Acute Glomerulonephritis

1. Acute Glomerulonephritis
BY
DR S. S. GHODESWAR (M.D. MEDICINE)
ASSOCIATE PROFESSOR
DEPARTMENT OF GENERAL MEDICINE
SVNGMC YAVATMAL

2. Introduction
 GLOMERULONEPHRITIS - inflammation of the glomeruli and
 Acute nephritic syndromes classically present with hypertension,
hematuria, red blood cell casts, pyuria, and mild to moderate
proteinuria.
 Extensive inflammatory damage to glomeruli causes a fall in GFR and
eventually produces uremic symptoms with salt and water retention,
leading to edema and hypertension.

3. Characteristics -
 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).The most common subtypes are discussed
here

4. ETIOLOGY
Hypovolemia
Diarrhoea, vomiting
Bleeding, Burns, CCF
Ascitis, Anasarca
Renal A / V thrombosis
Autoimmune disorders
Vasculitis, anti GBM dis
Diabetes, tubular dis.
Toxins, infections,
metabolic.
Ureteral, urethral
obstruction. Stone,
papillary necrosis,
bladder dis, prostate,
drugs, cancer.

5. Pathogenesis of
Glomerulonephritis
The two main prosseses are involved in the pathogenesis of glomerulonephritis.
The histological pattern is characterized by cellular proliferation (mesangial and
endothelial) and inflammatory cell infiltration (neutrophils, macrophages).
1. Autoimmune:
antibodies (antiglomerular basement membrane) react with an antigen in the
glomerular basement membrane and produce glomerulonephritis (5% cases).
2. Immune complex theory.
Streptococcal or other antigenes provoke antibody response, and the
subsequent antigenantibody complexes in the circulation are deposited in the glomerular
cappillary walls. These complexes activate the complement pathway with the liberation of
chemotactic factors causing polymorpho-leucocytic infiltration the release of lysosomal
enzymes from neutrophils and the direct effect of the complement system lead to damage
of the capillary wall including the glomerular basal lamina.

6. Renal Filtration Unit:

7. Endothelium
Basement Mem
Epithelium
FILTRATION SLITS

8. CLINICAL FEATURES
 Haematuria (macroscopic or microscopic) – red-cell casts are typically
seen on urine microscopy
 Proteinuria
 Hypertension
 Oedema (periorbital, leg or sacral)
 oliguria and uraemia.

9. HOW TO
INVESTIGATE

10. Acute Nephritic Syndromes
 Poststreptococcal Glomerulonephritis
 Non-streptococcal post-infectious glomerulonephritis, e.g. Staphylococcus,
pneumococcus, Legionella, syphilis, mumps, varicella, hepatitis B and C, echovirus,
Epstein– Barr virus, toxoplasmosis, malaria, schistosomiasis, trichinosis
 Subacute Bacterial Endocarditis
 Lupus Nephritis
 Antiglomerular Basement Membrane Disease
 IgA Nephropathy
 ANCA Small Vessel Vasculitis
 Membranoproliferative Glomerulonephritis
 Mesangioproliferative Glomerulonephritis

11. Poststreptococcal Glomerulonephritis
Poststreptococcal glomerulonephritis is an immune mediated disease
involving:
 Streptococcal antigens
 Circulating immune complexes
 Activation of complement in association with cell-mediated injury.
Poststreptococcal glomerulonephritis is prototypical for acute endocapillary
proliferative glomerulonephritis.
Streptococcal throat infection, otitis media or cellulitis can all be responsible.
The infecting organism is group A β-haemolytic streptococcus of a
nephritogenic type
Acute poststreptococcal GN
•90% of cases affect children between the ages of 2 and 14 years
•10% of cases are patients older than 40

12.  The classic presentation is an acute nephritic picture with hematuria,
pyuria, red blood cell casts, edema, hypertension, and oliguric renal
failure, which may be severe enough to appear as RPGN.
 Systemic symptoms of headache, malaise, anorexia, and flank pain (due
to swelling of the renal capsule) are reported in as many as 50% of cases.
 Poststreptococcal glomerulonephritis caused by impetigo and
streptococcal pharyngitis:
 Impetigo: 2–6 weeks after skin infection
 Streptococcal pharyngitis: 1–3 weeks after infection
Poststreptococcal Glomerulonephritis

13. CLINICAL FEATURES
HEMATURIA - Smoky brown or Cola colored, Glomerular: dysmorphic RBC,
casts in freshly spun urine
PROTEINURIA - Mild to moderate but nephrotic range is rare
OLIGURIA Transient in 50%, Anuria rare
EDEMA : in 85% more likely face and legs
Mild : periorbital or pedal Severe : hypertension, pleural effusion or
ascites
HYPERTENSION: in 80% with symptoms - Headache, Somnolence
Changes in mental status Anorexia, Nausea , Convulsions
HYPERTENSIVE EMERGENCY: 10% BP > 30% increased for age &sex
Evidence of encephalopathy, Heart failure or pulmonary edema
AZOTEMIA : varying degrees
CIRCULATORY CONGESTION : 20% - Dyspnoea, Orthopnoea Cough,
Tachycardia, Gallop rhythm, Basal crepitations, CCF, Pulmonary edema

14. 7 – 14 days after pharyngitis 2 wks – 6 wks after skin infection

15. 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

16.  Epidemics of nephritis have been described in association
with throat (serotypes M1, M4, M25, M12) and skin
(serotype M49) infections
• PATHOGENESIS
• Trapping of circulating immune complexes in glomeruli
• Molecular mimicry between streptococcal antigens and renal antigens
(glomerular tissue acts as auto antigen reacts with circulating
antibodies formed against strep antigens)
• In situ immune complex formation against anti strep antibodies and
glomeruli
• Direct complement activation

17. Pathology
The renal biopsy in poststreptococcal
glomerulonephritis demonstrates:
• Hypercellularity of mesangial and endothelial
cells
• Glomerular infiltrates of polymorphonuclear
leukocytes
• Granular subendothelial immune deposits of
IgG, IgM, C3, C4, and C5-9
• Subepithelial deposits (which appear as
"humps")
Poststreptococcal Glomerulonephritis

18. Treatment
 Treatment is supportive, with control of hypertension, edema, and dialysis
as needed.
 Antibiotic treatment for streptococcal infection should be given to all
patients and their cohabitants.
 There is no role for immunosuppressive therapy, even in the setting of
crescents.
 Overall, the prognosis is good, with permanent renal failure being very
uncommon (1–3%), and even less so in children.
 Complete resolution of the hematuria and proteinuria in children occurs
within 3–6 weeks of the onset of nephritis.
Poststreptococcal Glomerulonephritis

19. • DIET –
• The intake of sodium, potassium and fluids should be
restricted until blood levels of urea reduce and urine
output increases
• DIURETICS –
• Oral FUROSEMIDE( 1- 3 mg /kg) – for edema
• IV FUROSEMIDE ( 2- 4 mg /kg) – pulmonary edema

20. HYPERTENSION
• Mild – restriction of salt and water
• Anti hypertensive agents – AMLODIPINE, NIFEDIPINE
• Hypertensive emergencies – IV NITROPRUSSIDE or LABETALOL
ACUTE LVF
• Hypertension control
• IV furosemide as diuretics
• This will lead to improvement in LVF
• If no diuresis – dialysis initiated
• Respiratory support – positive end expiratory pressure

21. Rapidly progressive
glomerulonephritis (RPGN)
 The term Rapidly progressive glomerulonephritis (RPGN) refers to a clinical
syndrome characterized by a rapid loss of kidney function(GFR>50%)from a
few days to weeks, often accompanied by oliguria or anuria, and by features
of glomerulonephritis, including Dysmorphic erythrocyturia, Erythrocyte
cylindruria, and Glomerular proteinuria
 *The clinical term rapidly progressive glomerulonephritis is used
interchangeably with the Pathologic term crescentic glomerulonephritis.
 *It is the result of focal rupture of glomerular capillary walls that allows
inflammatory mediators and leukocytes to enter Bowman’s space, where
they induce epithelial cell proliferation and macrophage influx and
maturation that together produce cellular crescents

23. * Infectious diseases
* Post-streptococcal GN
* Infectious endocarditis
* Visceral sepsis
* Hepatitis B or C infection with
vasculitis and/or
cryoimmunoglobulinemia
* Multisystemic diseases
* Systemic lupus erythematosus
* Goodpasture’s disease
* Henoch-Schonlein purpura
* Necrotizing vasculitis (including
Wegener’s gransulomatosis)
* Neoplasia
* Relapsing polychondritis
* Behcet’s disease
* Idiopathic
* Type I: Antiglomerular basement
membrane antibody disease
* Type II: immune complex-mediated
disease
* Type III: pauci-immune (ANCA-
associated) disease
* Type IV: mixed and anti-GBM and
ANCA associated disease
* Superimposed on primary glomerular
disease
* Membranoproliferative GN (type I, II)
* Membranous GN
* IgA nephropathy
* Drugs and toxic agents
* Allopurinol
* D-Penicillamine
* Hydralazine
* Rifampicin
C

24. CLINICAL FEATURES
*The onset of renal anti-GBM disease is typically characterized by
an abrupt, acute glomerulonephritis with severe oliguria or anuria.
There is a high risk of progression to ESKD.
*The onset of disease may be associated with arthralgias, fever,
myalgias, and abdominal pain.

25. TREATMENT
*The standard treatment for anti-GBM disease is combination of below
1.Intensive plasmapheresis
2.Corticosteroids
3.Cyclophosphamide.
* Plasmapheresis consists of removal of 2 to 4 L of plasma and its
replacement with a 5% albumin solution continued on a daily basis
until circulating antibody levels become undetectable.
*In those patients with pulmonary hemorrhage, clotting factors should
be replaced by administering fresh-frozen plasma at the end of each
treatment.

26. *Prednisone should be administered starting at a dose of 1 mg/kg
of body weight for at least the first month and then tapered to
alternate-day therapy during the second and third months of
treatment.
*Cyclophosphamide is administered orally (at a dosage of 2 mg/kg/day,
adjusted with consideration for the degree of impairment of kidney
function and the white blood cell count) for 8 to 12 weeks.
*When the regimen of aggressive plasmapheresis with corticosteroids
and cyclophosphamide is used, patient survival is approximately 85%
with 40% progression to ESKD.
*Patients who have both circulating anti-GBM antibodies and ANCAs,
may have a better chance of recovery of kidney function. In these
patients, immunosuppressive therapy should not be withheld, even
with serum creatinine levels higher than 7 mg/dL,

27. Subacute Bacterial Endocarditis
 GN occurs rarely in patients with infective endocarditis (usually i.v. drug users).
It usually manifests itself as the acute nephritic syndrome.
 A similar presentation is in patients with infected ventriculoperitoneal shunt
(shunt nephritis).
 Grossly, the kidneys in subacute bacterial endocarditis have subcapsular
hemorrhages with a "flea-bitten" appearance.
 Microscopy on renal biopsy reveals a focal proliferation around foci of
necrosis associated with abundant mesangial, subendothelial, and
subepithelial immune deposits of IgG, IgM, and C3.
 The pathogenesis hinges on the renal deposition of circulating immune
complexes in the kidney with complement activation

28.  FLEE BITTEN KIDNEY

29. Subacute Bacterial Endocarditis
Patients present with:
• Gross hematuria
• Microscopic hematuria
• Pyuria
• Mild proteinuria
• RPGN with rapid loss of renal function (less common)
 Primary treatment is eradication of the infection with 4–6 weeks of
antibiotics, and if accomplished expeditiously, the prognosis for renal
recovery is good.

30. Lupus nephritis
 Lupus nephritis is a common and serious complication of systemic
lupus erythematosus (SLE) and most severe in African-American
female adolescents.
 Thirty to fifty percent of patients will have clinical manifestations of
renal disease at the time of diagnosis.
 Sixty percent of adults and eighty percent of children develop renal
abnormalities at some point in the course of their disease.
 The most common clinical sign of renal disease is proteinuria, but
hematuria, hypertension, varying degrees of renal failure, and an
active urine sediment with red blood cell casts can all be present.

31. Lupus Nephritis
Lupus nephritis results from the deposition of
circulating immune complexes:
• Which activate the complement cascade
• Leads to complement-mediated damage
• Leukocyte infiltration
• Activation of procoagulant factors
• Release of various cytokines

33. Lupus Nephritis
 Hypocomplementemia is common in patients with acute lupus nephritis
(70–90%) and declining complement levels may herald a flare.
 Renal biopsy, however, is the only reliable method of identifying the
morphologic variants of lupus nephritis.
 Patients with crescents on biopsy may have a rapidly progressive decline
in renal function.
 Without treatment, this aggressive lesion has the worst renal prognosis.

34. Lupus Nephritis - Treatment
 Treatment must combine high-dose steroids with either
cyclophosphamide or mycophenolate mofetil.
 Current evidence suggests that inducing a remission with
administration of steroids and either cyclophosphamide or
mycophenolate mofetil for 2–6 months, followed by maintenance
therapy with lower doses of the same

36. Antiglomerular Basement
Membrane Disease
 Patients who develop autoantibodies directed against glomerular
basement antigens frequently develop a glomerulonephritis termed
antiglomerular basement membrane (anti-GBM) disease.
 When they present with lung hemorrhage and glomerulonephritis, they
have a pulmonary-renal syndrome called Goodpasture's syndrome.
 Goodpasture's syndrome appears in two age groups:
 Young men in their late 20s
 Men and women in their 60–70s

37. Antiglomerular Basement
Membrane Disease
 Disease in the younger age group is usually explosive with following
presentation:
 Hemoptysis
 Sudden fall in hemoglobin
 Fever
 Dyspnea
 Hematuria
 The performance of an urgent kidney biopsy is important in suspected
cases of Goodpasture's syndrome to confirm the diagnosis and assess
prognosis.

38. Antiglomerular Basement
Membrane Disease
 Renal biopsies typically show focal or segmental necrosis that later, with
aggressive destruction of the capillaries by cellular proliferation, leads to
crescent formation in Bowman's space The presence of anti-GBM antibodies
and complement is recognized on biopsy by linear immunofluorescent staining
for IgG (rarely IgA).

39. Antiglomerular Basement
Membrane Disease
 Prognosis at presentation is worse if the following
 >50% crescents on renal biopsy with advanced fibrosis
 Serum creatinine is >5–6 mg/dL
 Oliguria is present
 Need for acute dialysis
 Patients with advanced renal failure who present with hemoptysis
should still be treated for their lung hemorrhage, as it responds to
plasmapheresis and can be lifesaving.
 Treated patients with less severe disease typically respond to 8–10
treatments of plasmapheresis accompanied by oral prednisone and
cyclophosphamide in the first 2 weeks.

40. IgA Nephropathy
 IgA nephropathy is an immune complex-mediated glomerulonephritis
defined by the presence of diffuse mesangial IgA deposits often
associated with mesangial hypercellularity.
 IgA nephropathy is one of the most common forms of
glomerulonephritis worldwide.
 There is a male preponderance, a peak incidence in the second and
third decades of life, and rare familial clustering.

41. IgA Nephropathy
 Deposits of IgA are also found in the glomerular mesangium in a
variety of systemic diseases, including:
 Chronic liver disease
 Crohn's disease
 Gastrointestinal adenocarcinoma
 Chronic obstructive bronchiectasis
 Idiopathic interstitial pneumonia
 Dermatitis herpetiformis
 Mycosis fungoides
 Leprosy
 Ankylosing spondylitis

42. IgA Nephropathy
 The two most common presentations of IgA nephropathy
are recurrent episodes of macroscopic hematuria during or
immediately following an upper respiratory infection in
children (Henoch-Schönlein purpura) or asymptomatic
microscopic hematuria most often seen in adults.
 Rarely, patients can present with acute renal failure and a
rapidly progressive clinical picture.
 Risk factors for the loss of renal function include the
presence of hypertension or proteinuria, the absence of
episodes of macroscopic hematuria, male, older age of
onset, and more severe changes on renal biopsy.

43. IgA Nephropathy
 Studies of patients with IgA nephropathy support the use
of angiotensin-converting enzyme (ACE) inhibitors in
patients with proteinuria or declining renal function.
 When presenting as RPGN, patients typically receive:
 Steroids
 Cytotoxic agents
 Plasmapheresis

44. ANCA Small Vessel Vasculitis
 A group of patients with small-vessel vasculitis (arterioles,
capillaries, and venules; rarely small arteries) and
glomerulonephritis who have serum ANCA positivity.
 they are ANCA-positive and have a pauci-immune
glomerulonephritis with few immune complexes in small vessels
and glomerular capillaries.

45. ANCA Small Vessel Vasculitis
 The antibodies are of two types:
 Anti-proteinase 3 (PR3)
 Anti-myeloperoxidase (MPO)
 Wegener's granulomatosis (PR3)
 Microscopic polyangiitis (MPO)
 Churg-Strauss syndrome (MPO)
 Treatment –
 Induction therapy usually includes some combination of
plasmapheresis, methylprednisolone, and cyclophosphamide.
 The steroids are tapered soon after acute inflammation subsides, and
patients are maintained on cyclophosphamide or azathioprine for up
to a year to minimize the risk of relapse.

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