Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma

Abstract

BACKGROUND: Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC). METHODS: Cohort A comprised 120 consecutive patients with mRCC receiving subcutaneous, low-dose interleukin-2 and interferon-a. Hyponatremia was assessed in univariate and multivariate analyses. An independent cohort of another 120 patients with mRCC was used for validation (cohort B). RESULTS: In cohort A, estimated 5-year survival was 15% and median survival was 15.1 months. Serum sodium ranged between 126 and 144 mM. Twenty-four patients (20%) had serum sodium levels below normal range (o136 mM). In multivariate analysis, significant independent risk factors for short survival were low serum sodium (P ¼ 0.014), high neutrophils (P ¼ 0.018), lactate dehydrogenase 41.5 upper normal level (P ¼ 0.002), and number of metastatic sites ( þ 3) (P ¼ 0.003). In cohort B, serum sodium ranged between 128 and 146 mM. Seventeen patients (14%) had sodium levels below normal range. In multivariate analysis, serum sodium was validated as an independent prognostic factor (P ¼ 0.001). A significant association between lack of response and hyponatremia was observed in both cohorts (P ¼ 0.003 and P ¼ 0.02, respectively). CONCLUSION: Low serum sodium is a new, validated, independent prognostic, and predictive factor in patients with mRCC.

The Impact of Low Serum Sodium on Treatment Outcome of Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Cancer Database Consortium

“…In this same study, the authors observed that hyponatremic patients had lower survival in multivariate analysis. Furthermore, hyponatremia was associated with lack of response (by RECIST) to cytokines [9]. …”

“…Serum sodium has been analyzed in mRCC patients treated with cytokines [9], and hyponatremia was found to be associated with a worse outcome. Similar observations have been made in malignancies, such as advanced hepatocellular carcinoma [10], advanced gastric cancer [11], advanced small cell lung cancer [12], and localized RCC [13].…”

Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy

“…Furthermore, hyponatremia is reported to be associated with poor survival in several carcinomas, such as hepatocellular carcinoma, 11 gastric cancer 12 and small cell lung cancer 13 . In terms of RCC, hyponatremia has been associated with poor survival in localized RCC and mRCC treated with immunotherapy 14–16 . However, there are no reports on the relationship between hyponatremia and the prognosis of mRCC treated with molecular targeted therapy.…”

Hyponatremia and thrombocytopenia associated with sorafenib treatment for renal carcinoma: an alert of an adverse event

“…Another reason for the hyponatremia may be a renal dysfunction in the exchange mechanism of sodium in the tubules. Jeppesen et al [12] reported that low values of serum sodium were significantly prognostic and predictive factors in patients with metastatic renal cell carcinoma. Although we were not able to specify the mechanism of hyponatremia in our case, the toxic effects of sorafenib include decreased papillary solute content and maximal urinary osmolality, which are major factors for increasing vasopressin secretion.…”