Examining Dysnatremias in Patients With Chronic Kidney Disease

Dysnatremias, an imbalance in serum sodium levels, can increase the risk of death and kidney failure in patients with chronic kidney disease (CKD). Until recently, there was limited information about the incidence and risk factors associated with sodium levels in an outpatient CKD population.

“It’s well recognized that hyponatremia or hypernatremia can contribute to adverse outcomes in the general population, but there is limited long term data regarding an ambulatory CKD patient,” explains nephrologist Jonathan Taliercio, DO, senior investigator of a new study published in Kidney Medicine.

He continues, “If you tell a patient with CKD they have low sodium, they may understandably ask: ‘How common is this? Or what does this mean for me?”

He says, “The first thing that patients ask is if they should be eating more dietary salt to correct their low sodium,” adding, “this is a misconception and, in the majority of cases, patients should be drinking less water since sodium levels are actually a reflection of fluid balance.”

In search of clinically meaningful answers, the research team set out to analyze baseline characteristics of hyponatremia and hypernatremia and time-dependent factors associated with kidney failure and mortality. They used the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective, multicenter study established in 2003 to investigate CKD progression, cardiovascular disease, and mortality.

While previous studies have explored the prevalence and associations in dysnatremias, theirs is the first to use data from the CRIC Study, which includes clinical data collected from patients’ routine ambulatory lab work. “In other words,” says Dr. Taliercio, “Our analysis only includes lab data from when people are feeling fine, as opposed to other trials that used sporadic serum sodium labs values that may have been obtained at times when the patient was ill or in the emergency department for a different reason. Lab work obtained during illness is not a good reflection of a true outpatient CKD population.”

Common in patients with CKD, associated with mortality and kidney failure

Importantly, its longitudinal nature enabled investigators to examine associations with serum sodium changes in overtime and how it was associated with kidney failure and mortality. The analysis of 5,444 CKD patients revealed the following baseline characteristics:

• 5 + 10.7 years old
• 3% males
• 5% hypertensive
• 8% CKD Stage 3a

In the study cohort, 486 (9%) had hyponatremia (Na < 136 mmol/L) and 53 (1%) had hypernatremia (Na < 145 mmol/L). In Cox models, time-dependent dysnatremias were both 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. In addition, baseline and time-dependent hyponatremia were associated with an increased risk of kidney failure in patients younger than 65 but not among patients aged > 65 years. Time-dependent hypernatremia, however, was associated with an increased risk of kidney failure at any age.

But are they driving the outcomes?

Dr. Taliercio says despite their best efforts to control for other diseases in the study, dysnatremias may be another marker of illness, not independently linked to kidney failure and death. “I suspect the abnormal sodium values are a harbinger or surrogate for additional medical conditions that we were not able to control for in the study, and that is what is really driving the outcomes.”

Regardless, the findings affirm previous findings, and offer new insight about the associations of dysnatremias with progression to kidney failure and death. The study emphasizes the importance of recognizing the potential risk of dysnatremias in patients with CKD.

Dr. Taliercio cautions, “except in cases of extreme symptomatic dysnatremias, there is typically no need to be alarmed or correct it immediately. Rather, it’s an opportunity to pay close attention to other comorbidities—ones we may not have considered—to better understand the underlying driver or pathology.”