Nephritis (inflammation of the kidneys)

Grading Toxicity

Definition: A disorder characterized by the acute loss of renal function and is traditionally classified as pre-renal, renal, and post-renal.

Assess for other etiologies, such as infection
Eliminate potentially nephrotoxic medications
Ensure adequate hydration daily
Evaluate for progressive kidney/adrenal/pelvic metastases that may be contributing to kidney dysfunction
Early intervention to maintain or improve physical function and impact on QOL

Anticipate immunotherapy to continue
Perform detailed review of concomitant medications (prescribed and OTC), herbals, vitamins, anticipating possible discontinuation of nephrotoxic agents
Avoid/minimize addition of nephrotoxic agents, such as contrast media for radiology tests
Anticipate close monitoring of creatinine (i.e., weekly)
Educate patient/family on importance of adequate daily hydration and set individualized hydration goals
Review symptoms to watch for with patient and family and remember to assess at subsequent visits

Ipilimumab to be withheld for any Grade 2 event (until Grade 0/1) and discontinued for events persisting ≥6 weeks or inability to reduce steroid dose to 7.5 mg prednisone/day
Pembrolizumab or nivolumab to be withheld for Grade 2 events persisting ≥12 weeks or inability to reduce steroid dose to ≤10 mg prednisone or equivalent per day
Anticipate increase in frequency of creatinine monitoring (i.e., every 2–3 days until improvement)
Immunosuppressive medications to be initiated to treat immune-mediated nephritis
- Systemic corticosteroids (e.g., prednisone) 0.5–1 mg/kg/day until symptom improve to baseline followed by slow taper over at least 1 month
- Anticipate increased in corticosteroid dosing (i.e., treat as if Grade 3 nephritis) if creatinine does not improve within 48–72 hours
- Anticipate use of additional supportive care medications
Upon symptoms resolution to patient’s baseline, or Grade 1, begin to taper corticosteroid dose slowly over 1 month
Anticipatory guidance on proper administration
Anticipate the use of IV fluid to ensure adequate hydration
Anticipate that nephrology consultation may be initiated by provider
Assess patient & family understanding of recommendations and rationale
Identify barriers to adherence

Pembrolizumab or nivolumab to be withheld for first-occurrence Grade 3/4 event and discontinued if:
- Grade 3/4 event recurs
- Persists ≥12 weeks
- Requires >10 mg prednisone or equivalent per day for more than 12 weeks.
Ipilimumab to be discontinued for any Grade 3/4 event
Immunosuppressive medications to be initiated to treat immune-mediated nephritis
- Corticosteroids (e.g., prednisone 1–2 mg/kg/day, in divided doses) until symptoms improve to baseline and then slow taper over at least 1 month
- If symptoms do not improve within 48–72 hours, additional immunosuppressive medications will be considered
Anticipate nephrology consultation will be initiated by provider
Anticipate that renal biopsy will be considered
Hemodialysis may be considered
Anticipate possible hospital admission for Grade 4 elevations in creatinine or in patients with multiple comorbidities

Identify individuals with pre-existing renal dysfunction prior to initiating immunotherapy. Ensure baseline creatinine has been obtained
Check kidney function prior to each dose of immunotherapy
Monitor creatinine more frequently if levels appear to be rising, and for Grade 1 toxicity
Educate patients that new urinary symptoms should be reported immediately
Anticipate the steroid requirements to manage immune-mediated nephritis are high (up to 1–2 mg/kg/d) and patients will be on corticosteroid therapy for at least 1 month
Educate patients and family about the rationale for discontinuation of immunotherapy in patients who develop severe nephritis

Risk of acute onset
Risk of mortality if unrecognized or treatment is delayed
Risk of immune-mediated nephritis is greater in patients receiving combination immunotherapy regimens and PD-1 inhibitors
In addition to acute interstitial nephritis seen from PD-1 inhibitors, there are case reports of lupus-like nephritis and granulomatous acute interstitial nephritis