7) Secondary nephropathies: amyloidosis and lupus nephropathy Flashcards
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
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
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
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
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
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2) mesangial proliferative Ln -
mesangial hypercellularity through LM
IF - mesangial full house including C1q and C3 - gig ,igm
very good prognosis
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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
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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
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5) membranous LN
good prognosis
subepithelila and intramembrnaous immune deposits
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6) advanced sclerosing LN
more than 90 parent of the glomeruli globally sclerosed
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
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
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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
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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
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
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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
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plasmaphoresisi is combined with corticosteroid or immunosuppressive agents
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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
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in severe reduction in GFR = hemodialysisi and renal transplant
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
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AA
spleen , liver , kidney
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ATTR
what are the most common systemic amyloidosis ?
primary - AL
and secondary - AA
what causes primary amyloidosis ?
multiple myeloma ,
waldenstrome macroglobulinemia
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
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
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
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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
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
