CKD
Terri D’Arrigo
Data from several studies have shown mixed evidence about whether and when to prescribe renin-angiotensin system inhibitors (ACE inhibitors and ARBs) for patients with advanced chronic kidney disease (CKD). The American Heart Association currently recommends these medications as first-line therapy for patients with hypertension and stage 3 or higher CKD to slow the progression of kidney disease, but studies such as the STOP-ACEi trial found that withdrawing these medications in patients with stage 4 or 5 CKD did not affect the rate of decline in eGFR.
However, a review and meta-analysis published July 2, 2024, in the Annals of Internal Medicine suggests that renin-angiotensin system inhibitors lower the risk of kidney failure with replacement therapy in people with advanced CKD.
Researchers analyzed data from 18 randomized controlled trials that included a total of 1,739 patients with advanced CKD, defined as eGFR less than 30 mL/min/1.73 m2, and with a mean eGFR of 22.2 mL/min/1.73 m2. The studies that were included in the analysis compared either an ACE inhibitor or ARB to placebo or to other antihypertensives. The research team found that initiating treatment with either an ACE inhibitor or an ARB resulted in a 34% lower risk of progression to kidney failure with replacement therapy compared with placebo or other antihypertensive medications.
“I think it’s reassuring that even patients with advanced CKD benefit from initiating renin-angiotensin system inhibitors,” said Mark J. Sarnak, MD, senior study author and chief of nephrology at Tufts University School of Medicine. “We shouldn’t say that the eGFR is too low and it’s too late to try.”
Consider quality of life
The analysis did not show that renin-angiotensin system inhibitors lowered the risk of death. However, that does not mean patients with advanced CKD should not be offered these medications.
“It’s terrifying for persons with CKD to get to the point where they need kidney replacement therapy to survive,” said Wendy L. St. Peter, PharmD, a professor at the University of Minnesota College of Pharmacy and an investigator with the United States Renal Data System, who was not involved in the research. “Most people who need kidney replacement therapy are initiated on in-center hemodialysis, which greatly reduces patient quality of life.”
She added that even though some patients choose more patient-centered kidney replacement therapy such as home hemodialysis or peritoneal dialysis, all kidney replacement therapy is time consuming and has its own set of challenges.
“In my opinion, the only persons with CKD who should not be initiated on ACE inhibitors or ARBs are those with an ongoing episode of acute kidney injury or those with hyperkalemia that has not been controlled with diet or potassium binders,” St. Peter said.
Sarnak agreed but noted that the concern for hyperkalemia is more pressing in real-world practice than in the tightly controlled environment of a clinical trial.
“You have to be aware of whether they are susceptible to kidney injury or hyperkalemia or are taking medications that increase potassium,” he said. “Follow the potassium.”
What pharmacists can do
St. Peter said that any patient with a diagnosis of CKD should be evaluated for an ACE inhibitor or ARB to prevent the risk of future kidney failure with the need for kidney replacement therapy.
She offered the following clinical pearls to help pharmacists who work with nephrologists or other physicians who treat patients with CKD:
Get a baseline urine albumin-creatinine ratio and sCr with eGFR and potassium level before initiating an ACE inhibitor or ARB.
Start with the lowest dose and titrate over 2 to 4 weeks to the highest approved or tolerated dose, and start lower in older patients who take diuretics or SGLT-2 inhibitors.
Test for SCr with eGFR, potassium, and BP within 1 to 2 weeks of initiating a dose or increasing a dose.
Do not take the patient off an ACE inhibitor or ARB if possible. Instead, reduce the dose if sCr rises more than 30% above baseline. If the patient develops hyperkalemia, reduce the dose and offer guidance on dietary potassium restrictions, consider increasing diuretic dose (if possible), or institute potassium binders to enable patients to continue taking their medication. ■