The Effects of Pre-Existing Hyponatremia and Subsequent-Developing Acute Kidney Injury on In-Hospital Mortality: A Retrospective Cohort Study

Abstract

Background and objectives: Both hyponatremia and acute kidney injury (AKI) are common and harmful in hospitalized patients. However, their combined effects on patient mortality have been little studied.

Methods: We retrospectively enrolled 19191 adult patients who were admitted for 1 year. Pre-existing hyponatremia was defined as a serum sodium level < 135 mmol/L on the first measurement of their admission. AKI was defined as a rise in serum creatinine by ≥ 26.5 μmol/L or ≥ 1.5 times of the baseline value of creatinine during the hospital stay.

Results: The prevalence of pre-existing hyponatremia was 8.2%. During a median 6.0 days of hospital stay, the incidence rates of AKI and in-hospital patient mortality were 5.1% and 0.9%, respectively. Pre-existing hyponatremia independently predicted AKI development and in-hospital mortality (adjusted hazard ratio [HR] 1.300, P = 0.004; HR 2.481, P = 0.002, respectively). Pre-existing hyponatremia and subsequent development of AKI increased in-hospital mortality by 85 times, compared to the patients with normonatremia and no AKI. In subgroup analysis, the AKI group showed higher rates of de novo hypernatremia than the non-AKI group during the admission. De novo hypernatremia, which might be associated with over-correction of hyponatremia, increased in-hospital mortality (HR 3.297, P <0.001), and patients with AKI showed significantly higher rates of de novo hypernatremia than patients without AKI (16.2% vs. 1.4%, P < 0.001, respectively).

Conclusion: Pre-existing hyponatremia may be associated with the development of AKI in hospitalized patients, and both hyponatremia and hospital-acquired AKI could have a detrimental effect on short term patient mortality, which might be related to the inappropriate correction of hyponatremia in AKI patients.

Fig 1. Algorithm for eligible patient selection.

Hypernatremia is defined as sodium 145 mmol/L or higher. ESRD, end stage renal disease; AKI, acute kidney injury.

Fig 2. Clinical outcomes according to sodium group.

* means P < 0.001 compared to normonatremia group. Error bar indicates standard error. AKI, acute kidney injury; ESRD, end stage renal disease.

Fig 3. Cumulative survival rate according to sodium (Na) and acute kidney injury (AKI) groups.

A, B and C show survival curves of sodium, AKI and combined sodium and AKI groups for the in-hospital mortality, respectively. * and † indicate P < 0.001 when compared to normonatremic patients without AKI and hyponatremic patients without AKI groups, respectively, and ‡ indicates P < 0.05 when compared to normonatremic with AKI group using log-rank test.

Fig 4. Proportion of de novo hypernatremia depending on the status of combined sodium (Na) and acute kidney injury (AKI) group.

Error bar indicates standard error. * indicates P < 0.05 by chi-square test when compared to the normoNa & non-AKI group.