1. Introduction to nephrology Acute and chronic glomerulonephritis
Internal medicine department №2
Assist. Kvasnitska O.S.

5. The mechanism of urine formation

6. Acute glomerulonephritis

7. Etiology Infectious Noninfectious Streptococcal
Nonstreptococcal postinfectious glomerulonephritis
Bacterial
Viral
Parasitic
Noninfectious
Multisystem systemic diseases
Primary glomerular diseases

8. Glomerulonephritis

9. Clinical syndromes
urinary (proteinuria ≤1 g/l/24 h, haematuria, leucocyturia),
nephritic (hypertension, gross haematuria, proteinuria 1-3 g/l/24 h, edemas),
nephrotic (proteinuria ≥3,5 g/l/24 h, hypoproteinemia, hypoalbuminemia, hypercholesterolemia, hypercoagulation, edemas),
mixed.

10. Glomerulonephritis – Diagnostic Tests
CBC (possible anemia, leucocytosis, formula shift to the left, increasing ESR)
Biochemical blood analysis (characterizes the kidney function by the parameters of urea, creatinine, total protein, albumin, serum electrolytes, cholesterol; functional state of the liver (on indicators of ALT, AST, bilirubin)
Examination of the urine (red cells, red-cell casts, nephrotic or sub-nephrotic range proteinuria)
ASO titer (anti streptolysine O)
Kidney scan or biopsy

11. 1= Light yellow, normal colour of urine
2=Light-brown, urine with presence of low proteinuria and microhaematuria 3=Dark-brown, urine with medium presence of proteinuria and microhaematuria 4=Blood-brown, urine with visible haematuria and high level of proteinuria
Source: The Internet Journal of Tropical Medicine ISSN:

12. Glomerulonephritis –Treatment
Dietary protein is restricted when renal insufficiency (elevated BUN) develop.
Sodium is restricted when the patient has hypertension, edema, and heart failure.
Loop diuretic and antihypertensive medications may be prescribed to control hypertension.
Bed rest during acute phase.

13. Treatment
Treat the underlying infections when acute GN is associated with chronic infections.
Antimicrobial therapy
Antibiotics (eg, penicillin) are used to control local symptoms and to prevent spread of infection to close contacts.
Antimicrobial therapy does not appear to prevent the development of GN, except if given within the first 36 hours.
Loop diuretic therapy
Loop diuretics may be required in patients who are edematous and hypertensive in order to remove excess fluid and to correct hypertension.
Relieves edema and controls volume, thereby helping to control volume-related elevation in BP
Using ACE-ingibitors, AIIRA (angiotensin II receptor antagonists), statins for treatment high BP and lipid abnormalities
Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may be used if severe hypertension or encephalopathy is present

14. Rapidly progressive glomerulonephritis (RPGN)
Characterized clinically by
A rapid decrease in the GFR of at least 50% over a short period, from a few days to 3 months
The term RPGN was first used to describe a
Group of patients who had an unusually fulminant poststreptococcal glomerulonephritis and a poor clinical outcome
Several years later,
The anti-GBM antibody was discovered to produce a crescentic glomerulonephritis in sheep, and, following this discovery,
The role of anti-GBM antibody in Goodpasture syndrome was elucidated
Anti –GBM: antiglomerular basement membrane

15. RPGN: Pathology The main pathologic finding is
Extensive glomerular crescent formation
Focal rupture of glomerular capillary walls that can be seen by light microscopy and electron microscopy

16. RPGN: Classification
Immunological classification: based on the + or - of ANCAs
The disorders are also classified based on their clinical presentation

17. RPGN: Classification Anti-GBM antibody (Approx. 3% of cases)
Goodpasture syndrome (lung and kidney involvement)
Anti-GBM disease (only kidney involvement)
Note: 10-40% of patients may be ANCA positive

18. RPGN: Classification Immune complex
Postinfectious (staphylococci/streptococci)
Collagen-vascular disease
Lupus nephritis
Henoch-Schönlein purpura (immunoglobulin A and systemic vasculitis)
Immunoglobulin A nephropathy (no vasculitis)
Mixed cryoglobulinemia
Primary renal disease
Membranoproliferative glomerulonephritis
Fibrillary glomerulonephritis
Idiopathic
Note: Of all patients with crescentic immune complex glomerulonephritis, 25% are ANCA+; < 5% of patients with noncrescentic immune complex glomerulonephritis are ANCA+

19. RPGN: Classification Pauci-immune Wegener granulomatosis (WG)
Microscopic polyangiitis (MPA)
Renal-limited necrotizing crescentic glomerulonephritis (NCGN)
Churg-Strauss syndrome
Note: 80-90% of patients are ANCA+

20. RPGN: Symptoms
*Edema (swelling) of the face, eyes, ankles, feet, legs, or abdomen
*Blood in the urine
*Dark or smoke-colored urine
*Decreased urine volume
*Abdominal pain
*Cough & Diarrhea
*General ill feeling & Fever
*Joint aches & Muscle aches
*Loss of appetite & Shortness of breath

21. RPGN: Treatment Depends on the underlying cause
Corticosteroids may relieve symptoms in some cases
Medications that suppress the immune system may also be prescribed, depending on the cause
Plasmapheresis may relieve the symptoms in some cases
Persons should be closely watched for signs of progression to kidney failure
Dialysis or a kidney transplant may ultimately be necessary

22. Chronic glomerulonephritis

23. Chronic glomerulonephritis represents the end-stage of all glomerulonephritis with unfavorable evolution. This general (glomerular, vascular and interstitial) affection constitutes the so-called "end stage kidney". In most cases, it is associated with systemic hypertension. (Source:

24. Minimal-Change Disease
Nil disease or lipoid nephrosis - normal or very mild abnormalities of the glomeruli
Changes can only be seen through electron microscopy.
90 percent of cases of nephrotic syndrome in children under the age of 10
More than 50 percent of cases in older children
In adults: use of nonsteroidal antiinflammatory drugs (NSAIDs)
Malignancy: Hodgkin lymphoma
Source:
Source:

25. Membranous Nephropathy
Second most common cause of primary nephrotic syndrome in adults
Associated with hepatitis B infection
Autoimmune diseases, thyroid disease, use of certain drugs
Underlying cancer – solid tumor
Source:

26. Focal segmental glomerulosclerosis

27. Mesangiocapillary glomerulonephritis
The glomeruli are enlarged, markedly  lobulated and ‘rich’ in cells due to proliferation of mesangial cells (more than 2 cells in a plane section) and accumulation of basement membrane-like material.
The capillary walls are thick , their lumens – narrow due to the penetration of mesangium in  between the endothelium and basement membrane (so called  ‘mesangial interposition’).
With silver stain, this phenomenon is seen as a duplication of basement membrane (‘tram rails’ – metaphor)

28. Membranoproliferative glomerulonephritis

29. Clinical Manifestations
Uremia-specific findings
Edemas
Hypertension
Jugular venous distension (if severe volume overload is present)
Pulmonary rales (if pulmonary edema is present)
Pericardial friction rub in pericarditis
Tenderness in the epigastric region or blood in the stool (possible indicators for uremic gastritis or enteropathy)
Decreased sensation and asterixis (indicators for advanced uremia)

30. Characteristics of common glomerular diseases at presentation
Heavy proteinuria
Proteinuria & haematuria
Predominant haematuria
Minimal changes
Lupus nephritis
Acute poststreptococcal glomerulonephritis
Focal sclerosis
Membranoproliferativeglomerulonephritis
RPGN (crescentic)
Membranous nephropathy
Henoch-Schonlein purpura
Haemolityc uraemic syndrome
Diabetes mellitus
Endocarditis
Amyloidosis of kidney

31. Acute Nephritic Syndrome
Syndrome characterised in typical cases by:
Haematuria
Proteinuria (1-3 g/l/24 hours)
oliguria
oedema
hypertension
reduced GFR
fluid overload

32. Nephrotic Syndrome
Proteinuria > 3.5g / 24hrs , due to excessive permeability of glomerular capillary wall.
Leads to hypoproteinemia, hypoalbuminemia, decreased colloid oncotic pressure and edema.
Accompanied by sodium and water retention, hyperlipidemia, vulnerability to infection and thrombotic complications.

33. Nephrotic syndrome biopsy histology in adults at different ages

34. Indications to perform renal biopsy
Unexplained renal failure
Acute nephritic syndrome
Nephrotic syndrome
Isolated nonnephrotic proteinuria
Isolated glomerular hematuria 
Renal masses (primary or secondary)
Renal transplant rejection
Connective-tissue diseases (eg, systemic lupus erythematosus) 

35. Absolute contraindications to renal biopsy include the following:
Uncorrectable bleeding diathesis
Uncontrollable severe hypertension
Active renal or perirenal infection
Skin infection at biopsy site
The following are relative contraindications to renal biopsy:
Uncooperative patient
Anatomic abnormalities of the kidney which may increase risk
Small kidneys
Solitary kidney

36. Treatment of nephrotic syndrome
General measures
Dietary sodium restriction
Normal protein intake is advisable. A high-protein diet
(80–90 g protein daily) increases proteinuria and can be harmful in the long term
Infusion of albumin produces only a transient effect. It is only given to diuretic-resistant patients and those with oliguria and uraemia in the absence of severe glomerular damage, e.g. in minimal-change nephropathy. Albumin infusion is combined with diuretic therapy and diuresis often continues with diuretic treatment alone.

37. Treatment of nephrotic syndrome
The target pressure for patients with proteinuria greater than 1 g/d is less than 125/75 mm Hg; for patients with proteinuria less than 1 g/d, the target pressure is less than 130/80 mm Hg.
Angiotensin-converting enzyme inhibitors (ACEIs)
angiotensin II receptor blockers (ARBs)
combination therapy with ACEIs and ARBs. 
Diuretics are often required because of decreased free-water clearance, and high doses may be required to control edema and hypertension when the GFR falls to less than 25 mL/min.   
Beta-blockers, calcium channel blockers, central alpha-2 agonists (eg, clonidine), alpha-1 antagonists, and direct vasodilators (eg, minoxidil, nitrates) may be used to achieve the target pressure.

38. Treatment of nephrotic syndrome
Renal osteodystrophy can be managed early by replacing vitamin D and by administering phosphate binders.
Seek and treat nonuremic causes of anemia, such as iron deficiency, before instituting therapy with erythropoietin.
Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, renal transplantation).
Treat hyperlipidemia (if present)
Expose patients to educational programs for early rehabilitation from dialysis or transplantation.

39. Treatment of edema
Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid)
Secreted in the proximal tubules
Have high saluretic effect (decrease sodium reabsorbtion, increase natriuresis)
Quick diuretic effect
Efficiency is reduced due to decreasing of external cellular fluid
Side effects
Hypovolemia, hypokalemia, metabolic alcalosis
Impaired glucose tolerance
Arterial hypotension, irregular heart beat
Acute tubulointerstitial nephritis
Aplastic anemia, nausea, vomiting
Contraindications
Hypokalemia, hyponatremia
Hypovolemia with or without hypotension
Interaction:
Salycilates – increasing of toxic effects
Cardiac hlycosides, corticosteroids, penicillin – the risk of hypokalemia, hypomagnesemia
ACE-inhibitors – decreasing of blood pressure with impairment of renal function
NSAIDs – decreasing of hypotension and diuretic effects
Indirect anticoagulants – increasing diuresis and hypokalemia
Appropriate to use with potassium-sparing diuretics

40. Potassium-sparing diuretics (amiloride, triamterene, spironolactone)
Treatment of edema
Potassium-sparing diuretics (amiloride, triamterene, spironolactone)
Acting in the ultimate part of distal tubules
Spironolactone structurrally similar to aldosterone
Amiloride and triamterene are not aldosterone antagonists
Side effects
Vomiting, diarrhea
Increasing of asotemia
Menstrual disorders, amenorrhea
Allergic dermatitis
Hyperkalemia
Contraindications
Anuria
Acute renal failure
Chronic renal failure III-V st.
Interaction:
With other diuretics – potentiates their effect; It is recommended to reduce dose up to 50 %

41. Treatment of edema
Thiazide diuretics (benzothiadiazine, chlorothiazide, hydrochlorothiazide)
Acting in the distal tubules
Do not change concentration kidney ability
Increasing potassium, magnesium, chloride, phosphate excretion with urine
Delay the calcium in the body
No depend on the acid-base balance of the organism
Side effects
Gout exacerbation
Orthostatic hypotension, tachycardia
Photosensitivity
Necrotizing vasculitis
Hypokalaemia, hyperglycemia
Cholestatic jaundice
Contraindications
Gout
Hypersensitivity to sulfonamides
Liver insufficiency
GFR less than 30 ml/min
Diabetes mellitus
Interaction:
Not combined with potassium-sparing diuretics
Ganglioplegic – increasedohypotension

42. The most commonly used diuretics in nephrology
Medication
Route of administration
Initial single dose
Maximal dose
Top of effect
Duration of effect
Lasix
(furosemide)
i/v
0,5-1,0 mg/kg
2-4 mg/kg up to 200mg (in case of ARF mg/kg/24 hrs)
3-5 min
5-6 hours
Per os
2-5 mg/kg
30-60 min
7-8 hours
Hypothiazide (Hydrochloro-
thiazide)
2,5 mg/kg
1 hour
8-12 hours
Verospiron (spironolacton)
3-5 mg/kg/24 hours in 2-3 doses
10 mg/kg/24 hours
2-5 days
Triamterene
mg/24 hours
300 mg/24 hours
15-20 min
12-18 hours

43. Treatment Minimal change glomerulonephritis (MCGN)
Acute glomerulonephritis:
Prednisolone 1mg/kg/24 hours 4-6 weeks with next reduces of dose and addition of chlorbutin 0,2 mg/kg/24 hours or azathioprine 2 mg/kg/24 hours during of all period of prednisolone receiving
In the ineffectiveness of this treatment – cyclosporine A 3-5 mg/kg/24 hours in combination with mild doses of corticosteroids 6-12 weeks
Chronic glomerulonephritis:
Prednisolone 1mg/kg/24 hours 6-8 weeks to the disappearance or stabilization at the minimum level of proteinuria, further - to 0.5 mg/kg for 4 weeks followed by 5 mg cancellation of in a month. Cytostatics appointed along prednisolone cancellation.
Prognosis: 1% progress to ESRF.

44. Treatment Focal segmental glomerulosclerosis
Prednisolone 1mg/kg/24 hours 4-16 weeks. If the full or partial remission achieved, cyclophosphamide added 2 mg/kg or chlorbutin 0.15 mg/kg.
In the ineffectiveness of this treatment – prednisolone 0,5 mg/kg every other day and cyclosporine A 2-3 mg/kg during 12 monthes
Prognosis: 30–50% progress to ESRF.

45. Treatment
Membranous nephropathy Prednisolone 1mg/kg/24 hours and chlorbutin 0.15 mg/kg or cyclophosphamide 2-3 mg/kg 6-8 weeks In case of relapce or in the ineffectivenes - cyclosporine A 2-3 mg/kg/24 hours 12 monthes in combination with prednisolone 0,5 mg/kg every other day Prognosis: Untreated, 15% complete remission, 9% ESRF at 2–5yrs and 41% at 15yrs

46. Treatment
Mesangiocapillary glomerulonephritis Treatment: None is of proven benefit Prognosis: 50% develop ESRF Mesangial proliferative GN Antibiotics, diuretics, and antihypertensives as necessary. Dialysis is rarely required. Prognosis: Good.

47. Treatment
In the absence of morphological verification of diagnosis Prednisolone 1mg/kg/24 hours 6-8 weeks with subsequent dose reduction and addition of chlorbutin 0.2 mg / kg / day or azathioprine 2 mg / kg / day

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