Onconephrology

coming soon

Immune checkpoint inhibitors

nice review in NDT, broader multiorgan guidelines

Incidence:

ICI-AKI affects 2%–5% of patients receiving immune checkpoint inhibitors.
Median time 12-16 weeks post initiation (regardless of AIN or GN).
20% of cases are late onset ( post 3 weeks since last dose), 11% more than a year after initiation, can be early.

Diagnosis

Kidney biopsy is the most accurate diagnostic method due to non-specific clinical or biochemical markers. sterile pyruia(45%?) and sub nephrotic range protein - 29% had none. IRL you can usually just start steroids if clinical diagnosis can be made. Distal RTA can happen, persists post steroids.
Potentially helpful: CRP, hx of prior/past irAE.

Histopathology

Acute tubulointerstitial nephritis (ATIN) is the most common finding in ICI-AKI cases - 90%.
Of the Rare GN :Glom lesions or vasculitis possible - typically ANCA neg(27%), podocytopathys (24%) and c3GN (11%), and 41% have concomitant AIN according to KI Reports. 35% complete and 38% patrial remission of proteinuria., 25% needed RRT.

Risk Factors

Concurrent use of ATIN-associated drugs (e.g., proton pump inhibitors) increases the risk; avoiding these drugs during ICI therapy is recommended.Prior extra renal IRAE in 50-100%. Dual ICI blokade (CTLA-4 & PD1/PDL1) = OR1.3

Renal Recovery

Early corticosteroid initiation (within 3 days) significantly improves recovery chances. 1mg/kg to nearest 60mg. can pulse 250 if severe AKI3. Taper - 10/week to 20. then 5/week to 0.(don’t forget PJP prophylaxis.)
Steroid-Sparing Options: MMF, infliximab, rituximab.
pembro has a half life of 27.3 days, so longer taper may help
Relapse rate of ~10% post Pred withdrawal. No difference in relapse ( AKI or death composite) rates between longer vs shorter steroid regimes. Recurrence occurs earlie, within the month typically. Median 20 days in short steroid course and 5 in long.

ICI Re-challenge

Re-challenge is generally well tolerated, with ~20% experiencing recurrent ICI-AKI. Severity of AKI doesnt predict relapse. prophylactic pred probably doesn’t help. 6-10 weeks to recurrence, shorter latency time. do 2 weekly labs. Vast majority of patients will respond to steroids during a recurrence. A rechallenge can lead to other, non renal events e.g. myocarditis, hepatitis etc.

Notes

27- 50% of patient can have reactivation of autoimmune disease
Reactivation of MN
Tx - almost universal rejection with the PD-1 inhibitor, anti CLTLA-4 may have less risk

Tends to cause nuclear enlargement - atypical appearance on bx