Acute Nephritic Syndrome

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Acute Nephritic Syndrome

• Lawrence Mason MD
• PGY II
• NHRMC IM

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Introduction

• Acute nephritic syndromes classically present
  with the following
• Hypertension
• Hematuria
• Red blood cell casts
• Pyuria
• Mild to moderate proteinuria

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Introduction

• Extensive inflammatory damage to glomeruli can
  cause a fall in GFR and eventually produce uremic
  symptoms with salt and water retention, leading
  to edema and hypertension.

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Acute Nephritic Syndromes

• Poststreptococcal Glomerulonephritis
• Subacute Bacterial Endocarditis
• Lupus Nephritis
• Antiglomerular Basement Membrane Disease
• IgA Nephropathy
• ANCA Small Vessel Vasculitis
• Membranoproliferative Glomerulonephritis
• Mesangioproliferative Glomerulonephritis

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Poststreptococcal Glomerulonephritis

• Poststreptococcal glomerulonephritis is an
  immune-mediated disease involving
• Streptococcal antigens
• Circulating immune complexes
• Activation of complement in association with
  cell-mediated injury.

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Poststreptococcal Glomerulonephritis

• Poststreptococcal glomerulonephritis is
  prototypical for acute endocapillary
  proliferative glomerulonephritis.
• Acute poststreptococcal GN
• 90 of cases affect children between the ages of
  2 and 14 years
• 10 of cases are patients older than 40

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Poststreptococcal Glomerulonephritis

• 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.

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Poststreptococcal Glomerulonephritis

• Poststreptococcal glomerulonephritis caused by
  impetigo and streptococcal pharyngitis
• Impetigo 26 weeks after skin infection
• Streptococcal pharyngitis 13 weeks after
  infection

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Poststreptococcal Glomerulonephritis

• 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.

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Poststreptococcal Glomerulonephritis

• Overall, the prognosis is good, with permanent
  renal failure being very uncommon (13), and
  even less so in children.
• Complete resolution of the hematuria and
  proteinuria in children occurs within 36 weeks
  of the onset of nephritis.

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Poststreptococcal Glomerulonephritis

• 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")

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Subacute Bacterial Endocarditis

• Endocarditis-associated glomerulonephritis is
  typically a complication of subacute bacterial
  endocarditis.
• Particularly in patients who
• Remain untreated for an extended period of time
• Have negative blood cultures
• Have right-sided endocarditis (IVDU)

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Subacute Bacterial Endocarditis

• 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.

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Subacute Bacterial Endocarditis

• The pathogenesis hinges on the renal deposition
  of circulating immune complexes in the kidney
  with complement activation.

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Subacute Bacterial Endocarditis

• Patients present with
• Gross hematuria
• Microscopic hematuria
• Pyuria
• Mild proteinuria
• RPGN with rapid loss of renal function (less
  common)

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Subacute Bacterial Endocarditis

• Primary treatment is eradication of the infection
  with 46 weeks of antibiotics, and if
  accomplished expeditiously, the prognosis for
  renal recovery is good.

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Lupus Nephritis

• Lupus nephritis is a common and serious
  complication of systemic lupus erythematosus
  (SLE) and most severe in African-American female
  adolescents.

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Lupus Nephritis

• 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.

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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

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Lupus Nephritis

• 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.

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Lupus Nephritis

• Hypocomplementemia is common in patients with
  acute lupus nephritis (7090) and declining
  complement levels may herald a flare.
• Renal biopsy, however, is the only reliable
  method of identifying the morphologic variants of
  lupus nephritis.

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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.

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Lupus Nephritis

• 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 26 months, followed by maintenance therapy
  with lower doses of the same

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Antiglomerular Basement Membrane Disease

• Patients who develop autoantibodies directed
  against glomerular basement antigens frequently
  develop a glomerulonephritis termed
  antiglomerular basement membrane (anti-GBM)
  disease.

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Antiglomerular Basement Membrane Disease

• When they present with lung hemorrhage and
  glomerulonephritis, they have a pulmonary-renal
  syndrome called Goodpasture's syndrome.

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Antiglomerular Basement Membrane Disease

• Goodpasture's syndrome appears in two age groups
  
• Young men in their late 20s
• Men and women in their 6070s
• Disease in the younger age group is usually
  explosive
• Hemoptysis
• Sudden fall in hemoglobin
• Fever
• Dyspnea
• Hematuria

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Antiglomerular Basement Membrane Disease

• The performance of an urgent kidney biopsy is
  important in suspected cases of Goodpasture's
  syndrome to confirm the diagnosis and assess
  prognosis.
• 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

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Antiglomerular Basement Membrane Disease

• The presence of anti-GBM antibodies and
  complement is recognized on biopsy by linear
  immunofluorescent staining for IgG (rarely IgA).

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Antiglomerular Basement Membrane Disease

• Prognosis at presentation is worse if the
  following
• gt50 crescents on renal biopsy with advanced
  fibrosis
• Serum creatinine is gt56 mg/dL
• Oliguria is present
• Need for acute dialysis

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Antiglomerular Basement Membrane Disease

• 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 810 treatments of
  plasmapheresis accompanied by oral prednisone and
  cyclophosphamide in the first 2 weeks.

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IgA Nephropathy

• IgA nephropathy is an immune complex-mediated
  glomerulonephritis defined by the presence of
  diffuse mesangial IgA deposits often associated
  with mesangial hypercellularity.

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IgA Nephropathy

• 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.

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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

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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.

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IgA Nephropathy

• 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.

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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.

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IgA Nephropathy

• When presenting as RPGN, patients typically
  receive
• Steroids
• Cytotoxic agents
• Plasmapheresis

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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.
• The antibodies are of two types
• Anti-proteinase 3 (PR3)
• Anti-myeloperoxidase (MPO)

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ANCA Small Vessel Vasculitis

• Wegener's granulomatosis (PR3)
• Microscopic polyangiitis (MPO)
• Churg-Strauss syndrome (MPO)
• Belong to this group because they are
  ANCA-positive and have a pauci-immune
  glomerulonephritis with few immune complexes in
  small vessels and glomerular capillaries.

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ANCA Small Vessel Vasculitis

• 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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Membranoproliferative Glomerulonephritis

• MPGN is sometimes called mesangiocapillary
  glomerulonephritis or lobar glomerulonephritis.
• It is an immune-mediated glomerulonephritis
  characterized by thickening of the GBM with
  mesangioproliferative changes 70 of patients
  have hypocomplementemia.

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Membranoproliferative Glomerulonephritis

• MPGN is subdivided pathologically
• Type I
• Type II (idiopathic)
• Type III (idiopathic)

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Membranoproliferative Glomerulonephritis

• Type I MPGN is commonly associated with
• Persistent hepatitis C infections
• Autoimmune diseases (lupus)
• Cryoglobulinemia
• Neoplastic diseases

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Membranoproliferative Glomerulonephritis

• Type I MPGN, the most proliferative of the three
  types.
• Tram-tracking - mesangial proliferation with
  lobular segmentation on renal biopsy and
  mesangial interposition between the capillary
  basement membrane and endothelial cells.

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Membranoproliferative Glomerulonephritis

• Type I MPGN is secondary to glomerular deposition
  of circulating immune complexes
• Patients with MPGN present with
• Proteinuria
• Hematuria
• Pyuria (30)
• Systemic symptoms of fatigue and malaise that are
  most common in children with Type I disease.

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Membranoproliferative Glomerulonephritis

• In the presence of proteinuria, treatment with
  inhibitors of the renin-angiotensin system is
  prudent.
• There is some evidence supporting the efficacy of
  treatment of primary MPGN with steroids,
  particularly in children.
• In secondary MPGN, treating the associated
  infection, autoimmune disease, or neoplasms is of
  demonstrated benefit.

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Mesangioproliferative Glomerulonephritis

• Mesangioproliferative glomerulonephritis is
  characterized by expansion of the mesangium,
  sometimes associated with mesangial
  hypercellularity thin, single contoured
  capillary walls and mesangial immune deposits.

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Mesangioproliferative Glomerulonephritis

• Clinically, it can present with varying degrees
  of proteinuria and, commonly, hematuria.

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Mesangioproliferative Glomerulonephritis

• Mesangioproliferative disease may be seen in
• IgA nephropathy
• P. falciparum malaria
• Resolving postinfectious glomerulonephritis
• Lupus nephritis

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Mesangioproliferative Glomerulonephritis

• There is little agreement on treatment, but some
  clinical reports suggest benefit from use of
• Inhibitors of the renin-angiotensin system
• Steroid therapy
• Cytotoxic agents

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THE END

• Questions?