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
=============
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
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
=========
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
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
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
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
======
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
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
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
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
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
QHAT IS DIALYSIS RELATED AMYLOIDOSIS ?
TYPE OF SYSTEMIC AMYLOIDOSIS IN PATIENTS UNDERGOING LONG TERM HEMODIALYSIS - this protein b2 micro globulin is not effectively removed
in gross pathology how does in amyloid kidney look like ?
enlarged
pale
and waxy appearing on cut surfaces
