granular kidneys and end-stage renal failure.
Evolution of chronic glomerulonephritis
varies considerably (10 – 20 years or more)
depending upon the nature of the disease and
the presence or absence the complications,
especially hypertension. 25
 CLINICAL FORMS OF CHRONIC
NEPHRITIS
•Hypertensive
•Nephrotic syndrome
•Miscellaneous
•Latent
•Terminal (end stage)

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 NEPHROTIC SYNDROME

Chronic glomerulonephritis is often

assotiated with nephrotic syndrome
Nephrotic syndrome - massive proteinuria
(more than 3.5 g in 24 h. in adults). It is often
associated with edema, hypoalbuminemia
(less than 30 g/l), hyperlipidemia and lipiduria.

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 COMMON CAUSES OF NEPHROTIC
SYNDROME

•Primary glomerulonephritis or associated

with allergy, Hodgkin's disease, NSAIDs,
systemic lupus erythematosus, Henoch-
Schonlein syndrome a.o.
•Congenital nephrotic syndrome,
•Amyloidosis
•Diabetic nephropathy

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PATHOGENESIS AND PATHOLOGY

Minimal-change glomerular lesions or

membranous nephropathy or focal segmental
glomerular sclerosis usually associated with
isolated nephrotic syndrome with bland urine
sediments
Mesangiocapillary and mesangioproliferative
changes as a rule accompanied by mixed
nephrotic/nephritic syndrome with active
urine sediments
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PATHOGNESIS AND PATHOLOGY
The profound proteinuria due to increase in the
glomeruler capillary permeability is responsible
for most of the clinical manifestations of nephrotic
syndrome. If the glomerular damage is severe,
albumin and immunoglobulins appear in the
urine, whereas with mild damage, only albumin
escapes in urine. The former is called
nonselective proteinuria and the latter, selective
proteinuria. Thus, assessing the selectivity of
proteinuria helps in assessing the degree of
damage to the glomerular filtering mechanism.
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PATHOGNESIS AND PATHOLOGY
The loss of protein in the urine results in
hypoalbuminemia. However, poor intake,
defective synthesis, and abnormal catabolism
can exaggerate this phenomenon. Reduction
in serum albumin results in the shift of fluid
from the intravascular to the extravascular
compartment to produce edema and arterial
hypotension. In addition to the levels of
serum cholesterol and lipids increase on
account of associated defects in lipid
metabolism. 31
 CLINICAL FEATURES OF NEPHROTIC
SYNDROME

Initially edema presents in the dependent

areas of the body such as the lower extremities;
however, it can become generalized. Patients
can experience dyspenea due to pulmonary
edema, pleural effusions, and diaphragmatic
compromise with ascites. Complaints of
abdominal fullness may also be present in
patients with ascites.
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 CLINICAL FEATURES OF NEPHROTIC
SYNDROME
Patients may show signs and symptoms of
infection more frequently than the general
population owing to loss of immunoglobulins and
certain complement moieties in the urine
Patients with serum albumin less than 2 g/dL
can become hypercoagulable. Nephrotic patients
have urinary losses of antithrombin III, protein C,
and protein S and increased platelet activation.
Patients are prone to renal vein thrombosis and
other venous thromboemboli, like pulmonary
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embolism.
 DIAGNOSIS OF NEPHROTIC
SYNDROME
•Persistent proteinuria and/or hematuria
•Unexplained anemia and/or elevated blood
uric nitrogen and creatinine
•Bilateral small kidneys
•Proves of secondary hypertension
•Clinical exacerbations of GN triggered by
pharyngitis (synpharyngitic) or other
infections
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DIAGNOSIS OF CHRONIC NEPHRITIS
•Persistent proteinuria and/or hematuria
•Unexplained anemia and/or elevated blood
uric nitrogen and creatinine
•Bilateral small kidneys
•Proves of secondary hypertension
•Clinical exacerbations of GN triggered by
pharyngitis (synpharyngitic) or other
infections
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DIAGNOSIS OF CHRONIC NEPHRITIS
Renal biopsy reveals
• variable combinations of proliferative,
membranous and sclerotic changes
• arteriolosclerosis induced by secondary
hypertension
• additional findings: tubulointersticial
inflammation and scarring
Glomerular hypertension and hyperfiltration
through remnant functioning nephrons
stimulate progression to ESRD 36
 MANAGEMENT OF CHRONIC
NEPHRITIS
The daily total dietary protein intake should
replace the daily urinary protein losses so as to
avoid negative nitrogen balance. Protein
malnutrition often occurs with urinary protein
losses greater than 10 g/d.
Protein restriction to 0.6 g/kg/d in patients with a
GFR < 25 mL/min prior to starting dialysis is
recommended.

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 MANAGEMENT OF CHRONIC
NEPHRITIS
Dietary salt restriction is essential for managing
edema; however, most patients also require
diuretic therapy. Commonly used diuretics include
thiazide and loop diuretics. Both are highly
protein-bound. With hypoalbuminemia, diuretic
delivery to the kidney is reduced, and patients
often require large doses. The combination of
loop and thiazide diuretics can potentiate the
diuretic effect. This may be needed for patients
with refractory fluid retention associated with
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pleural effusions and ascites.
 MANAGEMENT OF CHRONIC
NEPHRITIS
Dietary management of hypercholesterolemia
and hypertriglyceridemia in patients with
nephrotic syndrome is of little value; however,
dietary modification and exercise should be
advocated. Aggressive pharmacologic treatment
should be pursued.
Patients with renal vein thrombosis and recurrent
thromboemboli require indefinite anticoagulation.

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