EXCESS SODIUM CAN EXACERBATE UNDERLYING CONDITIONS IN PATIENTS AT RISK FOR HYPERKALEMIA

Patients with CKD and heart failure who are at risk for hyperkalemia are vulnerable to even a small increase in sodium load from medications

Excess dietary sodium is a major public health problem worldwide. While considerable efforts are being made to reduce dietary sodium intake in general—especially in vulnerable patient populations—certain formulations of medicines such as effervescent, dispersible, and soluble formulations contain large amounts of sodium. In some cases, one drug alone may exceed the maximum daily allowance of sodium recommended for even healthy individuals. Added to a typical Western diet, use of such drugs could result in high sodium intake, putting patients at risk for complications.1

According to a population-based nested case-control study that used the UK Clinical Practice Research Datalink (CPRD) database, there was a significant trend between patients prescribed sodium-containing formulations and the risk of cardiovascular outcomes as well as all cause mortality (P<0.01) based on patients' cumulative sodium exposure. The CPRD database contains medical records from over 500 primary care practices, with 4.4 million active patients. This study population comprised all patients aged 18 or over who received at least 2 prescriptions of sodium-containing formulations or matched standard formulations of the same drug from January 1987 to December 2010.1

Compared to patients prescribed non–sodium-containing drugs (controls), patients prescribed sodium-containing formulations were at increased risk of1:

  • Incident hypertension
  • Incident stroke
  • All-cause mortality

The authors did not observe an increase in the incidence of heart failure, despite an increase in hypertension. Patients experiencing incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death had a greater exposure to sodium-containing drugs than controls.1

This study found that the median sodium consumption from sodium-containing drugs alone was higher than the current recommended total dietary intake per day. Patients must rely on healthcare professionals to help determine safe and appropriate therapies. The authors recommend caution if prescribing sodium-containing formulations of drugs.1

Excess sodium is associated with adverse cardiovascular outcomes and more

Most US adults consume sodium far in excess of physiological need and guideline recommendations. New animal and human studies continue to provide important evidence that excess sodium promotes structural and functional impairment of the heart, great vessels, and kidneys. These pathophysiological changes can progress over time to severe disease manifested by acute clinical events, costly hospitalizations for cardiac failure, end-stage renal disease, and death.2

Although many of the harmful effects of high sodium intake are related to increased blood pressure, excess sodium intake also produces adverse effects through blood pressure–independent mechanisms.2

Independent of increased blood pressure, high sodium intake can result in2:

  • Massive albumin excretion
  • Oxidative stress
  • Severe renal arteriolar damage
  • Interstitial fibrosis
  • Increased glomerular hydrostatic pressure
  • Glomerular hyalinization
  • Fibrosis
  • End-stage renal disease

Moreover, excess sodium intake can decrease the beneficial effects of many antihypertensive drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi), whereas reducing sodium intake enhances these effects.2

Additionally, excess salt intake or high dietary sodium has been associated with edema, congestive heart failure, and high blood pressure.3

Sodium restriction is commonly recommended in patients at increased risk for hyperkalemia

Several factors contribute to the chronic risk for hyperkalemia in patients with CKD and heart failure.4 Control of sodium and volume status is crucial in the management of diabetic and nondiabetic CKD patients for control of blood pressure and proteinuria, and eventually prevention of progressive renal function loss and its complications.5

In CKD, blood pressure is usually sodium sensitive. Proteinuria reduction by sodium restriction typically remains significant after an adjustment for the fall in blood pressure, suggesting an independent renoprotective effect of sodium restriction, both as a single measure and in combination with blockade of the renin-angiotensin-aldosterone system (RAAS). A blood pressure–independent effect of dietary sodium on the kidney is substantiated by data in healthy volunteers, in which a lower sodium diet is associated with lower urinary albumin excretion without a detectable effect on blood pressure.5

For patients with heart failure, dietary sodium restriction is commonly recommended to prevent6:

  • Fluid retention
  • Exacerbation of symptoms
  • Hospitalization for acute decompensated heart failure

Clinical data mine: Explore professional guidelines about sodium in patients at risk for hyperkalemia

(Click on any link below to expand and view clinical guidelines.)

PROFESSIONAL GUIDELINES RECOMMEND REDUCED SODIUM

Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend reduced sodium for patients with CKD

Salt intake

The KDIGO guidelines recommend lowering salt intake to <90 mmol (<2 g) per day of sodium (corresponding to 5 g of sodium chloride) in adults, unless contraindicated.7

RATIONALE
In subjects with CKD, impaired excretion of sodium is often present. High sodium intake increases blood pressure and proteinuria, induces glomerular hyperfiltration, and blunts the response to RAAS blockade.7

  • Lowering salt intake not only reduces blood pressure, but also lowers albuminuria. The importance of salt intake in the general management of CKD patients cannot be overemphasized7
  • There are some conditions in which salt restriction may be harmful, and hence the qualifier "unless contraindicated." These conditions include salt-losing nephropathies and those prone to hypotension and volume contraction who do not have heart failure7

The American Diabetes Association recommends increased sodium reduction for patients with diabetes and hypertension

Sodium

  • The recommendation for the general population to reduce sodium to less than 2300 mg/day is also appropriate for people with diabetes8
  • For individuals with both diabetes and hypertension, further reduction in sodium intake should be individualized8

RATIONALE
A review found that decreasing sodium intake reduces blood pressure in those with diabetes. Incrementally lowering sodium intake (ie, to 1500 mg/day) has shown beneficial effects on blood pressure.8

  • The American Heart Association recommends 1500 mg/day for African Americans, people diagnosed with hypertension, diabetes, or CKD and those over 51 years of age. However, other studies have warranted caution for universal sodium restriction to 1500 mg in this population8
  • For individuals with diabetes and hypertension, setting a sodium intake goal of 2300 mg/day should be considered on an individual basis8
  • Sodium intake recommendations should take into account palatability, availability, additional cost of specialty low-sodium products, and the difficulty of achieving both low sodium recommendations and a nutritionally adequate diet8

American College of Cardiology Foundation and American Heart Association guidelines recommend reduced sodium for patients with heart failure

Sodium restriction

Sodium restriction is reasonable for patients with symptomatic heart failure to reduce congestive symptoms.9

RATIONALE
Dietary sodium restriction is commonly recommended to patients with heart failure and is endorsed by many guidelines.9

  • The data on which this recommendation is drawn upon, however, are modest, and variances in protocols, fluid intake, measurement of sodium intake, compliance, and other clinical and therapeutic characteristics among these studies make it challenging to compare data and draw definitive conclusions9
  • Observational data suggest an association between dietary sodium intake with fluid retention and risk for hospitalization9
  • Other studies, however, have signaled a worsening neurohormonal profile with sodium restriction in heart failure9
  • Sodium homeostasis is altered in patients with heart failure as opposed to healthy individuals, which may partially explain these trends. In most of these studies, patients were not receiving guideline-directed medical therapy; no study to date has evaluated the effects of sodium restriction on neurohormonal activation and outcomes in optimally treated patients with heart failure9
  • With the exception of 1 observational study that evaluated patients with HFpEF, all other studies have focused on patients with HFrEF. These data are mostly from white patients; when the differences in cardiovascular and renal pathophysiology among races are considered, the effects of sodium restriction in nonwhite patients with heart failure cannot be ascertained from these studies. To make this more complicated, the 3 randomized, controlled trials that assessed outcomes with sodium restriction have all shown that lower sodium intake is associated with worse outcomes in patients with HFrEF9
  • These limitations make it difficult to give precise recommendations about daily sodium intake and whether it should vary with respect to the type of heart failure (eg, HFrEF vs HFpEF), disease severity (eg, NYHA class), heart failure–related comorbidities (eg, renal dysfunction), or other characteristics (eg, age or race)9
  • Because of the association between sodium intake and hypertension, left ventricular hypertrophy, and cardiovascular disease, the American Heart Association recommendation for restriction of sodium to 1500 mg/day appears to be appropriate for most patients with stage A and B heart failure9
  • However, for patients with stage C and D heart failure, currently there are insufficient data to endorse any specific level of sodium intake. Because sodium intake is typically high (>4 g/day) in the general population, clinicians should consider some degree (eg, <3 g/day) of sodium restriction in patients with stage C and D heart failure for symptom improvement9

Less than 50% of patients can successfully follow dietary recommendations for sodium restriction

Common reasons for not following a low sodium diet include6:

  • Bland taste of food without added salt
  • Cost of fresh fruit and vegetables
  • Limited food choices
  • Not receiving adequate (or any) instructions on how to follow the diet
  • Difficulty staying on diet when away from home
  • Social conflicts when others do not follow the same diet

Patients with comorbid conditions, such as hyperkalemia, may be asked to follow more than one restrictive diet—which creates an additional barrier.6

Moreover, recommendations to manage heart failure by reducing dietary sodium intake may inadvertently lead patients to select low-sodium foods enriched with potassium or potassium-containing salt substitutes, which may in turn compound their risk for hyperkalemia.4

In patients with CKD with and without heart failure, hyperkalemia is a common and clinically relevant problem with potentially serious consequences that can lead to mortality. For this vulnerable patient population, control of sodium is crucial to manage blood pressure and proteinuria—and ultimately to delay the progression of renal function loss. In patients with CKD with and without heart failure, hyperkalemia is a common and clinically relevant problem with potentially serious consequences that can lead to mortality. For this vulnerable patient population, control of sodium is crucial to manage blood pressure and proteinuria—and ultimately to delay the progression of renal function loss.