7) Secondary nephropathies: amyloidosis and lupus nephropathy Flashcards Preview

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Flashcards in 7) Secondary nephropathies: amyloidosis and lupus nephropathy Deck (21)
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1

who does SLE predominantly affect ?

women 10 times more than men
however LN affects both equally

they are more predominate in back ,asians and hispanics

2

what is the pathophsyioogy of lupus nephritis ?

antigen sepcifically directed against nucleosome or double stranded dna - anti -dsDNA creating immune complexes which are brought to the glomeruli

in the glomuerli this starts the complement cascade system

these cationic autoantibodies have high affinity for the anionic basement membrane - there can be cross linking between there

igG3 AND C1Q

3

what is the etiology of SLE ?

HLA-DR2 and HLA-DR3 a

Genetic deficiency of classical pathway complement proteins (C1q, C2, C4)


environment
uv light
ebv
smoking

medication - procainamide

4

what are the general clinical features of lupus ?

photosensitivity,

butterfly rash ,

limbs sacks endocarditis

raynaud phenomena

arthritis ,myalgia

nervous system - seizures psychosis

lungs pneumonia
oral and nasal ulcers

5

what are the classification of lupus nephritis and how we cam diagnose that ?

ISN / rps classification

1) minimal mesangial LN -
normal glomeruli through LM

IF mesangial immune deposits igG by IF

very good prognosis

=============

2) mesangial proliferative Ln -

mesangial hypercellularity through LM

IF - mesangial full house including C1q and C3 - gig ,igm

very good prognosis

============

3) focal LN - less than 50 percent of glomeruli affected

LM - segmental or global

proliferation of endothelial diffuse thickening of the capillaries
mesangial cells proliferation

IF - full house , majorly deposited in subendothlium

a- active lesion
c - chronic lesion
a/c

========

4) diffuse LN - similar but now more than or equal to 50 percent of glomeruli affected

can be global or segmental

a - active lesion
C - chronic lesion
a/c

worst renal prognosis

===============

5) membranous LN
good prognosis

subepithelila and intramembrnaous immune deposits

=========

6) advanced sclerosing LN
more than 90 parent of the glomeruli globally sclerosed

6

what are the clinical findings according to the isn and RPS classification

class 1 and 2 good prognosis

class 2 - mild hypertension

3a or 3a/c = moderate hypertension

focal LN - 3C - glomerular scarring - usually have hypertension and reduced renal function

if there is more necrotising features and crescent formation prognosis similar to class 4a

class 4 - hypertension malignant type
=givig you headache , casual disturbances
progressive cardiac and renal insufficiency
nephrotic syndrome - frothy urine
edema
hypercoaguble state
hyperlipidemia

class 5 - features of nephrotic syndrome
HIGH blood pressure
less clinical renal
but heavily predisposed to thrombotic complication such as renal vein thrombosis and pulmonary emboli

class 6 - high hypertension
chronic kidney disease

7

diagnosis of lupus nephritis ?

1) symptoms in more than two of the organ
2) positive ana test
3) anti-dsDNA antibody testing
associated with lupus nephritis
or anti - sm antibody


=========
anti -T and b LYMPHOCYTE ANTIBODIES

antiphosphlidi antibodies

low C3 and C4 complements - IF IT DECREASES ITS A SIGN OF ACTIVITY

ESR is elevated whilst crp is often normal

increase of creation levels

============

1 = no proteinurea

2 = mild proteinurea (less than <0.5g /day)
and maybe microhematurea

3a / 3a/c =
active urine sediment ( Active urinary sediment was defined as >5 RBCs and >5 WBCs per high‐power field (hpf) and/or cellular casts limited to RBC and abc where none previously existed in the absence of infection )
microhematurea
low complement levels
moderate proteinurea (below 2g / day )

focal LN -- 3C = reduced GFR but without active urinary sediment

4= heavy proteinurea - nephrotic syndrome
reduced GFR
high serological activity =
low serum complement and high anti-dsDNA binding activity
active urinary sediment

5= nephrotic syndrome
proteinurea
low serological activity

6 = perisiatnt microheamturea
and some proteinurea
decreased GFR

8

what is the treatmnet of lupus nephritis ?

ISN class 1 and 2 - no therapy directed towards the kidney but basic SLE therapy which is hydroxycholoquine
with low dose , short term ,oral glucocorticoids

=======

proliferative lupus nephritis

IV methyl prednisolone for 1-3 days before oral prednisone
nd it is tapered over several weeks
WITH
cyclophosphamide - Iv monthly for 6 months / oral
WITH
MMF - first choice /
cyclosporin /
tacrolimus

==========

plasmaphoresisi is combined with corticosteroid or immunosuppressive agents

=====
anticoagulants
Iv heparin
or low molecular heparin - subcutaneous

treatmmte continue with oral anticoagulants

======
if nephrotic edema - use albumin infusion or diuretics
dietary sodium restriction
water restriction
loop diuretics

PORTEINUREA ACEI AND ARB

DYLIIDEMIA - STATINS

if hypertension - ACEI or alpha blockers

======
in severe reduction in GFR = hemodialysisi and renal transplant

9

what is the classification of amyloidosis ?

SYSTEMIC

AL - ig light chains
affected organ - kidney , heart , liver , spleen , lung , vessels , GIT
, nervous

due to multiple myeloma


========

AA

spleen , liver , kidney


=====
ATTR

10

what are the most common systemic amyloidosis ?

primary - AL
and secondary - AA

11

what causes primary amyloidosis ?

multiple myeloma ,
waldenstrome macroglobulinemia

12

what are the clinical manifestations of AL amyloidosis ?

weakness , weight loss , bone pain if multiple myeloma

kidney :
nephrotic syndrome - selective porteinurea (majorly albumin) - (frothy urine, high coagulable state , dyslipidemia )
ABCSNCE OF MICRO OR MACROHEMTAUREA

polyuria-polydipsia - due to urinary concentration defect

orthostatic hypotension

HYPERTENSION IS ABSENT!t even with renal impairment

musculoskeletal
carpal tunnel

heart
restrictive cardiomyopathy
amyloid induce arrhythmia and sick sinus syndrome
av block

GI - common -
decrease motility ,
malabsorption , haemorrhage and obstructing
macroglossia

hyposplenism / splenomegaly - infections

nerve :
painful sensory polyneuropathy - later motor deficits

13

how is amyloidosis different from many types of kidney diseases ?

the kidney is found to be often enlarged and there is hypertension even if the renal function is impaired

14

what is the diagnosis of al amyloidosis ?

nephrotic syndrome
The nephrotic syndrome occurs with or without elevations in creatinine and blood urea concentration two biochemical markers of kidney injury.

immunofixation of serum and urine

or protein electrophoresis - m spike for aparaportein

bone marrow biopsy - plasmacytosis

biopsy of affected organ
- usually abdominal fat biopsy is enough
congo red staining

======
types of amyloid is indistinguishable by LM or EM

most direct way = mass spectrometry or amino acid sequencing

however the most definative method used is immunofluorescence
and immunohistochemical staining

15

what is the treatment for AL amyloidosis ?

M-DEX - oral melphalon and dexamethasone each month

high dose melphalan followed by autologous stem cell transplant

bortezomibe with dexamethazone

thalidomides

plasmapheresis and immunoadsorption

dialysis

kidney transplant

dialysis

kidney transplant

16

what are the causes for secondary amyloidosis ?

chronic bacterial infection / chronic inflammatory conditions - ra , inflammatory bowel disease

high magnitude of acute phase saa response

familial mediterranean fever trait

hodgkin lymphoma

17

what are the clinical manifestation of secondary amyloidosis ?

can be acute with nephrotic syndrome

nephrogenic diabetes inspidus

GI disturbances - diarrhea , constipation , malabsorption
, hepatosplenomegaly

in contrast AL amylidosis - peripheral neuropathy , macroglossia , carpal tunnel syndrome is infrequent

18

what is the diagnosis of AA amyloidosis ?

kidney biopsy
biopsy of accessory salivary gland and abdominal fat

immunohistochemical staining using antibodies against SAA is required to confirm that the congo red positive amyloid is the AA type

SAP scintigraphy - shows bones are not affected unlike AL amyloidosis

19

what is the treatment for aa amyloidosis ?

control of chronic purulent infections by antibacterial agents

immunosuppressive therapy and immunomodulators

colchicine = effective in mediterranean fever

plasmapheresis

20

QHAT IS DIALYSIS RELATED AMYLOIDOSIS ?

TYPE OF SYSTEMIC AMYLOIDOSIS IN PATIENTS UNDERGOING LONG TERM HEMODIALYSIS - this protein b2 micro globulin is not effectively removed

21

in gross pathology how does in amyloid kidney look like ?

enlarged
pale
and waxy appearing on cut surfaces