Transcript Glomerulonephritis

Glomerulonephropathy
Internal Medicine Lecture Series
September 20, 2006
Dolan Wenner D.O.
Glomerulonephritis
Inflammation of the glomeruli of the kidney
Inflammation causes a decrease in the
kidney’s ability to filter substances out of
the bloodstream
Blood
Protein
Lipids
Glomerulonephritis
Inflammation causes damage to the major
components of the glomerulus
Epithelium
Basement Membrane
Capillary Endothelium
Mesangium
Glomerulus
Glomerulus (EM)
Major Determinants of Glomerular
Injury
The nature of the primary insult and
secondary mediator systems it invokes
The site of injury within the glomerulus
The speed of onset, the extent, and
intensity of disease
Primary vs. Secondary
Primary Glomerular Disease
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Disorders in which the glomerulus is the sole
or predominant tissue involved. These
diseases are typically idiopathic.
Secondary Glomerular Disease
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Glomerular injury is a feature of a systemic
disease involving multiple organs or systems.
Primary Insult
Immunologic
Metabolic
Hemodynamic
Toxic
Deposition
Infectious
Inherited
Acute, Subacute, & Chronic
Acute  injury occurring over days to
weeks
Subacute  injury rapidly progressive
over weeks or months
Chronic  injury occurring over months to
years
Focal vs. Diffuse
Focal lesions  involve less than 50% of
the glomerulus
Diffuse lesions  involve greater than
50% of the glomerulus
Segmental vs. Global
Segmental lesions  involve only part of
the glomerular tuft
Global lesions  involve almost all of the
glomerular tuft
Intracapillary vs. Extracapillary
Intracapillary  refers to endothelial or
mesangial cells
Extracapillary  refers to Bowman’s
space
Classification of Glomerulopathy
Nephritic syndrome
Nephrotic syndrome
Nephritic Syndrome
Presents with sudden onset of hematuria
(RBC casts hallmark) and variable
proteinuria (<3g/24 hrs)
Decreased GFR with increase in BUN and
creatinine
Nephritic Syndrome
Signs and symptoms
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Oliguria
Macroscopic hematuria (smoky-brown urine)
Hypertension
Possibly edema in low-pressure areas
(periorbital and scrotal areas)
Nephritic Syndrome
Causes
Post-streptococcal glomerulonephritis
IgA nephropathy (Berger’s disease)
Wegener’s granulomatosis
Alport’s syndrome
Goodpasture’s syndrome
SLE
Post-streptococcal
Glomerulonephritis
Group A β-hemolytic strep
H & P  Oliguria, edema, htn., smokybrown urine
Labs and Histology  Low serum C3,
increased ASO titer, lumpy-bumpy
immunofluorescence (IF)
Treatment  supportive, most have
complete recovery
Post-Streptococcal
Glomerulonephritis
IgA Nephropathy
(Berger’s disease)
Most common type of nephritic syndrome,
associated with upper respiratory or GI
infections; commonly in young men
H & P  gross hematuria
Labs and Histology  may see elevated
serum IgA; biopsy and IF will show
mesangial IgA deposits
Treatment  corticosteroids; 20%
progress to ESRD
IgA Nephropathy
Wegener’s Granulomatosis
Granulomatous inflammation of the respiratory
tract and kidney with necrotizing vasculitis
H & P  fever, wt. loss, hematuria, respiratory
and sinus symptoms; cavitary pulmonary lesions
bleed and cause hemoptysis
Labs and Histology  c-Anca (cell mediated
immune response)
Treatment  High-dose corticosteroids and
cytotoxic agents; pts tend to have frequent
relapses
Alport’s syndrome
Hereditary glomerulonephritis; present in boys 520 years old
H & P  asymptomatic hematuria associated
with nerve deafness and eye disorders
Labs and Histology  GBM splitting on electron
microscopy
Treatment  Progresses to renal failure; antiGBM nephritis may recur after transplant
Alport’s syndrome
Goodpasture’s syndrome
Glomerulonephritis with pulmonary hemorrhage;
peak incidence in men in their mid-20s; an
immune form of RPGN
H & P  hemoptysis, dyspnea, possibly
respiratory failure
Labs and Histology  linear anti-GBM on IF,
iron deficiency anemia, hemosiderin-filled
macrophages in sputum, pulmonary infiltrates on
CXR
Treatment  plasma exchange therapy, pulsed
steroids; may progress to ESRD
Goodpasture’s Syndrome
Nephritic Syndrome
Treatment
Treat hypertension, fluid overload, and uremia
Salt and water restriction
Diuretics
Dialysis if necessary
Protein restricted to approx. 1 g/kg/day
Corticosteroids are sometimes useful to
decrease glomerular inflammation
Treat underlying disease; possible biopsy for
diagnosis
Nephrotic Syndrome
Defined as > 3.5 g urinary protein/24 hrs,
albumin < 3 g/dL, and peripheral edema.
Pts. may also have associated
hyperlipidemia and hypercoagulable states
Nephrotic Syndrome
Causes
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Diabetic nephropathy
Lupus nephropathy
Renal amyloidosis
Membranoproliferative nephropathy
Minimal Change Disease
Idiopathic etiology; common in children
H & P  tendency toward infections and
thrombotic events
Labs and Histology  light microscopy
appears normal; electron microscopy
shows fusion of epithelial foot processes
with lipid-laden renal cortices
Treatment  steroids; excellent prognosis
Minimal Change Disease
Focal Segmental
Glomerulosclerosis (FSGS)
Idiopathic, IVDU, HIV infection
H & P  typical patient is young black
male with uncontrolled htn.
Labs and Histology  microscopic
hematuria; biopsy shows sclerosis in
capillary tufts
Treatment  prednisone, cytotoxic
therapy
Focal Segmental
Glomerulosclerosis
Membranous Nephropathy
Most common Caucasian adult
nephropathy; an immune complex disease
H & P  associated with HBV, syphilis,
malaria, and gold
Labs and Histology  “spike and dome”
appearance due to granular deposits of
IgG and C3 at basement membrane
Treatment  prednisone and cytotoxic
therapy for severe disease
Membranous Nephropathy
Diabetic Nephropathy
Two characteristic forms: diffuse hyalinization
and nodular glomerulosclerosis (KimmelstielWilson lesions)
H & P  long standing, poorly controlled DM
Labs and Histology  thickened GBM;
increased mesangial matrix
Treatment  tight control of blood sugar; protein
restriction; ACEIs
Diabetic Nephropathy
Lupus Nephritis
Both nephrotic and nephritic; severity
determines prognosis
H & P  proteinuria or RBCs on UA may
be found in SLE pts
Labs and Histology  mesangial
proliferation; subendothelial immune
complex deposition
Treatment  prednisone and cytotoxic
therapy may slow disease progression
Lupus Nephritis
Renal Amyloidosis
Primary (plasma cell dyscrasia) and Secondary
(infectious or inflammatory) most common
H & P  may have multiple myeloma or a
chronic inflammatory disease (e.g. rheumatoid
arthritis, TB)
Labs and Histology  abdominal fat biopsy;
seen with Congo red stain; apple-green
birefringence under polarized light
Treatment  prednisone and melphalan; bone
marrow transplant may be used for multiple
myeloma
Renal amyloidosis
Membranoproliferative
nephropathy
Can also be a nephritic syndrome
H & P  slowly progressing renal failure
Labs and Histology  “Tram-track” double
layered basement membrane; Type I has
subendothelial deposits, Type II involves a
C3 nephritic factor and decreased C3
Treatment  corticosteroids and cytotoxic
agents may help
Membranoproliferative
Nephropathy
Nephrotic Syndrome
Treatment
Treat proteinuria
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Low salt and saturated fat diet
Limited protein intake
Furosemide for peripheral edema
If diabetic  consider ACEi
Fluid restriction (hyponatremia)
Statin for hyperlipidemia
Anticoagulation for pts. with thrombosis
May need biopsy for diagnosis
Clinical Manifestations of
Glomerular Disease
Asymptomatic proteinuria
Nephrotic syndrome (proteinuria,
hypoproteinemia, hyperlipidemia, edema)
Asymptomatic hematuria
Glomerulonephritis (hematuria,
proteinuria, hypertension, renal failure)
Clinical Manifestations of
Glomerular Disease (con’t)
Acute glomerulonephritis (nephritis with
short term renal failure)
Crescentic Glomerulonephritis (nephritis
with rapidly progressive renal failure)
Chronic Glomerulonephritis (chronic
progression of renal failure)
End Stage Renal Disease (irreversible
renal failure)
Question 1
Which of the glomerulopathies shows a
characteristic “tram-track” double layered
basement membrane?
a. Minimal change disease
b. Membranoproliferative nephropathy
c. Focal Segmental Glomerulosclerosis
d. Berger’s Disease
Question 1
Which of the glomerulopathies shows a
characteristic “tram-track” double layered
basement membrane?
a. Minimal change disease
b. Membranoproliferative nephropathy
c. Focal Segmental Glomerulosclerosis
d. Berger’s Disease
Question 2
Which of the following is present in
Wegener’s granulomatosis?
a. p-Anca
b. d-Anca
c. c-Anca
d. s-Anca
Question 2
Which of the following is present in
Wegener’s granulomatosis?
a. p-Anca
b. d-Anca
c. c-Anca
d. s-Anca
Question 3
Which class of medications is indicated in
patients with diabetic nephropathy?
a. ACEIs
b. NSAIDs
c. Macrolides
d. Aminoglycosides
Question 3
Which class of medications is indicated in
patients with diabetic nephropathy?
a. ACEIs
b. NSAIDs
c. Macrolides
d. Aminoglycosides
Thank You!