The Medical Renal Biopsy Dr Kelvin St.Pierre-Robson
The Medical Renal Biopsy •
Diagnosis
• •
treatment and management
Degree of chronic damage
•
may guide prognosis beyond primary diagnosis
•
Systematic examination of different compartments
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glomerulus
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tubules
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interstitium
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blood vessels
Renal biopsy panel •
H&E x 2
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Silver stain
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PAS
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Trichrome
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Congo Red
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Is this enough?
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clinical features - do they correlate?
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immunofluorescence or immunohistochemistry
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electron microscopic findings
Renal biopsy IHC/IMF •
IgG
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IgA
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IgM
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C9
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C3
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+/-C1q
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Kappa
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Lambda
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Specific challenges
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limited responses to injury
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size of biopsy
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identifying the primary lesion
• •
does the pathology effect more than one compartment
disease progression to end stage features
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Renal disease may have similar clinical presentations
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microalbuminuria
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subnephrotic proteinuria
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nephrotic proteinuria
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asymptomatic haematuria
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microhaematuria
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hypertension
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rapidly progressive GN
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acute kidney injury
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chronic renal faliure
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Microalbuminuria
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20-200mg/l (spot check) or 30 -300mg/24hrs
Nephrotic syndrome
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protein in the urine, low blood albumin, high blood lipids, and significant swelling
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>3.5g per 1.73m2 per day
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hypoalbuminaemia 2.5g/dl
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Frequency of various diagnoses Nephrotic syndrome
•
FSGS
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Membranous GN
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Minimal change
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Diabetic GN
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Membranoproliferative GN type 1
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Amyloidosis
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C1q
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Fibrillary GN
Frequency of various diagnoses •
Haematuria
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Lupus nephritis
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IgA nephropathy
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Pauci immune GN
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Post infectious GN
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Thin basement membrane disease
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Anti GBM disease
Frequency of various diagnoses •
•
Other GN that cause acute renal failure
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Thrombotic microangiopathy
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Acute TIN
•
Light chain cast nephropathy
That manifest as chronic renal failure
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Arterionephrosclerosis
Definitions •
Focal
•
•
Diffuse
• •
involving all glomeruli
Segmental
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involving some glomeruli
involving part of a glomerular tuft
Global
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involving total glomerular tuft
Definitions •
Crescent
• •
Spikes
•
•
proliferation of parietal epithelial cells (layer of 2 cells or more that partially or completely fill Bowman’s space)
Projections of glomerular basement membrane between subepithelial immune deposits
Endocapillary proliferation
•
Proliferation of mesangial and/or endothelial cells and infiltrating inflammatory cells filling up and distending capillary lumens
Definitions •
Tram track
• •
double contour of glomerular basement membrane due to deposits
Wire loop
•
thick, rigid appearance of capillary loop due to massive subendothelial deposits
Definitions •
Activity
• •
treatment sensitive lesions i.e. crescents, cellular infiltrate, necrosis, proliferation
Chronicity
•
probable irreversible lesions i.e. extent of tubular atrophy, interstitial fibrosis, fibrous crescents, sclerosis
Renal biopsy assessment •
Develop a structure to differential diagnosis
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based on clinical presentation
• •
what might you be expecting
based on pattern of response
•
does this correlate with the clinical information
Report Structure
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Useful to have headings (or not as you prefer)
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Micro
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Glomeruli
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Tubules and Interstitium
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Vessels
•
Immunohistochemistry/fluorescence
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Electron microscopy
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Comment
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Conclusion
Case 1 •
66 yr old male
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CKD, persistent haematuria
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Reduced complement
•
?GN
Case 1
Case 1 •
IHC/IMF negative
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What would you do next?
•
Why?
Case 1
Case 1
•
Diagnosis?
•
Normal biopsy, no pathology
Case 2 •
27 yr old female
•
Persistent proteinuria
•
ACR 124
IgG
Case 2 •
IgM, C9 and C3C similar
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IgA also positive but less intense
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Diagnosis?
•
What will you see on EM?
Case 2
Case 2
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Diagnosis
•
Lupus nephropathy Class V
Case 3 •
48 yr old male
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Nephrotic range proteinuria
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Urinary ACR 450
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Haematuria
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CR 112
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Nephrotic syndrome
Case 3
Case 3 diagnosis = Membranous GN •
Membranous nephropathy
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Primary – Idiopathic (most common)
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Secondary – Drugs, Infections and malignancy
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Commonest presentation
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Nephrotic syndrome
•
Haematuria +/-
Membranous • • • • • • • •
4 Stages Stage I - Normal light nicroscopy DIF – fine granular capillary wall IgG EM – Small subepithelial electron dense deposits and foot process effacement Stage II Diffuse thickening of the capillary wall Silver stains – spikes on the capillary wall (extensions of basement membrane in between the deposits)
Membranous • • • • • • • • •
DIF coarse granular IgG and C3 (most cases) EM Many subepithelial deposits Stage III Severe thickening of the basement membrane Silver staining lucent areas( holes in the basement membrane) EM- Subepithelial deposits covered by a new layer of basement membrane Stage IV Severe thickening of the basement membrane associated with segmental or global glomerulosclerosis. Intramembranous deposits some of which are electron lucent due to resorption.
Case 4 •
44 yr old male
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AKI
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Blood and protein in urine
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Hypertension
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Nephrotic range proteinuria
Case 4
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What might your differential diagnosis be?
IgA
Case 4 •
What is your diagnosis?
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Why?
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Features favour a fibrillary GN.
Case 4 •
Fibrillary GN
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Typically MPGN on light microscopy
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Congo red negative
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Smudgy IgG and C3
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Randomly arranged fibrils on EM
Differential diagnosis of fibrils •
Fibrillary GN
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Immunotactoid GN
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Organised, parallel, microtubular (>30nm)
Amyloid
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Fibrils random, 12-24 nm (mostly 18-20nm)
Random, 8-15nm (mostly 10-12 nm)
Cryoglobulinamia
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Microtubular or vague, short fibrillary
Case 5 •
64 yr old female
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eGFR 20
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Nephrotic range proteinuria
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Rapid decline in renal function
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ACR 600 +
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ANA and ANCA negative
Case 5
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What could be a differential diagnosis?
•
How would you resolve ?
Diagnoses to consider with a nodular pattern •
Amyloid
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Light chain deposition disease
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MPGN type 1 (and its diseases)
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Diabetic nephropathy
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Dense deposit disease
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Fibrillary GN
Case 5 diagnosis = Amyloid •
• • • • • • •
Amyloid - important cause of nephrotic range proteinuria in the elderly group. May be the main presenting symptom Kidney – nodular glomerulosclerosis Frequently involves the blood vessels and interstitium. Glomerulus replaced by amorphous pink material Silver negative and PAS negative Sirius red and Congo red positive Early biopsy may be subtle and EM may be necessary for the diagnosis EM shows non branching fibrils
Case 6 •
54 yr old male
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Raised BP
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CR 174
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ACR 581
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ANA and ANCA -ve
Case 6
Case 6 diagnosis =Diabetic Glomerulosclerosis
Diabetic nephropathy almost always associated with retinopathy Presents commonly with nephrotic range proteinuria Characterstic lesions in kidney Diffuse and nodular glomerulosclerosis PAS positive, silver positive and congo red negative KW lesions, Capsular drop and Fibrin caps Afferent and Efferent arteriolar hyalinosis DIF – pseudolinear IgG EM – Thickened basement membranes
Case 7 •
60 yr old male
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Renal impairment of unknown cause
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Cr 168 eGFR 37
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Gout on allopurinol
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Urine dip 1+ protein and 4+ blood
Case 7 •
Diagnosis?
•
IgA nephropathy
•
May use Oxford Classification if your clinicians require
IgA disease Commonest glomerulonephritis Commonest presentation haematuria but variable Nephrotic range proteinuria to acute renal failure Variable histology from normal to crescentic glomerulonephritis DIF – Mesangial IgA and in most cases C3 EM – Mesangial, paramesangial and sometimes sub endothelial deposits
Haematuria • Common causes of isolated haematuria • IgA nephropathy • Thin membrane nephropathy • Common causes of nephritic syndrome • IgA nephropathy • Post infectious glomerulonephritis • Mesangiocapillary glomerulonephritis
Case 8 •
30 yr old female
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Episode of frank haematuria
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Rising creatinine now 167
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Urine dip 3+ blood and 4+ protein
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ACR 651
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Negative ANA and ANCA
Case 8
Case 8
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Diagnosis = Vasculitic IgA nephropathy
Crescents in GN •
Pauci immune GN
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Anti GBM disease
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FSGS
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IgA/HSP
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Lupus GN
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Fibrillary GN
Case 9 •
72 yr old
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Nephrotic range proteinuria
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eGFR 27
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ANCA positive
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MPO and PR3 negative
Case 9
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Diagnosis?
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MPGN type 1
MPGN •
Diagnosis?
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Or pattern?
•
What disease present with MPGN patterns?
MPGN Pattern Disease •
Primary MPGN type 1
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Lupus
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Fibrillary
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Amyloid
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Monoclonal immunoglobulin deposition disease
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Dense deposit disease
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Cryoglobulinaemia
Case 10 •
21 yr old male
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AKI
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Blood 3+
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Protein 2+
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Glucose 3+
Case 10
Case 10
•
Diagnosis = severe acute tubular interstitial nephritis
Acute Tubulointerstitial Nephritis
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Renal failure
•
Drugs – NSAIDS, antibiotics and PPI Inhibitors
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Presence of tubulitis
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Interstitial Inflammation
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Lymphocytes, Plasma cells and Eosinophils
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TINU – TIN and Bilateral Uveitis
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Sarcodosis – Granulomatous inflammation (case 27)
Case 11 •
78 yr old male
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AKI
•
Cr 88-736
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Urine dip 3+ blood, 1+ protein
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PCR 93
Case 11
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Diagnosis?
•
Granulomatous interstitial nephritis
Case 12 •
56 yr old male
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Hypertension
•
CKD Cr 150
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1month history NSAID and PPI
•
Cr now 390
Case 12
Case 12
Case 12
Case 12
Case 12
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What clinical information are you going to seek?
Case 12
•
Diagnosis = Cast nephropathy
Cast Nephropathy •
Most common cause of Acute renal failure in Multiple Myeloma Patients.
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Casts are rigid and fractured
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Surrounded by desquamated epithelial cells
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Can be associated with a foreign body giant cell reaction
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Casts can be IgA positive
Classifications to be aware of
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Lupus GN
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Oxford classification of IgA
Lupus nephritis
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Type I
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Normal Lm few EM mesangial deposits
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Type II
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Mesangial proliferative nephritis
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DIF- full house pattern in mesangium
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EM – numerous mesangial deposits few sub endothelial deposits
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Type III
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Focal lupus nephritis (Less than 50% glomeruli)
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Active/inactive, global/ segmental
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Acute/chronic
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IIIA,IIIA/C and IIIC
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DIF - capillary wall and mesangium
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EM – Few sub endothelial deposits
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TypeIV
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Diffuse lupus nephritis
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(more than 50% of all glomeruli)
• • •
TypeIVS more than 50% of involved glomeruli segmental lesions TypeIVG more than 50% of involved glomeruli global lesions Segmental – less than half the glomerular tuft
•
Various combinations
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TYPEIVS/A
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TYPEIVG/A
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TYPEIVS(A/C)
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TYPEIV(S/C)
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TYPEIVG(C)
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DIF full house subendothelial and mostly mesangial
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EM Large numbers of subendthelial deposits
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Wire loop lesions and hyaline thrombi often seen
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Type V
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Membranous may be associated with different types
Lupus type II
Lupus typeII
Lupus typeIVS(A)
Lupus typeIVS(A)
Lupus typeIVS(A)
Lupus typeIVG(A)
Lupus typeIVG(A)
Lupus typeIVG(A)
Lupus typeIVG(A)
Lupus typeV
Lupus typeV