Glomerulonephritis facultative therapy.ppt

Glomerulonephritis
Facultative therapy
Internal medicine
MBBS

1. ЛЕКЦИЯ
GLOMERULAR DISEASES

2. Glomerulonephritis (GN) is a general
term for a group of disorders in
which:
there is primarily an immunologically mediated
injury to glomeruli, although renal interstitial
damage is a regular accompaniment
the kidneys are involved symmetrically
secondary mechanisms of glomerular injury come
into play following an initial immune insult such as
fibrin deposition, platelet aggregation, neutrophil
infiltration and free radical-induced damage
Renal lesions may be part of a generalized disease
(e.g.systemic lupus erythematosus, SLE).

3. ПРО
LESIONS OF THE GLOMERULI ARE
MANIFESTED:
CHANGES ONLY IN URINE TESTS
(LATENT GN);
GROSS HEMATURIA;
NEPHROTIC SYNDROME
(PROTEINURIA, HYPOPROTEINEMIA,
OEDEMA);
NEPHRITIC SYNDROME

4. Classification of GN
Acute glomerulonephritis AGN
(acute nephritic syndrome) –
abrupt onset of glomerular
haematuria, non-nephrotic range
( 3.0 g/day), proteinuria,
≤
oedema, hypertension and
transient renal impairment.

5. Classification of GN
Rapidly progressive glomerulonephritis –
features of acute nephritis, focal necrosis
with or without crescents and rapidly
progressive renal failure over weeks.
Chronic glomerulonephritis - haematuria,
proteinuria or both.

6. Nephrotic syndrome – massive
proteinuria (>3.5 g/day),
hypoalbuminaemia, oedema,
lipiduria and hyperlipidaemia.
Classification of GN

7. Classification of GN
(morphological)
•Mesangiocapillary (membranoproliferative)
glomerulonephritis (MCGN)
•Mesangial proliferative GN (IgM nephropathy,
C1q nephropathy)
•Membranous
•Glomerulonephritis with minimal
changes(minimal-change nephropathy, minimal-
change disease, MCD)
•Focal segmental glomerulosclerosis (FSGS)
•Fibroplastic

8. Acute glomerulonephritis (definition)
Acute glomerulonephritis – acute
immune inflammation of the kidneys
with primary renal damage glomeruli
by type of diffuse generalized
proliferative or exudative damage.
The average age of patients is 6 years
(3-7 years).

9. ETIOLOGY
It can be installed in 80-90% of
cases
1. Acute bacterial infections

10. ETIOLOGY
1. Streptococcal pharyngitis
2. Streptoderma
3. IE
4. Pneumococcal pneumonia
5. Sepsis
6. Meningococcal infection
7. Infectious mononucleosis

11. ETIOLOGY
2. Viral infection
1. Viral hepatitis B
2. Mumps
3. Varicella
4. Infections caused by Coxsackie virus

12. ETIOLOGY
3. Toxic substance:
- organic solvent,
- alcohol,
- drugs,
- compounds of mercury, lead, lithium,
etc.

13. ETIOLOGY
4. Drug sensitization (by sulfonamides,
penicillins, phenylbutazone),
5. Sensitization by food products, plant
pollen,

14. ETIOLOGY
The disease can be induced by the
introduction of vaccines, serums.
Cooling is an important starting
factor in the development of fire,
often having an independent
value.

15. Pathogenesis
GN is considered to be an immunologically
mediated disorder with involvement of
cellular immunity (T-lymphocytes,
macrophages /dendritic cells),
humoral immunity (antibodies, immune
complexes, complement) and
other inflammatory mediators (including
cytokines, chemokines and the coagulation
cascade).

16. PATHOGENESIS
The immune response to the
antigen leads to the development
of antibodies with the formation
of immune complexes or to the
activation of cellular immunity
reactions, or both mechanisms
simultaneously.

17. The immune response can be directed
against known target antigens,
particularly when GN complicates
infections, neoplasia or drugs.
More frequently the underlying
antigenic target is unknown
PATHOGENESIS

18. Acute glomerulonephritis
(acute nephritic syndrome)
This comprises (include):
Haematuria (macroscopic or microscopic) –
Proteinuria
Hypertension
Oedema (periorbital, leg or sacral)
Temporarily (transiently) oliguria and
uraemia.

19. Post-streptococcal glomerulonephritis
(PSGN)
The patient, usually a child, suffers a
streptococcal infection 1–3 weeks before
the onset of the acute nephritic syndrome.
The latent interval between the infection
and development of symptoms and signs
of renal involvement reflects the time taken
for immune complex formation and
deposition and glomerular injury to occur.

20. CLASSIFICATION
Clinical form
1. AGN with acute nephritic
syndrome (classic expanded form)
Edematous symptom complex – in
80-90 % of cases (mainly on the
face, together with pallor create a
"nephritic face"), after 2-3 weeks
of treatment usually disappear.

21. Arterial hypertension - in 70-90% of cases is
associated with impaired kidney function.
Acute development of hypertension makes it
difficult for the heart work and can manifest
acute heart failure, more often left
ventricular. Most often it is 140-160 mm Hg,
less often it is 180-190 mm Hg.

22. Urinary symptom complex:
a) proteinuria – the number of
protein in the urine from 1 to 10 g/l
b) haematuria – a permanent sign
of AGN, more often microhaematuria

23. c) cylindruria - Single hyaline and
granular cylinders are found;
d) leucocyturia – is not typical for the
AGN

24. One of the first symptoms of AGN is a
decrease of urine (400-700 ml per day),
which is associated with inflammation
of the glomeruli and a decrease in their
filtration.
One of the characteristic signs of AGN
may be bradycardia, which is usually
combined with hypertension.

25. 2. AGN with urinary syndrome -
characterized by a gradual (erased)
onset of the disease with minimal
extrarenal symptoms (pasty face,
shortness of breath). Perhaps the only
manifestation of the disease is only a
urinary symptom complex (moderate
proteinuria, haematuria of different
severity, leukocyturia and cylindruria)

26. 3. AGN with nephrotic syndrome -
characterized by severe edema,
massive proteinuria (3,5 g of protein
per day or more), protein metabolism
disorders (hypoproteinemia,
hypoalbuinemia, hyperglobulinemia),
lipid metabolism disorders
(hyperholesterinemia)

27. Complications

acute renal failure;

acute renal hypertensive
encephalopathy (preeclampsia,
eclampsia);

acute heart failure (often left
ventricular with attacks of cardiac
asthma, pulmonary edema);

acute violation of cerebral circulation;

acute visual impairment

28. Example of diagnosis formulation
Acute glomerulonephritis of
streptococcal etiology, infectious-
immune, with acute nephritic syndrome,
cyclic course.

29. Diagnostics
General blood test:
slight decrease in Hb
concentration due to blood
dilution;
ESR is moderately elevated.

30. Diagnostics
Biochemical blood test:
Increasing the concentration of serum
creatinine and electrolytes (K, Na),
hypoproteinemia with hypoalbuminemia,
dysproteinemia with a predominance of
α2-and γ-fractions of globulins,
hypercholesterolemia is possible.

31. Diagnostics
immunological test

increasing the titer of Streptococcus
AB to AG

the concentration of the C3
component of the complement is
reduced (it reflects the severity of the
inflammatory process in the kidneys,
it persists for 6-8 weeks)

32. Diagnostics
Urine test:
General urine analysis -
proteinuria
haematuria
cylindruria
sometimes leukocyturia
the relative density is not reduced

33. Diagnostics
urine analysis according to
Nechyporenko:
hematuria (micro -, macro-hematuria)
leukocyturia (limfozitoza)
red blood cell cylinders

34. Diagnostics
Urine analysis by Zimnitsky:
the concentration function of the
kidneys at the initial stages of the
disease is not impaired

35. Diagnostics
Rehberg-Tareev Test:
there may be a decrease in the glomerular
filtration rate (important for the selection of
drugs)
Determination of daily proteinuria
High proteinuria (more than 3 g/day) often leads
to the development of nephrotic syndrome. Non-
selective proteinuria.

36. Diagnostics
Additional research methods
1.Swab from the throat to detect Streptococcus;
2. Examination of the eyeground – changes
occur in hypertension: narrowing of arterioles,
sometimes the phenomenon of pathological
arteriovenous intersection, edema of the optic
nerve disk, possible point hemorrhages.

37. Diagnostics
3. ECG: changes in the position of the electrical axis
of the heart, signs of overload of the left heart,
pulmonary hypertension, electrolyte
disturbances (signs of intracellular hyperkalemia)
4. Echocardiography: possible dilation of the heart
cavities, increased pressure in the pulmonary
artery, detection of fluid in the pericardial cavity

38. Diagnostics
5. Ultrasound - kidney sizes are not changed or
slightly increased (normally length 75-120
mm, width 45-65 mm, thickness 35-50 mm),
reveal puffiness of the kidney parenchyma.
The cup-pelvis system has not been changed.
6. Chest X-ray - signs of stagnation in the small
circle of blood circulation, interstitial edema.

39. Diagnostics
Kidney biopsy is indicated for
prolonged course of the disease,
when there is a need for active
therapy (corticosteroids,
cytostatics).

40. Treatment
The complex of medical
measures of AGN includes:
1. rational mode;
2. diet;
3. etiological (anti-streptococcal)
treatment;
4. pathogenetic treatment
5. prophylactic medical
examination
1.

41. Treatment
Mode
If the clinical picture is pronounced, the
patient should be hospitalized in a
nephrological or therapeutic
Department.
Bed rest is prescribed until the
elimination of edema and
hypertension, in the absence of these
symptoms for 2 to 4 weeks.

42. Diet
Basic requirement:
restriction of table salt and water;
limiting simple carbohydrates;
restriction of protein;
reducing the energy value of the diet;
Exclusion of extractive substances from
the diet and full provision of the patient's
body with vitamins and minerals.

43. Diet
Diet consists mainly of potatoes, rice,
vegetables (tomatoes, carrots,
cucumbers, cabbage), bread (salt-
free), berries, fruits, honey and sugar.

Daily monitoring of the amount of
liquid consumed and excreted.

44. 1. Treatment
1. Impact on streptococcal infection (with its
proven etiological role) - treatment with
penicillin in/m for 500 000 UNITS every 4 hours
for 10-14 days.
2. Amoxicillin (in case of sinusitis, pneumonia);
3. Cefalexinum
4. Benzylpenicillin (for persistent infection);
5. Doxycycline;
6. Cefaclor

45. If patient are allergic to beta-
lactam antibiotics:
Erythromycin (Azithromycin,
Roxithromycin)
If tonsillectomy is indicated, it is
performed no earlier than 12
months. after the onset of acute
nephritis.

46. Symptomatic therapy
Diuretics are prescribed only for
fluid retention, increased blood
pressure and the appearance of
heart failure. Furosemide is most
effective (80-120 mg).

47. Symptomatic therapy
Hypotensive drugs are prescribed for
hypertension:
ACE/ARB inhibitors as monotherapy or in
combination with calcium antagonists of
the non-dihydropyridine series or
prolonged forms of the dihydropyridine
series;

48. Immunosuppressive therapy
1. Glucocorticoids - prednisone at a dose of 1
mg/kg/ day for 1-1.5 months. with the subsequent
gradual reduction of the dose.
Indications: nephrotic syndrome, prolonged course
of AGN.
2. Cytostatic are prescribed either if
glucocorticosteroids are ineffective, or if there are
contraindications to their appointment.
For fast-progressing GN, pulse therapy with
methylprednisolone 500-1000 mg/day for 3-5 days
is indicated.

49. Treatment of complications
1. Hypertensive encephalopathy
Furosemide in high doses, for convulsions
diazepam
2. Pulmonary oedema - loop diuretics
(furosemide), narcotic analgesics
(morphine), vasodilators (liquid nitrates)
3. Acute kidney failure - restriction of salt,
potassium, protein and fluid. Hemodialysis.

50. Treatment of hematuric syndrome
When expressed hematuria -
dicinon in/m 2 ml of 12.5% solution
2 times a day for 7-10 days, and
then with continued hematuria -
inside in tablets of 0.25 g 1-2 tab 3
times a day.

51. Prevention
Prevention of AGN is reduced to
effective treatment of focal infection,
rational hardening.
In order to timely detect the onset of
the disease after vaccination, acute
respiratory infections in all patients, it
is necessary to examine the urine
analysis.

52. CHRONIC
GLOMERULONEPHRITIS

53. Definition
Chronic glomerulonephritis (CGN) –
(Bright's disease, 1805) is a combined
group of diseases, different in origin and
morphological manifestations,
characterized by immuno-inflammatory
damage of the kidneys glomerular and
progressive course with the development
of nephrosclerosis and chronic renal failure.

54. Etiology
The main etiological factors of CGN are the same
as for AGN (in 5-10% of cases).
- Transferred acute glomerulonephritis
-Primary chronic glomerulonephritis without
previous acute period
- СGN may be part of a generalized disease
(e.g.systemic lupus erythematosus, SLE)
- Often the cause of the disease can not be found
out

55. Pathogenesis
Immune mechanisms are involved in
the development and maintenance
of inflammation in the glomeruli
and tubulointerstitial tissue:
1. Immunocomplex
2. Antibody (autoantigenic)

56. В патогенезе
Pathogenesis

Activation of complement,

attraction of circulating monocytes,

synthesis of cytokines,

growth factors,

release of proteolytic enzymes and
oxygen radicals,

activation of the coagulation cascade,

production of proinflammatory
prostaglandins.

57. Nonimmune mechanisms are also
involved in the progression of CGN:

Hemodynamic changes,

Hypertension and hyperfiltration

Proteinuria

Lipidemia

Obesity

58. Pathogenesis
The chronic course of the process
is caused by the constant
production of autoantibodies to
the capillary basal membrane
antigens.

59. Pathogenesis
Long-term inflammatory process
leads to:

sclerosis

Hyalinosis

development of chronic kidney failure

60. CLASSIFICATION
CHRONIC GLOMERULONEPHRITIS
ON THE ETIOLOGY AND PATHOGENESIS
- Infectious - immune (outcome of acute
streptococcal nephritis, less often than other
infections)
- Non-infectious-immune (gradual development
through nephrotic nephritis, serum, medicinal,
etc.)
- CGN systemic diseases (diseases Henoch -
Schonlein purpura, nodular periarteritis, lupus,
rheumatoid arthritis etc.)
- Special forms of CGN (genetic, radiation, etc.)

61. CLASSIFICATION
CHRONIC GLOMERULONEPHRITIS
ACCORDING TO CLINICAL FORMS

Latent (with isolated urinary syndrome)

Haematuric (Berger's disease)

Hypertonic

Nephrotic

Mixed (urinary syndrome in combination
with other)
As an independent form, subacute (rapidly
progressive), extracapillary
glomerulonephritis is isolated

62. CLASSIFICATION
CHRONIC GLOMERULONEPHRITIS
ON MORPHOLOGY

Diffuse proliferative

Mesangioproliferative

Membranoproliferative

Membranous

Glomerulonephritis with minimal changes

Focal segmental glomerulosclerosis

Fibroplastic

63. COMPLICATIONS

Chronic renal failure

Chronic heart failure

Retinopathy

Anemia

Uremic stomatitis, bronchitis,
gastritis, colitis, polyserositis

64. Сlinical pattern
Three main syndromes
1.Urinary
2.Arterial hypertension
3.oedema

65. Latent
glomerulonephritis
The main syndrome is urinary:
moderate proteinuria,
haematuria, cylindruria
The course of the disease is
favorable

66. Hematuric GN
(Berger's disease)
It manifests as persistent
haematuria, sometimes with
episodes of macrohaematuria.
The course of the disease is
favorable

67. Hypertonic form of CGN
Arterial hypertension is the
main syndrome.
Can be proteinuria up to 1G\
day.

68. Nephrotic form of CGN
characterized by massive
proteinuria (3,5 g of protein per day
or more), protein metabolism
disorders (hypoproteinemia,
hypoalbuinemia,
hyperglobulinemia), severe
oedema, lipid metabolism
disorders (hyperholesterinemia)

69. Mixed form of glomerulonephritis -
combination of nephrotic syndrome
and arterial hypertension.

70. 
.Rapidly progressive
glomerulonephritis – features of
acute nephritis, focal necrosis
with or without crescents and
rapidly progressive renal failure
over weeks.

71. Diagnostics
Blood test:
decrease in Hb concentration, ESR is
moderately elevated.

72. Diagnostics
Biochemical blood test:
Increasing the concentration of serum
creatinine and electrolytes (K, Na),
hypoproteinemia with hypoalbuminemia,
dysproteinemia with a predominance of
α2-and γ-fractions of globulins,
hypercholesterolemia is possible.

73. Diagnostics
Urine test:
General urine analysis -
proteinuria
haematuria
cylindruria
sometimes leukocyturia
the relative density is not reduced

74. Diagnostics
urine analysis according to
Nechyporenko:
hematuria (micro -, macro-hematuria)
leukocyturia (limfozitoza)
red blood cell cylinders

75. Diagnostics
Urine analysis by Zimnitsky:
the concentration function of the
kidneys is impaired
Glomerular filtration rate (GFR) is
decrease

76. Diagnostics
Determination of daily proteinuria
High proteinuria (more than 3 g/day) often
leads to the development of nephrotic
syndrome. Non-selective proteinuria.

77. Diagnostics
3. ECG: changes in the position of the electrical
axis of the heart, signs of overload of the left
heart, electrolyte disturbances (signs of
intracellular hyperkalemia)

78. Diagnostics
4. Ultrasound - kidney size decreases
5. Chest X-ray - signs of stagnation in the
small circle of blood circulation, interstitial
edema.

79. Diagnostics
Kidney biopsy-performed to
determine the morphological form
of CGN, which is necessary for
choosing the right treatment.

80. Treatment
The complex of medical measures
of CGN includes:
1. diet;
2. pathogenetic treatment
Immunosuppressive therapy;
Correction of blood PRESSURE.
Correction of hyperlipidemia and
hypercoagulation.
3. Elimination from the blood of the
products of nitrogen metabolism
(hemodialysis, hemosorption);

81. Diet

restriction of table salt and water;
restriction of protein -
A low-protein diet of up to 0.3 g/kg /day
Exclusion of extractive substances from
the diet and full provision of the patient's
body with vitamins and minerals.

82. Symptomatic therapy
Hypotensive drugs are prescribed for
hypertension:
ACE/ARB inhibitors as monotherapy or in
combination with calcium antagonists of
the non-dihydropyridine series or
prolonged forms of the dihydropyridine
series;

83. Immunosuppressive therapy
1.Glucocorticoids
2. Cytostatic

84. Immunosuppressive therapy
1.Glucocorticosteroids: use two ways of
introduction –
inside: the average daily dose is prednisone
1 mg / kg, (usually prescribed for a period
of 2 months), followed by a gradual
decrease (5 mg / week to a dose of 30 mg
/ day, then 2.5-1.25 mg/week until
complete withdrawal)

85. Immunosuppressive therapy
2. Pulse therapy-
methylprednisolone at a dose of 1000 mg IV
drip 1 time a day for 3 consecutive days.
Usually prescribed for severe nephrotic
syndrome, rapid progression of the disease.

86. Immunosuppressive therapy
Cytostatics are prescribed for the following
indications:
1. ineffectiveness of corticosteroids;
2. presence of corticosteroid therapy
complications;
Cyclophosphamide is used at 2-3 mg / kg / day
Or in the form of pulse therapy at 15 mg
/kg/month.

87. Anticoagulants and antiplatelet agents
Heparin – anticoagulant
Curantylum – antiaggregant

88. Combined therapy
four-component scheme =
glucocorticoids +
cytostatics +
antiplatelet agents +
heparin

89. Symptomatic therapy
Diuretics
Furosemide is most effective (80-120
mg).

90. Symptomatic therapy
Hypotensive drugs are prescribed for
hypertension:
ACE/ARB inhibitors as monotherapy or in
combination with calcium antagonists of
the non-dihydropyridine series or
prolonged forms of the dihydropyridine
series;

91. Treatment
Renal replacement therapy (haemodialysis)
Kidney transplantation

92. Thank you
for your attention