Transcript GLOMERULONEPHROPATHIES

GLOMERULONEPHROPATHIES
Internal Medicine Lecture Series
November 30, 2005
Julia Faller, D.O., PGY1
The Kidney
Nephron
Glomerulus
Glomerulonephritis
Glomerulonephritis
Glomerulonephritis and glomerulopathy are used
interchangeable to denote glomerular injury.
The injury involves damage to the major
components of the glomerulus:
 epithelium
 basement membrane
 capillary endothelium
 mesangium
Primary versus Secondary
Primary—pathology confined to the kidney
-any systemic features are a direct consequence
of glomerular dysfunction
-usually idopathic
Secondary—part of a multisystem disorder
Acute, Subacute & Chronic
 Acute—injury occurring over days or weeks
 Subacute—rapidly progressive over weeks or
months
 Chronic—months to years
Focal versus diffuse
 Lesions are classifed as:


Focal—involving less than 50% of glomeruli
Diffuse—involving over 50% of glomeruli
Focal versus Diffuse
Segmental versus Global


Segmental—involve part of the glomerular tuft
Global—involve almost all of the glomerular tuft
Segmental versus Global
Intracapillary versus
Extracapillary
Intracapillary—refers to endothelial or mesangial
cells
Extracapillary—refers to Bowman’s space
Other Descriptive Terms
 Proliferation—describes and increase in glomerular
cell number
 Crescent—half-moon-shaped collection of cells in
Bowman’s space, composed of proliferating parietal
epithelial cells and infiltrating macrophages
 Sclerosis—an increase in the amount of nonfibrous
extracellular material of similar composition to
GBM and mesangium
 Fibrosis—depostition of collagens type I and III
Classification
Most glomerulopathies are classified according to
their morphologic features
1. Nephritic syndrome (inflammatory)
2. Nephrotic syndrome
3. Deposition diseases
Nephrotic and Nephritic
Nephritic Syndrome
 1. Focal proliferative glomerularnephritis
 2. Diffuse proliferative glomerulonephritis
 3. Crescentic glomerulonephritis
Nephritic Syndrome
 Usually present with presence of RBC’s, red
blood cell casts, leukocytes and sub
nephrotic proteinuria of <3g/24hr
Nephrotic Syndrome
 Affects glomerular filtration barrier for
proteins
 1. Membranous glomerulopathy
 2. Minimal change disease
 3. Focal and segmental glomerulosclerosis
Nephrotic Syndrome
 Present with nephrotic range proteinuria of
>3g/24 hr, few RBC’s, leukocytes, cellular
casts
 Associated with hypoalbuminemia, edema,
hyperlipidemia, and lipiduria and a
prothombotic state
Deposition Diseases
 Prominent extravascular depostion of a
paraprotein or fibrillar material
 Can either trigger nephritic, nephrotic or
combination
Major Determinants of
glomerular injury
 1. The nature of the primary insult and
secondary mediator systems it invokes
 2. The site of injury within the glomerulus
 3. The speed of onset, the extent, and
intensity of disease
Primary Insult
 1.
 2.
 3.
 4.
 5.
 6.
 7.
Immunologic
Metabolic
Hemodynamic
Toxic
Depostion
Infectious
Inherited
Major Mechanismas of
Glomerular injury
 1. Inherited glomerular diseases
 2. Immunologic glomerular injury
 3. Nonimmunologic glomerular injurty
 4. Final common pathways of injury in
glomerular disease
Clinical Manifestations of
Glomerular Disease
 asymptomatic proteinuria
 nephrotic syndrome
(proteinuria, hypoproteinemia, lyperlipidemia,
edema)
 asymptomatic hematuria
 glomerulonephritis
(hematuria, proteinuria, hypertension, renal failure)
Clinical Manifestations of
Glomerular Disease con’t
 acute glomerulonephritis
(neprhitis 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)
Case Presentation
 A 53 year old African American male with a
history of hypertension and bipolar disorder
that was treated with lithium presented to an
emergency room complaining of "not feeling
well".
Lab Studies
 Evaluation revealed edema, proteinuria, creatinine
3.1 mg/dl and BUN 57 mg/dl. Four days later the
creatinine was 5.3 mg/dl and BUN 74 mg/dl. He
was hospitalized for further evaluation, which
revealed BP 150/80, edema, 8.7 gm/24hr
proteinuria, >20 RBC/hpf, serum albumin 1.5 g/dl,
cholesterol 200 mg/dl, positive anti-nuclear
antibody (ANA) at a titer of 1:320 and normal
serum complement.
Additional Information
 He gave no history of prior renal disease and
had not taken nonsteroidal anti-inflammatory
drugs. Over the next week his creatinine rose
to 6.8 mg/dl. A renal biopsy was performed.
Follow up
 The lithium was discontinued and the patient
was treated with prednisone (60 mg/day).
Five days after biopsy his creatinine was 6.1
mg/dl, and was 1.1 mg/dl one month later, at
which time there was 1 g/24 hrs proteinuria.
Within two months the proteinuria had
disappeared and the serum albumin was 3.6
g/dl.
Minimal change glomerulopathy
with acute renal failure syndrome
 one of the most gratifying diagnoses that a renal
pathologist can make
 prior to biopsy the patients are often thought to
have either rapidly progressive glomerulonephritis
or severe irreversible chronic glomerular disease
 Minimal change glomerulopathy with acute renal
failure has a very good prognosis because the
nephrosis usually responds to steroid treatment and
the renal failure almost always resolves
Case Presentation
 A 49 yr old man was well until 1 mos ago,
when he developed dyspnea, fatigue,
decreased appetite, and cough that produces
blood tinged sputum. Three days ago, he had
3 episodes of frank hemoptysis. He has had
no fever or chills. He has a 7 yr history of
hypertension and has been a smoker for 15
years. He takes no medications.
Physical Exam
 The patient is alert and in no distress but is pallid.
BP 155/88, HR 90, resp 18, temp 98.6. Skin exam
is normal. Optic funduscopy shows mild sclerosis
and constriction. The carotids and thyroid are
normal. The pharynx is clear. Lungs have coarse
crackles in the right mid-lung field. CV NSR, no
gallop. Abdomen is soft with no organomegaly.
No redness or swelling of the joints are present.
Lab Studies
 WBC 9.2, Hgb 8.7, hct 26%, platelet 443,
creatinine 4.4 (was 1.3 1 mos earlier), Protein
6.3, Albumin 3.7
 24hr protein 3.5
 urinalysis: 4+ protein, 3+ hemoglobinuria,
25-50 RBC’s, 5-15 WBC’s, dysmorphic
erythrocytes and casts
Renal Biopsy
 Proliferative glomerulonephritis with 50% of
glomeruli having crescents
 Immunofluorescence shows linear staining
with IgG
What do you think?
 1.
 2.
 3.
 4.
Rapidly progressive glomerulonephritis
Nephrotic syndrome
Chronic renal failure
Acute tubular necrosis
Question 1
 The most likely disease to have a nephritictype presentation is:
 1. Minimal change glomerulonephropathy
 2. Membranous glomerulonephropathy
 3. Focal segmental glomerulosclerosis
 4. Crescentic glomerulonephritis
Question 2



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The term focal in describing kidney disease means:
1. Only some of the glomerular tuft is affect
2. All of the glomerular tuft is affected
3. Less than 50% of the glomeruli are affected
4. Greater than 50% of the glomeruli are affected
Question 3
 Major Determinants of glomerular injury are:
 1. The nature of the primary insult and
secondary mediator systems it invokes
 2. The site of injury within the glomeruli
 3. The speed of onset, the extent, and
intensity of disease
 4. All of the above