麻豆传媒

SAN DIEGO -- Intensive glycemic control slightly reduced macroalbuminuria over time in people with type 2 diabetes at high risk for cardiovascular disease, according to a secondary analysis of the ACCORD trial.

In the trial of 10,000+ patients, those who were randomized to have tight glucose control -- an HbA1c of less than 6% -- had a slight drop in the risk for composite kidney outcomes compared with those with a more lax glucose goal of 7-7.9% (HR 0.92, 95% CI 0.86-0.98), reported Amy Mottl, MD, MPH, of the University of North Carolina Kidney Center in Chapel Hill, and colleagues.

This risk reduction, however, was mainly driven by a significant drop in incident macroalbuminuria (HR 0.68, 95% CI 0.59-0.77), while other outcomes including doubling of creatinine, need for dialysis, and all-cause mortality did not significantly differ between target glycemic ranges.

The findings were presented here at the American Society of Nephrology (ASN) Kidney Week 2018 and simultaneously published in the .

Looking at the ACCORDION extension study, which later took half of the ACCORD participants and randomized them into a blood pressure (BP) trial or lipid trial, differing kidney outcomes were reported.

As for the blood pressure (BP) trial, intensive treatment -- a target systolic BP of <120 mmHg -- was tied to a 16% higher risk for the composite kidney outcome compared with a target systolic BP of <140 mmHg (HR 1.16, 95% CI 1.05-1.28). Similarly in the lipid trial, fenofibrate use was also tied to a 16% higher risk for composite kidney outcome compared with placebo (HR 1.16, 95% CI 1.06-1.27).

The researchers reported that in both the BP and the lipid trials, which each included approximately 5,000 participants, this increased risk in kidney outcomes was driven only by a doubling in serum creatinine, as follows:

• Intensive BP: HR 1.64 (95% CI 1.30-2.06)
• Fenofibrate use: HR 2.00 (95% CI 1.61-2.49)

Other outcomes, including incident macroalbuminuria, dialysis, and mortality, were not different between treatment groups.

Not Surprised, Quite Surprised

"We were not surprised by the benefit of intensive glycemic control to decreasing the risk for incident high levels of protein in the urine, but we were quite surprised by the adverse effects of intensive blood pressure targets and fenofibrates on worsening kidney function," Mottl told 麻豆传媒.

"While the original ACCORD and its follow-on ACCORDION study showed no benefit of intensive glucose, blood pressure targets, and fenofibrate use on MACE [major adverse cardiovascular events], we thought there could be a chance they might benefit kidney outcomes," she continued. The results also highlighted how "kidney outcomes typically take longer to occur, so long-term follow-up is extremely important."

This secondary analysis of kidney outcomes included all participants from the original ACCORD trial who had surveillance of kidney-related outcomes following randomization in the trial. Incident macroalbuminuria was defined as a urine albumin-to-creatinine ratio >300 µg/mg, while the need for dialysis was self-reported.

"Compared with the effects on [end-stage kidney disease] from the ACCORDION study alone or other recent trials of similar BP targets (the SPRINT) or fenofibrate use (the ), inconsistency is again seen between the effects on ESKD compared with those seen on doubling of serum creatinine," noted Vlado Perkovic, MBBS, PhD, of The George Institute for Global Health, in Australia, and co-authors, writing in an .

However, the editorialists warned against assuming that the doubling of serum creatinine seen with intensive BP control and fibrate use automatically equates to kidney harm. Instead, they suggested that these findings should be interpreted as "inconclusive" given the wide 95% confidence intervals for the more reliable end-stage kidney disease [ESKD] outcomes" and the "limitations of the small number of creatinine measurements available." Perkovic and co-authors did note, though, that they believe there is potential benefit for ESKD with intensive glucose control.

Mottl recommended that healthcare providers approach patient care with the mindset that "one size does not fit all," adding that "in this era of precision medicine, we have to be sure to fit the right treatment strategies with the right patient."

"In caring for older patients with type 2 diabetes and high risk for cardiovascular events, one needs to be particularly careful to not be overly aggressive in setting targets for blood pressure and I recommend caution in the use of fibrate therapy as well," she said. "Setting targets for glycemic control really depends on the individual patient and their overall risk for hypoglycemia, cardiovascular events, and progressive kidney disease."