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 GN,
- Venous and segmental sclerosis and hyalinosis,
- Membranose GN,
- Membranoproliferative (mesangiocapillary) GH,
- Idiopathic IgA GN.
Acute Poststreptococous
glomerulonephritis
 Definition:
Diffuse endocapillary proliferative glomerulonephritis, which starts acutely
after a previous streptococcal infection and occurs exclusively with nephritic
syndrome.
It affects predominantly patients in thier childhood and adolescence, but in
practice can be met at any age. It is more common with male individuals.
Because of the frequency of streptococcal infections during the cold months
of the year it is more often occuring in winter.
Acute Poststreptococous
glomerulonephritis
 More than 90% of the cases occur after a beta-hemolytic infection
Streptococcus group A. nephrotoxic strains having M protein - most often
serotype 12 and less requently serotypes 1, 2, 4, 28, 25, 49, 55, 57 and 60
isolated from the skin or throat.
 No streptococcal endoantigen can be found in the kidneys with
immunofluorescence.
 Many endo-and exoantigens have been discovered in the pathogenesis of
the disease. Of these, it is essential to screen for: 1) Endo-tryptosine -
activates the complement on the alternative path; 2) Streptococcal
pyrogenic exotoxin-B - is a cationic protease with plasmin binding
properties. Cationic antigens pass easily through negative loaded basal
membrane where they form in situ form immune complexes.
Acute Poststreptococous
glomerulonephritis
 Diffuse proliferation is detected by light
microscopy of endothelial and mesangial cells
with leukocyte infiltration of glomeruli.
 The immunofluorescence assay shows grain
deposits of C3 and IgG in the mesangium and
suboptimal.
 Dense deposits are observed on electron
microscopy in the form of a hump.

There are other sources of antigenic irritation of

streptococcal products - neuraminidase,
streptokinase, basal membrane binding protein,
and others.
Acute Poststreptococous
glomerulonephritis
Clinical Presentation
 The disease starts acutely 1-2 weeks after streptococcal angina or 3 to 6
weeks post streptococcal skin infection (scarlet fever, impetigo).
 It occurs with a typical nephritic syndrome: oedema, hypertonia,
haematuria, oliguria. In 90 - 95% of patients with OPCWG identified at least
two of the symptoms.
 oedema - due to increased retention of water and sodium due to decreased
glomerular filtration and increased inverse resorption of sodium and water in
the distal tubule. They are pale, soft, testy, cold, painless. They appear early
in the morning and are localized mainly on the face and around the eyes, and
in 5% of the patients have anaazarka.
 Hypertension - seen in 80% of patients. It is due increased plasma volume and
increased peripheral vascular resistance. It is usually of moderate type, but the
sudden rise in arterial blood pressure the background pressure of these
hemodynamic changes may be manifestations with congestive heart failure or
symptomatic side effects of the CNS (hypertonic encephalopathy, eclampsic
forms).
 Haematuria - occurs in 100% of cases and is the result of the increased
permeability of the glomerular filter. In 70% of patients haematuria is
macroscopic, stays for no more than a week and disappears along with the
oliguria. In the remaining patients, the hematuria is microscopic, can persist for
months.
 Oliguria - a result of reduced glomerular filtration and increased reabsorption
of sodium and water.
Acute Poststreptococous
glomerulonephritis
Laboratory studies
 Urine:
- high relative weight and reduced quantity.
- Proteinuria is moderate 1 - 3 g / 24h.
- In the urine sediment we can find dysmorphic erythrocyte with
erythrocyte cylinders.
- Often polymorphonuclear leukocytes and epithelial cells can be detected.
- Of particular importance is the detection of microscopic erythrocyturia in
the latency period, immediately after the end of the streptococcus infection.
Acute Poststreptococous
glomerulonephritis
Laboratory studies
 Blood Test:
- hemoglobin can to be slightly decreased in relation to the increased plasma
volume.
- In heavier anemic syndrome can be assumed for chronic glomerulonephritis
or otherwise concomitant illness.
- ESR is accelerated since the onset of the disease, related to the previous
angina, after that to the inflammatory process in the kidneys.
- Urea and Creatinin are normal or slightly elevated in relation to reduced
glomerular filtration.
- Proteinogram is the normal.
Acute Poststreptococous
glomerulonephritis
Laboratory studies
Important for diagnosis:
 The isolation of nephrotoxic streptococci from the throat or skin.
 The detection of antibodies against streptococcal antigens:
- Antistreptolisin O (AST) titer is elevated in 2/3 of the patients with upper
respiratory tract infection and 1/3 of patients with impetigo.
- Antistreptokinase, Antihialoronidase, Antideoxyribonuclease-B; Anti-
nicotinamide adenine dinucleotidase (streptozyme test, including the five
antibodies) positives in 95% of patients.
Acute Poststreptococous
glomerulonephritis
Diagnosis
 The diagnosis is made if there are enough anamnestic, clinical and laboratory data of
the presence of streptococcal infection and the characteristic course of the disease.
 Percutaneous renal biopsy is not recommended for a typical case of APSGN.
 PRB is recommended when:
- Lack of reliable data on previous streptococcal infection;
- Lack of latency between streptococcal infection and kidney events;
- GFR <30 mL / min and azotemia for more than 2 weeks;
- Hypertension with a duration of more than 4 weeks;
- Nephrotic syndrome;
- Persistent microhematuria and low-grade proteinuria over 18 months.
Acute Poststreptococous
glomerulonephritis
Treatment
 With elevated AST and isolated streptococci from the throat or skin it is appropriate to
administer antibiotic therapy - penicillin or erythromycin at optimal doses for 7 to 10 days
in order to eradicate the infection.
 APSGN therapy is predominantly symptomatic:
- loop diuretics to control swelling syndrome volume load.
- In the absence of response to diuretic therapy and development of acute kidney injury -
hemodialysis.
- Antihypertensive drugs - calcium antagonists, vasodilators. Also application of ACE
inhibitors has a good effect not only on the arterial pressure, but also improves GF in patients
with APSGN.
- The patients are advised to rest and reduce the intake of water and salt.
Acute Poststreptococous
glomerulonephritis
Prognosis

 Clinical manifestations resolve after 1 to 2 weeks.

 In 20 - 25% of cases a transition to chronic glomerulonephritis

 In 3-5% of them - in rapidly progressive glomerulonephritis.

 The lethality is below 1%.

The WHO clasification of the
glomerulonephritis
 1. Acute Poststreptococous glomerulonephritis.
 2. Rapidly progressive glomerulonephritis.
 3. Chronic glomerulonephritis:
- GM with minor changes,
- Mesangioproliferative GH,
- Venous and segmental sclerosis and hyalinosis,
- Membranose GH,
- Membranoproliferative (mesangiocapillary) GH,
- Idiopathic IgA GH.
Rapidly progressive glomerulonephritis

 Definition:

A group of diseases characterized by glomerulonephritis with a

rapid evolution and progression of the disease. They have a
common pathomorphological feature - establishment of extensive
glomerular crescent formation in over 50% of glomeruli.
Rapidly progressive glomerulonephritis

Diseases that can occur with a rapidly deteriorating renal

function and formation of glomerular crescents are:

 Primary glomerular diseases

1. Idiopathic RPGN:
a) Type 1 - anti-basalmembrane GN without haemoptoe;
b) Type 2 - immunocomplex GN;
c) Type 3 - with no immune deposits;
2. Diffuse semilunar GN - superimposed on primary glomerular disease
3. Mesangiocapillar GN;
4. Membranose GN;
5. IgA nephropathy;
Rapidly progressive glomerulonephritis

Diseases that can occur with a rapidly deteriorating renal function and
formation of glomerular crescents are:
 Systemic and other diseases
1) Post-Streptococcal GH;
2) Infectious endocarditis;
3) Bacterial sepsis;
4) Goodpasser's syndrome;
5) Abscesses;
6) Henoch-schonlein purpura;
7) Polyarthritis;
8) Granulomatosis with polyangiitis (Wegener's granulomatosis);
9) Microscopic polyangiitis;
10) Cryoglobulinemia;
11) Scleroderma;
12) Neoplasms.
Rapidly progressive glomerulonephritis
Histology
Glomerular crescents are formed when a
rupture of the capillary occurs a wall with a
flood of fibrin in the capsule space.
This leads to penetration of monocytes,
which together with the Baumann capsule
epithelial cells undergo transformation and
proliferation.
Rapidly progressive glomerulonephritis

 To define glomerulonephritis as a rapid progression, the crescents must cover over

50% of the glomeruli.

 In immunofluorescence:
1) Type 1 RPGN - antibacterial, linear deposits of IgG accompanied by C3 near the
basal membrane;
2) Type 2 - immunocomplex RPGN are observed granular deposits of IgG or IgM, along
with C3 in the mesangium;
3) Type 3 RPGN, which occurs with a cell-mediated mechanism and immune deposits
are absent.
Rapidly progressive glomerulonephritis

Clinical Presentation
 RPGN occurs exclusively with a typical nephritic syndrome. It starts sharp with
an oliguria and progresses to anuria.
 Later on, swellings appear around the face and limbs, as well as hypertension,
which is moderate at first.
 Swelling and hypertension rapidly progress to anasarca and malignant
hypertension.
 It is possible that the disease starts with high blood pressure and manifestation of
left ventricular weakness - cardiac asthma.
Rapidly progressive glomerulonephritis

Clinical Presentation
 Type 1, anti-basalmembrane GN:
 Antibase membrane GN accounts for 10-20% of all RPGN.
 It can be found in all age groups and sex, but more often young men and older women.
 At a young age, it presents itself as typical Pulmonary-Renal Syndrome – RPGN in
combination with pulmonary haemorrhage.
 In older patients it is usually renal-limited without pulmonary events.
 The lack of blood clot and pulmonitis distinguish the idiopathic RPGN type 1 from
Goodpasser's syndrome.
 The most characteristic of the clinical presentation is the progressive worsening of
kidney function, which in a few weeks one month reaches terminal renal failure.
 Nephrotic syndrome can develop in 10 to 45% of cases.
Rapidly progressive glomerulonephritis

Clinical Presentation
 Type 2, immunocomplex GN:
 Fever and fatigue occure with all of the above symptoms,

 Usually the hypertension is mild.

 Frequently, there is evidence of a previous APSGN.

Rapidly progressive glomerulonephritis

Clinical Presentation
 Type 3, with no immune deposits:

 Affects mostly the middle and advanced age, predominantly males,

 Its clinical presentation mirror the characteristics of other rapidly progressive GN but
there are a few systemic manifestations - fever, arthralgia, vasculitis, abdominal pain.
Rapidly progressive glomerulonephritis

Laboratory studies
 Urine:
 relatively low urine weight,

 non-selective moderate proteinuria,

 In the case of nephrotic syndrome - massive proteinuria (over 3 g / 24h).

 From the sediment – dismorthic erythrocytes and erythrocyte cylinders.

Rapidly progressive glomerulonephritis

Laboratory studies
 Blood tests:
 There is is normocytic, normochromatic anemia that deepens with progression
of renal insufficiency.
 Already in the first studies urea and creatinine are elevated and rapidly rising.
 GF is limited and is often under 15 mL / min.
 Coagulation status has a tendency for hypercoagulability.
Rapidly progressive glomerulonephritis

Laboratory studies
 For type 1 RPGN
 C3 the complement fraction is normal and is detect anti-basalmembrane antibodies.
 For type 2, RPGN
 C3 complement and others parts of the complement system are lowered
 circulating immune complexes and cryoglobulins are often found in higher
quantities than normal.
 For Type 3 RPGN
 the complement components are normal, there is no anti-basalmembrane
antibodies and circulating immune complexes.
 ANCA antibodies can be found.
Rapidly progressive glomerulonephritis

Treatment
It is aggressive and involves combination therapy
 Corticosteroids - start a 3 to 6-day pulse treatment every month with high doses of methylprednisolone 10 - 15
mg/kg, followed by conventional oral corticosteroids therapy - prednisolone 1 - 2 mg/kg in combination with
oral
 Cyclophosphamide - at a dose of 2 mg/kg/day or a monthly pulse treatment with dosage of 5-10 mg/kg (lower
cumulative dose and less toxicity).
 Plasmapheresis is carried out daily for several weeks, to prevent re-synthesis of antibody it is synchronized with
the pulse with Cyclophosphamide.
If there is a good therapeutic response the immunosuppressive therapy continues in decreasing doses usually for 6
months.
Corticosteroids are decreased smoothly with one 5mg per week until reaching maintenance dose 10-15 mg.
We can include in the treatment direct and indirect anticoagulants due to participation of the coagulation system in
the formation of glomeruli crescents. We start with doses15,000-30,000 IU daily of Heparin intravenously, after
the end of the first month can be switched to indirect anticoagulants. It is proved that the early application
correlates with decreasing the crescent formations and less likely progression of the renal failure.