#NephMadness 2023: There is Nothing to Fear but Fear Itself… and Apparently Hyperkalemia

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Jordana Cohen @jordy_bc

Dr. Jordana (Jordy) Cohen is an Assistant Professor of Medicine and Epidemiology in the Renal-Electrolyte and Hypertension Division at the University of Pennsylvania. She leads several research studies evaluating mechanisms and epidemiologic effects of antihypertensive medications in high-risk patient populations.

Competitors for the Mineralocorticoid Receptor Antagonists (MRAs) Region

Team 1: Steroidal MRA vs Team 2: Nonsteroidal MRA

Mr. S was referred to my hypertension clinic by his longtime nephrologist. He had CKD hovering between stage 3b and 4. His eGFR had been slowly declining over the past 10 years, attributed to his 25+ year history of diabetes. His blood pressures were running in the 160s/80s mmHg at his clinic visits despite maximum tolerated doses of a dihydropyridine calcium channel blocker, an ACE-inhibitor, a loop diuretic, a combined beta- and alpha-antagonist, hydralazine, and a clonidine patch. His nephrologist was thinking of adding minoxidil, but wanted my opinion before doing so.

Mr. S’s 24-hour ambulatory blood pressure monitoring confirmed his elevated office readings. He was adamant that he never missed a dose of medication, which matched with his pharmacy refill records in the EHR. I checked his renin and aldosterone, which were normal. I was delighted to see that his loop diuretic seemed to be providing adequate kaliuresis, and his serum potassium was 4.4 mEq/L. I asked Mr. S if he’d ever tried a mineralocorticoid receptor (MR) antagonist before, like spironolactone or eplerenone. He said he’d never heard of them. I started eplerenone, and uptitrated it over about three months to 50mg BID, rechecking his potassium levels between dose adjustments. His blood pressures started to trickle down, first to the 150s/80s, then to the 140s/70s, and finally to the 130s/70s. He said he hadn’t seen blood pressures that low in several years. His serum potassium plateaued at 5.2 mEq/L. His eGFR had declined about 20% from when he first came to see me. He felt well overall. I referred Mr. S back to his primary nephrologist with a letter documenting his successful improvement in blood pressure and what I perceived to be an anticipated change in kidney function with the addition of the MR antagonist and improvement in blood pressure.

Three months later, when I was on inpatient service, I was saddened to see Mr. S admitted with volume overload. It turned out that his nephrologist saw his most recent labs upon returning to his care, stopped the MR antagonist “due to hyperkalemia and AKI on CKD,” and started him on minoxidil.

Too many nephrologists suffer from an irrational fear of MR antagonists, despite ample, high-quality data supporting their use for the treatment of resistant hypertension. In a cohort of almost 270,000 US Veterans with new onset resistant hypertension followed for up to 20 years, we found that only 13% were ever started on an MR antagonist; nephrologists were 30% less likely than cardiologists and half as likely as endocrinologists to prescribe MR antagonists. This translates to a recent publication by An et al. showing that among patients with CKD and resistant or refractory hypertension (which amounted to almost 40% of patients with CKD) seen at Kaiser Permanente of Southern California or the Veterans Health Administration, only 8% were prescribed an MR antagonist.

Is this fear of MR antagonists entirely rooted in hyperkalemia? There is insufficient data to know for sure whether nonsteroidal MR antagonists have a lower risk of hyperkalemia than steroidal MR antagonists: both drugs require close monitoring of potassium and potential need for binders. Before we embrace the shiny new drug, I vote that we get better at the basics.

– Guest Post written by Jordana Cohen @jordy_bc

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post, and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

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