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Intensive Glucose Control Linked with ESRD Reduction

Researchers saw long-term reduction in end-stage renal disease, without evidence of increased risk for cardiovascular events or death.

Preserved kidney function and well-controlled blood pressure further elevated the benefits of intensive glucose control, according to researchers.

Vlado Perkovic, MBBS, PhD, FASN, FRACP, executive director of the George Institute in Australia, and colleagues evaluated data from the ADVANCE trial on 8,494 adults aged 55 years or older with type 2 diabetes to determine the long-term effects of intensive glucose control on the risk for ESRD and other outcomes. In-trial follow-up was conducted for a median 5 years, post-trial follow-up for a median 5.4 years and total follow-up for a median 9.9 years.

With intensive glucose control there was a significant reduction in the risk for ESRD during the in-trial period (P = .02) and after a total 9.9 years of follow-up (P < .01).

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Released Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Researchers examined the long-term effects of intensive glucose control on risk of ESKD and other outcomes.

Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes.

A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26).

From the results, researchers concluded that intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.

As chronic kidney disease stage increased, there was a graded reduction in the strength of the effect of intensive glucose control on ESRD (P = .04 for heterogeneity). Compared with participants with baseline systolic BP levels greater than 140 mm Hg, a greater risk reduction in ESRD was found for those with systolic BP levels lower than 140 mm Hg (P = .01 for heterogeneity).

There was a nonsignificant effect on the risk for death due to renal disease during the in-trial period (HR = 0.85; 95% CI, 0.45-1.62) that remained after 9.9 years of follow-up (HR = 0.89; 95% CI, 0.6-1.31).

“Our data build on a growing body of evidence indicating an important role for intensive glucose control in limiting the progression of kidney disease and in curbing the growing number of patients around the world with type 2 diabetes requiring dialysis or transplantation as a result of diabetic kidney disease,” the researchers wrote.

After following the ADVANCE trial cohort for a total of 9.9 years, researchers concluded that a prior period of intensive glucose control continues to protect against the development of ESKD in patients with type 2 diabetes. The patients who appear to benefit the most are those with preserved kidney function, with intermediate effects in the group with CKD stage 1 or 2 and lesser effects in participants with CKD stage 3 or greater at baseline. Greater reductions in ESKD were also observed in participants with better blood pressure control at baseline (SBP40 mmHg). More importantly, the impact of intensive glucose control on mortality or major cardiovascular events was not adversely affected by CKD at baseline during either the trial or overall study follow-up.

The researchers conclude their data provide the strongest evidence to date regarding the renal benefits of intensive glucose lowering and are consistent with data on intermediate outcomes from other studies. These include the Epidemiology of Diabetes Interventions and Control (EDIC) study in a population of younger individuals with type 1 diabetes, which reported that a prior period of intensive glucose control reduced the long-term risk of developing renal impairment (eGFR 60mL/min/1.73 m2) by 50% after a median follow-up of 22 years.

Practice Pearls:

  • Long-term reduction in end-stage renal disease is linked with intensive glucose control.
  • Preserved kidney function and well-controlled blood pressure further elevated the benefits.
  • With intensive glucose control there was a significant reduction in the risk for ESRD

Researched and prepared by Steve Freed, BPHarm, Diabetes Educator, Publisher and reviewed by Dave Joffe, BSPharm, CDE

 

Wong MG, et al. Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON. Diabetes Care. 2016;doi:10.2337/dc15-2322.