Low Predictive Power of Biomarkers for Estimated Glomerular Filtration Rate Decline

While certain biomarkers are associated with estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes (T2D), their predictive power is low, according to study results published in Diabetes Care.

The study included participants from the PROVALID study (PROspective cohort study in patients with type 2 diabetes for VALIDation of biomarkers), consisting of participants with T2D with follow-up of more than 24 months (n=2560). The researchers used Luminex and enzyme-linked immunosorbent assay (ELISA) to measure 17 plasma biomarkers at baseline in 481 samples. They used linear mixed modeling to predict eGFR decline.

The baseline median eGFR was 84 mL/min/1.73 m², and the median urine albumin-to-creatinine ratio was 8.1 mg/g.

After univariable analyses, the researchers found that 9 biomarkers showed significant differences in median concentrations between stable and fast-progressing patients. Using a linear mixed model for eGFR, they found an adjusted R² of 62%.

The researchers found that 12 biomarkers accounted for 34% of the total explained variability, of which 32% could be attributed to 5 biomarkers.

After the multivariable analysis of eGFR decline, 5 biomarkers remained significant but exhibited only modest predictive power. These 5 biomarkers include KIM1, FGF23, NTproBNP, HGF, and MMP1.

The researchers found that the individual contribution of each biomarker to the prediction of eGFR decline on top of clinical predictors was generally low.

After including baseline eGFR into their model, it showed the largest explained variability of eGFR decline (R² of 79%). In this model, the contribution of each biomarker dropped below 1%.

“Given the inferior performance of this highly selected set of biomarkers in early-stage [chronic kidney disease] patients to predict future eGFR loss, these markers are not likely to be useful for clinical decision making,” the researchers wrote.

Reference

Heinzel A, Kammer M, Mayer G, et al. Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes [published online July 6, 2018]. Diabetes Care. doi:10.2337/dc18-0532.