Abstract: SA-PO1000

Warburg Effect – Unusual Cause of Lactic Acidosis in Cancer Patients

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Khan, Nasir, Yale School of Medicine, New Haven, Connecticut, United States
  • Cantley, Lloyd G., Yale University School of Medicine, New Haven, Connecticut, United States
Background

Lactic acidosis is the most common cause of anion gap metabolic acidosis in critically ill patients and is associated with significant mortality. While most cases of severe lactic acidosis are from either decreased tissue perfusion or oxygenation (type-A lactic acidosis), other causes should be considered in the differential diagnosis, especially in cancer patients. We present a case of repeated episodes of lactic acidosis, first from tumor lysis syndrome (TLS) and then from anaerobic tumor metabolism in a critically ill patient with Non-Hodgkin Lymphoma (NHL).

Methods

A 75 year old woman with widespread Diffuse Large B-Cell Lymphoma diagnosed three years previously, complicated by severe TLS during induction chemotherapy requiring renal replacement therapy in the past, was admitted with severe metabolic acidemia from lactic acidosis (serum lactate peaked at 30 mmol/L) in the setting of another severe TLS episode triggered by ibrutinib chemotherapy. She was treated with rasburicase and intravenous fluids as well as temporary renal replacement therapy. Her clinical and laboratory parameters improved quickly with resolution of her lactic acidosis, and she was taken off of renal replacement therapy with return of her renal function to normal. One week later she developed persistent hypoglycemia (glucose values in the 50 mg/dl range despite D10W infusion) followed rapidly by severe lactic acidosis with arterial pH below 7 and serum lactate peak of 29 mmol/L. She remained hemodynamically stable with normal liver and renal function, and her labs did not support TLS: her LDH was only moderately elevated, with normal serum uric acid, calcium and phosphate. Based on her lab findings of persistent hypoglycemia as well as severe lactic acidosis, and CT scan showing progression of her lymphoma, we attributed her lactic acidosis to anaerobic metabolism by her rapidly growing tumor.

Conclusion

The Warburg Effect, described by Dr Otto Heinrich Warburg in 1924, is the metabolic shift of malignant cells to anaerobic glycolysis for ATP production, especially during phases of rapid tumor growth. The resultant inefficient utilization of glucose and generation of large amounts of lactate can lead to clinically significant hypoglycemia and severe lactic acidosis.