New biomarkers may identify diabetic nephropathy earlier than current test

Two newly found biomarkers can detect diabetic nephropathy in children and teenagers earlier than the conventional urine microalbumin test, according to researchers who presented their results August 2, 2016 at the American Association for Clinical Chemistry’s 68th Annual Scientific Meeting & Clinical Lab Expo, held in Philadelphia, PA.

If validated, these risk markers could help pediatric patients get necessary treatment earlier to prevent renal failure, which often follows diabetic nephropathy.

Currently, clinicians detect diabetic nephropathy by measuring increased urinary albumin excretion. But for this study, the investigators pointed to a growing amount of research that suggests that the risk for developing diabetic nephropathy actually begins when levels of urinary albumin excretion are still within the normal range.

The researchers reasoned that if the onset of nephropathy could be detected before urinary albumin begins to rise, then patients could begin treatment earlier to slow or even prevent its development.

The investigators focused on two proteins—GDF-15 and YKL-40—that are believed to be implicated in cardio-renal events. They recruited 56 patients (ages 9 to 15) who had type 1 diabetes and 49 healthy subjects (ages 6 to 19) as controls.

Along with standard blood and urine tests, the researchers measured levels of YKL-40 and GDF-15 in subjects at the beginning of the study and again at 12 to 15 months. The researchers also evaluated subjects’ kidney function by measuring cystatin C and neutrophil gelatinase associated lipocalin (NGAL) at both time points.

At baseline, average YKL-40 and GDF-15 levels were not significantly different between children with diabetes and controls. But after 12 to 15 months, GDF-15 levels in diabetes patients were significantly higher (366.7 pg/mL) than in healthy controls (278.6 pg/mL). Likewise, mean YKL-40 levels in diabetes patients also increased (from 17.4 ng/mL to 20.5 ng/mL).

In addition, GDF-15 levels correlated negatively with estimated glomerular filtration rates (eGFR) in patients with diabetes, while YKL-40 levels correlated positively with NGAL and GDF-15—which indicated that rises in both proteins reflected a decline in kidney function.

“This is the first study to demonstrate a predictive role for serum GDF-15 and YKL-40 as early markers of diabetic nephropathy in children and adolescents with [type 1 diabetes] before severe overt nephropathy occurs,” said lead researcher Ioannis Papassotiriou, PhD, of Aghia Sophia Children’s Hospital in Athens, Greece.

“Defining new predictors as supplementary tests to urinary albumin excretion for the early diagnosis of diabetic nephropathy could accelerate effective management and treatment approaches needed to minimize the rates of severe renal morbidity and mortality in young patients with [type 1 diabetes],” Dr. Papassotiriou predicted.