Cancer-Associated Type B Lactic Acidosis

Fig 2 Sia et al AJKD

Fig 2 Sia et al, © National Kidney Foundation.

Lactic acidosis is an acid-base disturbance commonly seen in hospitalized patients. Most cases of lactic acidosis are due to hypoperfusion (type A lactic acidosis), which results in higher anaerobic lactate production and decreased lactate clearance due to hepatic or kidney dysfunction. Type B lactic acidosis is not associated with tissue hypoperfusion and can be seen in the setting of patients with various cancers, typically hematologic, as well as those taking certain medications such as metformin, linezolid, and propofol. Because type B lactic acidosis occurs less commonly, lack of familiarity with this diagnosis may delay appropriate management and contribute to poorer outcomes.

In the September issue of AJKD, Sia and colleagues discuss a patient with multiple myeloma refractory to two autologous stem cell transplants who presented with progressive dyspnea and was initially found to have severe metabolic acidosis with a markedly elevated serum lactate level. A diagnosis of type B lactic acidosis was made on the basis of hemodynamic stability and no other identifiable causes for type A lactic acidosis. The patient was found to have recurrent myeloma with 52% plasma cells in his bone marrow biopsy. In spite of the initiation of multiple chemotherapeutic agents and intravenous bicarbonate, his lactic acidosis worsened, necessitating renal replacement therapy. Unfortunately, this measure was not effective at reversing his clinical decline, and the patient died on hospital day 14.

This teaching case highlights the importance of recognizing type B lactic acidosis and implementing prompt treatment. Sia and colleagues present an informative discussion on the pathophysiology of type B lactic acidosis in patients with malignancy, examining mechanisms such as altered lactate metabolism due to liver and kidney dysfunction, lactate production by tumor cells, preferential glycolytic metabolism in tumor cells, tumor necrosis factor α, thiamine deficiency, and chemotherapy. Interestingly, the kidney plays a rather important role in the metabolism of lactate. Lactate is freely filtered by the glomerulus and mostly reabsorbed by the proximal tubule; however, in states of high serum lactate levels, urinary excretion of lactate increases. As stated by the authors, renal lactate clearance nearly triples at a pH of 6.75 compared to at a pH of 7.45. Increased lactate production by tumor cells may also contribute to the problem, a phenomenon which is partly explained by tumor cell overproduction of hexokinase and insulin-like growth factors that promote glycolysis even under aerobic conditions (Warburg effect). The recognition of thiamine deficiency is particularly relevant to the care of the patient in this case, as he was found to be thiamine deficient by lab testing, and thiamine supplementation was instituted.

The cornerstone of therapy for cancer-associated type B lactic acidosis is treatment of the underlying malignancy. The authors recommend exercising caution with the use of sodium bicarbonate to treat type B lactic acidosis, citing two examples in the literature in which infusing sodium bicarbonate actually increased lactate production. However, in patients with severe acidosis, the clinician may be obligated to use bicarbonate to prevent consequent adverse hemodynamic and cardiac effects. While renal replacement therapies may help to correct the acidosis, they are less effective at correcting high lactate levels, which generally respond only to effective treatment of the malignancy with chemotherapy.

As the field of onco-nephrology continues to grow, it will be increasingly important for nephrologists to be familiar with the associations between malignancy and acid-base disturbances such as type B lactic acidosis so that we can promptly institute proper therapy.

Albert Q. Lam, MD
Brigham and Women’s Hospital
Harvard Medical School

eAJKD Contributor

To view the article abstract or full-text (subscription required), please visit AJKD.org.

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