Photo Credit: Md Babul Hosen

Researchers investigated the potential link between eGFR slope and diabetes complications such as mortality, kidney disease, and cardiovascular events.

Variability in estimated glomerular filtration rate (eGFR) over time is significantly associated with chronic complications in patients with type 2 diabetes, according to findings published in the Journal of Diabetes Research.

Previous analyses have suggested a significant link between eGFR decline and the risk for end-stage kidney disease (ESKD) and mortality. However, prior reviews have depended on only two eGFR measurements.

“A more complete approach on the microvascular kidney complications has recently been introduced, based on eGFR slope using multiple measurements,” explained Giovanni Sartore, MD, and coauthors from the University of Padova.

To investigate the potential link between eGFR slope and diabetes-related complications, researchers conducted a systematic review using PubMed. They identified 987 English-language studies published between January 2003 and April 2023. After evaluating the articles, investigators included six on all-cause mortality, eight on cardiovascular events, 11 on ESKD, and two on microvascular complications.

eGFR Slope Linked to Multiple Complications

Dr. Sartore and colleagues found that eGFR slope was associated with all complications included in the review. Compared with patients with stable eGFR slope, those with declining eGFR slope had significant risks for the following:

• All-cause mortality: HR, 2.31 (95% CI, 1.70-3.15)
• Cardiovascular events: HR, 1.73 (95% CI, 1.43-2.08)
• ESKD: HR, 1.54 (95% CI, 1.45-1.64)
• Microvascular complications: HR, 2.07 (95% CI, 1.57-2.73)

One study accounted for four measures of decline in eGFR slope and showed that greater declines were linked to greater risk for all-cause mortality.

The researchers also combined the findings and reported that patients with declining eGFR slope had a significant overall risk of 1.82 (95% CI, 1.72-1.92) for all complications included in the review.

“This risk measure includes all-cause mortality together with macro- and microvascular complications, giving an overview of how the decline in the eGFR slope reflects the progression of type 2 diabetes,” Dr. Sartore and colleagues wrote.

Guidance & Measurements

In the 2012 Kidney Disease: Improving Global Outcomes guidelines, a significant decline in eGFR slope is defined as a reduction greater than -5 mL/min/1.73m²/year. Authors noted that many studies on patients with type 2 diabetes have used less stringent cutoffs such as -3 mL/min/1.73m²/year. They recommended more research into the use of smaller eGFR slopes as practical surrogate endpoints for patients with diabetes.

“The problem with defining the cutoffs is due, in part, to the fact that people with diabetes have a nonconstant rate of decline in eGFR and, in part, to the fact that the observation period for adverse events is not standardized, and it varies among the studies,” researchers explained.

The Chronic Kidney Disease Epidemiology Collaboration’s two-slope model accounts for eGFR slope in the first 3 months of follow-up as well as a second long-term phase. Researchers wrote that this model provides a more realistic overall picture of eGFR over time than the single-slope model, which is based on only two eGFR measurements.

Dr. Sartore and colleagues concluded that eGFR slope has value for predicting chronic complications in type 2 diabetes and called for greater efforts to standardize its measurement.

“The renewed approach to diabetes therapy focused on its complications suggests that although glycemic control is undoubtedly relevant, it should not be the only indicator to take into consideration,” Dr. Sartore and coauthors wrote. “Acting with drugs that preserve kidney function and therefore prevent the rapid decline of the eGFR slope is desirable and in line with the most recent recommendations.”