Elevated UACR means not just kidney disease, but increased CVD risk in diabetes patients

Elevated levels of UACR in type 2 diabetes patients at high cardiovascular risk are linked to increased risks for all-cause death and adverse cardiovascular outcomes, researchers reported this week in JAMA Cardiology.

It’s not uncommon for individuals with type 2 diabetes (T2D) to develop chronic kidney disease, first author Benjamin M. Scirica, MD, MPH, and colleagues wrote in the study—it’s a well-known complication that affects between 30 and 40 percent of T2D patients. Risk for kidney disease can be estimated through measuring a patient’s estimated glomerular filtration rates (eGFR) or urinary albumin to creatinine ratio (UACR).

Higher levels of urinary albumin, Scirica and co-authors explained, are a red light for kidney damage and, in T2D patients, often mark the presence of diabetic nephropathy.

The SAVOR-TIMI 53 trial, a study that evaluated the cardiovascular efficacy and safety of the drug saxagliptin, found the majority of a 16,000 patient population saw no difference in risk of cardiovascular death, heart attack or stroke. SAVOR-TIMI 53 researchers also noticed saxagliptin seemed to improve UACR over time for patients taking the medication.

Because of this, Scirica and colleagues sought to determine whether UACR offered any incremental prognostic benefits beyond established risk factors and plasma cardiovascular biomarkers. They drew 15,760 patients from the SAVOR-TIMI 3 study, 33 percent of whom were women, and found the majority of those patients—36.8 percent—recorded UACR rates of less than 10 mg/g. Nearly 25 percent of patients’ levels were between 10 and 30 mg/g, 28 percent were between 30 and 300 mg/g and 10.4 percent were greater than 300 mg/g, according to the research. In healthy adults, UACR is typically less than 10 mg/g—this group’s average was 17 mg/g.

Patients who recorded higher UACR levels were less likely to be white, had higher baseline systolic blood pressures, had lived with diabetes for longer, had more dyslipidemia and hypertension and tended to have established athersclerotic disease, Scirica et al. wrote. They also recorded higher levels of cardiac biomarkers like natriuretic peptides and high-sensitivity troponin.

After adjusting for baseline characteristics and eGFR, the researchers found UACR was significantly associated with an increased risk of all-cause death, cardiovascular mortality, myocardial infarction and hospitalization for heart failure. Data showed a consistent, stepwise pattern of increased cardiovascular risk with each increased level of UACR.

When analyzed with three common cardiac plasma biomarkers, though, Scirica and colleagues found the incremental prognostic value of UACR was minimal.

“This was not expected given the strong association between cardiac biomarkers and cardiovascular outcomes in patients with T2D,” the authors wrote. “To our knowledge, no practice guidelines, however, currently recommend their use in stable patients with diabetes.”

So, Scirica and his team wrote, UACR could be a successful assessor of cardiovascular risk of T2D patients, but it all depends on whether or not established cardiac biomarkers are also being assessed.

“The apparent discordance between the minor reductions in UACR with saxagliptin without any corresponding benefit in major adverse cardiovascular events with saxagliptin may be because of a median follow-up of two years that may have been sufficient to improve UACR but not sufficient to observe any cardiovascular benefit,” they wrote. “Moreover, it is not known whether UACR per se would result in improved outcomes.”