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Case history

image A 76-year-old man presented with a left submandibular mass. His medical history included type 2 diabetes mellitus and pulmonary embolism.

Ultrasound of the left neck and fine needle aspiration cytology demonstrated an enlarged lymph node containing malignant melanoma. Total skin examination was unremarkable, as was the staging CT of the body and MRI of the head and neck. He underwent excision of the lymph node together with radical left neck dissection, which confirmed no further spread of the cancer. The melanoma was BRAF and NRAS wild-type.

As he was at high risk of cancer relapse the specialist melanoma multidisciplinary team recommended surveillance 6 monthly CT body imaging alongside MRI head and neck.

While on surveillance, he developed multiple small-volume lung metastases. He was asymptomatic. He received combination ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) immunotherapy 3 weekly and underwent repeat imaging after cycle 4, which demonstrated a partial response to treatment.

He continued with immunotherapy with maintenance nivolumab 3 mg/kg every 2 weeks. After two cycles his renal function deteriorated from baseline creatinine 94 μmol/l to 175 μmol/l. He was well and had no radiological evidence of disease progression, dehydration or infection. He had not been started on new medication. Maintenance nivolumab was stopped.

He was commenced on 70 mg oral prednisolone (1 mg/kg per day) but his renal function deteriorated further with a creatinine rise to 212 μmol/l. As his renal function was refractory to oral corticosteroids, he was commenced on oral mycophenolate mofetil 1 g twice daily, together with the pre-existing dose of oral prednisolone.

His creatinine level improved steadily over a 4 week period to 188 μmol/l and plateaued at 148–135 μmol/l. The corticosteroid dose was weaned by 10 mg per week and he continues with 10 mg oral prednisolone and mycophenolate mofetil while awaiting interval imaging.

What is the initial work-up for acute kidney injury (AKI)?

What is the optimal management of immunotherapy-induced AKI?

What factors are important when considering the need for renal replacement therapy?

What is the evidence for the effect of combination immunosuppression on metastatic melanoma?

What is the initial work-up for AKI?

Acute management of AKI includes evaluation of fluid status, acid-base balance and imaging to diagnose urinary obstruction or disease progression. Life-threatening uraemia and hyperkalaemia should be excluded. Urine dipstick should be performed along with urine microscopy for casts, crystals and culture. Vasculitic and autoimmune profile should be requested to exclude an intrinsic renal cause.

What is the optimal management of immunotherapy-induced AKI?

Immunotherapy rarely causes AKI. The incidence of AKI is 4.9% with combination anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy, and 0.4% and 1.4% with anti-CTLA-4 and anti-PD-1 single agents, respectively.13

Clinical presentation is varied. In this case, the patient was asymptomatic with deteriorating renal function noted on a standard ...

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