Transcript Rapidly progressive glomerulonephritis

Rapidly progressive
renal failure
Dr.
Overview
 Introduction
 Etiology
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Pathology
Clinical features
Management
 Conclusions
Introduction
 Rapidly progressive renal
failure (RPRF)
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Deterioration of the
GFR, associated with
the accumulation of
wastes such as urea
and creatinine
(azotemia) within
weeks to months
[Note: Acute renal failure
(ARF) duration is hours to
weeks]
GFR – Glomerular Filtration Rate
Etiology
 RPRF may be due to various causes
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Pre-renal
Renal
Post-renal
Etiology
 Acute Nephritis
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Rapidly progressive glomerulonephritis
(RPGN)
 Acute – on – chronic renal failure
RPGN
 Characterized clinically by
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A rapid decrease in the GFR of at least
50% over a short period, from a few days
to 3 months
RPGN: History
 The term RPGN was first used to describe a
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Group of patients who had an unusually fulminant
poststreptococcal glomerulonephritis and a poor
clinical outcome
 Several years later,
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The anti-GBM antibody was discovered to produce
a crescentic glomerulonephritis in sheep, and,
following this discovery,
The role of anti-GBM antibody in Goodpasture
syndrome was elucidated
Anti –GBM: antiglomerular basement membrane
RPGN: History (Contd)
 Soon afterward,
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The role of the anti-GBM antibody in
RPGN associated with Goodpasture
disease was established
 In the mid 1970s,
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A group of patients was described who fit
the clinical criteria for RPGN but in whom
no cause could be established
RPGN: History (Contd)
 Many of these cases were
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Associated with systemic signs of vascular
inflammation (systemic vasculitis), but
some cases were characterized only by
renal disease
 A distinct feature of these cases was
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The virtual absence of antibody deposition
after immunofluorescence staining of the
biopsy specimens, which led to the label
pauci-immune RPGN
RPGN: History (Contd)
 More than 80% of patients with pauci-
immune RPGN were subsequently found
to have
 Circulating antineutrophil cytoplasmic
antibodies (ANCAs), and,
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Thus, this form of RPGN is now termed
ANCA-associated vasculitis
RPGN: Causes
 Abscess of any internal organ
 Anti- GBM antibody disease
 Blood vessel diseases such as
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Vasculitis or polyarteritis
 Collagen vascular disease such as
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Lupus nephritis and Henoch-Schonlein purpura
Goodpasture syndrome
IgA nephropathy & History of cancer
Membranoproliferative GN
Blood or lymphatic system disorders
Exposure to hydrocarbon solvents
RPGN: Pathology
 The main pathologic
finding is
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Extensive glomerular
crescent formation
Focal rupture of
glomerular capillary
walls that can be
seen by light
microscopy and
electron microscopy
RPGN: Classification
Immunological classification: based on the + or - of ANCAs
The disorders are also classified based on their clinical
presentation
RPGN: Classification (Contd)
 Anti-GBM antibody (Approx. 3% of
cases)
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Goodpasture syndrome (lung and
kidney involvement)
Anti-GBM disease (only kidney
involvement)
Note: 10-40% of patients may be
ANCA positive
RPGN: Classification (Contd)
 Immune complex
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Postinfectious (staphylococci/streptococci)
Collagen-vascular disease
Lupus nephritis
Henoch-Schönlein purpura
(immunoglobulin A and systemic vasculitis)
Immunoglobulin A nephropathy (no
vasculitis)
Mixed cryoglobulinemia
RPGN: Classification (Contd)
 Immune complex – contd.
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Primary renal disease
Membranoproliferative glomerulonephritis
Fibrillary glomerulonephritis
Idiopathic
 Note:
Of all patients with crescentic immune
complex glomerulonephritis, 25% are ANCA+;
< 5% of patients with noncrescentic immune
complex glomerulonephritis are ANCA+
RPGN: Classification (Contd)
 Pauci-immune
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Wegener granulomatosis (WG)
Microscopic polyangiitis (MPA)
Renal-limited necrotizing crescentic
glomerulonephritis (NCGN)
Churg-Strauss syndrome
Note: 80-90% of patients are ANCA+
RPGN: Symptoms
*Edema (swelling) of the face, eyes, ankles, feet, legs,
or abdomen
*Blood in the urine
*Dark or smoke-colored urine
*Decreased urine volume
*Abdominal pain
*Cough & Diarrhea
*General ill feeling & Fever
*Joint aches & Muscle aches
*Loss of appetite & Shortness of breath
RPGN: Signs
 A physical examination reveals edema
(swelling)
 Abnormal heart and lung sounds may be
present
 Blood pressure may be high
RPGN: Tests & diagnosis
 Anti-glomerular basement membrane
antibody tests
 Antineutrophil cytoplasmic antibodies
 BUN and creatinine
 Complement levels
 Creatinine clearance & Urinalysis
RPGN: Treatment
 Depends on the underlying cause
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Corticosteroids may relieve symptoms in
some cases
Medications that suppress the immune
system may also be prescribed, depending
on the cause
Plasmapheresis may relieve the symptoms
in some cases
RPGN: Treatment
 Persons should be closely watched for
signs of progression to kidney failure
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Dialysis or a kidney transplant may
ultimately be necessary
RPGN: Prognosis
Without treatment, RPGN often worsens rapidly
to kidney failure and end-stage kidney disease in
≤ 6 months, although a few cases may just go
away on their own
Those who receive treatment may recover some
or rarely all of their original kidney function
The extent of recovery is related to the degree of
kidney function at diagnosis and degree of
crescent formation
The disorder may recur
If the disease occurs in childhood, it is likely that
kidney failure will eventually develop
RPGN: Prevention
The prompt treatment of disorders that can
cause RPGN may prevent the development
of this disease
RPGN:Complications
*Congestive heart failure
*Pulmonary edema
*Hyperkalemia
*Acute renal failure
*Chronic renal failure
*End-stage renal disease
RPRF: Other causes
 Hepatorenal syndrome (HRS)
 Frerichs (1861) and Flint (1863): first
noted association of liver disease and
oliguria without renal histologic changes
HRS: Types
 Type 1
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Rapidly progressive renal failure
Doubling of creatinine
Precipitating factor frequently identified
 Type 2
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Moderate, steady renal failure
Milder elevation of creatinine
May arise spontaneously
HRS: Aggravating factors
HRS: Pathologphysiology
 Hallmark: Intense renal
vasoconstriction
 Starts at an early time point and
progresses with worsening liver disease
HRS: Pathophysiology (Contd)
 Peripheral (splanchnic) arterial
vasodilation subsequent renal
vasoconstriction
 Stimulation of renal sympathetic nervous
system
 Cardiac dysfunction circulatory
derangements and renal hypoperfusion
 Cytokine/mediator action on renal
circulation
HRS: Pathophysiology (Contd)
HRS: Prognosis
 Type 1: RPRF
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80% 2 week mortality,
90% 3 month
 Prognosis worse if precipitating factor
exists
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Severity of liver disease a determinant of
survival
HRS: Treatment
 General measures:
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Central venous access
Monitor fluid status
Volume: albumin/furosemide to titrate CVP
Nutrition critical: avoid high protein; low
salt, free water restriction
HRS: Treatment (Contd)
 Spcific measures
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Renal vasodilators
Systemic vasoconstrictors
TIPS
Renal replacement therapy
Liver/renal replacement therapy
Liver transplantation
TIPS: Transjugular intrahepatic portosystemic shunt
RPRF: Other causes
 Multiple Myeloma
Myeloma Kidney:Epidemiology
 In two large multiple myeloma studies,
43% (of 998 pts) had a creatinine > 1.5
and 22% (of 423 pts) had a Cr > 2.0
 The one-year survival was 80% in pts
with Cr < 1.5 compared to 50% in pts
with a Cr > 2.3
 Prognosis is especially poor in pts who
require dialysis
Meyloma Kidney: Causes of
renal failure in MM
 Cast nephropathy
 Light chain deposition disease
 Primary amyloidosis
 Hypercalcemia
 Renal tubular dysfunction
 Volume depletion
 IV contrast dye, nephrotoxic meds
Meyloma Kidney: Causes of
renal failure in MM
Cast Nephropathy
Myeloma Kidney: Treatment of
renal failure in MM
 Hydration with IV fluids
 Treatment of hypercalcemia
 Loop diuretics
 Caution with bisphosphonates
 Treatment of myeloma
 Pulse steroids +/- thalidomide
 VAD chemotherapy
 Possible role for plasmapheresis
 Dialysis, as necessary
Myeloma Kindey: Prevention
of renal failure in MM
 IVF hydration
 Discontinuation of nephrotoxic drugs (i.e.
NSAIDs, etc.)
 Chemotherapy/steroids – treatment of
multiple myeloma to decrease the
filtered light chain load
RPRF: Other causes
 Drug induced, e.g.
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Acyclovir
Orlistat
 The
increased intraluminal free fatty acids
complex with intraluminal calcium ions,
competitively inhibiting the precipitation of
oxalate with calcium
 The increase in soluble uncomplexed oxalate
facilitates oxalate absorption, resulting in
hyperoxaluria and oxalate stone
RPRF: Other causes
 Type 2 Diabetes with renal failure,
Factors Affecting Progression of
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hypoalbuminemia, anemia, higher mean
blood pressure, and lack of use of insulin
predict rapid progression of renal failure,
but HbA1c does not, and insulin therapy
may be possibly an indicator of the delay in
progression of renal failure
Diabetes Care, May 2003;26(5):1530
RPRF: Other causes (Contd)
 Diabetes: Dietary acid load and rapid
progression to end-stage renal disease
 High ingestion of nonvolatile acids with food
increases susceptibility for progression to endstage renal failure
 These high dietary acid loads lead to
compensatory increases in renal acid excretion
and ammoniagenesis.
 The price paid for maintenance of acid-base
homeostasis is renal tubulointerstitial injury,
with subsequent decline in renal function and
induction of hypertension
J Nephrol. 2010 Sep 24
RPRF: Other causes (Contd)
 Causes of acute-on-chronic renal failure
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Dehydration
Drugs
Disease relapse/acceleration
Infection
Obstruction
Hypercalcemia
Hypertension
Heart failure
Interstitial nephritis
Conclusions
 RPRF is defined based on duration of
decline in renal function (weeks to
months) with various etiologies
 Patient should be evaluated for the
cause and treated accordingly
 RPGN is common group for RPRF
 Diabetes, HRS, Multiple myeloma may
also be the reasons for RPRF
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