Nephritis (inflammation of the kidneys)

Grading Toxicity 

Acute Kidney Injury, Elevated Creatinine

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

  • Creatinine level >0.3 mg/dL; creatinine 1.5–2× ULN
  • Creatinine 2–3× ULN
  • Creatinine >3× ULN or > 4.0 mg/dL; hospitalization indicated
  • Life-threatening consequences; dialysis indicated


Overall Strategy:

  • 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

Nursing Implementation:

  • 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