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Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes

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  • Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for re

    Rights statement: This is the AAM accepted by Kidney International on 07/01/2016. None of the authors have any competing interests to disclose in relation to the manuscript. This research was supported by an innovation grant from Kidney Research UK, the Edinburgh and Lothians Diabetes Research Foundation and the Chief Scientist Office of the Scottish Government. The ET2DS is funded by the Medical Research Council UK.

    Accepted author manuscript, 141 KB, Word document

    Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Original languageEnglish
Pages (from-to)1125–1135
JournalKidney International
Issue number5
Early online date7 Mar 2016
Publication statusPublished - 1 May 2016


Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycaemia and hypertension synergise to promote renal pathological changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of DN rats compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than x2-fold reduced in DN rats in comparison with controls. To assess the clinical utility of urinary EGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study (ET2DS) who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF:creatinine ratio was associated with new-onset eGFR <60 ml/min/1.73m2 (OR 0.48; 95%CI [0.26-0.90]), rapid (>5% per annum) decline in renal function (OR 0.44; 95%CI [0.27-0.72]) or the composite of both outcomes (OR 0.38; 95%CI [0.24-0.62]). The utility of low uEGF:creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

    Research areas

  • peptidomics, diabetic nephropathy , epidermal growth factor

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