Transcript Glomerulonephritis

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Urine Microscopy
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Nephrotic Syndrome
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Nephritic Syndrome
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Rapidly Progressive
Glomerulonephritis
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Cases
Mark D. Purcell DO
Nephrology/Internal Medicine
Carolina Nephrology, PA
203 Mills Avenue
Greenville, SC 29605
(864) 271-1844
[email protected]
Pre-renal
Renal
Post-renal
Intrinsic (Renal) Causes of Acute Kidney Injury
Acute Glomerulonephritis (5%)
Acute Tubular Necrosis
Ischemic (50%)
Toxins (35%)
Acute Interstitial Nephritis (10%)
Acute Glomerulonephritis
5-10% of ARF
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Causes
Anti-glomerular basement membrane antibody
Disease
Immune Complex Glomerulonephritis
Pauci-immune Glomerulonephritis
Diagnosis
RBC cast
Rapidly rising creatinine
Renal biopsy findings
Urine Microscopy
Essential in discussion of
Glomerulonephritis (GN)
Sedimentary Cells
Epithelial Cell Cast
Prominent nuclei
RBC Cast
Red Cell Cast 2
Urine of Acute GN
Red Cell Cast (broad)
Leukocyte Cast
Bilobulated
nuclei
Waxy Cast
Granular & Hyaline Casts
Muddy Granular Casts
Nephrotic Syndrome
Elsevier items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
Urinalysis
Your Analysis?
Your Analysis?
Your Analysis?
Your Analysis??
Case
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A 26-y/o male presents to your office as your first morning
pt of the day. He c/o LE edema worse at the end of the
day with “frothy urine – like the head of a beer.” He
reports recent sinusitis for which he is using amoxicillin and
OTC Ibuprofen. He denies any gross hematuria.
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PE is essentially normal except for significant peri-orbital
edema noted.
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You perform a 24-hr urine and order some laboratories.
Case
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24-hr urine reveals 16.8 gms protein with estimated
creatinine clearance of 116 ml/min
UA was negative for rbc’s
BUN: 16.8
Cr: 0.8
Electrolytes: normal
Complement levels: normal
Case
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Which of the following is your NEXT step in the
management of this patient?
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1.
2.
3.
4.
5.
Refer the patient for urgent renal biopsy
Start the patient on po prednisone given the proteinuria
Refer to a nephrologist
Have pt discontinue OTC agents
Have the patient perform an additional 24-hour urine b/c
of your concerns of inaccurate collection
Acute GN
Definitions
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Nephrotic syndrome
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Massive proteinuria > 3.5
grams/day
Hypoalbuminemia
Hyperlipidemia
Edema
Non-inflammatory process
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Nephritic syndrome
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Hematuria and/or red cell
casts
Low grade proteinuria
Hypertension
Edema
Decreased renal function
Inflammatory process
Glomerulonephritis
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Acute renal failure associated with hypertension,
hematuria, and edema
Decreased urine output with azotemia
Result of inflammatory attack on glomerulus
Can be primary kidney disorder or secondary to
another systemic disease
Hallmark is hematuria and red cell casts
Causes of Glomerulonephritis
Primary Renal Disorders
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Membranoproliferative GN
Cresentric GN
Fibrillary GN
IgA nephropathy
Secondary Renal Disorders
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SLE
Post-streptococcal GN
Hepatitis C
Vasculitis-related
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Wegener’s Granulomatosis
Microscopic Polyangiitis
Churg-Strauss Syndrome
Infective Endocarditis
Glomerular Filtration Barrier
Geometry
GVEC block
90% of total SA
Copyright ©2007 American Society for Clinical Investigation
Quaggin, S. E. J. Clin. Invest. 2007;117:1480-1483
Nephrotic Syndrome
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≥ 3.5 gm/d
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Frequently associated with underlying glomerular
disease
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Hypoalbuminemia, hyperlipidemia, and edema
Nephrotic Syndrome
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Minimal Change Disease
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Focal Segmental Glomerulosclerosis (FSGS)
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Membranous
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Diabetic Nephropathy
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Most common cause of nephrotic syndrome in the US
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Amyloidosis
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* MPGN (usually 2º cause)
Minimal Change Disease
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Most common disease in children.
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Benign urinary sediment, normotensive,
preserved renal function
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85% responsive to steroids
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Secondary causes include NSAIDS,
Non-Hodgkin’s Lymphoma
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Liquid tumors
Normal Glomerulus on LM
Minimal Change Disease
Courtesy of www.uptodate.com
Minimal Change Disease
Elsevier items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
Focal Segmental Glomerulosclerosis
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Primary or secondary
May present w/ renal insufficiency,
HTN in addition to nephrotic
syndrome
Multiple secondary causes
May respond to
immunosuppression
Collapsing glomerulopathy
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Worst variant
2 H’s and 2 P’s
Inevitable deterioration to ESRD
HIV Nephropathy (HIVAN)
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Collapsing FSGS
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Echogenic/Large Kidneys
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Almost exclusively in African Americans with profound
proteinuria
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Treatment is HAART, ACE Inhibitors, corticosteroids
(controversial), dialysis
Focal Segmental Glomerulosclersosis
Primary/Idiopathic:
 Caused by circulating
permeability factor
Secondary Causes:
 Viral (HIV)
 Obesity
 Hyperfiltration injury
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Prior nephrectomy
sickle cell disease
reflux nephropathy
IV drugs (“Heroin
nephropathy”)
FSGS
Elsevier items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
Membranous Glomerulopathy
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Primary or secondary
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Associated with malignancy in elderly
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Spontaneous resolution in 1/3 of patients
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High risk groups may respond chemotherapy
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PE/Renal Vein Thrombosis
Membranous Nephropathy: Secondary Causes
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Infection: Syphilis, Hepatitis B, HIV
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Medications: NSAIDs, Captopril
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Malignancy: solid tumors
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SLE
Systemic lupus erythematosus
Subendothelial deposits
Membranous Nephropathy
Elsevier items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
Diabetes Mellitus
Early Stages of Diabetic
Nephropathy
Late Stages of Diabetic
Nephropathy
Amyloidosis
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Congo Red positive staining
eosinophilic, amorphous deposits
w/in kidney
AL – associated w. Lamda light
chains
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lambda “lays down amyloid”
kappa “kills”, light chain nephropathy
Negative Congo red staining
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Immunotactoid
Fibrillary GN
END OF LECTURE 5
Begin Lecture 6
Begin discussion of Nephritic
End Nephrotic
RBC Cast
Dysmorphic Glomerular Erythrocytes
Elsevier items
and derived
items © 2007
by Mosby,
Inc., an
affiliate of
Elsevier Inc.
Case Vignette #2
A 15 yo M c/o dark colored urine. He is found to
have 3+ proteinuria, numerous RBC’s, RBC casts.
Scr = 2.4.
What is your first question?
a. Family history?
b. Any medication recently?
c. When was your sore throat?
d. Have you been drinking excessive cola drinks?
Immune Complex GN
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Timing of events
C3, C4 low; ASO titres
Antinuclear Antibody
Therapy
No biopsy needed for post-infectious GN
 No treatment necessary for post-infectious GN
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Post-streptococcal GN
Post-streptococcal GN
Sub epithelial humps
Acute Post-Streptococcal
Glomerulonephritis
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Latent period 6-10 days after throat infection
10-14 days after cutaneous infection
Nephritogenic steptococi identified by serotyping a cell wall
antigen (M protein)
Immunity to M protein is type specific & long lasting
Common in children 6-10 years
Pathology: diffuse endocapillary proliferative GN
with PMN and Monocyte Infiltration and crescents
I.F. granular IgG and C3, EM: subepithelial humps
NEPHRITIC SYNDROME
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Oliguria
Hematuria with red cell casts
Proteinuria - usually < 3 gms/day
Edema
HTN abrupt onset
Nephritic
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SLE
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Post-Infectious GN (PIGN)
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IgA Nephropathy (Berger’s Dz)
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HSP
Membranoproliferative Glomerulonephritis (MPGN)
IgA Nephropathy
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Most common glomerular disease worldwide*
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Episodic hematuria
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Acute with infection and exercise
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Majority benign: 85-90% renal survival at 10 yrs.
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Treatment
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? Fish Oil
Anti-RAAS agents
Prednisone/Immunosuppressants
Normal complements/C3 levels
Membranoproliferative Glomerulonephritis (MPGN)
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SLE
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Hepatitis C
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↓ C3 level
Membranoproliferative Glomerulonephritis (MPGN)
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Type I: Mesangiocapillary GN
Type II: Dense deposit
Type III: Mixed Type I,
membranous features
Secondary causes:
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Hepatitis C
Autoimmune disease
Dysproteinemias
Clues to Cryoglobulinemia
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Hepatitis C positive
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Palpable purpura (leucocytoclastic vasculitis), livedo reticularis, leg ulcers,
acrocyanosis, Raynaud’s phenomenon, necrosis of tips of digits
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Arthralgias, weakness
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Hepatosplenomegaly or LFT abnormalities
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Peripheral neuropathy (mononeuritis multiplex), CNS or abdominal vasculitis,
pulmonary hemorrhage
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Markedly low C4, normal or slightly depressed C3
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Strongly positive Rheumatoid Factor
Hypocomplementemia in Renal Disease
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SLE nephritis: C3 and C4 equally depressed
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PSGN (PIGN): Low C3, Normal C4
 Lasts < 3 months
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MPGN: Low C3, normal C4
 Lasts > 3 months (persistent)
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Cryoglobulinemic GN: Markedly low C4, normal or slightly depressed C3
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Miscellaneous: Atheroembolism, HUS/TTP, liver disease, and sepsis (decreased
synthesis)
Vasculitis
Vasculitis
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Multi-Organ involvement
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Mononeuritis multiplex
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Nerve areas in two separate parts of the body are
affected
Classify according to vessel size**
Systemic Vasculitis
Small Vessel Vasculitis
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Pauci-Immune
Wegener’s Granulomatosis
 Churg-Strauss Syndrome
 Microscopic Polyangiitis
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Immune-Complex
Henoch-Schonlein Purpura
 Essential Cryoglobulinemic Vasculitis
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Anti neutrophilic cytoplasmic antibodies
(ANCA)
c-ANCA
Proteinase-3
p-ANCA
Myeloperoxidase
Approximate Frequencies of ANCA’s
in Pauci-Immune Vasculitis
Microscopic
Polyangiitis
Wegener’s
Granulomatosis
Churg-Strauss
Syndrome
c-ANCA
(PR3)
40%
75%
10%
p-ANCA
(MPO)
50%
20%
60%
ANCA
negative
10%
5%
30%
Wegener’s Granulomatosis
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Necrotizing granulomatous inflammation
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Respiratory tract involvement
Treatment of Wegener’s granulomatosis
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Prompt recognition
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IV methylprednisolone
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Cyclophosphamide
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Trimethoprim-sulfamethoxasole
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Intravenous immunoglobulin
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(Plasmapheresis)
Cyclophosphamide
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Short term side effects
 alopecia
 neutropenia
 nausea/emesis
 opportunistic infection
 hemorrhagic cystitis
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Long term side effects
 Malignancy
 amenorrhea / sterility
Churg-Strauss Syndrome
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Necrotizing granulomatous inflammation
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Asthma
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Eosinophilia
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Renal involvement less common than Wegener’s
and Microscopic Polyangiitis
Microscopic Polyangiitis
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Absence of granulomatous inflammation
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Absence of asthma and eosinophilia
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p-ANCA positive
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Differentiate from Polyarteritis nodosa (P-AN)
Case Vignette #3
A 44 yo F has generalized arthralgias, chronic
sinusitis of 6 months duration,
experiences hemoptysis with cough and R
foot drop.
PE: BP 150/94 Afebrile
Saddle nose deformity, no rash or joint
effusions, R basilar ronchi. 1+ pitting
edema, strength 3/5 in dorsiflexion of R
foot.
CXR reveals bilateral infiltrates, Scr 3.2 with
active urinary sediment.
The most likely serum findings?
a.
Hypocomplementemia, ANA +, dsDNA +
b.
+ C-ANCA (anti-proteinase3)
c.
+ P-ANCA (anti Myeloperoxidase)
d.
Hepatitis C Antibody +, complement normal
Rapidly Progressive
Glomerulonephritis (RPGN)
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Rapidly rising Scr ( i.e. acute renal failure)
Active urinary sediment (RBC casts)
Nephritic proteinuria (<3.5 gm / 24hrs.)
Crescentic Glomerulonephritis
Rapid recognition, therapy essential to preservation
of renal function
Rapidly Progressive GN
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Anti-GBM
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Immune Complex
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PIGN
SLE
Pauci-immune (ANCA GN)
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Goodpasture’s Disease
Wegener’s GN
Microscopic PAN
Endocarditis
Pulmonary – Renal Syndrome
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More Common
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Goodpasture’s Disease
SLE
Microscopic Polyangiitis
Wegener’s Granulomatosis
Less Common
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Churg-Strauss Syndrome
Henoch-Schonlein purpura
Hemolytic uremic syndrome
Behcet’s disease
Mixed cryoglobulinemia
Rheumatoid vasculitis
Penicillamine treatment
Elsevier items and derived items © 2007 by
Mosby, Inc., an affiliate of Elsevier Inc.
Case Vignette #4
A 64 yo previously healthy WF arrives to ER c/o dyspnea,
hemoptysis, bilateral alveolar infiltrates, and serum
creatinine of 3.6 mg/dL. UA reveals 3+ protein,
numerous RBC’s, RBC casts.
What is your next appropriate step?
a.
CT scan of chest r/o pulmonary embolism
b.
Kidney biopsy
c.
Bronchoscopy w. alveolar washing and brush biopsy
d.
Bolus IV Methylprednisolone (1 mg/kg) daily for 3 days
Electron Microscopy
Immunofluorescence
Linear staining pattern for antiGBM antibodies
Diagnostic Evaluation
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Prompt recognition
:20-30:60-70
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Bi Modal Age distribution:
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High correlation smoking, hydrocarbon exposure
Anti GBM antibodies
ANA, C3, C4
Anti-Neutrophilic Cytoplasmic Antibody titer
DLCO
Renal Biopsy
Treatment for Anti-GBM Disease
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Prompt recognition
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IV Methylprednisolone
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Plasmapheresis
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Cyclophosphamide
Cyclophosphamide
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Remission rates 93%
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Short term side effects
 alopecia
 neutropenia
 nausea/emesis
 opportunistic infection
 hemorrhagic cystitis
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Long term side effects
 Malignancy
 amenorrhea / sterility
Treatment of GN
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General Measures
Anti-HTN agents
 Diuretics for edema
 Hemodialysis for kidney failure
 Steroids for systemic disease
 Plasmapheresis for immune complex disease
 Antibiotics for infectious causes
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Treatment of GN
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Supportive treatment of HTN, proteinuria, edema,
hyperlipidemia, hypercoagulability
Methylprednisolone
Cyclophosphamide
Mycophenolate Mofetil
Imuran
Cyclosporine, Prograf
Rituximab
Plasmapharesis
ASA, Persantin, coumadin
Case A
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A 19-year-old woman is evaluated for sudden-onset
periorbital and pretibial edema. Three weeks ago, she
was diagnosed with pharyngitis that has since resolved
without treatment.
On physical examination, blood pressure is 150/100
mm Hg. Cardiac examination reveals a normal S1 and S2
with a soft S3. The lungs are clear and the abdominal
examination is normal. There is periorbital and bilateral
pitting pretibial edema. There are no rashes.
Laboratory Studies
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Blood urea nitrogen 30 mg/dL
Creatinine 1.5 mg/dL
Albumin 3.8 g/dL
Complement (C3) 15 mg/dL (low)
Complement (C4) 48 mg/dL (normal)
Urinalysis: 1+ protein; several erythrocytes,
dysmorphic erythrocytes, and erythrocyte casts/hpf
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Which of the following is the most likely diagnosis?
A. Antineutrophil cytoplasmic antibody–associated small-vessel
vasculitis
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B.
C.
D.
E.
Goodpasture's syndrome
IgA glomerulonephritis
Postinfectious glomerulonephritis
Systemic lupus erythematosus nephritis
Case B
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A 21-year-old woman is evaluated in the office for facial
and lower-extremity edema of 1 week's duration. For the
past 3 weeks, she has had fatigue. She has no history of
diabetes mellitus, cigarette smoking, or illicit drug use.
On physical examination, blood pressure is 90/55 mm
Hg. Cardiac and pulmonary examinations are normal.
The abdomen is soft and without masses. There is
periorbital edema and 2+ lower-extremity edema.
Laboratory Studies
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Creatinine 0.7 mg/dL
Total cholesterol 325 mg/dL
Albumin 2.9 g/dL
Complement (C3 and C4) Normal
Urinalysis
Specific gravity 1.026, 3+ protein
24-Hour urine protein excretion 15 g/24 h
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Which of the following is the most likely diagnosis?
A. Focal segmental glomerulosclerosis
B. Membranoproliferative glomerulonephritis
C. Membranous nephropathy
D. Minimal change glomerulopathy
E. Systemic lupus erythematosus nephritis
Questions
Mark D. Purcell, DO
e-mail: [email protected]