Dysnatremias, Mortality, and Kidney Failure in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Kidney Med. 2022 Oct 6;4(12):100554. doi: 10.1016/j.xkme.2022.100554. eCollection 2022 Dec.

Abstract

Rationale & objective: Dysnatremias have been associated with an increased risk of mortality in the chronic kidney disease (CKD) population. Our objective is to identify the prevalence of and risk factors associated with dysnatremias in a CKD population and assess the association of dysnatremias with kidney failure and mortality among patients with CKD enrolled in the Chronic Renal Insufficiency Cohort Study.

Study design: Analysis of prospective cohort study.

Setting & participants: Adult patients aged 21-74 years with CKD from the Chronic Renal Insufficiency Cohort study.

Predictors: Baseline and time-dependent hyponatremia and hypernatremia.

Outcomes: All-cause mortality and kidney failure.

Analytical approach: Baseline characteristics were compared using χ2 tests for categorical variables, analysis of variance for age, and Kruskal-Wallis tests for laboratory variables. Cox proportional hazards models and competing risk models were used to evaluate the association between baseline sodium level and overall mortality.

Results: Of a total of 5,444 patients with CKD, 486 (9%) had hyponatremia and 53 (1%) had hypernatremia. Altogether, 1,508 patients died and 1,206 reached kidney failure. In adjusted Cox models, time-dependent dysnatremias were strongly associated with mortality for both hyponatremia (HR, 1.38; 95% CI, 1.16-1.64) and hypernatremia (HR, 1.54; 95% CI, 1.04-2.29). Factors associated with hyponatremia included female sex, diabetes, and hypertension. Regardless of age, time-dependent hypernatremia was associated with an increased risk of kidney failure (HR, 1.64; 95% CI, 1.06-2.53). Baseline and time-dependent hyponatremia were associated with an increased risk of kidney failure in patients younger than 65 (baseline hyponatremia HR, 1.30; 95% CI, 1.03-1.64 and time-dependent hyponatremia HR, 1.36; 95% CI, 1.09-1.70) but not among patients aged >65 years.

Limitations: Inability to establish causality and lack of generalizability to hospitalized patients.

Conclusions: Dysnatremias are prevalent among ambulatory CKD patients and are associated with mortality and kidney failure. Time-dependent dysnatremias were significantly associated with mortality in patients with CKD. Time-dependent hypernatremia was associated with progression to kidney failure. Baseline and time-dependent hyponatremia were associated with an increased risk of progression to kidney failure in those younger than 65 years.

Keywords: CRIC; Chronic Renal Insufficiency Cohort; Chronic kidney disease; death; dysnatremias; hypernatremia; hyponatremia; kidney failure; mortality.