RPA nephrology Flashcards
Kidney donor risk index; and what is the best predictor of future graft function
Donor age - best predictor of future graft function Hypertension Diabetes Last creatinine Cause of death BMI DCD status
risk of ESKD in live kidney donor
increased risk compared with healthy non donors but still 100 in 100,000 (small absolute risk)
what GN is likely to recur after transplant
FSGS
absolute contraindication to transplant
active malignancy
uncontrolled infection (E.g. bronchiectasis)
chronic infections
unacceptable anaesthetic risk
smoking, alcohol, psychological
relative risks: severe sun damage, severe calcular disease, non adherence
what alleles are assessed in renal transplant
A, B, DR
what is the universa plasma donor
AB
what is a more sensitive test than Complement dependent cytotoxicity crossmatch
Lminex > Flow cross match > CDC crossmatch
CDC crossmatch only involves adding complement, look for lysis. It is crude and subjective
acute cellular kidney rejection histology
cellular - tubulitis, intersitital infiltrate
vascular - endothelialitis, glomerulitis, haemorrhage
antibody-mediated - PMNs, C4D+, PTC
chronic kidney rejection histology
glomerulopathy, chronic interstitial inflammation
type of kidney rejection
vascular kidney rejection
treatment of acute kidney rejection
- IV methylpred (90% effective)
- lymphocyte depleting antibody (ATG)
- steroid resistant OR vascular rejection
- Adjust immunosuppressants
- PLEX, IVIG (for Ab-mediated rejection)
- Rescue (high dose tac/myco)
how does the activated T cell signal for more T cell proliferation (in the context of kidney transplant rejection)
release of IL-2
where does belatacept work
fusion protein composed of the Fc fragment of a human IgG1 immunoglobulin linked to the extracellular domain of CTLA-4
blocks the co-stimulation of CD40 to CD40L (between the antigen presenting cell and T cell)
basiliximab MOA
a chimeric (mouse/human) monoclonal antibody which acts as an immunosuppressant by blocking the interleukin-2 receptor
what immunosuppresion is better for malignancy or Interstitial fibrosis and tubular atrophy (chronic scarred kidney)
mTOR
main adverse effects of mTOR
proteinuria
wound healing problems
main adverse effect of mycophenolate
bone marrow suppression
GIT symptoms (myfortic may be a slightly better alternative for GI symptoms)
which transplant immunosuppressant is assoc with a tremor
mTOR
which transplant immunosuppressant is the worst for lipids
mTOR
what transplant immuno are ok/not ok for pregnancy
pred/tac ok
myco and mTOR contraindicated in pregnancy
primary cells involved in acute kidney rejection
CD4T cells - main target of medications as well
what does glomuerlar scerosis and tubular atrophy suggest
dead and chronic changes in glom
anatomical abnormality for nephrotic syndrome
podocyte
Nephrotic Ddx
minimal change
FSGS
Membranous
Lupus class V
diabetic nephropathy
Amyloid
causes of nephritic syndrome
anca vasculitis
anti GMB
post strep GN
lupus III/IV
TMA
causes of nephritic/nephrotic overlap
IgA
MPGN
Lupus
Myeloma/MGRS
GN histological classification
- Glomerular involvement
- Diffuse or focal; segmental or generalised
- Cell involvement
- Changes in non-cellular components of the glomerulus
GNs that have a mesangial predominance
IgA
Mesangioproliferative GN
ImG nephropathy
Clas II lupus nephritis
diabetic nephropathy
is the podocyte on the urine or blood side
urine
what GNs affect the podocytes/epilepthium
minimal change
membranous
FSGS
what GNs affect the endothelial cells
these proccesses are usually immune sytem +++
see slides
nephrotic ++++ syndrome in young person with acute onset (sometimes with preceeding allergic rhinitis)
minimal change disease
minimal change histology
light microscopy look normal
EM - flattened podocytes
minimal change disease treatment
steroid
(second line cyclophosphamide, cyclo/tac, ritux
if not steroid responsive - consider other Ddx ?FSGS
FSGS histology
focal & segmental glomerulosclerosis and hyalinosis
secondary causes of FSGS
secondary FSGS (obesity, HTN, previous damage to kidney)
FSGS management
steroids (less responsive than minimal change)
high dose (60mg) for 6 months
2nd line - cyclophosphamide; cyclo/tac
suPAR use
to predict FSGS recurrence in transplant
most common cause of nephrotic syndrome that’s secondary to a GN
primary membranous nephropathy
Primary membranous nephropathy histology
LM: membranous
IF: granular IgG +/- C3
EM: subepithelial deposits; silver stain has intra-membranous Ig deposits, spikes
what are the proteinuria cut offs for risk stratification for membranous GN
>8g/day high risk
4.5-8 med risk
pathophysiology of primary membranous GN
podocyte specific antigen that some people develop an antibody for
causal biomarker is auto Ab to PLA2R. Titre antibody corresponds to the disease activity.
immune deposits on epithelial side
anti-PLA2R in GN
membranous nephropathy
used for:
diagnosis
risk stratification
differentiating between primary vs secondary
do not need kidney biospy; and only in primary
aside from the anti PLA2R, what other antibody is ass with membranous nephropathy
TSHD7A Ab (might be assos with malignancies)
primary membranous nephropathy treatment
cyclophshamide + pred
anticoagulation (warfarin if serum albumin <20mg/day)
HOWEVER, NEJM 2019 compared rituximab with cyclosporine in treatment membraneous nephropathy.
Rituximab was superior (although non inferiority trial). Awaiting PBS
secondary membranous GN causes
drugs, hepatitis, malignancy
most common form of GN worldwide
IgA nephropathy
pathogenesis of IgA nephropathy
O-linked glycans on IgAs are abnormal
the body recognises the abnromality and forms an IgG to this abnormal hinge region.
The immune complex deposits on the mesangium in IgA nephropathy. (it deposits on the endothelium in Henloch Purpura)
Not all people with this O-linked glycans develop IgA
treatment of IgA nephropathy
ACE-I +/- steroids
rapidly progressing glomerunonephriti vs crescentic glomerulonephriti
RPGN id the clinical syndrome and crescentic GN is the pathology
what is the most common type of RPGN and what age group does that syndrome occur in
anca vasculitis
older people 60-70
ANCA vs GBM histology
LM: - eosinophils + neutrophils
IF: pauciimmune (no immune deposits)
GBM:
IF: linear IgG
pathology if the crescents
disruption of GBM with proliferation of inflammatory cells and fibrin around the glom and decreases filtering capacity of the glomerulus
Treatment of rapidly progressing GN
Pred
cyclophosphamide
+/- PLEX (use in pulmonary haemorrhage; anti GBM)
ANCA assoc vasculitis
small vessel vasculitis, crescentic pauci-immune
variants of ANCA vasculitis
GPA (Wegner’s) - granulomas - PR3
EGPA (Churg-strauss) - asthma + eosinophilia + granulomas (PR3/MPO)
MPA - no granulomas MPO
PR3 = cANCA (worse prognosis)
MPO = pANCA
ANCA assos vasculitis treatment
pred + cyclo or ritux
(ritux can only be given if there’s a contraindication to cyclo or they failed cyclo)
ANCA vasculitis maintainence
ritux or aza
what lupus nephritis to immunosuppress
III + IV (diffuse or focal proliferative disease)
Corticosteroids + cyclo/mycophenolate
refractory: steroids + MMF + CNI
EM: subepithelial hump diagnosis
post-infectious GN
membranoproliferative GN histology
(same as mesangiocapillary)
describes a histological pattern due to some cause of immune deposition that causes inflammation and the development of a second membrane.
“double coutor” (reduplicaiton of membrane)
cellular proliferation, interstitial damage
if there is positive staining for complement and immunoglobins, look for causes of complexment/immune deposition
secondary causes of membranoproliferative GN
hep C
SLE
monoclonal gammopathy
CLassificaiton of TMA
histological diagnosis
classification
primary: hereditary - normally abnormality in complement regulatory genes
Acquired TMA - antibodies to something
pregnancy + fragments on blood film
HUS
diagnosis of atypical HUS
observable TMA + end organ damage
ddx TTP
eculizumab MOA
blocks C5 to stop the conversion to C5b and membrane attack complex
kimmelstiel wilson nodules on histology
diabetic nephropathy
when is eGFR not accurate
AKI
Children
extremes of body weight
patients taking extra creatinine/creatining
caution with drug dosing
when is the eGFR most useful
monitoring in CKD
stages of CKD
what antihypertensives have additional albuminuria reduction properties
ACE I/ARB
Non-dihydropyride CCB
Spironolactone
daily sodium restriction
1500-2000mg/day
MOA of thiazides
inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter.
they are vasodilating - but they are more likely to cause diluting hypontraemia
Iron study cut off for iron def in kidney disease
TSAT <20%
Ferritin <100
most common reason for refractory anaemia to EPO in CKD
iron deficiency
(other: chronic inflammation, high PTH, B12/folate, hypothyroid, marrow disorder, malignancy)
protein intake recommendations in CKD
0.6-0.8g/kg/day
mild reduction in protein is good for kidneys
bicarb aim in CKD
>21
oral sodibic replacement
Ca+, Phos and PTH management in CKD
no evidence that any intervention has mortality benefit in RCTs
phosphate binders are only on PBS for dialysis
tolvaptan indications
autosomal dominant PCKD
improves eGFR by 1mL/year compared to placebo
PBS for eGFR 30-89
resistant hypertension already max dose 3 drugs including diuretic, next step
spironolactone
which RTA is assos with hyperkalaemia
Type 4 RTA
found in hypoaldosteronism which is common in DM
Dialysis dysequilibrium syndrome
due to the reduction of plasma solute level over a limited time. Plasma becomes hypotonic compared to brain cells and water shifts from the plasma into the brain tissue
what drug is assos w SSc renal crisis
corticosteroids
alport syndrome genetics
COL4A5
mostl likely X-linked
ATN urinary sodium
sodium wasting
(as opposed to hepatorenal - low sodium <10)
expect pCO2
0.7 [HCO3] + 20 (range: +/- 5)
(or similar to the last 2 digits of the pH)
