A new analysis of the BEST-CLI trial has produced the first evidence-based glomerular filtration rate (eGFR) value—30 mL/min/1.73 m2—as the cutoff below which patients with chronic limb-threatening ischemia (CLTI) experience significantly worse outcomes after revascularization regardless of the treatment modality performed.
The data were part of a deep dive into the landmark study in an attempt to unpick the impact of chronic kidney disease (CKD) severity on outcomes from both open bypass and endovascular intervention for lower extremity infrainguinal revascularization.
Results from the analysis, led by UC San Diego chief of vascular and endovascular surgery Mahmoud Malas, MD, were delivered during the 2025 Southern Association for Vascular Surgery (SAVS) annual meeting in St. Thomas, the U.S. Virgin Island (Jan. 22–25) and simultaneously published by the Journal of Vascular Surgery.
“We identified GFR of less than 30 as the inflection point that is associated with double the risk of MALE [major adverse limb events] or death and triple the risk of cardiovascular events and all-cause mortality,” presenting author Mohammed Hamouda, MD, a postdoctoral fellow at UC San Diego in San Diego, California, told SAVS 2025. “We also see that, in the BEST-CLI trial, that those patients on dialysis had very poor long-term survival, which raises many questions of if we need to treat every single patient on dialysis or revascularize them.”
A total of 1,797 patients were included in the analysis, which categorized patients into three groups according to CKD stage: group A includes non-CKD and CKD stages 1 and 2 patients; group B stages 3 and 4; and group C stage 5 and dialysis-dependent patients. Three-quarters of the patients belonged to group A and 14.7% and 11.5% were in group B and group C, respectively.
Malas and colleagues established that those group C patients had double the risk of amputation with a hazard ratio [HR] of 2.13 (p<0.001), MALE or all-cause mortality (HR, 2.05; p<0.001), and more than triple the risk of all-cause mortality with an HR of 3.40 (p<0.001), compared with group A. In dialysis-dependent patients, endovascular therapy was associated with slightly better survival, but twice the risk of reintervention compared with open surgical bypass, they found.
But, Hamouda elaborated, this National Kidney Foundation staging system of CKD is not designed to investigate surgical outcomes, which then led the research team to carry out a spline analysis in order to establish the significant cutoff at which surgical outcomes in CLTI patients hit statistical significance. “The idea is that we use GFR as a continuous variable, and against it we plot the hazard of MALE or death,” he explained. “We wanted to see where the GFR hits statistical significance, or where is the inflection point at which the hazard of MALE or death becomes statistically significant.”
That then established a GFR of under 30 as statistically positive for increased hazard of MALE or death. “But we wanted to see if there was any confounding by treatment type,” Hamouda continued. Comparing those patients receiving open bypass and endovascular intervention, “we found similar results: as long as the GFR is below 30, there is no difference in the treatment modality when it comes to the hazard of MALE or death,” he added.
Those hazard ratios for eGFR <30 vs. ≥60 were 2.03 (95% confidence interval [CI], 1.68–2.43; p<0.001) and 3.46 (95% CI, 2.80–4.27; p<0.001) for MALE and mortality, respectively.
“One concerning but not surprising point we found during this study was that BEST-CLI was designed to include only patients who have more than two years of expected survival after the procedure, but, with those patients on dialysis in the trial, it doesn’t matter whether they are getting an open bypass or endovascular intervention: as long as they hit the three-year mark, survival was below 50%, which was very sobering.”
