Chapel Hill, NC—Bringing down blood pressure and cholesterol levels in type 2 diabetes patients at high risk for cardiovascular disease could have a very undesirable side effect: reduced kidney health.

That’s according to a new study published in the Clinical Journal of the American Society of Nephrology (CJASN) and presented at ASN Kidney Week 2018.

University of North Carolina Chapel Hill–led researchers found that in patients with type 2 diabetes at high risk for cardiovascular disease, targeting blood sugar to normal levels, i.e., hemoglobin A1c less than 6.0%, reduced the risk for macroalbuminuria over an average follow-up of 7.7 years but had no beneficial effect on more significant kidney outcomes such as serum creatinine doubling (or the need for dialysis or transplantation).

At the same time, the study determined, seeking to reduce blood pressure to less than 120 mmHg or prescribing fenofibrate to lower cholesterol increased the risk for doubling of serum creatinine, although it had no impact on the need for dialysis or transplantation.

“These results, along with those from the primary study which showed no benefit of the interventions on heart attacks and strokes, provide evidence against aggressive targets for glucose, blood pressure, and use of fenofibrate in adults with type 2 diabetes at high risk of cardiovascular events,” explained lead author Amy K. Mottl, MD, of the University of North Carolina Kidney Center.

Background information in the article notes that type 2 diabetes dramatically increases the risk for both cardiovascular disease and chronic kidney disease. Past research has suggested that “tight” control of blood sugar, blood pressure, and cholesterol has resulted in conflicting short-term effects on kidney health.

The current study focused on longer-term effects, using information from more than 10,000 participants in ACCORDION, which is an extension phase of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a multifactorial intervention study in people with type 2 diabetes who are at high risk for cardiovascular disease.

Examined in the intervention study were the effects on cardiovascular events and death of:
• Intensive glycemic control, defined as hemoglobin A1c <6.0% versus 7%–7.9%),
• Intensive blood pressure control, defined as systolic BP <120 mm Hg vs. <140 mm Hg; or
• Use of fenofibrate vs. placebo added to simvastatin on cardiovascular events and death.

During the study period, researchers report 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1,905 deaths.

Results indicate that hazard ratios (HRs) for the composite outcome with intensive glycemic control, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86-0.98), 1.16 (95% CI, 1.05-1.28), and 1.16 (95% CI, 1.06-1.27).

Secondary outcome analyses note that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59-0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30- 2.06 and HR, 2.00; 95% CI, 1.61- 2.49, respectively), according to the findings.

“In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events,” study authors conclude.

An accompanying editorial from The George Institute for Global Health in Australia questions some of the conclusions, however. “In our view, the findings observed for doubling of serum creatinine do not suggest harm to the kidneys, but rather are more likely to reflect the limitations of the small number of creatinine measurements available,” the commentators write. “We believe that the data actually suggest possible benefit for ESKD [end-stage kidney disease] with intensive glucose control, and remain inconclusive for intensive blood pressure control and fibrate use given the wide confidence intervals for the more reliable ESKD outcomes.”

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