K, kidneys, and ketoacidosis

Contraindications to sodium polystyrene sulfonate, alternative treatments for hyperkalemia, and SGLT2 inhibitors were covered at Wednesday's hospital medicine precourse in a quick review of issues in inpatient nephrology.


“How many of you have ordered Kayexalate in the last two weeks?” Andrew J. King, MD, asked attendees at Wednesday's hospital medicine precourse. Scattered hands rose around the room in response.

Sodium polystyrene sulfonate (SPS) is commonly used in hospitals, despite its doubtful benefits and definitive risks, according to Dr. King, a nephrologist with Scripps Clinic Medical Group in San Diego. Contraindications and alternative treatments for hyperkalemia were among the tips he offered during a quick review of issues in inpatient nephrology.

The drug was first approved back in 1958, when proof of efficacy was not yet a requirement. “Would it be approved today? I don't think so,” he said. In 2009, it got a black-box warning about the risk of colonic necrosis and other serious adverse gastrointestinal events, especially when used with sorbitol.

SPS used to come prepackaged with 70% sorbitol, and a switch to 33% sorbitol lessened the risks but did not eliminate them, Dr. King reported. “There were fewer complications, but the patterns were similar,” he said, citing a study published in Clinical Nephrology in January 2016 that reviewed the charts of 501 inpatients who received SPS and found two cases of bowel necrosis.

“That's a lot, because the consequences of bowel necrosis are huge,” Dr. King said. He highlighted some particular contraindications for the drug: postoperative care, ileus, opiate use, bowel obstruction, or bowel disease (e.g., ulcerative colitis, Clostridioides difficile).

The good news is that there are alternative agents. Potential replacements include patiromer and zirconium cyclosilicate. Disadvantages of patiromer include that it acts only in the colon and likely has slow onset, he noted. Zirconium cyclosilicate is fast-acting and works throughout the intestine. “I think this has promise,” said Dr. King. “I think this is going to be a drug that will supplant Kayexalate.”

Of course, it's hard to know how a drug will work out until it's been on the market a while, Dr. King cautioned. He devoted part of his talk to reviewing another relatively new class of drugs, the sodium-glucose cotransporter-2 (SGLT2) inhibitors.

“I've always thought we don't know a drug until about 15 years into a drug,” Dr. King said. SGLT2 inhibitors, approved to treat diabetes, have shown positive effects on renal and cardiovascular outcomes and thus caused excitement among the relevant subspecialists.

“Endocrinologists, nephrologists, and heart failure docs have a love affair with these,” he said. “As with any new drug, we're starting to learn their underbelly.”

One particular downside, relevant to hospitalists and nephrologists, is the associated risk of diabetic ketoacidosis. “It's euglycemic, generally with a glucose level less than 250 [mg/dL],” he said.

Patients will present with nausea, vomiting, and malaise. The condition is generally caused by fasting, so the drugs should be discontinued when patients aren't eating, for example, before and after surgery.

“There's a strong recommendation that SGLT2 inhibitors should be held at least three days and probably five days prior to surgery,” Dr. King said. “In general, I would recommend stopping this agent in all hospitalized patients.”

Research may eventually show that the associated risk of ketoacidosis differs among drugs within the class, but that's yet to be determined, he noted.

Speaking of variable risks, Dr. King would like physicians in the hospital to better differentiate emergent hyperkalemia from less serious cases. For example, it's not necessary to put a patient on cardiac monitoring for a slightly high potassium level.

“I can't tell you how many times I have people calling me for a [potassium of] 5.3 [mEq/L],” he said. “Every one of my outpatients would be on telemetry.”

Hyperkalemic emergencies generally require much higher potassium levels. “The serious manifestations occur in patients greater than 7 [mEq/L],” Dr. King said. Signs of an emergency include muscle weakness or paralysis, cardiac manifestations, or electrocardiogram changes.

Clinicians should also worry about patients with an ongoing cause of potassium generation (such as cell lysis, gastrointestinal bleeding, or a large hematoma) or a condition that makes them particularly vulnerable to adverse outcomes (for example, kidney disease or injury with non-anion gap acidosis or respiratory acidosis).

Patients with hyperkalemia should be put on cardiac monitoring and treated with calcium infusion, redistributive therapy, and a long-term plan to remove potassium, Dr. King advised. Such plans might include insulin and glucose—don't give one without the other, he noted.

Second-line therapies include epinephrine and albuterol. “Generally speaking, this is not used very often in clinical practice,” Dr. King said, although he noted that these drugs could be useful for patients awaiting hemodialysis.

This may be necessary because dialysis, although a reliable and effective method to remove potassium from the body, especially for patients with severe renal impairment, is “not available on a dime,” he noted. Other options include sodium bicarbonate, loop diuretics and saline, and of course, SPS and its new alternatives.