New Test Might Predict Kidney Disease in Pediatric Type 1 Diabetes Patients

A team of researchers led by Ioannis Papassotiriou, PhD, of Aghia Sophia Children’s Hospital in Athens, Greece has successfully tested a method for early diagnosis and treatment of pediatric diabetic nephropathy (kidney disease).

The innovative method was presented during the 68^th AACC Annual Scientific Meeting & Clinical Lab Expo.

Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the kidneys’ glomeruli, located at the start of the organ’s blood filtering system. The disease, which affects about 20-40% of patients with Type 1 and Type 2 diabetes, is characterized by nephrotic syndrome and widespread scarring of the glomeruli, and is a prime reason for dialysis in many developed countries.

In patients with Type 1 diabetes, kidney failure eventually develops in 50% of patients within 10 years after the onset of obvious nephropathy; and in greater than 75% by the 20 year mark.

Diabetic nephropathy is currently diagnosed by detecting increased urinary albumin excretion, but recent research indicates that the risk for developing diabetic nephropathy starts when urinary albumin excretion levels are still within the normal range. If the onset of nephropathy could be detected before urinary albumin rises, patients could potentially start treatment to prevent its development.

In the expo presentation “Evaluation of GDF-15 and YKL-40 as Early Markers of Subclinical Diabetic Nephropathy and Cardiovascular Morbidity in Young Patients with Type 1 Diabetes Mellitus,” researchers showed that two proteins—growth differentiation factor-15 (GDF-15) and chitinase-3-like protein 1 (YKL-40)—could be used to detect diabetic nephropathy at early stages.

GDF-15 is a protein belonging to the transforming growth factor beta superfamily that has a role in regulating inflammatory and apoptotic (cell death) pathways in injured tissues and during disease processes. YKL-40 is a protein able to communicate with other signal transduction pathways to control various physiological processes, such as inflammation, apoptosis, tissue remodeling, cell growth, and angiogenesis (development of new blood vessels).

In the study, 56 patients with Type 1 diabetes (average age 13.1 years) and 49 healthy controls (average age 12.8 years) were recruited. Along with standard blood and urine chemistry, measurements of serum Neutrophil Gelatinase Associated Lipocalin (NGAL), Cystatin C [to determine estimated glomerular filtration rate (eGFR)], YKL-40 and GDF-15 were performed at the baseline (beginning) and again after 12-15 months.

At baseline, average GDF-15 levels were not significantly different between children with diabetes (289.5 pg/mL) and controls (278.6 pg/mL). At re-evaluation, average GDF-15 in patients increased (366.7 pg/mL), and was significantly higher than in controls.

GDF-15 levels correlated negatively with eGFR values and positively with both total cholesterol and LDL-cholesterol at re-evaluation.

Average YKL-40 level in Type 1 diabetes patients increased from baseline (17.4 ng/mL) to re-evaluation (20.5 ng/mL), while no significant difference was observed between patients and controls at baseline.

YKL-40 levels correlated positively with NGAL, GDF-15, total cholesterol and triglycerides concentrations at both time-points of evaluation, indicating that rises in both proteins reflect a decline in kidney function. A positive correlation was also found between YKL-40 levels and Systolic Arterial Pressure (SAP) values at all evaluation points.

“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,” Papassotiriou said in a press release. “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].”

Other findings from additional diabetes related testing studies were also presented during the68^th AACC Annual Scientific Meeting & Clinical Lab Expo:

• “CircRNAs in metabolic disease during pregnancy” —  This study reported preliminary results showing that circular RNAs could be used to predict the development of metabolic disease during pregnancy before its onset.
• “Modified fasting glucose cutpoints reduce unnecessary tolerance testing in pregnant women from a large urban and rural population” — Results from this study showed that changes in the criteria used to diagnose gestational diabetes in pregnant women could reduce the tests for confirmatory glucose tolerance in 198 patients yearly.
• “Do samples without HbA have detected HbA1c?”  — This study investigated how five testing methods for hemoglobin A1c (HbA1c, a widely used biochemical marker for the management of diabetes mellitus) performed in patients who are missing the precursor to hemoglobin A1c, called hemoglobin A.

The AACC Annual Meeting was held July 31 – Aug. 4 in Philadelphia, Pa.

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