Abstract
Background
Malignant hypercalcemia is a common complication in cancer patients and can be predictive of poor prognosis and advanced malignancy. Cancer-related mechanisms of hypercalcemia depends either on ectopic hypersecretion of humoral factors (PTH, PTH-like molecules, Vit D) by the tumoral mass, or on osteolysis due to bone invasion. In consideration of the high renal and cardiac impact of severe hypercalcemia, its prompt recognition and treatment can be lifesaving. AKI is frequently associated with malignant hypercalcemia and recognizes a multifactorial pathogenesis (direct renal vasoconstriction, volume depletion, tubule-interstitial damage, etc.). Substitutive renal treatment can be necessary, but not always viable in patients with poor physical performance and is a difficult choice in cancer patients with advanced malignancies.
Case report
We present the case of a 46 years old woman with an infiltrating non special type (NST) carcinoma of the right breast (luminal B, ER 70%, PgR 60%, Ki67 35%, HER2 1+). Unfortunately, she quickly progressed after a neoadjuvant treatment with Epirubicin/Cyclophosfamide (4 cycles) followed by Paclitaxel (10 cycles). A first line hormonal treatment (Palbociclib, Letrozole and LHRH analogous) was then started, but a further rapid disease progression was observed. A new biopsy showed a muted and more aggressive cancer phenotype (high grade triple negative carcinoma with no PDL1 expression). Due to a rapid worsening of general conditions with cognitive impairment, the patient was admitted to the Oncology department. Blood test showed severe hypercalcemia (corrected calcium: 23.26 mg/dl) and severe hypokalemic metabolic alkalosis (blood pH 7.57; HCO-3 32 mmol/l; K+ 2.6 mmol/l) associated to AKI (creatinine doubled to 1.42 mg/dl; eGFR 45 ml/min/1,73 mq). Alkaline phosphatase and Vitamin D were normal and iPTH was < 2 pg/ml. ECG showed a significant QTc prolongation to 550 msec. Imaging exams revealed lung metastasis, lung carcinomatous lymphangitis and bilateral pleural effusion, while Bone Scan showed a low caption limited to right ribs. Oncologists and Intensive Care Physicians referred to our Nephrology and Dialysis Unit proposing Hemodialysis support. In consideration of the preserved diuresis, the advanced disease stage and the unstable hemodynamics, our advice was instead for a conservative medical approach. An i.v. infusion of 4000 ml NaCl 0.9% + KCl 60 mEq/24h; a continuous i.v. infusion of Furosemide 5mg/h were started and maintained for several days, leading to a progressive and full renal function recovery (creatinine decreased to 0.7 mg/dl) and metabolic alkalosis correction. However, corrected calcium remained largely over target, being 16.3 mg/dl. Sodium bicarbonate 80 mEq, Zoledronic acid 4 mg and Desametasone 4mg/day were administered and at day 16 even calcium was in normal range. We realized that this was a favourable window for acting on the underlaying cause of malignant hypercalcemia, that likely was the aberrant secretion of non-dosable PTH-like molecule(s). Thus, we suggested the Oncologist to start chemotherapy, and they were allowed to treat the patient with Carboplatin/Gemcitabine. The patient was successfully treated with stabilization of normocalcemia and is still alive.
Conclusion
Malignant hypercalcemia is a life-threatening complication in advanced malignancies. Our case report highlights the key role of the nephrologist in treating a complex and fragile oncologic patient, achieving the full correction of several severe renal disorders, hemodialysis avoidance and survival improvement.
Hypercalcemia-Induced Hypokalemic Metabolic Alkalosis in a Multiple Myeloma Patient: The Risk of Furosemide Use
