EASD: Intensive Glucose Control Cuts Renal Risks

Sophia Zoungas, MD, PhD, of the University of Sydney in Australia, reported during an oral session at the European Association for the Study of Diabetes that over a mean follow up of five years, those on intensive glucose control had a significant 65% decreased risk of ESRD, compared with those on standard glucose-lowering therapy.

Their risk of microalbuminuria or macroalbuminuria was also diminished, plus the renal outcomes should not be forgotten as an important part of care of patients with diabetes.

Blood glucose levels have been linked with a higher risk of kidney disease, but the effects of intensive glucose control on major kidney outcomes among diabetes patients aren't known.

Researchers looked at data from the ADVANCE trial, which compared the effects of an intensive glucose lowering target (HbA1c 6.5% or below) with a standard target of 7% or lower.

The original trial of 11,140 patients showed a 10% relative risk reduction in combined microvascular and macrovascular endpoints, as well as a 21% relative risk reduction in a secondary endpoint of nephropathy.To determine the effects of glucose lowering on renal outcomes, they assessed data from the full cohort for the following outcomes:  new microalbuminuria or macroalbuminuria = ESRD (defined as the need for dialysis or transplantation); renal death; and transient or sustained doubling of creatinine (more than 200 mmol/L).

Over a mean of five years of follow up, the researchers found a significantly lower risk of microalbuminuria and macroalbuminuria for those in the intensive arm (HR 0.91, 95% CI 0.85 to 0.98, P=0.012, and HR 0.70, 95% CI 0.57 to 0.85, P=0.0004, respectively). Intensive therapy patients also had a significant 65% reduction in risk of ESRD (95% CI 0.15 to 0.83, P=0.012).

While there was a trend toward a diminished risk of renal death for these patients, it was not significant, Zoungas reported. She said this was likely because of the number of patients that hit the endpoint in the trial. "The effect was small but in the right direction," she said. "If we have further cases, we would show it."

There was an increased likelihood of the doubling of creatinine for those in the intensely managed group, but it was not significant.

The interpretation of the doubling of creatinine "as a component of renal endpoints requires further consideration," Zoungas said.

She concluded that the overall effects on hard renal outcomes and microalbuminuria were generally consistent, and were likely mediated by the albuminuric pathway.

The study was limited by a small number of hard outcomes, by its open-label nature, and by the fact that the effects of glucose lowering, versus the specific effects of the drug therapy involved, could not be teased out.

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that intensive glucose-lowering (target HbA1c 6.5% or below) may protect against end-stage renal disease (ESRD) in diabetic patients.
• Note that the risk of microalbuminuria or macroalbuminuria was also diminished.

Zoungas S, et al "Intensive glucose lowering and end stage kidney disease: new data from the ADVANCE trial" EASD 2011; Abstract OP07-39.