Thread by @nephondemand

•PLEX in ANCA vasculitis @ #kidneywk• 1/n
"pheresis" = remove forcibly
1914: PLEX used to treat toxemia
1970s: PLEX reported to be used to treat Goodpasture's syndrome

•PLEX in ANCA vasculitis @ #kidneywk• 2/n
PLEX comes in 2 modalities: filtration (blood pumped through a filter) and centrifugation (blood separated into components and then the selected component is aspirated)

•PLEX in ANCA vasculitis @ #kidneywk• 3/n
Filtration: certain size molecules excluded, requires central vein access, requires heparin (systemic anticoagulation)
Centrifugation: no size restrictions, lower blood flow and can use a peripheral vein access, can use citrate

•PLEX in ANCA vasculitis @ #kidneywk• 4/n
For IgG, 1 plasma volume removes 63% and 1.5 plasma volumes removes about 78%; dosing is usually somewhere between 1.0 and 1.5 plasma volumes per treatment

•PLEX in ANCA vasculitis @ #kidneywk• 5/n
IgM is easily removed with limited rebound (so often only one PLEX session is needed); not so for IgG, where a rebound phenomenon occurs (and this will require more than 1 PLEX session)

•PLEX in ANCA vasculitis @ #kidneywk• 6/n
PLEX in ANCA: we are removing ANCA, but it is not clear if ANCA is pathogenetic (though JCI 2002 in mice showed that ANCA is pathogenetic);

•PLEX in ANCA vasculitis @ #kidneywk• 7/n
PLEX can be used as an anti-thrombotic agent; for example, aPTT can change based on what you replace after PLEX: human albumin replacement causes the aPTT to rise, but not so if replacement fluid is plasma

•PLEX in ANCA vasculitis @ #kidneywk• 8/n
PLEX is indicated for rapidly progressive GN and/or diffuse alveolar hemorrhage;
turns out that these 2 clinical entities that are most associated with a pathologic ANCA

•PLEX in ANCA vasculitis @ #kidneywk• 9/n
PLEX has no effect on mortality/remission in DAH, but this was not a randomized trial and it is thought that the sicker patients are the ones who receive PLEX

•PLEX in ANCA vasculitis @ #kidneywk• 10/n
MEPEX (methylprednisolone v PLEX; @JASN_News 2007): 1* endpoint was renal recovery, which did improve with PLEX but there was no improvement in mortality over time

•PLEX in ANCA vasculitis @ #kidneywk• 11/n
PEXIVAS: the 1st global ANCA vasculitis trial; 2 hypothesis: 1) does PLEX increase time of death or ESRD and 2) does lower steroid dose increase ESRD or death

•PLEX in ANCA vasculitis @ #kidneywk• 12/n
Inclusion: 704 patients w/eGFR < 50 and/or lung hemorrhage, GPA or MPA, ANCA positive and anti-GBM negative;
7 exchanges administered over 14 days (either filtration or centrifugation); 60 mL/kg exchange volumes w/albumin replacement

•PLEX in ANCA vasculitis @ #kidneywk• 13/n
MDs were allowed to use IV CYC, PO CYC, or RTX at their discretion
HR 0.89 for the primary composite endpoint (not significant)
But there was an early favor of PLEX which then disappears over time

•PLEX in ANCA vasculitis @ #kidneywk• 14/n
1* composite endpoint in PEXIVAS was not-significant in all sub-group analyses
No significant differences in any secondary outcome (components of the 1* outcome)

•PLEX in ANCA vasculitis @ #kidneywk• 15/n
Now, it turns out that in patients with severe alveolar hemorrhage, PLEX resulted in a lower mortality (6/31patients versus 11/30 in the no-PLEX group)..This is an exploratory result (no stats to report)

•PLEX in ANCA vasculitis @ #kidneywk• FIN
Future work derived from PEXIVAS:
1) detailed renal outcomes including identifying subgroups that may benefit
2) centrifugation v filtration PLEX
3) dosing of PLEX as measured by ANCA titer changes