Glomerulonephritis, GN, is a renal disease characterized by inflammation of the renal glomeruli.

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PATHOLOGICAL CLASSIFICATION OF GN
Glomerulonephritis

• Glomerulonephritis, GN, is a renal disease
  characterized by inflammation of the renal
  glomeruli.
• Glomerulonephritis is categorised into several
  different pathological patterns, which are
  broadly grouped into
• non-proliferative or proliferative types.
• Diagnosing the pattern of GN is important
  because the outcome and treatment differs in
  different types

• Clinical presentations of glomerulopathies
• Glomerular diseases have been classified in
  numerous ways.they are organized as four major
  glomerular syndromes
• Nephrotic syndrome massive proteinuria (gt 3.5
  g/day),
• hypoalbuminaemia, oedema, lipiduria and
  hyperlipidaemia.
• Acute glomerulonephritis (acute nephritic
  syndrome)
• abrupt onset of glomerular haematuria (RBC casts
  or
• dysmorphic RBC), non-nephrotic range proteinuria
  ,oedema, hypertension and transient renal
  impairment.
• Rapidly progressive glomerulonephritis and
  rapidly progressive renal failure over weeks.
• Asymptomatic haematuria, proteinuria or both.

• Non Proliferative
• This is characterised by the numbers of cells
  (lack of hypercellularity) in the glomeruli. They
  usually cause nephrotic syndrome. This includes
  the following types

• Minimal change GN
• This form of GN causes 80 of nephrotic syndrome
  in children, but only 20 in adults. As the name
  indicates, there are no changes visible on simple
  light microscopy, but on electron microscopy
  there is fusion of podocytes (supportive cells in
  the glomerulus).
• Immunohistochemistry staining is negative.
• Treatment consists of supportive care for the
  massive fluid accumulation in the patients body
  ( oedema) and as well as steroids to halt the
  disease process (typically Prednisone 1 mg/kg).
  Over 90 of children respond well to steroids,
  being essentially cured after 3 months of
  treatment.
• Adults have a lower response rate (80). Failure
  to respond to steroids ('steroid resistant') or
  return of the disease when steroids are stopped
  ('steroid dependent') may require cytotoxic
  therapy (such as cyclosporin) which is associated
  with many side-effects.

• Focal Segmental Glomerulosclerosis (FSGS)
• FSGS may be primary or secondary to reflux
  nephropathy, heroin abuse or HIV.
• FSGS presents as a nephrotic syndrome with
  varying degrees of impaired renal function (seen
  as a rising serum creatinine, hypertension). As
  the name suggests, only certain foci of glomeruli
  within the kidney are affected,. The pathological
  lesion is sclerosis within the glomerulus and
  hyalinisation of the feeding arterioles, but no
  increase in the number of cells (hence
  nonproliferative).
• Steroids are often tried but not shown to be
  effective. 50 of people with FSGS continue to
  have progressive deterioration of kidney
  function, ending in renal failure.

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• Membranous glomerulonephritis
• Membranous glomerulonephritis (MGN), a relatively
  common type of glomerulonephritis in adults,
  frequently produces a mixed nephrotic and
  nephritic picture.
• It is usually idiopathic, but may be associated
  with cancers of the lung and bowel, infection
  such as malaria, drugs including penicillamine,
  and connective tissue diseases such as systemic
  lupus erythematosus.
• Microscopically, MGN is characterized by a
  thickened glomerular basement membrane without a
  hypercellular glomerulus.
• Prognosis follows the rule of thirds one-third
  remain with MGN indefinitely, one-third remit,
  and one-third progress to end-stage renal
  failure.
• As the glomerulonephritis progresses, the tubules
  of the kidney become infected, leading to atrophy
  and hyalinisation. The kidney appears to shrink.
  Treatment with corticosteroids is attempted if
  the disease progresses.

• Proliferative
• This type is characterised by increased number of
  cells in the glomerulus (hypercellular). Usually
  present as a nephritic syndrome and usually
  progress to end-stage renal failure (ESRF) over
  weeks to years (depending on type).
• IgA nephropathy
• IgA nephropathy is the most common type of
  glomerulonephritis in adults worldwide. It
  usually presents as macroscopic haematuria
  (visibly bloody urine). It occasionally presents
  as a nephrotic syndrome. It often affects young
  males within days (24-48hrs) after an upper
  respiratory tract or gastrointestinal infection.
  Microscopic examination of biopsy specimens shows
  increased number of mesangial cells with
  increased matrix (the 'cement' which holds
  everything together). Immuno-staining is positive
  for immunoglobulin A deposits within the matrix.
  Prognosis is variable, 20 progress to ESRF.
  Steroids and immunosuppression are not effective
  treatments for this disease ACE inhibitors are
  the mainstay of treatment.
• Henoch-Schönlein purpura
• Henoch-Schönlein purpura (HSP) is a systemic
  variant of IgA nephropathy which causes a
  small-vessel vasculitis and associated
  glomerulonephritis.

Henoch Schönlein syndrome (purpura) This
clinical syndrome comprises a characteristic skin
rash, abdominal colic, joint pain and
glomerulonephritis. Approximately 3070 have
clinical evidence of renal disease with
haematuria and/or proteinuria. The renal disease
is usually mild but the nephrotic syndrome and
acute kidney injury can occur. The renal lesion
is a focal segmental proliferative
glomerulonephritis, sometimes with mesangial
hypercellularity

• Post-infectious
• Post-infectious glomerulonephritis can occur
  after essentially any infection, but classically
  occurs after infection with Streptococcus
  pyogenes. It typically occurs 1014 days after a
  skin or pharyngeal infection with this bacterium.
• Patients present with signs and symptoms of acute
  nephritic syndrome.
• Diagnosis is made based on these findings in an
  individual with a history of recent streptococcal
  infection. Streptococcal titers in the blood
  (antistreptolysin O titers) may support the
  diagnosis.
• Light microscopy demonstrates diffuse
  endocapillary hypercellularity due to
  proliferation of endothelial and mesangial cells,
  as well as an influx of neutrophils and
  monocytes. The Bowman space is compressed, in
  some cases to the extent that this produces a
  crescent formation characteristic of crescentic
  glomerulonephritis.
• Biopsy is seldom done as the disease usually
  regresses without complications. Treatment is
  supportive, and the disease generally resolves in
  24 weeks.
• Membranoproliferative/mesangiocapillary GN
• This is primary, or secondary to SLE, viral
  hepatitis, hypocomplementemia. One sees
  'hypercellular and hyperlobular' glomeruli due to
  proliferation of both cells and the matrix within
  the mesangium. Presents usually with as a
  nephrotic syndrome but can be nephritic, with
  inevitable progression to end stage renal
  failure.

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ACUTE GLOMERULONEPHRITIS (ACUTENEPHRITIC
SYNDROME)

• Rapidly progressive glomerulonephritis
• Rapidly progressive glomerulonephritis
  (Crescentic GN) has a poor prognosis, with rapid
  progression to kidney failure over weeks. Steroid
  therapy is sometimes used. Any of the above types
  of GN can be rapidly progressive. Additionally
  two further causes present as solely RPGN.
• One is Goodpasture's syndrome, an autoimmune
  disease whereby antibodies are directed against
  basal membrane antigens found in the kidney and
  lungs. As well as kidney failure, patient have
  hemoptysis . High dose immunosuppression is
  required (intravenous Methylprednisolone) and
  cyclophosphamide, plus plasmapheresis.
• The second cause is vasculitic disorders such as
  Wegener's granulomatosis and polyarteritis. blood
  tests are positive for ANCA antibody.

This comprises haematuria (macroscopic or
microscopic) red cell casts are typically seen
on urine microscopy proteinuria
hypertension oedema (periorbital, leg or
sacral) temporarily oliguria and uraemia.
Diseases commonly associated withthe acute
nephritic syndrome

• Post-streptococcal glomerulonephritis
• Non-streptococcal post-infectious
  glomerulonephritis, e.g.
• Staphylococcus,pneumococcus,Legionella,syphili
  s,mumps, varicella, hepatitis B and C, echovirus,
  EpsteinBarr virus, toxoplasmosis, malaria,
  schistosomiasis.
• Infective endocarditis
• Systemic lupus erythematosus
• HenochSchönlein syndrome

Investigation in glomerular diseasesinvestigation
s positive findings
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Diabetic nephropathy

• Diabetic renal disease is the leading cause of
  end-stage renal failure in the western world.
  Type 1 and type 2 diabetic patients, have
  equivalent rates of proteinuria, azotaemia, and
  ultimately end-stage renal failure. Both types of
  diabetes show strong similarities in their rate
  of renal functional deterioration, and onset of
  co-morbid complications. Pathology
• The kidneys enlarge initially and there is
  glomerular hyperfiltration (GFR gt 150 mL/min).
  The major early histological lesions seen are
  glomerular basement membrane thickening and
  mesangial expansion.
• Later, glomerulosclerosis develops with nodules
  (Kimmelstiel-Wilson lesion) and hyaline deposits
  in the glomerular arterioles . These later
  changes are associated with heavy proteinuria.
  The lesions seen in type 1 are also seen in type
  2.

• Treatment
• The timing of renoprotection therapy in diabetes
  is a subject of current investigation. Lifestyle
  changes (cessation of smoking and increase in
  exercise), hypertension, poor metabolic
  regulation, and hyperlidaemia should be addressed
  in every diabetic.
• Microalbuminuria is a reason to start treatment
  with ACE inhibitors or an angiotensin II receptor
  antagonist (AIIRA) in either type of diabetes,
  regardless of blood pressure elevation. Like
  other kidney diseases, however, nearly the entire
  course of renal injury in diabetes is clinically
  silent. Medical intervention during this silent
  phase is renoprotective, as judged by slowed loss
  of glomerular filtration. Despite intensified
  metabolic control and antihypertension treatment
  in diabetic patients, a substantial number still
  go on to develop end-stage renal failure.

• Symptoms of GN
• If glomerulonephritis is mild, it may not cause
  any symptoms. In that case, the disease may be
  discovered only if protein or blood is found in
  the urine during a routine test.
• In other people, the first clue can be the
  development of high blood pressure. If symptoms
  appear, they can include swelling around the
  feet, ankles, lower legs, and eyes, reduced
  urination and dark urine (due to the presence of
  red blood cells in the urine).
• High levels of protein in the urine can cause the
  urine to appear foamy.
• If high blood pressure develops, some people
  will have headaches although most people with
  high blood pressure have no symptoms. Fatigue,
  nausea and other common symptoms of renal failure
  due to glomerulonephritis. In severe cases,
  confusion or coma may develop.

• Signs of bad prognosis in a case of GN
• 1-Marked oliguria.
• 2-Un controlled hypertension, the higher the
  blood pressure the worse the prognosis.
• 3-Marked haematuria.
• 4-Age adults usually do worse than children.

• Complications of glomerulonephritis may include
• Acute kidney failure. Loss of function in the
  filtering part of the nephron may cause waste
  products to accumulate rapidly.
• Chronic kidney failure. In this extremely serious
  complication, the kidneys gradually lose
  function. Kidney function at less than 10 percent
  of normal capacity indicates end-stage kidney
  disease, which usually requires dialysis or
  kidney transplant .
• Hpertension.

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• Tests and diagnosis of GN
• Specific signs and symptoms may suggest
  glomerulonephritis, but the condition often comes
  to light when a routine urinalysis is abnormal.
• The urinalysis may show
• Red blood cells and red cell casts, epithelial
  casts and hyaline casts, an indicator of possible
  damage to the glomeruli
• White blood cells, a common indicator of
  infection or inflammation
• Increased protein, which may indicate nephron
  damage
• Other indicators, such as increased blood levels
  of creatinine or urea, also are red flags.

• Imaging tests. visualization of the kidneys, by
  kidney X-ray, an ultrasound examination or a
  computerized tomography (CT) scan.
• Kidney biopsy. This procedure involves using a
  special needle to extract small pieces of kidney
  tissue for microscopic examination to help
  determine the cause of the inflammation. A kidney
  biopsy is almost always necessary to confirm a
  diagnosis of glomerulonephritis.

• Treatments and drugs
• Treatment of glomerulonephritis and the outcome
  depend on
• Whether it is an acute or chronic form of the
  disease
• The underlying cause
• The type and severity of the signs and symptoms
• Some cases of acute glomerulonephritis,
  especially those that follow a strep infection,
  often improve on their own and require no
  specific treatment.

• To control the high blood pressure and slow the
  decline in kidney function, several medications,
  including
• Diuretics
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor agonists

• Nephrotic syndrome. This is a group of signs and
  symptoms that may accompany glomerulonephritis
  and other conditions that affect the filtering
  ability of the glomeruli.
• Nephrotic syndrome is characterized by
• high protein levels in the urine(massive
  proteinuria ), resulting in low protein levels in
  the blood (hypoalbuminemia ) high blood
  cholesterol and swelling (generalized edema )
  edema of the eyelids, feet and abdomen

• Glomerulopathies associated with the nephrotic
  syndrome
• Nephrotic syndrome with bland urine sediments
• Primary glomerular disease
• Minimal-change glomerular lesion
• Focal segmental glomerular sclerosis
• Membranous nephropathy
• Amyloidosis
• Diabetic nephropathy
• Nephrotic syndrome with active urine sediments
• (mixed nephrotic/nephritic)
• Primary glomerular disease
• Mesangial proliferative glomerulonephritis
• Systemic lupus erythematosus
• HenochSchönlein syndrome

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• Management of nephrotic syndrome
• General measures
• Initial treatment should be with dietary sodium
  restriction and a thiazide diuretic .
  Unresponsive patients require furosemide 40120
  mg daily with the addition of amiloride (5 mg
  daily), with the serum potassium concentration
  monitored regularly.
• Normal protein intake is advisable. A
  high-protein diet(8090 g protein daily)
  increases proteinuria and can be harmful in the
  long term. Infusion of albumin produces only a
  transient effect.

• Hypercoagulable states predispose to venous
  thrombosis. The hypercoagulable state is due to
  loss of clotting factors (e.g. antithrombin) in
  the urine and an increase in hepatic production
  of fibrinogen. Prolonged bed rest should
  therefore be avoided as thromboembolism is very
  common in the nephrotic syndrome. In the absence
  of any contraindication, longterm prophylactic
  anticoagulation is desirable.
• If renal vein thrombosis occurs, permanent
  anticoagulation is required

Sepsis is a major cause of death in
nephrotic patients.The increased susceptibility
to infection is partly due to loss of
immunoglobulin in the urine. Pneumococcal
infections are particularly common and
pneumococcal vaccine should be given. Lipid
abnormalities are responsible for an increase in
the risk of cardiovascular disease in patients
with proteinuria. Treatment of hypercholesterolaem
ia starts with an HMG-CoA reductase inhibitor.
ACE inhibitors and/or angiotensin II receptor
antagonists (AIIRA) are used for their
antiproteinuric properties in all types of GN.
These groups of drugs reduce proteinuria by
lowering glomerular capillary filtration
pressure the blood pressure and renal function
should be monitored regularly.