What are the causes of hypophosphatemia and hypokalemia?

From the Guidelines

Low phosphate (hypophosphatemia) and low potassium (hypokalemia) can occur due to various causes, often related to dietary, gastrointestinal, renal, or metabolic factors, with the most recent evidence suggesting that intensive kidney replacement therapy (KRT) is a major risk factor for the development of hypophosphatemia and hypokalemia 1. For hypophosphatemia, common causes include inadequate dietary intake, malabsorption syndromes, vitamin D deficiency, alcoholism, diabetic ketoacidosis, refeeding syndrome, and certain medications like antacids containing aluminum or magnesium. Excessive urinary phosphate loss can occur with hyperparathyroidism or certain kidney disorders. For hypokalemia, causes include insufficient dietary intake, excessive gastrointestinal losses through vomiting, diarrhea, or laxative abuse, and increased urinary excretion due to diuretics (especially thiazides and loop diuretics), certain antibiotics, or kidney disorders. Hormonal imbalances like hyperaldosteronism, Cushing's syndrome, and metabolic alkalosis can also deplete potassium. Both electrolyte deficiencies can be worsened by severe burns, trauma, or surgery. Some key points to consider are:

• Hypophosphatemia has a reported prevalence of up to 60-80% among ICU patients and is associated with a global negative impact on patients' outcome 1.
• Hypokalemia is another usual complication observed among hospitalized patients, with a prevalence ranging from 12 to 20% 1.
• The initiation of KRT is a major risk factor for the development of hypophosphatemia and hypokalemia 1.
• Dialysis solutions containing potassium, phosphate, and magnesium should be used to prevent electrolyte disorders during KRT 1. Treatment typically involves identifying and addressing the underlying cause while supplementing the deficient electrolyte, either orally or intravenously depending on severity. Regular monitoring of electrolyte levels is essential during correction to prevent overcorrection or other imbalances. The use of phosphate-containing KRT solutions has been reported as a safe and effective strategy to prevent CKRT-related hypophosphatemia, limiting the need for exogenous supplementations 1. Similarly, the onset of hypokalemia in course of CKRT has been successfully minimized by using replacement and/or dialysate solutions with a potassium concentration of 4 mEq/L 1. In terms of prevention, using dialysis solutions containing potassium, phosphate, and magnesium can help prevent electrolyte disorders during KRT, and this approach is recommended based on the most recent evidence 1.

From the FDA Drug Label

For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxications, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop e.g., digitalized patients or patients with significant cardiac arrhythmias, hepatic cirrhosis with ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, and certain diarrheal states

The causes of low potassium mentioned are:

• Diuretic therapy
• Digitalis intoxications
• Hypokalemic familial periodic paralysis
• Significant cardiac arrhythmias
• Hepatic cirrhosis with ascites
• States of aldosterone excess with normal renal function
• Potassium-losing nephropathy
• Certain diarrheal states

There is no information about the causes of low phosphate. 2

From the Research

Causes of Low Phosphate

• Inadequate intake, decreased intestinal absorption, excessive urinary excretion, or a shift of phosphate from the extracellular to the intracellular compartments can cause hypophosphatemia 3
• Renal phosphate wasting can result from genetic or acquired renal disorders, such as vitamin D deficiency, hyperparathyroidism, oncogenic osteomalacia, and Fanconi syndrome 3
• Acquired renal phosphate wasting syndromes can also result from certain medical conditions 3

Causes of Low Potassium

• Hypokalaemia is common in patients with cardiovascular disease, and its causes are not fully understood, but it is thought to be related to mechanisms of potassium homeostasis maintenance 4
• There is no direct evidence in the provided studies on the specific causes of low potassium, but it is mentioned that hypokalaemia can occur in patients with cardiovascular disease 4
• Dietary habits, such as low potassium intake, may contribute to the development of hypokalaemia, but more research is needed to confirm this 5, 6

Relationship between Phosphate and Potassium

• There is limited evidence on the relationship between phosphate and potassium levels in the body, but it is known that both electrolytes are important for maintaining proper bodily functions 5, 6
• Dietary interventions, such as restricting sodium, phosphate, and potassium intake, may be recommended for patients with kidney disease, but more research is needed to determine the efficacy of these interventions 5, 6
• Treatment with diuretics can affect serum phosphate levels, and may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate 7