Glomerulonephritis

Definition
 Glomerulonephritis are a heterogeneous group of diseases,
where glomeruli are the only or the most affected tissue. They
always affect both kidney injuries. The etiology, immune
pathogenesis of glomerulonephritis are unclear.
 For the most part they are idiotic, but there are secondary forms
as a result of various diseases (infections, neoplasms, systemic
processes), medication acceptance, environmental factors
environment.
 The pathogenesis of glomerular diseases is associated with a
disorder in the immune system involving both humoral and
cellular immunity that leads to a pathological response of the
body to exo- or endoantigens.
The WHO clasification of the
glomerulonephritis
 1. Acute Poststreptococous glomerulonephritis.
 2. Idiopatic rapidly progressive glomerulonephritis.
 3. Chronic glomerulonephritis:
- GM with minor changes,
- Mesangioproliferative GH,
- Focal and segmental sclerosis and hyalinosis,
- Membranose GH,
- Membranoproliferative (mesangiocapillary) GH,
- Idiopathic IgA GH.
The WHO clasification of the
glomerulonephritis
 1. Acute Poststreptococous glomerulonephritis.
 2. Idiopatic rapidly progressive glomerulonephritis.
 3. Chronic glomerulonephritis:
- GM with minor changes,
- Mesangioproliferative GH,
- Focal and segmental sclerosis and hyalinosis,
- Membranose GH,
- Membranoproliferative (mesangiocapillary) GH,
- Idiopathic IgA GH.
Chronic glomerulonephritis

Nephrotic syndrome
 Itis charactarised by proteinuria of 3 grams or more
per day of protein into the urine.

 Nephrotic syndrome is the combination of nephrotic-

range proteinuria with a low serum albumin level and
edema.
Chronic glomerulonephritis

Nephrotic syndrome
 The pathogenesis of the edema of GN with minimal
changes is associated, with massive protein loss
through urine, leading to a decrease in oncotic
pressure. As a result, the fluid from the vessels “floods"
in the interstitial space (soft, dough-like, interstitial
edema). This, on the other hand, leads to a relative
hypovolemia, to which the organism reacts with
activation of RAAS.
Chronic glomerulonephritis

Nephrotic syndrome
 Increased aldosterone production stimulates reverse reabsorption
of water and Na+ in distal tubules. The retained water and
sodium, due to reduced oncotic pressure, once again move into
the interstitium, cause cell hyperhydration with transselectrolyte
shift and the release of K+ from the cells. Endogenous
hyperkalaemia, which further stimulates the adrenal gland to
increase the aldosterone production, which results in a circle that
exacerbates the nephrotic syndrome. In some cases, with severe
and prolonged proteinuria, AKI may occur.
Idiopathic nephrotic syndrome

 In idiopathic nephrotic syndrome, three morphological

variants of chronic glomerulonephritis:

- Minimal­-change nephropathy,
- Mesangioproliferative glomerulonephritis,
- Focal and segmental glomerulosclerosis
Idiopathic nephrotic syndrome
What they have in common:
1. Unknown etiology;
2. Their pathogenesis is associated with T-cell immunity. Missing
deposits and C3 complement in immunofluorescence assay;
3. The three diseases are identical in appearance, but with different
intensity variations. Characterized by heavy structural changes in
sub-cytokines and changes in the mesangium.
Most authors view these as phases of the same process;
4. Leading in all three is the recurrent nephrotic syndrome.
Minimal-change nephropathy

 Also known as lipoid nephrosis or nil disease.

 It is a chronic glomerulonephritis, whose major
morphological characterization – injury of the podocyte
and is only established by electronic microscopy.
 It presents itself with exclusively nephrotic syndrome that
often relapses but there are also cases of spontaneous
remissions. It is the most common single form of nephrotic
syndrome in children, but it can also occur in adults.
Minimal-change nephropathy

 Pathogenesis is still unclear, but is thought to be due to

T-cell-dysregulation with a pathological production of
one or more circulating permeability factors.
 Different lymphocytokines cause alterations in the
anionic charge of the basal membrane, as well as
neutralizing the negatively charged podocytes surfaces
and podocyte foot processes fusion.
 As a result, the increased glomerular filter
permeability to plasma proteins occurs.
Minimal-change
nephropathy
On light microscopy the
intact glomeruli or minor
alterations, which may
result in a slight increase in
the mesangial matrix,
without compromising the
capillary lumen, are
detected.
Minimal-change nephropathy

 Tubular lesions are associated with increased protein

and lipid resorption in the form of drops in tubular
epithelial cells.
 The immunofluorescence test is negative. Electronic
microscopy reflects the main patomorphological
characteristic - podocyte foot process fusion and
erasure.
Minimal-change nephropathy

Clinical Presentation
 GN with minimal changes is manifested by symptoms
associated with the development of nephrotic
syndrome.
 It includes swellings that most often occur suddenly,
the most prominent in the morning, initially covering
the eyelids and the face, and later on spreading across
the limbs, in the sacral region and can generalize to an
anasara with leak in the body cavities.
Minimal-change nephropathy

Clinical Presentation
 Patientscomplain of abdominal discomfort associated
with the presence of ascites, sometimes diarrhea
(caused by the gut wall edema), scrotum edema,
orthopaenia in connection with hydrotrophic
development.
 There is an increased tendency for infections and
thrombotic events.
Minimal-change nephropathy

Laboratory tests
 There is high proteinuria >3,5g/24h.
 The sediment is poor with single erythrocytes,
leukocytes and hyalinic cylinders.
 Normal hemoglobin and erythrocytes levels are
observed in the CBC, but in more severe cases they
might be slightly elevated due to hypovolaemia and
hemoconcentration.
Minimal-change nephropathy

Laboratory tests
 Renal function is preserved.
 Hypoproteinaemia with hypoalbuminemia and
hyperlipidemia is observed.
 Itis appropriate to study the complement components
and antinuclear antibodies in order to exclude other
causes of nephrotic syndrome.
Minimal-change nephropathy

Diagnosis
 It is based on the nephrotic syndrome without evidence
of haematuria and hypertension,

 laboratory tests

 histological data by electron microscopy.

Minimal-change nephropathy

Treatment
 The diet is limits the salt, water and protein intake.
 The first-line therapy MCNP is the use of corticosteroids. It starts with a
3-day course at high doses of methylprednisolone 10-15 mg/kg followed
by conventional oral corticosteroid - prednisone 1-2 mg/kg, usually 40
mg in the morning after breakfast and 20mg in the evening after dinner.
 Ifthe patient has a good response of the immunosuppressive therapy, it
continues in decreasing doses usually for not less than 6 months.
 P.O.corticosteroids are gradually reduced by one tablet per week until a
maintenance dose of 10-15 mg is reached, then switched to an alternate
regimen (the two-day dose is taken at once in the morning at 48 hours).
Minimal-change nephropathy
Treatment
 Direct and indirect anticoagulants are included in the therapeutic scheme in
connection with the occurrence of hypercoagulation. Apply 15,000-30,000 IU
Heparin intravenously, and after the end of the first month, the patient can
be switched to indirect anticoagulants.
 The majority of corticosteroids-sensitive patients - both children and adults -
often relapse during various infections but remain susceptible to
corticosteroid therapy.
 Relapses are treated with shorter courses of prednisone.
 Patients with frequent recurrences are indicated for additiomal
immunosuppressive therapy with cyclophosphamide 2 mg/kg orally for 12
weeks. Oral administration may be replaced by monthly pulses of
cyclophosphamide 5 - 10 mg/kg in combination with corticosteroids.
Minimal-change nephropathy

Treatment
 Patientsshould be monitored for bone marrow and
gonadal toxicity that are directly related to the
cumulative dose of cyclophosphamide.
 In the absence of an effect of the combined
corticosteroid and immunosuppressive treatment,
cyclosporine A is administered at an initial dose of 3-7
mg/kg, and dosing then depends on its blood levels.
Minimal-change nephropathy

Treatment
 High doses of immunovenin intact (255 mg / kg per
course) can be administered if the patient does not
respond to the threatment above. It is administered
three times daily, at a dose of 85 mg/kg intravenously.
 Symptomatic treatment of nephrotic syndrome
includes infusions of PPV and humanalbumin,
diuretics, lipid lowering agents.
Minimal-change nephropathy

Prognosis

 The evolution of the disease lasts for years with partial

or complete remissions that occur spontaneously or
under the influence of pathogenetic therapy.
Mesangioproliferative
glomerulonephritis
Chronic glomerulonephritis

Nephrotic syndrome