"Practice ischemia" on an arm reduces contrast nephropathy after procedures (RCT)

Contrast-induced nephropathy (kidney damage) is a serious problem that can occur after many medical tests and procedures, but coronary angiography (cardiac catheterization) is the main culprit. People with pre-existing renal disease are most susceptible to contrast-induced nephropathy (CIN) -- about 1 in 8 of them develop a "bump" in creatinine of >0.5 mg/dL after cardiac cath. It usually improves, but as many as 18% (or about 1-2% overall) have a permanent decrement in renal function 3 months after cardiac catheterization. Since people with renal impairment often also have coronary artery disease, preventing contrast-induced nephropathy is a worthy goal.

What They Did

Fikret Er, Amir Nia, Natig Gassanov et al randomized 100 patients with creatinine (Cr) ~ 1.6 mg/dL, GFR ~39 mL/min, who were about to undergo elective cardiac catheterization to receive either ischemic preconditioning, or sham. All patients were well-hydrated and received N-acetylcysteine before and after their procedures.

In their protocol of ischemic preconditioning, "practice ischemia" was induced by inflating a blood pressure cuff on the arm to 50 mm Hg above systolic blood pressure for five minutes, releasing pressure for 5 minutes, then repeating for four cycles total. OUCH! In the sham arm, the cuff was inflated only to diastolic BP. Subjects then got their cardiac caths 45 minutes later.

What They Found

Practice ischemia before cardiac catheterization provided remarkable protection against contrast-induced nephropathy: only 12% of those in the CIN intervention arm developed contrast nephropathy (an increase of Cr by >0.5 or of >25% within 48 hours), while 40% of those in the sham group did (p=0.002). This was despite the CIN arm receiving significantly more contrast. Patients receiving ischemic preconditioning also had a large reduction in a composite secondary end point of 6-week death, rehospitalization, or hemodialysis: this occurred in 38% of sham-treated patients and only 16% of ischemic-preconditioned patients (p =0.018).

There were no reported side effects from ischemic preconditioning; cursing the person inflating the blood pressure cuff, and his mother too, was not considered an adverse event. Only 2 patients had to limit the number of inflation cycles due to pain.

What It Means

Ischemic preconditioning is believed to activate undefined natural protective mechanisms that result in protective humoral factors being released and self-protective responses of the vascular endothelium. No one knows how it works exactly, but no one has yet worked out all the complexities of contrast nephropathy, either.

This is a small but exciting study, which if replicated could herald a new standard of care and thousands of kidneys saved. But remember that although N-acetylcysteine (NAC) added to IV fluid hydration was initially believed to prevent contrast nephropathy, a larger 2004 trial of NAC failed to show an effect, and 2009 brought another negative randomized trial of NAC, leading many to doubt it provides any benefit.

Fikret Er et al. Ischemic Preconditioning for Prevention of Contrast Medium–Induced Nephropathy. Randomized Pilot RenPro Trial (Renal Protection Trial). Circulation 2012; 126: 296-303.