Diet Low in Potassium May Not Treat Hyperkalemia, Chronic Kidney Disease

Researchers outline new findings about the connection between hyperkalemia and renin-angiotensin-aldosterone system inhibitors during a session at ASN Kidney Week.

RAAS inhibitors can slow the progression of chronic kidney disease (CKD), however studies have shown that they have the potential to increase the risk of hyperkalemia 2-fold, Charles Wingo, MD, said during a presentation called “Advances in Therapies for Recurrent Hyperkalemia in Patients with CKD and ESRD,” during a session at the American Society of Nephrology Kidney Week conference.

Prior research suggests the use of potassium binders alongside the RAAS inhibitor to prevent hyperkalemia. A common binder is the sodium-glucose cotransporter-2 (SGLT2) inhibitor, but there are still cons to this alternative.

“[Potassium binders] allow(s) maximum RAAS blockage and benefit to slow progression of CKD,” Wingo said in his presentation. However, “potassium binders effectively reduce potassium intake, which may increase progression of CKD.”

RAAS inhibitors (including angiotensin-converting enzyme [ACE] inhibitors) can be an effective therapeutic agent for patients with CKD because they slow the progression of CKD and proteinuria—excessively high levels of protein in the urine.

Common RAAS inhibitors include benazepril, ramipril, and spironolactone, which can benefit heart health. Further, aldosterone antagonists can reduce all-cause mortality.

“Spironolactone reduced mortality by 30% in 1663 patients on (ACE) inhibitors and standard of care,” Wingo said in referencing the RALES study.

However, Wingo added that the observed improvement in all-cause mortality does not consider all the untoward effects of the medication, specifically in that it did not fully reduce the risk of hyperkalemia.

The kidneys play a critical role in excreting potassium, noted Chou-Long Huang, MD, PhD, a speaker at the session. The kidneys are also extremely adaptable—which Huang highlighted in a study looking at adaptive kidney function—and try to balance potassium.

But when potassium levels are not balanced in the body, this leads to hyperkalemia. This is characterized by higher-than-normal potassium levels, compared to hypokalemia, which is potassium deficiency. Hyperkalemia can increase the risk of acute kidney injury and worsen disease progression to kidney failure.

Studies have looked at loop diuretics to treat hyperkalemia. Aggressive hemodialysis was used to treat patients with chronic hyperkalemia, which Wingo referred to as “the bane of [nephrologists’] existence,” but it was not found to be as effective. Nor was limiting dietary potassium. Although some have suggested limiting dietary potassium to improve the condition, it is simply “not palatable,” Wingo said. He also referenced studies that found it to worsen progressing CKD.

Finerenone is a third generation, non-steroidal, aldosterone antagonist for CKD that has recently entered the market. Although it does decrease proteinuria, it does not significantly decrease hyperkalemia.

Wingo suggests that endothelin blockers, glucagon-like peptide-1 receptor antagonists, and heart failure drugs—which include valsartan and sacubitril—may address hyperkalemia from RAAS inhibitors and suggests further research.

“RAAS blockade certainly have some proven benefits,” Wingo said. “But it predisposes to hyperkalemia…Promising data suggest that aldosterone antagonists and SGLT2 inhibitors may have independent effects to slow the progression of CKD. [But] future studies are needed.”

Reference

Huang, Chou-Long, Wingo, Charles, Update on the Management of Recurrent Hyperkalemia Associated with RAAS Inhibitors in Patients with CKD and ESRD. ASN Kidney Week. November 4, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-session-details.aspx?sessId=439548