Hyponatremia and the risk of sepsis in the setting of chronic kidney disease not on dialysis.

Background: Hyponatremia occurring in the presence of chronic kidney disease (CKD) is associated with increased mortality. Hyponatremia is also associated with sepsis in hypertensive patients without CKD taking thiazide diuretics. It is not known whether hyponatremia in CKD is associated with sepsis.

Methods: This retrospective cohort study addressed the hypothesis that hyponatremia in the setting of CKD is associated with sepsis. This study utilized the TriNetX federated health research network that contains medical records of approximately 93 million patients. Inclusion criteria: 40-90 years old, CKD stage 3, 4 or 5 occurring between 1 January 2010 and 31 December 2021. Hyponatremia cohort serum sodium is defined as ≤135 mmol/L. Comparison cohort has a serum sodium 136-144 mmol/L. Primary outcome is diagnosis with sepsis. Secondary outcomes are diagnosis with pneumonia, urinary tract infection, bacteremia, coronavirus disease 2019 (COVID-19), influenza, herpes zoster, meningitis, osteomyelitis and cellulitis.

Results: Patients in the hyponatremia cohort had a higher hazard of sepsis than comparison cohort [hazard ratio 1.683 (95% confidence interval 1.526, 1.857), P < .001]. Patients in the hyponatremia cohort also had a higher hazard of bacteremia, pneumonia, COVID-19, osteomyelitis, urinary tract infection and cellulitis.

Discussion: Chronic hyponatremia in CKD is associated with higher hazard of sepsis and a variety of infectious illnesses. These findings may help inform future efforts to prospectively identify patients at risk for sepsis and possibly allow earlier intervention. Further study is needed to determine whether the risk of sepsis in the hyponatremia population is due to hyponatremia or due to unmeasured covariates.