Acute kidney injury was detected three days after the second course of cisplatin. Plasma creatinine level increased to 257 µmol/L. The patient was hyperkalemic with a plasma potassium of 6.6 mmol/L and blood urea nitrogen of 15.9 mmol/L. In addition to hyperkalemia, the patient had elevated urea at 29.7 mmol/L, hyperphosphatemia at 2.5 mmol/L, and mild metabolic acidosis. Mild oliguria was treated sufficiently with IV furosemide. Hypertension reached a maximum systolic value of 151. Ultrasound of the kidneys was normal. No specific urine tests were conducted in connection with the diagnosis of the patient’s acute kidney injury (AKI), and no kidney biopsy was performed either.

Hemodialysis to clear any potentially nephrotoxic drugs from the blood was discussed but deemed without value since cisplatin is more than 90% protein-bound in the blood and therefore not dialyzable. Additionally, from a pharmacokinetic perspective, it was considered that the toxic “hit” from cisplatin had already occurred. Relevant symptomatic treatment was given for the biochemical imbalances caused by the acute kidney insufficiency. Various nephroprotective treatments were discussed, including erythropoietin (EPO) and N-acetyl cysteine (NAC), but studies at that time did not show effectiveness for these treatments.

During the week following the initial kidney injury, plasma creatinine increased to a maximum of 431 µmol/L (Fig. 1), and a slow recovery of renal function followed, as creatinine stabilized around 100 µmol/L. Prior to the following HDM course, creatinine was 94 µmol/L, and the HDM course was given at full dose, resulting in a slight increase in creatinine that again stabilized after the course of HDM. Due to prolonged methotrexate excretion and previous kidney injury, the last pre-surgery HDM course was omitted.

In treatment week 11, as per protocol, radical limb-sparing surgery was performed, and plasma creatinine decreased further. However, we believe this decrease was more likely due to a substantial change in muscle mass following surgery than further renal recovery. This assumption was supported by a DTPA scan three months’ post-surgery showing an stGFR of 41 ml/min/1.73m2 while plasma creatinine level was 72 µmol/L and eGFR > 90 ml/min/1.73m2.

The patient completed treatment according to the Euramos-1 protocol. However, as we found 95% necrosis in the removed tumor, we opted to discard the remaining HDM courses in the last two MAP series. The patient had positive blood cultures for coagulase-negative staphylococci three months post-surgery and was treated with vancomycin (40 mg/kg/d) for 11 days. She tolerated this without any increase in creatinine. No further Amphotericin B was given throughout the treatment (Fig. 1).

Depicting creatinine levels over time in relation to treatment. Cis/Dox: Cisplatin/Doxorubicin. HDM: High Dose Methotrexate

A DTPA scan performed ten months after the initial insult revealed an stGFR of 50 ml/min/1.73m2, with a corresponding creatinine of 89 µmol/L. Now, four years after the completion of treatment, the patient shows no signs of recurrent disease and has near-normal, stable kidney function, as determined by a creatinine level of 89 µmol/L.