Decreased eGFR and Increased Albuminuria Highly Predictive of Major Clinical Outcomes in T2DM Patients

Combined analysis of eGFR (estimated Glomerular Filtration Rate) and albuminuria over 2 years has been shown to predict T2DM patients’ risk for major macrovascular outcomes.

Diabetes patients face an increased risk of mortality caused by the many complications that accompany diabetes. One of the most common complications of diabetes is chronic kidney disease. Chronic kidney disease contributes to cardiovascular disease, further increasing risk of morbidity and mortality. While greater control of hyperglycemia has been sought through novel antidiabetic treatments over the past few decades, it is also important to acknowledge the importance of recognizing and treating diabetic kidney disease.

Due in part to the slow progression of chronic kidney disease, there are limited clinical trials on which to base clinical decisions for these patients. To this point, clinical trials including the well-known Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) randomized, controlled trial, have shown that decrease in eGFR and an increase in urine albumin-to-creatinine ratio (UACR) over 2 years in patients with type 2 diabetes are independently associated with cardiovascular events, all-cause mortality and kidney events. There was a need for a study to analyze the combined effect of eGFR and UACR on risk for major clinical outcomes. A newly published study addressed this area of interest.

This observational study looked at patients within the ADVANCE and ADVANCE-ON study (5.5 years followup of ADVANCE), a factorial, randomized, controlled trial evaluating the effects of blood pressure lowering and intensive blood glucose lowering therapy on vascular outcomes in patients with type 2 diabetes. This analysis identified participants with diabetes that experienced changes in eGFR and UACR from baseline to 2 years. The population of 8,766 participants was 43% women, with an average age of 66 years old, mean duration of diabetes of 7.8 years, mean eGFR of 75 ml/min/1.73m2 and median UACR of 14.1 mcg/mg. Both markers were broken down into three groups: a decrease of 40%, a decrease of <40% – increase <40%, and an increase of 40%. The primary study outcome was the composite of major macrovascular events (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (a requirement for kidney replacement therapy or kidney death), and all-cause mortality.

Throughout the course of the study, 2,191 patients (25%) developed the primary outcome, 1,392 (16%) experienced a major macrovascular event, 108 (1%) experienced a major kidney event and 1,416 (16%) died. With adjustment for eGFR, UACR and other cardiovascular risk factors from baseline, an increase in eGFR was associated with a lower risk of the primary outcome. Compared with minor change (decrease of <40% – increase <40%), the hazard ratio (HR) for a decrease in eGFR of 40%, was 1.58 (95% CI, 1.27-1.95). The HR for an increase in eGFR of 40% was 0.82 (95% CI, 0.64-1.04). After the same adjustments, an increase in UACR was associated with a higher risk of the primary outcome. Compared with minor change, the HR for a decrease in UACR of 40% was 0.96 (95% CI, 0.85-1.07) while the HR for an increase in UACR 40% was 1.32 (95% CI, 1.19-1.46). The results were not affected by randomized blood pressure and glucose treatments or HbA1c. It is important to note that a combined decrease in eGFR and an increase in UACR were associated with a 2.31 (95% CI, 1.67-3.18) higher risk of the primary outcome.

From this study, both decrease in eGFR and increase in UACR over 2 years, independently and combined, significantly increase the risk for major cardiovascular outcomes in patients with type 2 diabetes. 40% of changes in both markers are strongly predictive of major clinical outcomes. This study had a large population of diverse backgrounds from a landmark randomized controlled trial and therefore has produced generalizable results.

Practice Pearls:

• The decrease in eGFR and the increase in albuminuria is strongly indicative of future major cardiovascular outcomes in patients with type 2 diabetes.
• A new observational study pulled data from the ADVANCE and ADVANCE-ON trials; it was identified that the combined assessment of eGFR and albuminuria can predict clinical outcomes compared to the separate assessment of each marker.
• It is important to monitor eGFR and albuminuria in T2DM patients in order to identify high-risk patients.

Ohkuma, Toshiaki, et al. “Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes.” Clinical Journal of the American Society of Nephrology, vol. 14, no. 6, 2019, pp. 862–872., doi:10.2215/cjn.13391118.

 Amber Satz, PharmD Candidate, LECOM School of Pharmacy