As early as the 18th century, physicians noticed that some
cancer patients went into remission after developing fevers from infections.
This led to the idea that the immune system, which protects from infection,
might also fight cancer. What is now known as “immunotherapy” is a treatment
that targets the immune system to recognize and eradicate cancer cells. Modern
immunotherapy has focused on “checkpoint” proteins, such as cytotoxic
T-lymphocyte-associated-protein-4 (CTLA-4) and programmed death-1 protein (PD-1),
which are receptors on the surface of immune cells that act like a brake, or
checkpoint, preventing the development of autoimmunity.1 The CTLA-4 receptor
has homology to the T-cell activator co-stimulatory molecule CD28 and prevents
T-cell activation by outcompeting CD28 for its ligand, the B7 receptor on
antigen presenting cells (APCs).2 Likewise, binding of PD-1 with programmed
death ligand 1 (PD-L1) — a protein expressed by immune, endothelial, and
neoplastic cells — results in T-cell anergy.3 In both cases, an unwanted
inflammatory response is suppressed.
Educational objectives:
Upon completion of this activity, participants should be
able to:
- Recognize the spectrum of renal toxicities associated with
immune checkpoint inhibitors
- Improve their diagnostic skill for identifying ATIN
associated with immune checkpoint inhibitors
- Improve their management of ATIN associated with immune
checkpoint inhibitors
Reading Resources:
- Wanchoo
R, Karam S, Uppal NN, et al. Adverse Renal Effects of Immune Checkpoint
Inhibitors: A Narrative Review. Am J
Nephrol. 2017;45(2):160-169.
- Cortazar
FB, Marrone KA, Troxell ML, et al. Clinicopathological features of acute kidney
injury associated with immune checkpoint inhibitors. Kidney Int. 2016;90(3):638-647.
- Nishimura
H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune
diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying
immunoreceptor. Immunity. 1999;11(2):141-151.
- Shirali
AC, Perazella MA, Gettinger S. Association of Acute Interstitial Nephritis With
Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients. Am J Kidney Dis. 2016;68(2):287-291.
- Spain L, Diem S, Larkin J. Management of toxicities of
immune checkpoint inhibitors. Cancer
Treat Rev. 2016;44:51-60.
Disclosures:
Drs. Ong and Rondon-Berrios has reported no relevant
relationships with any entities producing health care goods or services.
All presenters disclosure of relevant financial
relationships with any entity producing, marketing, re-selling, or distributing
health care goods or services, used on, or consumed by, patients is listed
above. No other planners, members of the planning committee, speakers,
presenters, authors, content reviewers and/or anyone else in a position to
control the content of this education activity have relevant financial
relationships to disclose.
Accreditation Statement:
The University of Pittsburgh School of Medicine is
accredited by the Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for physicians.
The University of Pittsburgh School of Medicine designates
this enduring material for a maximum of .5 AMA PRA Category 1
Credits™. Each physician should only claim credit commensurate with
the extent of their participation in the activity. Other health care
professionals are awarded (0.05) continuing education units (CEU) which are
equivalent to .5 contact hour.
For your credit transcript, please access our website 4
weeks post-completion at http://ccehs.upmc.com and follow the link to the
Credit Transcript page. If you do not provide the last 5 digits of your SSN on
the next page you will not be able to access a CME credit transcript. Providing
your SSN is voluntary.
Release Date: 8/22/2017 | Last Modified On: 8/22/2017 | Expires: 8/22/2018
