Urinary Epidermal Growth Factor Investigated for Diabetes Nephropathy

Type 1 diabetes mellitus is an auto-immune metabolic disease with chronic hyperglycemia. For many patients with type 1 diabetes (T1DM), it is challenging to maintain near-normal glucose blood levels and to reduce the risk of both acute (hypoglycemia, ketoacidosis) and chronic microvascular (retinopathy, neuropathy and nephropathy) and macrovascular complications.

Epidermal growth factor (EGF) stimulates cell growth, proliferation and differentiation by binding to its receptor EGFR. In the kidney, EGF is involved in the repairing process of kidney structures. EGF is synthetized along the kidney tubules and excreted into the urine, making urinary EGF a potential hallmark for regenerative functional capacity of the tubulointerstitial compartment of the kidney.

Pediatric Nephrologists at the University of Antwerp (Antwerp, Belgium) and their colleagues included in a study 158 children with type 1 diabetes mellitus and 40 healthy controls. Serum and urine samples were collected three times with an interval of at least one month to determine creatinine (serum and urine), epidermal growth factor and albumin (urine).

The team explored whether urinary epidermal growth factor (uEGF) might serve as an early marker of diabetes nephropathy compared to microalbuminuria in children and adolescents. Urinary EGF was measured using an EGF human Elisa kit (Invitrogen, Waltham, MA, USA). The detection limit of this assay was 3.9 pg/mL. For the comparative analysis in children and adolescents, the scientists corrected the values accounting for growth. Serum and urine creatinine, urine total protein and microalbuminuria were analyzed with the Dimension Vista system (Siemens Healthcare Diagnostics, Deerfield, MA, USA).

The investigators reported that urinary EGF was significantly lower in T1DM compared to healthy children. In children with T1DM, the mean duration of diabetes was 5.49 ± 3.29 years with a mean HbA1c of 7.7 ± 1.0% (60 ± 11 mmol/mol) and a mean insulin need of 0.87 ± 0.20 units/kg/day. Forty-four children (27.8%) were younger than six years when T1DM was diagnosed. A relatively lower glomerular filtration rate (eGFR) was associated with a decreased uEGF. The uEGF was independently associated with eGFR in a multivariate analysis. None of the patients with an eGFR < 90 mL/min/1.73 m2 had microalbuminuria > 30 mg/g creatinine, while 9.5% and 10.1% of the patients with an eGFR 90–110 mL/min/1.73 m2 and > 110 mL/min/1.73 m2 respectively did have microalbuminuria > 30 mg/g creatinine.

The authors concluded that uEGF is a promising ‘next generation’ biomarker associated with early signs of diabetes nephropathy in children and adolescents and worth further investigation as a single biomarker or as one of a multi-biomarker panel. The study was published on July 7, 2021 in the journal Diabetes Research and Clinical Practice.

Related Links:

University of Antwerp
Invitrogen
Siemens Healthcare Diagnostics