The development of hyponatremia in patients with cirrhosis or heart failure carries a poor prognosis. Does it carry the same implications in patients with cancer? Doshi et al, in the February issue of the American Journal of Kidney Diseases, looked at this electrolyte disorder in cancer patients and its impact on clinical outcomes. Dr. Abdullah Salahudeen (AS), the senior author of the paper discussed this topic with eAJKD blog editor Dr. Kenar Jhaveri (eAJKD).
eAJKD: What was the reason you performed this study?
AS: After coming to The University of Texas M.D. Anderson Cancer Center, an institution dedicated to cancer treatment and research, it became clear from my clinical practice that hyponatremia in hospitalized cancer patients is probably far more common than in noncancer patients. At this time, a colleague of mine was prospectively collecting data to assess the extent of diabetes and diabetic control. This data was well suited to analyze the incidence of hyponatremia in cancer patients, and its impact on clinical outcomes. We wanted to evaluate whether the clinical outcome of these cancer patients was affected significantly by hyponatremia.
eAJKD: Hyponatremia in noncancer patients is associated with high morbidity and mortality. Did you expect it to be different in cancer patients?
AS: A number of studies have appeared in noncancer patients over decades indicating the incidence of hyponatremia. Lately, articles accessing the influence of hyponatremia on these patients’ morbidity and mortality have also appeared. There is a strong association between hyponatremia and a poor clinical outcome in hospitalized patients with noncancer conditions. We find a similar strong association in hospitalized cancer patients between hyponatremia and clinical outcomes, whether it is prolonged hospitalization, in hospital mortality, or subsequent mortality.
eAJKD: 47% of first time hospital admissions at your cancer hospital had hyponatremia. That seems like a very high number. Did that surprise you? Also, given the tertiary referral nature for MD Anderson as a cancer center, could these patients be sicker?
AS: Yes. Hyponatremia turned out to be at a much higher frequency in our hospitalized cancer patients compared to published-frequencies in noncancer patients, 35% in noncancer vs 47% in our patients, and this came as a surprise. Nearly one in two patients at our cancer center seem to have some degree of hyponatremia, although the majority had milder form. We did not have data to assess the relationship between severity of illness and hyponatremia, and similar to patients with liver or heart failure, hyponatremia in our population seems to be associated with extent of disease.
eAJKD: Pain in cancer patients can be a significant cause of hyponatremia. Any thoughts on whether this is a major contributing factor? In cancer patients, it might be hard to control for pain control as a potential cause. Any thoughts?
AS: It is well described that pain is a strong stimulus of ADH secretion. In addition, most of the morphine-derivatives can potentiate the effect of ADH at tubular level and enhance the ant diuretic effect causing hyponatremia. Therefore, both pain and pain medications are associated with hyponatremia, and pain is indeed a common symptom in patients with advanced cancer. Most of our patients have multiple issues potentially contributing to hyponatremia, and it is somewhat difficult to distinguish one cause from another. Although not formally analyzed in this study, hypovolemia seems to be an important mechanism for hyponatremia in large number of hospitalized cancer patients. Overall, we believe hypovolemia, drug-induced hyponatremia, and SIADH are the main causes of hyponatremia in our patient population.
eAJKD: V2 receptor antagonists may play a role in treating hyponatremia. Do you think they will benefit cancer patients?
AS: We believe that V2-receptor antagonist could be very useful in treating hyponatremia in a certain subset of patients who are not hypovolemic but unable to tolerate salt tablets. Although V2-receptor antagonists have been shown to be effective in promptly correcting hyponatremia in clinical studies, these studies have largely excluded cancer patients. Now that the high incidence of hyponatremia is noted in hospitalized cancer patients, the use of V2-receptor antagonist in this population has to be considered. Indeed, a randomized; double blinded controlled trial is underway to assess the efficacy of the V2-receptor antagonist tolvaptan in treating hyponatremia in cancer patients. Our clinical experience so far with these agents is that they work effectively in correcting hyponatremia in cancer patients. No major drug interactions or adverse effects have not been noted, however, the high price of these agents remains a major concern and limitation.