1. 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
- Author
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Jonathan R. Manning, David J. Webb, Carolynn Cairns, Jane Goddard, Jackie F. Price, Douglas J. Lamont, Stela McLachlan, Mark W. J. Strachan, John J. Mullins, Boris Betz, Sara J. Jenks, Bryan R. Conway, Andrew D. Cronshaw, and Jeremy Hughes
- Subjects
Male ,Proteomics ,0301 basic medicine ,Receptor, ErbB-2 ,030232 urology & nephrology ,Kaplan-Meier Estimate ,Kidney ,Mass Spectrometry ,Diabetic nephropathy ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Odds Ratio ,Diabetic Nephropathies ,Proteinuria ,Middle Aged ,ErbB Receptors ,epidermal growth factor ,medicine.anatomical_structure ,Nephrology ,Creatinine ,Hypertension ,Disease Progression ,Female ,Rats, Transgenic ,medicine.symptom ,Glomerular Filtration Rate ,medicine.medical_specialty ,Urinary system ,Urology ,Renal function ,Enzyme-Linked Immunosorbent Assay ,Urinalysis ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,medicine ,Animals ,Humans ,Aged ,Chi-Square Distribution ,business.industry ,diabetic nephropathy ,peptidomics ,Odds ratio ,medicine.disease ,Disease Models, Animal ,Logistic Models ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Scotland ,chemistry ,Case-Control Studies ,Multivariate Analysis ,Albuminuria ,business ,Biomarkers - Abstract
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 hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN 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 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m2 (odds ratio 0.48; 95% confidence interval, 0.26–0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27–0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24–0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.
- Published
- 2016
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