Table 6.

Management of Renal irAEs in Patients Treated With ICPis

6.0 Renal Toxicities
Nephritis and renal dysfunction: diagnosis and monitoring  For any suspected immune-mediated adverse reactions, exclude other causes  Monitor patients for elevated serum creatinine prior to every dose  Routine urinalysis is not necessary, other than to rule out UTIs, etc; nephrology may consider further  If no potential alternative cause of AKI identified, then one should forego biopsy and proceed directly with immunosuppressive therapy  Swift treatment of autoimmune component important
6.1 Nephritis
Definition: Inflammation of the kidney affecting the structure
Grading	Management
G1: Creatinine level increase of > 0.3 mg/dL; creatinine 1.5–2.0 × over baseline	Consider temporarily holding ICPi, pending consideration of potential alternative etiologies (recent IV contrast, medications, fluid status) and baseline renal function.  A change that is still < 1.5 ULN could be meaningful
G2: Creatinine 2–3 × above baseline	Hold ICPi temporarily Consult nephrology  Evaluate for other causes (recent IV contrast, medications, fluid status, etc); if other etiologies ruled out, administer 0.5–1 mg/kg/d prednisone equivalents  If worsening or no improvement: 1 to 2 mg/kg/d prednisone equivalents and permanently discontinue treatment  If improved to G1 or less, taper corticosteroids over 4–6 weeks  If no recurrence of chronic renal insufficiency, discuss resumption of ICPI with patient after taking into account the risks and benefits.
G3: Creatinine > 3 × baseline or > 4.0 mg/dL; hospitalization indicated	Permanently discontinue ICPi
G4: Life-threatening consequences; dialysis indicated	Consult nephrology  Evaluate for other causes (recent IV contrast, medications, fluid status, etc)  Administercorticosteroids (initial dose of 1–2 mg/kg/d prednisone or equivalent)
Additional considerations  Monitor creatinine weekly  Reflex kidney biopsy should be discouraged until corticosteroid treatment has been attempted
6.2 Symptomatic nephritis: follow-up
Grading	Management
G1	If improved to baseline, resume routine creatinine monitoring
G2	If improved to G1, taper corticosteroids over at least 3 weeks before resuming treatment with routine creatinine monitoring If elevations persist > 7 days or worsen and no other cause found, treat as G3
G3	If improved to G1, taper corticosteroids over at least 4 weeks If elevations persist > 3–5 days orworsen, consider additional immunosuppression (eg, mycophenolate)
G4	If improved to G1, taper corticosteroids over at least 4 weeks Ifelevations persist > 2–3 days orworsen, consideradditional immunosuppression (eg, mycophenolate)
All recommendations are expert consensus based, with benefits outweighing harms, and strength of recommendations are moderate.

Abbreviations: AKI, acute kidney injury; G, grade; ICPi, immune checkpoint inhibitor; irAE, immune-related adverse event; IV, intravenous; ULN, upper limit of normal; UTI, urinary tract infection.